What are the signs of insulin reaction. How can diabetic shock be prevented. What causes hypoglycemia in diabetics. When should you seek emergency care for low blood sugar. How is severe hypoglycemia treated.

Understanding Diabetic Shock and Insulin Reactions

Diabetic shock, also known as severe hypoglycemia or insulin reaction, is a serious condition that can affect individuals with diabetes. It occurs when there’s an imbalance between the insulin in the body, food intake, and physical activity levels. This potentially life-threatening situation requires immediate attention and understanding to manage effectively.

What is Hypoglycemia?

Hypoglycemia refers to abnormally low blood sugar levels. Our body’s cells rely on sugar from carbohydrates for energy, and insulin plays a crucial role in allowing this sugar to enter the cells. In individuals with diabetes, the body either doesn’t produce enough insulin or can’t use it effectively, necessitating careful management of blood sugar levels through medication, diet, and lifestyle choices.

Causes of Hypoglycemia in Diabetics

Several factors can trigger hypoglycemia in individuals with diabetes:

• Increased physical activity without adjusting insulin or food intake
• Skipping or delaying meals
• Changes in usual eating patterns or portion sizes
• Incorrect dosage or timing of insulin or diabetes medication
• Excessive alcohol consumption without food

Understanding these triggers is essential for preventing insulin reactions and maintaining stable blood sugar levels.

Recognizing the Symptoms of Insulin Reaction

The symptoms of hypoglycemia can range from mild to severe. Recognizing these signs early is crucial for prompt treatment and prevention of complications.

Mild to Moderate Symptoms

Early signs of an insulin reaction may include:

• Shakiness or trembling
• Sweating
• Hunger
• Rapid heartbeat
• Anxiety or nervousness
• Irritability
• Pale skin
• Fatigue
• Difficulty concentrating

Severe Symptoms

As hypoglycemia progresses, more serious symptoms may develop:

• Confusion or disorientation
• Seizures
• Loss of consciousness
• Difficulty speaking
• Blurred or double vision
• Headaches
• Weakness

Nocturnal Hypoglycemia

Hypoglycemia can also occur during sleep, presenting with symptoms such as:

• Crying out or having nightmares
• Damp pajamas or sheets from excessive sweating
• Waking up feeling tired, irritable, or confused

Immediate Treatment for Hypoglycemia

Prompt action is crucial when experiencing symptoms of hypoglycemia. For mild to moderate cases, the goal is to quickly raise blood sugar levels.

The 15-15 Rule

A common approach to treating mild hypoglycemia is the 15-15 rule:

1. Consume 15 to 20 grams of fast-acting carbohydrates
2. Wait 15 minutes
3. Recheck blood sugar levels
4. If still low, repeat the process

Quick-acting Carbohydrate Sources

Effective options for raising blood sugar quickly include:

• 3-4 glucose tablets
• 1/2 cup of fruit juice
• 1/2 can of regular soda (not diet)
• 1 tablespoon of sugar, honey, or corn syrup
• 5-6 hard candies

After blood sugar levels normalize, it’s advisable to eat a small snack to prevent recurrence.

Emergency Treatment for Severe Hypoglycemia

Severe hypoglycemia requires immediate medical attention. If an individual loses consciousness or is unable to swallow safely, emergency intervention is necessary.

Glucagon Injection

For severe cases, a glucagon injection may be administered. Glucagon is a hormone that stimulates the liver to release stored glucose into the bloodstream. Family members and caregivers of individuals with diabetes should be trained to use glucagon kits in emergencies.

When to Seek Emergency Care

Call for emergency medical services if:

• The person loses consciousness
• Seizures occur
• Symptoms persist despite treatment
• The individual is unable to swallow safely

Preventing Insulin Reactions and Diabetic Shock

Prevention is key in managing diabetes and avoiding dangerous hypoglycemic episodes. Several strategies can help minimize the risk of insulin reactions:

Regular Blood Sugar Monitoring

Frequent checking of blood glucose levels helps identify trends and potential problems before they become severe. How often should you check your blood sugar? The frequency depends on your diabetes management plan, but typically includes checks before meals, at bedtime, and sometimes during the night or before driving.

Consistent Meal Planning

Maintaining a regular eating schedule and balancing carbohydrate intake with insulin dosage is crucial. Working with a registered dietitian can help create a meal plan that suits your lifestyle and diabetes management needs.

Adjusting Insulin for Activity

Physical activity can lower blood sugar levels. How can you safely exercise with diabetes? Consult with your healthcare provider about adjusting insulin doses or having a snack before exercising to prevent hypoglycemia.

Alcohol Awareness

Alcohol can cause delayed hypoglycemia, especially when consumed without food. If you choose to drink, do so in moderation and always with a meal or snack.

Education for Family and Friends

Ensure that those close to you know the signs of hypoglycemia and how to respond. This includes teaching them how to use glucagon kits in emergencies.

Long-term Management of Diabetes to Prevent Complications

While managing acute hypoglycemic episodes is crucial, long-term diabetes management is equally important in preventing complications and maintaining overall health.

Regular Medical Check-ups

Routine visits to your healthcare provider allow for adjustments to your diabetes management plan and early detection of any complications. How often should diabetics see their doctor? Typically, visits are recommended every 3-6 months, but this may vary based on individual needs.

Continuous Glucose Monitoring (CGM)

CGM devices can provide real-time data on blood sugar levels, helping to identify trends and prevent hypoglycemic episodes. These devices can be particularly useful for those prone to frequent or severe low blood sugar events.

Medication Management

Work closely with your healthcare provider to ensure your insulin or other diabetes medications are optimally dosed. This may involve periodic adjustments based on your blood sugar patterns, lifestyle changes, or other health factors.

Stress Management

Stress can affect blood sugar levels. Incorporating stress-reduction techniques such as meditation, yoga, or regular exercise can contribute to better diabetes management.

Emerging Technologies in Diabetes Management

Advancements in technology are continually improving the landscape of diabetes care, offering new tools to prevent and manage hypoglycemia.

Artificial Pancreas Systems

These closed-loop systems combine continuous glucose monitoring with insulin pump technology to automatically adjust insulin delivery based on real-time blood sugar data. How do artificial pancreas systems work? They use algorithms to predict blood sugar trends and adjust insulin dosage accordingly, mimicking the function of a healthy pancreas.

Smart Insulin Pens

These devices can track insulin doses and timing, and some can even suggest dose adjustments based on blood sugar readings and carbohydrate intake.

Diabetes Management Apps

Smartphone applications can help track blood sugar levels, medication doses, diet, and exercise, providing valuable insights and reminders to support diabetes management.

By understanding the causes, symptoms, and treatments of diabetic shock and insulin reactions, individuals with diabetes can better manage their condition and reduce the risk of severe hypoglycemic episodes. Regular monitoring, consistent self-care, and staying informed about the latest management strategies are key to maintaining stable blood sugar levels and overall health. Remember, diabetes management is a collaborative effort between you and your healthcare team, so don’t hesitate to reach out for support and guidance in navigating the complexities of this condition.

Diabetic Shock and Insulin Reactions: Causes, Symptoms, and Treatments

Severe hypoglycemia, or insulin shock, is a serious health risk for anyone with diabetes. Also called insulin reaction, bcause of too much insulin, it can occur anytime there is an imbalance between the insulin in your system, the amount of food you eat, or your level of physical activity. It can even happen while you are doing all you think you can do to manage your diabetes.

The symptoms of insulin shock may seem mild at first. But they should not be ignored. If it isn’t treated quickly, hypoglycemia can become a very serious condition that causes you to faint, requiring immediate medical attention. Insulin shock can also lead to a coma and death. It’s important that not only you, but your family and others around you, learn to recognize the signs of hypoglycemia and know what to do about them. It could save your life.

What Is Hypoglycemia?

Hypoglycemia is a low level of blood sugar. The cells in your body use sugar from carbohydrates for energy. Insulin, which normally is made in the pancreas, is necessary for sugar to enter the cells. It helps keep the levels of sugar in the blood from getting too high.

It’s important to maintain the proper level of sugar in your blood. Levels that are too high can cause severe dehydration, which can be life-threatening. Over time, excess sugar in the body does serious damage to organs such as your heart, eyes, and nervous system.

Ordinarily, the production of insulin is regulated inside your body so that you naturally have the amount of insulin you need to help control the level of sugar. But if your body doesn’t make its own insulin or if it can’t effectively use the insulin it does produce, you need to inject insulin as a medicine or take another medication that will increase the amount of insulin your body does make. So if you need to medicate with insulin, it becomes your responsibility to see that you have the amount of insulin you need when you need it.

When to take insulin or another medication and how much to use depends on when, what, and how much food you eat. It also depends on your level of physical activity since the cells in your body use more sugar when you are active. Hypoglycemia is a reaction to too much insulin in your system. The insulin speeds up the lowering of the blood glucose level. Then without eating or with your body burning sugar faster because of physical activity, the level of sugar becomes dangerously low.

What Causes Hypoglycemia?

Several things can cause hypoglycemia. Your blood sugar level could be low if you:

• Become more physically active than usual
• Miss a meal
• Change when or how much you normally eat
• Take your insulin or medication in a different amount or at a different time than usual
• Drink alcohol excessively without eating

Are There Symptoms of Hypoglycemia or Warning Signs of Insulin Shock?

The symptoms of hypoglycemia can be classified as mild or early, moderate, and severe. Mild symptoms include:

When hypoglycemia becomes severe, symptoms may include:

Hypoglycemia can also occur overnight while you sleep. Symptoms may include:

• Crying out in your sleep
• Nightmares
• Damp pajamas or sheets resulting from perspiration
• Waking tired, irritable, or confused

If you experience any possible signs of mild hypoglycemia, it’s important to check your blood sugar if you can to make sure it isn’t low. If it is, you should treat it quickly or seek emergency care. If you can’t check your blood sugar level for some reason, you should go ahead and treat yourself for low blood sugar if you notice symptoms or seek emergency care. If symptoms are severe or you are unable to help yourself, seek emergency medical attention.

How Is Hypoglycemia Treated?

If your hypoglycemia is mild or moderate, the best way to raise your blood sugar level quickly is to eat or drink something that contains 15 to 20 grams of glucose or other sugar. You might take 3 to 4 glucose tablets or 1/3 to 1/2 tube of glucose in gel form, which you can buy at the drugstore. Or you may want to drink a half cup of fruit juice (orange juice or apple juice).

Other snacks you can use to raise your sugar level include:

• One-half cup of regular soda — not diet
• Cup of milk
• 1 tablespoon of sugar
• 1 tablespoon of honey, molasses, or corn syrup
• One-quarter cup raisins
• 2 large or 6 small sugar cubes dissolved in water
• 5 hard candies

You can also ask your doctor or dietitian for recommendations for other snack items that can help raise your blood sugar level when you need to.

After you’ve taken a snack, wait 15 minutes and check your blood sugar level again. If it is still low, eat another snack, then wait 15 minutes and check it again. Repeat the process until your blood sugar level is in its normal target range. Following that, eat another small snack if your regular meal is more than an hour away, such as half a sandwich, 1 ounce of cheese with 4 to 6 crackers, or 1 tablespoon peanut butter with 4 to 6 crackers.

If you lose consciousness, you will need immediate medical attention. It’s important that you educate the people in your family and the people you work with about insulin shock and about what to do if it happens. Someone should call 911 or arrange to get you to an emergency room if that’s not possible. If you go to the hospital, doctors may give sugar through a vein (intravenously).

You can ask your doctor to prescribe a glucagon rescue kit and then teach others how to use it. Glucagon is a natural hormone that rapidly causes the level of sugar in your blood to rise. If you are unconscious, someone injecting you with glucagon even before emergency help arrives can prevent further complications and help you recover.

Diabetic Insulin Reaction

You’ve been treated for an insulin reaction today. You had low blood sugar (hypoglycemia). This happens when insulin causes your blood sugar to get too low.

Your blood sugar may drop if you take too much insulin. Or it may happen when you take your normal amount of insulin but don’t get enough food. This can be from vomiting or loss of appetite. Other causes of low blood sugar are:

• Heavy exercise

• Strong emotions

• Alcohol

• Tobacco

• Caffeine

Some medicines can also affect blood sugar. These include:

Try caffeine-free drinks if you think caffeine may lower your blood sugar. If you smoke, get help to quit. This is one of the best things you can do to protect your health. If you take any of the medicines listed above, talk with your healthcare provider about switching to some other type.

A class of medicines called beta-blockers is used for high blood pressure, rapid heart rate, and other health problems. These may mask the early signs of low blood sugar. You may not know when your blood sugar is getting low. If you are taking a beta-blocker, talk with your healthcare provider about switching to a different class. Some beta-blockers are:

• Propranolol

• Atenolol

• Metoprolol

• Nadolol

• Labetalol

• Carvedilol

Home care

If symptoms of low blood sugar return

• Check your blood sugar 15 minutes after treating yourself. If it’s still low, take another 15 to 20 grams of fast-acting sugar. Test again in 15 minutes. If it’s still low, go to an emergency room.

• Once your blood sugar is normal again, eat a snack or meal with protein to keep your blood sugar in a safe range.

In the future, you may need to lower your insulin dose if you aren’t able to eat your normal amount at each meal because of illness or vomiting. Call your healthcare provider right away. Ask him or her about changing your dose for a little bit.

Check your blood sugar every 4 to 6 hours. Do this until you can start eating normal amounts again.

Wear a medical alert bracelet or necklace or carry a card in your wallet that says you have diabetes. It will help healthcare providers give you correct care if you have a severe low blood sugar reaction and can’t tell them you have the disease.

Follow-up care

Follow up with your healthcare provider, or as advised.

Check and write down your blood sugar and insulin dose twice a day. Do this before breakfast and before dinner. Do this for the next 5 days. See your healthcare provider in the next week to review these records. This will help tell if you need to change your insulin dose.

If you often have episodes of low blood sugar, your healthcare provider may give you glucagon shots. Or the provider may give you these shots if your episodes of low blood sugar are severe. These shots quickly raise your blood sugar. One of your family members or friends will need to learn how to give you this shot.

To learn more about diabetes, visit the American Diabetes Association’s website at www.diabetes.org.

When to seek medical advice

Call your healthcare provider right away if any of these symptoms of low blood sugar occur and they don’t go away with the above steps:

Call

911

Call 911 or get emergency care if any of these occur and don’t go away quickly with the above steps:

Insulin Side Effects

If you have recently been prescribed insulin, or have switched to a new type of insulin, you may be concerned about the side effects.

You might also be experiencing side effects and not know where they are coming from.

Similarly, you may be looking for information for a friend or family member.

What are the side effects of insulin?

Insulin side effects amongst diabetics are rare, but when they do occur, allergic reactions can be severe and can pose a significant risk to health.

What do I do if I have an adverse reaction to my insulin?

If you experience mild allergic reactions such as swelling, itching or redness around the injection site, experts advise diabetics to consult their GPs. Similarly, sustained nausea and vomiting are signs of insulin allergy.

How do I know if my insulin is working?

When taking insulin, diabetics are advised by experts to regularly check blood glucose levels using testing kits.

If blood glucose tests show fluctuating or above-average blood sugar levels, diabetes is not being properly controlled and insulin is not working.

Transcript

Insulin is the oldest medication for diabetes and is usually well tolerated by most people. There are various side effects that occur from insulin. Hypoglycemia is the most common, but not the only one. The side effects mentioned in this video are those that are included in patient information leaflets for a number of different insulin types.

Check your insulin’s patient information leaflet to see which side effects are listed as applicable to the insulin you are taking. If you notice any of the side effects, tell your doctor.

Insulin is injected to reduce blood glucose levels and may lead to hypoglycemia. Hypoglycemia is a low blood glucose level which should be treated with carbohydrate. For more information on this specific area please see our treating hypoglycemia video

Some people may get a local allergy –that is itching, redness or swelling at the site of the injection. This will usually clear up within a few days or weeks.

In rare some cases people may get a more severe allergic reaction, known as a systemic allergy, which can include:

• A rash across the body
• Trouble breathing
• Nausea
• Rapid heartbeat
• Sweating
• Drop in blood pressure

Tell your doctor immediately if you have these symptoms.

Lipodystrophy is a relatively rare side effect that causes thickening or pitting of the skin.
It can be described as an abnormality in the way fat is distributed. If you notice bulges or any caving in of the skin, speak to your doctor.

Oedema is known as a swelling of the arms or ankles as a result of fluid retention. Oedema may result from starting or a change to insulin therapy.

And finally, some types of insulin list eyesight problems as a rarer side effect.

Download a FREE insulin duration chart for your phone, desktop or as a printout.

Avoiding infection when taking insulin

When taking insulin, try to avoid infection by using disposable needles and syringes, and sterilising any reusable equipment.

Do some drugs interact with insulin?

Some drugs are known to interact with insulin, and diabetics should be aware of this list. Your GP or physician should provide detailed information of how any extra drug affects insulin.

Some medications that are known to influence insulin are shown below, but diabetics should consult their GP for further information:

• ACE inhibitors – Accupril and Lotensin
• Anabolic steroids – Anadrol-50
• Appetite suppressants – Tenuate
• Aspirin
• Beta-blocking blood pressure medicines – Tenormin and Lopressor
• Diuretics – Lasix and Dyazide
• Epinephrine (EpiPen)
• Estrogens – Premarin
• Isoniazid (Nydrazid)
• Major tranquilizers – Mellaril and Thorazine
• MAO inhibitors (antidepressants Nardil and Parnate)
• Niacin (Nicobid)
• Octreotide (Sandostatin)
• Oral contraceptives
• Oral drugs for diabetes – Diabinese and Orinase
• Phenytoin (Dilantin)
• Steroid medications – prednisone
• Sulfa antibiotics – Bactrim and Septra
• Thyroid medications – Synthroid

If you cannot find the answers that you need here, please ask a question in the Diabetes Forum

Which are the signs and symptoms of insulin allergy?

Hypoglycemia (Low Blood Glucose) | ADA

Throughout the day, depending on multiple factors, blood sugar (also called blood glucose) levels will vary—up or down. This is normal. If it varies within a certain range, you probably won’t be able to tell. But if it goes below the healthy range and is not treated, it can get dangerous.

Low blood sugar is when your blood sugar levels have fallen low enough that you need to take action to bring them back to your target range. This is usually when your blood sugar is less than 70 mg/dL. However, talk to your diabetes care team about your own blood sugar targets, and what level is too low for you.

Low blood sugar may also be referred to as an insulin reaction, or insulin shock.

Signs and symptoms of low blood sugar (happen quickly)

Each person’s reaction to low blood sugar is different. Learn your own signs and symptoms of when your blood sugar is low. Taking time to write these symptoms down may help you learn your own symptoms of when your blood sugar is low. From milder, more common indicators to most severe, signs and symptoms of low blood sugar include:

• Feeling shaky
• Being nervous or anxious
• Sweating, chills and clamminess
• Irritability or impatience
• Confusion
• Fast heartbeat
• Feeling lightheaded or dizzy
• Hunger
• Nausea
• Color draining from the skin (pallor)
• Feeling sleepy
• Feeling weak or having no energy
• Blurred/impaired vision
• Tingling or numbness in the lips, tongue or cheeks
• Headaches
• Coordination problems, clumsiness
• Nightmares or crying out during sleep
• Seizures

The only sure way to know whether you are experiencing low blood sugar is to check your blood sugar, if possible. If you are experiencing symptoms and you are unable to check your blood sugar for any reason, treat the hypoglycemia. 

A low blood sugar level triggers the release of epinephrine (adrenaline), the “fight-or-flight” hormone. Epinephrine is what can cause the symptoms of hypoglycemia such as thumping heart, sweating, tingling and anxiety.

If the blood sugar level continues to drop, the brain does not get enough glucose and stops functioning as it should. This can lead to blurred vision, difficulty concentrating, confused thinking, slurred speech, numbness, and drowsiness. If blood sugar stays low for too long, starving the brain of glucose, it may lead to seizures, coma and very rarely death. 

Treatment—The “15-15 Rule”

The 15-15 rule—have 15 grams of carbohydrate to raise your blood sugar and check it after 15 minutes. If it’s still below 70 mg/dL, have another serving.

Repeat these steps until your blood sugar is at least 70 mg/dL. Once your blood sugar is back to normal, eat a meal or snack to make sure it doesn’t lower again.

This may be:

• Glucose tablets (see instructions)
• Gel tube (see instructions)
• 4 ounces (1/2 cup) of juice or regular soda (not diet)
• 1 tablespoon of sugar, honey, or corn syrup
• Hard candies, jellybeans or gumdrops—see food label for how many to consume

Make a note about any episodes of low blood sugar and talk with your health care team about why it happened. They can suggest ways to avoid low blood sugar in the future. 

Many people tend to want to eat as much as they can until they feel better. This can cause blood sugar levels to shoot way up. Using the step-wise approach of the “15-15 Rule” can help you avoid this, preventing high blood sugar levels.

Note:

• Young children usually need less than 15 grams of carbs to fix a low blood sugar level: Infants may need 6 grams, toddlers may need 8 grams, and small children may need 10 grams. This needs to be individualized for the patient, so discuss the amount needed with your diabetes team.
• When treating a low, the choice of carbohydrate source is important. Complex carbohydrates, or foods that contain fats along with carbs (like chocolate) can slow the absorption of glucose and should not be used to treat an emergency low.

Severe hypoglycemia

When low blood sugar isn’t treated and you need someone to help you recover, it is considered a severe event. 

Treating severe hypoglycemia

Glucagon is a hormone produced in the pancreas that stimulates your liver to release stored glucose into your bloodstream when your blood sugar levels are too low. Glucagon is used to treat someone with diabetes when their blood sugar is too low to treat using the 15-15 rule.

Glucagon is available by prescription and is either injected or administered or puffed into the nostril. For those who are familiar with injectable glucagon, there are now two injectable glucagon products on the market—one that comes in a kit and one that is pre-mixed and ready to use. Speak with your doctor about whether you should buy a glucagon product, and how and when to use it.

The people you are in frequent contact with (for example, friends, family members and coworkers) should be instructed on how to give you glucagon to treat severe hypoglycemia. If you have needed glucagon, let your doctor know so you can discuss ways to prevent severe hypoglycemia in the future.

Find products for dealing with low blood glucose

Steps for treating a person with symptoms keeping them from being able to treat themselves.

1. If the glucagon is injectable, inject it into the buttock, arm or thigh, following the instructions in the kit. If your glucagon is inhalable, follow the instructions on the package to administer it into the nostril.
2. When the person regains consciousness (usually in 5-15 minutes), they may experience nausea and vomiting. 

Don’t hesitate to call 911. If someone is unconscious and glucagon is not available or someone does not know how to use it, call 911 immediately.

Do NOT:

• Inject insulin (it will lower the person’s blood sugar even more)
• Provide food or fluids (they can choke)

Causes of low blood sugar

Low blood sugar is common for people with type 1 diabetes and can occur in people with type 2 diabetes taking insulin or certain medications. The average person with type 1 diabetes may experience up to two episodes of mild low blood sugar each week, and that’s only counting episodes with symptoms. If you add in lows without symptoms and the ones that happen overnight, the number would likely be higher.

Insulin

Too much insulin is a definite cause of low blood sugar. One reason newer insulins are preferred over NPH and regular insulin is that they’re less likely to cause blood sugar lows, particularly overnight. Insulin pumps may also reduce the risk for low blood sugar. Accidentally injecting the wrong insulin type, too much insulin, or injecting directly into the muscle (instead of just under the skin), can cause low blood sugar.

Food

What you eat can cause low blood sugar, including:

• Not enough carbohydrates.
• Eating foods with less carbohydrate than usual without reducing the amount of insulin taken. 
• Timing of insulin based on whether your carbs are from liquids versus solids can affect blood sugar levels. Liquids are absorbed much faster than solids, so timing the insulin dose to the absorption of glucose from foods can be tricky. 
• The composition of the meal—how much fat, protein, and fiber are present—can also affect the absorption of carbohydrates.

Physical activity

Exercise has many benefits. The tricky thing for people with type 1 diabetes is that it can lower blood sugar in both the short and long-term. Nearly half of children in a type 1 diabetes study who exercised an hour during the day experienced a low blood sugar reaction overnight. The intensity, duration and timing of exercise can all affect the risk for going low. 

Medical IDs

Many people with diabetes, particularly those who use insulin, should have a medical ID with them at all times.

In the event of a severe hypoglycemic episode, a car accident or other emergency, the medical ID can provide critical information about the person’s health status, such as the fact that they have diabetes, whether or not they use insulin, whether they have any allergies, etc. Emergency medical personnel are trained to look for a medical ID when they are caring for someone who can’t speak for themselves.

Medical IDs are usually worn as a bracelet or a necklace. Traditional IDs are etched with basic, key health information about the person, and some IDs now include compact USB drives that can carry a person’s full medical record for use in an emergency.

Hypoglycemia unawareness

Very often, hypoglycemia symptoms occur when blood sugar levels fall below 70 mg/dL. As unpleasant as they may be, the symptoms of low blood sugar are useful. These symptoms tell you that you your blood sugar is low and you need to take action to bring it back into a safe range. But, many people have blood sugar readings below this level and feel no symptoms. This is called hypoglycemia unawareness.

People with hypoglycemia unawareness can’t tell when their blood sugar gets low so they don’t know they need to treat it. Hypoglycemia unawareness puts the person at increased risk for severe low blood sugar reactions (when they need someone to help them recover). People with hypoglycemia unawareness are also less likely to be awakened from sleep when hypoglycemia occurs at night. People with hypoglycemia unawareness need to take extra care to check blood sugar frequently. This is especially important prior to and during critical tasks such as driving. A continuous glucose monitor (CGM) can sound an alarm when blood sugar levels are low or start to fall. This can be a big help for people with hypoglycemia unawareness.

Hypoglycemia unawareness occurs more frequently in those who:

• Frequently have low blood sugar episodes (which can cause you to stop sensing the early warning signs of hypoglycemia).
• Have had diabetes for a long time.
• Tightly control their diabetes (which increases your chances of having low blood sugar reactions).

If you think you have hypoglycemia unawareness, speak with your health care provider. Your health care provider may adjust/raise your blood sugar targets to avoid further hypoglycemia and risk of future episodes.

Regaining hypoglycemia awareness

It’s possible to get your early warning symptoms back by avoiding any, even mild, hypoglycemia for several weeks. This helps your body re-learn how to react to low blood sugar levels. This may mean increasing your target blood sugar level (a new target that needs to be worked out with your diabetes care team). It may even result in a higher A1C level, but regaining the ability to feel symptoms of lows is worth the temporary rise in blood sugar levels.

Other causes of symptoms

Other people may start to have symptoms of hypoglycemia when their blood sugar levels are higher than 70 mg/dL. This can happen when your blood sugar levels are very high and start to go down quickly. If this is happening, discuss treatment with your diabetes care team.

How can I prevent low blood sugar?

Your best bet is to practice good diabetes management and learn to detect hypoglycemia so you can treat it early—before it gets worse.

Monitoring blood sugar, with either a meter or a CGM, is the tried and true method for preventing hypoglycemia. Studies consistently show that the more a person checks blood sugar, the lower his or her risk of hypoglycemia. This is because you can see when blood sugar levels are dropping and can treat it before it gets too low.

If you can, check often!  

• Check before and after meals.
• Check before and after exercise (or during, if it’s a long or intense session).
• Check before bed.
• After intense exercise, also check in the middle of the night.
• Check more if things around you change such as, a new insulin routine, a different work schedule, an increase in physical activity, or travel across time zones.

Why am I having lows?

If you are experiencing low blood sugar and you’re not sure why, bring a record of blood sugar, insulin, exercise and food data to a health care provider. Together, you can review all your data to figure out the cause of the lows. 

The more information you can give your health care provider, the better they can work with you to understand what’s causing the lows. Your provider may be able to help prevent low blood sugar by adjusting the timing of insulin dosing, exercise and meals or snacks. Changing insulin doses or the types of food you eat may also do the trick.

If you’re new to type 2 diabetes, join our free Living With Type 2 Diabetes program to get help and support during your first year.

Insulin Allergies + Type 1

Read Help Get Answers for Jack – a story of an 8-year-old boy who suffers a severe allergy to insulin, the life-saving medicine required for managing his Type 1 diabetes.

Editor’s Note: If you suspect you have an allergy to insulin or any item that is a part of your Type 1 diabetes management, consult your physician and diabetes team. This article has been verified by Dan Desalvo, MD, Assistant Professor of Pediatrics in Pediatric Diabetes & Endocrinology at Baylor College of Medicine/Texas Children’s Hospital. 

Now imagine being allergic to the very thing that keeps you alive. Allergic reactions to insulin are rare, but they do exist.

What is an insulin allergy?

Adverse reactions to insulin can occur as soon as 30 seconds after an insulin injection or later, after several minutes or even after hours have passed (INDependent Diabetes Trust). It’s possible that someone with Type 1 could be allergic to one type of insulin, but not another. Just over 2% of people with diabetes exhibit some signs of an allergy to insulin, most commonly a local reaction (Insulin Nation).

Why do allergic reactions to insulin occur?

Before the 1980s, bovine (beef) and porcine (pork) insulin preparations were common, and often triggered allergic reactions. Fortunately, adverse reactions to insulin have significantly diminished since the introduction of scientifically engineered human insulin preparations in the 1980s. However, even with the genetically modified human insulins available today, allergic reactions still occur (though rarely) and can be quite dangerous. In some cases, the allergic reaction is to the insulin molecule itself, but it may also be to different types of fillers, preservatives, or amino acid combinations found in various insulin preparations (Joslin Diabetes Center).

Signs and Symptoms

If you’re allergic to insulin, you might experience a localized reaction near the injection site. You may also develop a systemic reaction, which is much more rare, and affects the entire body, usually over a longer period of time.

Symptoms to look out for include:

• Irritation, swelling, or hives at injection site
• Rash throughout the body
• Low blood pressure
• Shortness of breath
• Anaphylaxis (throat and mouth swelling that restricts airways) – a life-threatening reaction

What does it mean for people with Type 1?

As we all know, with Type 1, insulin is necessary for survival, so stopping insulin is not a choice. Discovering the exact cause of the allergic reaction is important, so doctors will typically run tests to identify if a particular type of insulin, preservative or delivery method is the culprit.

Treatment options include taking antihistamines to help minimize allergy symptoms, as well as steroids to dampen the immune system’s negative response to insulin (Joslin Diabetes Center). In some cases, giving small doses of insulin subcutaneously (via a pump) with low basal rates and avoiding large bolus doses, may desensitize the body, and the adverse reactions will stop. Sometimes, simply switching from one type of insulin to another can solve the problem.

“Specific immunotherapy” has been successful in treating severe cases of insulin allergy that do not respond to other treatments. Specific immunotherapy consists of giving a very tiny dose of insulin initially (i.e. 0.00001 units), and slowly increasing the dose over a couple of days to allow the body to desensitize to insulin.  It requires close monitoring in the hospital setting in case of an emergency.

What to do in the event of a possible insulin allergy 

Let your doctor and your diabetes team know right away. You’ll likely need to see an allergist and get a skin prick test or undergo intradermal testing to determine the exact cause of the reaction.

The course of treatment depends on the severity and the ultimate cause of the reaction. Several studies report that taking insulin inconsistently can aggravate allergy symptoms or cause them to reappear.

If you feel that the type of insulin you’re taking isn’t right for you or that you could better manage your Type 1 with another treatment approach, don’t be afraid to speak up and tell your diabetes team. Do your own research, know your body and be an informed consumer of your insulin.

Be sure to rule out the possibilities of an allergic reaction to the following:

• Type or brand of insulin
• Infusion set cannula (tubing that goes under skin) in pumps
• Metal of needle
• Tape or adhesive
• Preservative in the insulins (type of preservative used may vary in insulins)

Possible treatments your doctor may recommend:

• Trying a different type of insulin
• The use of antihistamines
• Desensitization (slowly and consistently introducing an insulin, usually with an insulin pump at low basal rate)
• The temporary use of a steroid
• Adding cortisone (steroid) to the insulin injection
• Switching to multiple daily injections (MDI) from a pump (if the cannula)
• Trying different adhesives

REFERENCES –

Diabetes U.K.: Animal Insulin, History of Insulin

Diabetic Lifestyle: Insulin: Its History and Future

Heinzerling, L., Raile, K., Rochlitz, H., Zuberbier, T., Worm, M. “Insulin allergy: clinical manifestations and management strategies.” Allergy: European Journal of Allergy and Clinical Immunology, 2008 Jan: 63(2): 1398-9995.

Joslin Diabetes Center: Insulin Allergies

InDependent Diabetes Trust: Choices—The Evidence, Allergic Reactions to Insulin

Insulin Nation: Insulin Allergies are For Real

Read Help Get Answers for Jack.

Diabetic hypoglycemia – Symptoms and causes

Overview

Diabetic hypoglycemia occurs when someone with diabetes doesn’t have enough sugar (glucose) in his or her blood. Glucose is the main source of fuel for the body and brain, so you can’t function well if you don’t have enough.

Low blood sugar (hypoglycemia) is defined as a blood sugar level below 70 milligrams per deciliter (mg/dL), or 3.9 millimoles per liter (mmol/L).

Pay attention to the early warning signs of hypoglycemia, and treat low blood sugar promptly. You can raise your blood sugar quickly by eating or drinking a simple sugar source, such as glucose tablets or fruit juice. Tell family and friends what symptoms to look for and what to do if you’re not able to treat the condition yourself.

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Symptoms

Early warning signs and symptoms

Initial signs and symptoms of diabetic hypoglycemia include:

• Shakiness
• Dizziness
• Sweating
• Hunger
• Fast heartbeat
• Inability to concentrate
• Confusion
• Irritability or moodiness
• Anxiety or nervousness
• Headache

Nighttime signs and symptoms

If diabetic hypoglycemia occurs when you’re sleeping, signs and symptoms that may awaken you include:

• Damp sheets or nightclothes due to perspiration
• Nightmares
• Tiredness, irritability or confusion upon waking

Severe signs and symptoms

If diabetic hypoglycemia isn’t treated, signs and symptoms of severe hypoglycemia can occur. These include:

• Clumsiness or jerky movements
• Inability to eat or drink
• Muscle weakness
• Difficulty speaking or slurred speech
• Blurry or double vision
• Drowsiness
• Confusion
• Convulsions or seizures
• Unconsciousness
• Death, rarely

Symptoms can differ from person to person or from episode to episode. Some people don’t have any noticeable symptoms. It’s also possible you won’t have any symptoms of hypoglycemia, so it’s important to monitor your blood sugar levels regularly and keep track of how you’re feeling when your blood sugar is low.

When to see a doctor

Severe hypoglycemia can lead to serious problems, including seizures or unconsciousness, that require emergency care. Make sure your family, friends and co-workers know what to do in an emergency.

If you’re with someone who loses consciousness or can’t swallow due to low blood sugar:

• Don’t inject insulin, as this will cause blood sugar levels to drop even further
• Don’t give fluids or food, because these could cause choking
• Give glucagon — a hormone that stimulates the release of sugar into the blood — through injection or nasally
• Call 911 or emergency services in your area for immediate treatment if glucagon isn’t on hand

If you have symptoms of hypoglycemia several times a week or more, see your doctor. You may need to change your medication dosage or timing, or otherwise adjust your diabetes treatment regimen.

Causes

Low blood sugar is most common among people who take insulin, but it can also occur if you’re taking certain oral diabetes medications.

Common causes of diabetic hypoglycemia include:

• Taking too much insulin or diabetes medication
• Not eating enough
• Postponing or skipping a meal or snack
• Increasing exercise or physical activity without eating more or adjusting your medications
• Drinking alcohol

Blood sugar regulation

The hormone insulin lowers blood sugar levels when blood sugar is too high. If you have type 1 or type 2 diabetes and need insulin to control your blood sugar, taking more insulin than you need can cause your blood sugar level to drop too low and result in hypoglycemia.

Your blood sugar can also drop too low if, after taking your diabetes medication, you eat less than usual (most of the body’s glucose comes from food), or if you exercise more than you normally do, which uses extra glucose. Maintaining the balance between insulin, food and activity isn’t always easy, but your doctor or diabetes educator can work with you to try to prevent low blood sugar levels.

Risk factors

Some people have a greater risk of diabetic hypoglycemia, including:

• People using insulin
• People taking certain oral diabetes drugs (sulfonylureas)
• Young children and older adults
• Those with impaired liver or kidney function
• People who’ve had diabetes for a longer time
• People who don’t feel low blood sugar symptoms (hypoglycemia unawareness)
• Those taking multiple medications
• Anyone with a disability that prevents a quick response to falling blood sugar levels
• People who drink alcohol

Complications

If you ignore the symptoms of hypoglycemia too long, you may lose consciousness. That’s because your brain needs glucose to function. Recognize the signs and symptoms of hypoglycemia early, because if untreated, hypoglycemia can lead to:

• Seizures
• Loss of consciousness
• Death

Take your early symptoms seriously. Diabetic hypoglycemia can increase the risk of serious — even deadly — accidents.

Prevention

To help prevent diabetic hypoglycemia:

• Monitor your blood sugar. Depending on your treatment plan, you may check and record your blood sugar level several times a week or multiple times a day. Careful monitoring is the only way to make sure that your blood sugar level remains within your target range.
• Don’t skip or delay meals or snacks. If you take insulin or oral diabetes medication, be consistent about the amount you eat and the timing of your meals and snacks.
• Measure medication carefully, and take it on time. Take your medication as recommended by your doctor.
• Adjust your medication or eat additional snacks if you increase your physical activity. The adjustment depends on the blood sugar test results, the type and length of the activity, and what medications you take.
• Eat a meal or snack with alcohol, if you choose to drink. Drinking alcohol on an empty stomach can cause hypoglycemia. Alcohol may also cause delayed hypoglycemia hours later, making blood sugar monitoring even more important.
• Record your low glucose reactions. This can help you and your health care team identify patterns contributing to hypoglycemia and find ways to prevent them.
• Carry some form of diabetes identification so that in an emergency others will know that you have diabetes. Use a medical identification necklace or bracelet and wallet card.

90,000 Insulin reaction (hypoglycemia) – Medical center “Liko-Med”

What is an insulin response (hypoglycemia)?

Insulin reaction – a decrease in the amount of sugar in the blood to a level below normal (70 mg / dl, 3.5 mmol / l) in patients with diabetes as a result of skipping meals, increased physical activity or the use of a large dose of insulin. Hypoglycemia causes confusion, excessive sweating, hunger, headache, and fatigue. If not taken care of, low blood sugar can cause fainting, seizures, or coma.Therefore, it is important to recognize the insulin response in time and return the sugar level to normal. All you need to do is drink fruit juice, eat lollipop, or take glucose tablets.

Ambulance.

Seek emergency help immediately if your symptoms do not improve after consuming glucose, convulsions, or fainting.

What to expect?

The first signs of low blood sugar are hunger and feeling warm.This is followed by confusion, fatigue, sweating, anxiety, and headache. Symptoms differ from person to person. Critically low blood sugar levels can lead to fainting, seizures, and coma. To avoid severe symptoms of hypoglycemia, follow your diabetes treatment plan and control your blood sugar. Taking action to raise blood sugar as soon as symptoms appear is the main treatment for hypoglycemia.

How does it get worse?

Lack of measures to increase the amount of sugar in the blood at the time of the onset of symptoms.Drinking alcohol, skipping meals, being physically active, and taking a large dose of insulin will lower your blood sugar.

Treatment.

Consuming foods or beverages high in glucose usually helps to eliminate the insulin response. In severe cases, glucose injections may be required.

What to do yourself?

You can prevent hypoglycemia on your own by eating about 15 grams of carbohydrates.To do this:

– take three glucose tablets;

– drink half a cup of fruit juice or one glass of milk;

– Eat 5-6 caramels or a tablespoon of sugar.

Please wait 15 minutes. Then re-measure your blood sugar. If it’s still below normal, take another 15 grams of carbs. Repeat until blood sugar levels return. When using long-acting insulin or oral antidiabetic drugs, the blood sugar test should be repeated after a few hours to ensure that there is no insulin response.

When to see a doctor?

See your doctor if your blood sugar drops frequently.

What to ask a doctor?

1. Could the insulin response be caused by a high dose of insulin or a high sugar diet?

2. Do I need to change the dose of the medication?

3. What should I do if the insulin reaction occurs again?

4. How often should blood sugar be measured?

5.Is it possible my symptoms are caused by a condition other than low blood sugar?

Making a diagnosis.

Patients with diabetes mellitus should regularly measure the amount of sugar in their blood. If you have frequent episodes of hypoglycemia, see your doctor to find out if you need dietary changes, exercise, or medication.

90,000 Different persons of insulin resistance

P. M. Schwarzburd,
Doctor of Biological Sciences, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino
“Chemistry and Life” No. 7, 2013

Diabetes

In recent years, many developed countries have faced an epidemic increase in type 2 diabetes mellitus (hereinafter simply “diabetes”).According to a review by University of California professor Jerold Olefsky (“ Cell ”, 2013, 152, 673-687, doi: 10.1016 / j.cell.2013.01.041), more than 300 million people worldwide suffer from this form of diabetes. , of which 55 million in India, 25 million in the United States and 80 million in China, with the number of patients doubling every 10-15 years. Type 2 diabetes develops when some of the patient’s tissues are insensitive to the action of insulin, that is, they acquire insulin resistance.This ailment should not be confused with the rarer type 1 diabetes (juvenile diabetes), a disease in which immune cells, for no reason, attack and destroy the specialized beta cells of the pancreas that produce the hormone insulin.

As a result, the pancreas is unable to synthesize a sufficient amount of insulin, and patients are forced to inject it regularly. Any diabetes is dangerous with severe complications: blindness, blood clotting disorders, blood supply to the extremities, the work of the nervous and cardiovascular systems.

In an effort to combat type 2 diabetes, doctors and researchers are paying particular attention to its formidable precursor – insulin resistance. The main physiological function of insulin is to ensure the flow of glucose from the peripheral blood into cells (primarily muscle and adipose tissue) and to suppress excess glucose production in liver cells. It performs this task by stimulating the expression of special transporter proteins that drag glucose from the peripheral blood through the cell membrane into the cell (Fig.1). As a result of the action of insulin, the number of transporter proteins on the membrane increases 5–10 times, and their content inside the cell decreases by 50–60%.

The sensitivity of cells to insulin depends primarily on the number of insulin receptors and their activity. So, fat cells and hepatocytes (liver cells) contain 200-300 thousand receptors, and monocytes and erythrocytes – an order of magnitude less. The number of receptors and their affinity (affinity) for insulin are variable: in healthy people they are higher in the evening and at night, and lower in the morning; increase with physical exertion, decrease in the elderly.Normally, insulin also causes relaxation of the smooth muscle wall of blood vessels due to the release of nitric oxide, but this ability is also impaired in patients with insulin resistance and obesity.

If the susceptibility of peripheral tissues to the action of insulin for some reason is reduced, a person develops compensatory hyperinsulinemia – his pancreas synthesizes and releases an increased amount of insulin into the blood. As long as beta cells can work in an emergency mode and maintain a level of the hormone in the blood plasma sufficient to overcome insulin resistance, patients maintain a normal blood sugar concentration.However, the reserves of the pancreas are not unlimited, the beta cells “run out”, and then the sugar level begins to rise.

The situation is aggravated by the fact that the liver does not work properly with insulin resistance. Usually, this organ maintains the required concentration of sugar by breaking down glycogen or synthesizing glucose from non-carbon substances. When insulin levels rise, a healthy liver decreases glucose production. And with insulin resistance, the liver, as if nothing had happened, continues to throw it into the blood, which causes hyperglycemia in a hungry patient.

In other words, when beta cells lose their ability to constantly increase hormone production, insulin resistance spills over into type 2 diabetes mellitus, which is characterized by a chronic lack of insulin and, as a result, increased blood glucose. However, the blood sugar level is only an indicator of the problem, the essence of which is that glucose cannot enter the cells, they starve and do not perform their functions well.

The question of the causes of insulin resistance remains open.It was found that it develops more often with overweight and obesity, in people over 45 years old, with insufficient physical activity, stress and high blood pressure. How does obesity contribute to the development of insulin resistance?

Obesity and inflammation

Specialists from the US National Diabetes Institute have studied the Pima Indians living in Arizona and Mexico for over 30 years. They found that half of all adult Indians living on Arizona reservations have diabetes and 95% of them are obese, while Mexican Pimas are rare and obese because they eat low-calorie, high-content foods. dietary fiber and physically much more active than their foreign counterparts.The researchers concluded that obesity is the main risk factor for type 2 diabetes. Moreover, the risk of obesity can be reduced even with a hereditary predisposition to it, if you lead a correct lifestyle.

In recent decades, there has been an epidemic increase in the number of overweight people (see: Caloria and its history, “Chemistry and Life”, 2013, No. 2). Thus, in the United States, about 65% of adults are overweight and about 32% are obese. As we remember, obesity is often combined with insulin resistance.If a person’s weight exceeds ideal by 35-40%, then insulin sensitivity decreases by more than 40%. The development of insulin resistance is also facilitated by the increased release of fatty acids from adipocytes (adipose tissue cells) into the blood. Clinical studies have shown that pharmacological lipolysis inhibitors (drugs that slow the breakdown of fats and thereby lower the level of fatty acids in the blood) can quickly restore insulin sensitivity in obese patients. Weight loss also reduces fatty acid flow and improves insulin sensitivity.

There are two main ways of energy supply in the body: “daytime” and “nighttime”. With the “day” method of energy supply, the main source of energy is glucose and, to a lesser extent, fat. At night, on the contrary, the body draws energy mainly from fatty acids that enter the bloodstream during the breakdown of fatty deposits. According to the Leningrad medical professor Vladimir Mikhailovich Dilman, with obesity, the mechanism of daily switching of energy homeostasis is disturbed, and the body switches mainly to the fat supply path.But why is this happening?

It is known that in an adult organism the number of fat cells is constant. The accumulation of fat increases the volume of the adipocyte, which leads to a decrease in the density of insulin receptors on its enlarged surface, and the sensitivity of adipose tissue to the action of insulin decreases. However, if a person still overeats, cells are forced to continue to synthesize fats from those excess glucose that cannot be “spent” in other organs. The pancreas responds with an additional, compensatory increase in insulin production.

And yet, the “pumping” of adipocytes with fat cannot be endless. When adipose tissue is overloaded, hypoxia builds up in it and some adipocytes die, causing inflammation. Macrophages rush to the focus of inflammation from the bone marrow. Normally, adipose tissue contains no more than 5% of macrophages, but with obesity, their share increases to 50%. In this case, macrophages are activated and secrete inflammatory cytokines – small peptide molecules that mobilize the inflammatory response, in particular, tumor necrosis factor TNF-α (remember this abbreviation, we still need it) and interleukin-6.These cytokines, in turn, maintain insulin resistance in both adipocytes and liver and muscle cells (Fig. 2).

As established by American researchers led by Professor Stephen Grinspoon, director of the clinic at Harvard Medical School (Boston, USA), neutralization of pro-inflammatory TNF-α improves insulin sensitivity in obesity (“ Journal of Clinical Endocrinology & Metabolism ”, 2011, 96: E146 – E150). This discovery suggested that in obesity, adipose tissue becomes a source of chronic activation of inflammation, capable of maintaining insulin resistance (Fig.2, 3). The mechanisms of such activation of local and systemic inflammation are being intensively studied.

However, inflammation is not a disease, but a normal reaction of the body, in particular, to a bacterial infection. The goal of inflammation is to kill bacteria through a cytotoxic “respiratory” or “oxygen blast” reaction. It got this name because phagocytic cells that have captured bacteria or their decay products sharply (explosively) increase the consumption of oxygen and glucose, which are involved in the formation of highly active radicals with antibacterial activity.The reaction reaches its maximum within 50–120 seconds after the onset of phagocytosis. To carry out the “respiratory burst” reaction, rapid delivery of a large amount of glucose to activated phagocytes is required. It can be assumed that such a directed flow of glucose is provided by the physiological mechanism of insulin resistance, which temporarily limits the flow of glucose into muscles and fat cells, directing it mainly to neutrophils and macrophages (Fig. 3).

It turned out that insulin resistance regulates glucose flows in other adaptive situations, for example, during pregnancy.

Pregnancy and tumor growth

Glucose is the main source of energy for mother and fetus. As the fetus grows, it needs more and more glucose, and its consumption in the second half of pregnancy outstrips its availability. Therefore, the normal fetal blood glucose level is approximately 10–20 mg / 100 ml (0.6–1.1 mmol / L) lower than that of the mother. (The physiological norm for a pregnant woman is 3.3–6.6 mmol / l.) Noteworthy is the fact that during the period of maximum fetal growth, all pregnant women develop physiological insulin resistance, with the help of which glucose flows are probably redirected from organs of the mother to the growing fetus.This effect regulates the placenta, the main source of TNF-α secretion during pregnancy, especially in the second half. Approximately 94% of placental TNF-α is released into the mother’s bloodstream, and only 6% into the fetal bloodstream. Thus, a high level of TNF-α provides insulin resistance in maternal tissues.

After childbirth, its concentration sharply and rapidly decreases, and at the same time insulin sensitivity is restored. However, in overweight pregnant women, the TNF-α content is significantly higher than in normal weight pregnant women.Pregnancy is often complicated in overweight women, and insulin sensitivity is not restored after childbirth, but the risk of diabetes increases. However, with the correct course of pregnancy, adaptive insulin resistance helps the normal growth of the fetus.

In terms of isoenzyme and antigenic composition, as well as the type of cellular metabolism (glycolysis activation), embryonic tissues are similar to tumor ones. The question arises: does insulin resistance develop during tumor growth, and if so, what consequences does it lead to?

Cancer cells assimilate glucose 10–30 times more actively than normal cells.By consuming glucose at a rate greater than the rate at which it is delivered, the cancer acts as a powerful pump, pumping glucose out of the host’s body. Researchers at the University of Southern California Ethan Orgel and Stephen Mittelman have shown that most malignant tumors cause insulin resistance in muscle, liver and adipose tissue of the patient in parallel with an increase in the level of pro-inflammatory TNF-α (“ Current Diabetes Reports ”, 2013, 13, 213-222 , doi: 10.1007 / s11892-012-0356-6).This creates more favorable conditions for tumor growth to the detriment of the normal functioning of healthy organs and tissues.

Contrary to popular belief that cancer patients die from metastases to vital organs, many of them die from a complex of diseases known as paraneoplastic syndrome. These are secondary nonspecific dysfunctions of various organs and systems that are not directly related to the localization of the primary tumor. Paraneoplastic syndrome occurs in 60% of cancer patients.It is caused by the increasing synthesis of TNF-α, which in high concentration is converted to endotoxin, causing systemic inflammation and long-term restriction of glucose supply to muscles, liver and adipose tissue. As a result, the mass of muscle and adipose tissue decreases, and the patient significantly loses weight – the so-called cancer cachexia (Fig. 3). Therefore, in case of oncological diseases, it is advisable to use drugs that reduce systemic inflammation and increase the sensitivity of liver cells, muscles and adipose tissue to the action of insulin.They can not only slow down tumor growth, but also prevent the development of cachexia. It has long been noted that antidiabetic drugs (biguanides), restoring insulin resistance, increase the effectiveness of treatment of cancer patients, but they were not used to prevent the development of cachexia, probably due to insufficient attention to the effect of insulin resistance during tumor growth.

And insulin resistance can also lead to the development of polycystic ovary syndrome (the mechanism of development has not been established).In women with this disease, the menstrual cycle is disrupted and infertility develops. Six months treatment with the most famous biguanide metformin restores the regular ovulation cycle.

Insulin resistance – a defense reaction or a disease?

In order to choose the correct answer, a detailed analysis of the situation in which insulin resistance occurred is necessary, although this often becomes a separate challenge. In uncomplicated pregnancy or in the development of a short-term “respiratory explosion” reaction aimed at eliminating a bacterial infection, insulin resistance is an adaptive, physiologically justified response.After giving birth or defeating the infection, it goes away on its own and does not require treatment. However, according to professor-biologist Ya. A. Aleksandrovsky, a chronic increase in blood sugar levels in itself, without infection, can cause a “prolonged respiratory explosion” in neutrophils, which, accumulating near the walls of blood vessels, can damage them. Therefore, diabetes increases the risk of developing vascular complications. In other words, the physiological inflammatory reaction, as its duration increases, acquires pathological features, and then its action is directed not so much against bacteria as against blood vessels.

Insulin resistance is considered as a precursor of the clinical manifestation of type 2 diabetes mellitus, but it can also indicate the latent development of the tumor process. In such situations, a more detailed diagnosis is necessary, and during the examination, a person should avoid risk factors: excessive and improper nutrition, low physical activity, emotional stress. After examination, it is advisable to correct insulin resistance with biguanides, salicylates and other anti-inflammatory drugs.

It should be noted the amazing discoveries of recent years made in several foreign laboratories. According to Harvard Medical School professor Richard Hodin, intake of intestinal alkaline phosphatase mitigates the negative effects of excessive consumption of fatty foods (“ Proceedings of the National Academy of Sciences ,” 2013, 110, 17, 7003-7008, doi: 10.1073 / pnas.1220180110 ). It turns out that some representatives of the intestinal microflora can support or suppress the development of cancer and diabetes in the host’s body.Moreover, the microflora that contributes to the development of diabetes is sometimes transmitted from a pregnant woman with diabetes to the fetus, and in this way increases the risk of developing this pathology in a child. The influence of microflora on the development of diabetes is now being intensively studied, the future will show how true the assumptions of scientists are and whether it is possible to use them in practice.

The phenomenon of insulin resistance is multifaceted. Nature sparingly uses the same mechanism to achieve different goals: it provides both the antibacterial defense reaction of the “respiratory burst” and the normal development of the fetus.Alas, an improper lifestyle provokes a pathological course of the process, and then insulin resistance contributes to the occurrence of obesity, cancer or diabetes.

90,000 Skin lesions in diabetes mellitus. Dermatologist in Tashkent

Diabetes mellitus – the most common endocrine disease with a steadily increasing prevalence. This disease affects the blood vessels, nerve fibers, eyes, kidneys and

skin, which leads to significant financial losses and a decrease in the quality of life in affected patients.Long-term diabetes mellitus can disrupt skin homeostasis, resulting in cutaneous manifestations in at least one third of patients. Skin lesions may be the first sign of diabetes mellitus, so the corresponding skin symptoms can lead to a diagnosis of diabetes mellitus. In addition, skin symptoms may reflect the course of the disease as well as the success of therapeutic interventions.

Introduction

The International Diabetes Federation estimates that about 285 million adults worldwide suffer from diabetes (2010 data), and at least one third of patients have some type of skin manifestation associated with diabetes.These include bacterial and fungal infections, skin lesions that are complications of diabetes mellitus, drug-induced skin lesions. Thus, this review can be useful for both dermatologists and general practitioners, specialists in the field of diabetes mellitus, it will allow them to be more attentive in relation to the cutaneous manifestations of diabetes mellitus. The purpose of this review is to draw the attention of physicians to typical skin symptoms associated with impaired glucose metabolism.

Changes in the epidermal barrier

Diabetes mellitus can lead to disruption of skin homeostasis both through primary disorders of skin metabolism and through secondary associated complications such as vasculopathy and neuropathy. Literary sources are of the opinion that hyperglycemia-induced non-enzymatic glycation of structural and regulatory proteins plays a major role in the pathogenesis of complications of diabetes mellitus. Excessive glucose levels lead to non-enzymatic chemical interactions between the amino acids in the protein and the carbonyl groups of glucose – the Maillard reaction.The first stage of nonenzymatic glycation begins with the formation of Schiff bases, which are subsequently converted into stable compounds (Amadori rearrangement). Subsequent chemical transformations of Amadori rearrangement products lead to the formation and accumulation of advanced glycation end products (AGEs) in patients with diabetes mellitus (Figure 1). Specific receptors for AGEs (RAGE) have been found on the surface of various cell types. The accumulation of AGEs and their interaction with RAGE initiates various signaling pathways involved in the pathogenesis of possible complications of diabetes mellitus.In addition, in patients with diabetes mellitus, dysfunction of keratinocytes caused by the influence of insulin on their proliferation, differentiation and migration is often found, which leads to a disruption in the normal functioning of the epidermal barrier and slows down wound healing.

Opinions of literary sources about the influence of diabetes mellitus on the hydration of the stratum corneum are still controversial. Sakai et al. found a decrease in the level of hydration of the stratum corneum, a decrease in the amount of surface lipids and sebum secretion in mice with diabetes mellitus, while Seirafi et al.found no difference between the level of hydration of the stratum corneum in patients with diabetes mellitus and in a healthy population. In addition, the pH of the skin surface plays a key role in creating the skin barrier. Excessively high pH of the skin surface leads to excessive bacterial colonization, which is also found in the area of ​​chronic wounds. It is known that diseases such as atopic dermatitis or diaper dermatitis also affect skin pH. According to Yosipovitch et al, the pH of the skin surface in intertriginous areas in patients with diabetes mellitus is significantly higher than in patients without diabetes.It was also found that in patients with diabetes mellitus, the activity of the sebaceous glands is reduced, the elasticity of the skin is impaired against the background of normal hydration of the stratum corneum. Thus, there is insufficient data in the literature on this issue; additional studies are required to clarify the role of skin pH in diabetes mellitus.

Table 1. Skin manifestations of diabetes mellitus

1. 1. Skin infections

• Bacterial etiology
• Fungal etiology
• 2.Skin lesions that are complications of diabetes mellitus
• Diabetic ulcers
• Diabetic foot syndrome

3. 3. Skin lesions associated with diabetes mellitus

• Finger seals
• Papillomas
• Eruptive xanthomas
• Lichen planus
• Itching
• Annular granuloma
• Vitiligo
• Acanthosis black
• Lipoid necrobiosis
• Skleredema Adult Buschke
• Diabetic blisters
• Acquired reactive perforating collagenosis
• Yellow nails

4. 4.Skin lesions complicating diabetes therapy

• Skin reactions to insulin administration
• Skin reactions to oral hypoglycemic drugs

Skin infections

Violation of the integrity of the skin barrier in diabetes mellitus leads to an increased predisposition of patients to bacterial infections. Moreover, diabetes-induced vasculopathies and neuropathies also increase susceptibility to bacterial infections.For patients with diabetes mellitus, the development of bacterial and viral infections is characteristic; they occur in every second patient. The doctor’s attention should be attracted by recurrent bacterial infections – vulgar impetigo, abscesses, erythrasma, folliculitis, erysipelas or common fungal infections, this is the reason for examining the patient for diabetes. Severe and rare bacterial infections, often associated with diabetes mellitus – malignant otitis externa, mainly caused by Pseudomonas aeruginosa and associated with a high mortality rate.

A high concentration of glucose in the epidermis of patients with diabetes mellitus creates an optimal environment for the vital activity of saprophytic microorganisms, including fungi of the genus Candida. Literature data on the incidence of dermatophytes in patients with diabetes mellitus are very contradictory. It is reported that about 30% of patients (with and without diabetes mellitus) suffer from fungal infections, with Trichophyton rubrum being the most common. Infections caused by fungi of the genus Candida are found in 15-28% of cases.Also, with diabetes, the risk of developing vulvovaginal candidiasis increases. Thus, recurrent vulvovaginal candidiasis may indicate the presence of diabetes mellitus in the patient.

Skin lesions associated with diabetic vasculopathy and neuropathy

Vasculopathy is one of the most typical complications of diabetes mellitus, leading to retinopathy, nephropathy, skin lesions. The pathogenesis of this phenomenon has not been completely clarified. The formation of AGEs is thought to contribute to the development of macro- and microangiopathy.

Diabetic ulcers and diabetic foot syndrome

Diabetic foot syndrome is a severe cutaneous manifestation of diabetes mellitus that occurs in 15-20% of patients. (Figure 2) Micro- and macroangiopathy, as well as peripheral neuropathy, play a key role in the development of diabetic foot syndrome, however, most often it is based on a combination of causes – both sensory impairment and vasculopathy. In almost a quarter of cases, diabetic foot syndrome leads to limb amputation.The most common causes of diabetic ulcers are inadequate foot hygiene, foot deformities, and poorly fitted shoes. The most characteristic areas of ulceration are places of maximum pressure: under the heads of the metatarsal bones, in the area of ​​callosities. In addition, patients with diabetes mellitus suffer from impaired wound healing, as hyperglycemia leads to a decrease in the level of signaling mediators (neuropeptides, inflammatory cytokines) involved in the wound healing process.Thus, diabetic ulcers often delay various phases of wound healing, eventually leading to the formation of chronic ulcers. Treatment of diabetic ulcers includes eliminating excess plantar pressure by fitting orthopedic shoes, removing callosities, proper foot hygiene, moisturizing and maintaining the wound surface.

Gangrene in diabetes mellitus

The risk of gangrene and limb amputation is much higher in patients with diabetes mellitus.It is reported that about 70% of lower limb amputations in Germany were associated with diabetes. Dry gangrene more often affects the toes due to impaired tissue perfusion, while self-amputation of the toe is possible (Figure 3). In contrast, wet gangrene occurs when ulcers become infected and may require urgent surgery.

Diabetic dermopathy

Other signs of diabetic microangiopathy include diabetic dermopathy. It occurs in 10% of patients with diabetes mellitus and is most likely associated with peripheral neuropathy.Clinically, hyperpigmented, atrophic, well-defined skin lesions are found, localized mainly on the skin of the legs. A link has been established between diabetic dermopathy and damage to large vessels (especially coronary arteries), neuropathy, nephropathy, retinopathy. Thus, diabetic dermopathy can serve as a clinical marker reflecting the severity of systemic complications of diabetes mellitus.

Various skin symptoms

Finger seals

In 1986, Huntley et al.showed that the incidence of finger pebbles in diabetes mellitus is about 75% and 21% in non-diabetic patients. Digital seals – multiple small, grouped, dense papules localized on the extensor surface of the fingers of the hand with a pronounced emphasis in the interphalangeal joints. Histologically, hyperkeratosis is detected, as well as the proliferation of the papillae of the dermis. In comparison with chronic mechanical damage to the skin, in this case, the stratum corneum is usually intact.The pathogenesis has not been definitively identified. Among the various hypotheses of etiopathogenesis, nonenzymatic glycation, disorders of collagen metabolism, and the action of growth factors are considered. The presence of digital seals is considered an important dermatological sign of diabetes mellitus.

Papillomas

Papillomas – benign skin neoplasms, soft consistency, located on the leg, normal skin color, or hyperpigmented, most often localized on the neck, armpits, groin and eyelids.Multiple papillomas are associated with impaired glucose metabolism, which is associated with insulin-induced proliferation of keratinocytes. Sudy et al. showed that the presence of multiple papillomas on the skin in a patient is a more sensitive cutaneous marker of impaired glucose metabolism than acanthosis nigricans. On the skin of patients with diabetes mellitus, papillomas are found in 23% of cases, while in a healthy population this figure is 8%. A positive relationship was also found between the number of papillomas on the skin and blood glucose levels.Treatment is necessary only for cosmetic reasons. Surgical intervention or cryosurgery is possible.

Eruptive xanthomas

Eruptive xanthomas are associated with hypertriglyceridemia, which leads to the accumulation of chylomicrons and very low density lipoproteins (VLDL). Poorly controlled diabetes mellitus and alcohol abuse can cause secondary hypertriglyceridemia. Xanthomas are grouped papules that range in color from reddish to yellowish, located on an erythematous background; most often localized in the gluteal region, on the extensor surfaces of the limbs.Histologically, they are an accumulation of foamy cells (macrophages), an inflammatory infiltrate of lymphocytes and neutrophils, localized in the dermis. Treatment is aimed at normalizing lipid metabolism by changing diet and taking appropriate medications. Fast results can be achieved with surgical removal, curettage, laser therapy (CO2 or Erb: YAG laser)

Lichen planus

Based on data from Seyhan et al. impaired glucose metabolism is observed in half of patients with lichen planus.About 25% of patients with lichen planus suffer from diabetes mellitus. The association with diabetes mellitus is observed in 27% of patients with lichen planus of the oral mucosa. In addition, the relationship between lichen planus and thymoma, viral hepatitis C, liver disease and ulcerative colitis was found. Clinical symptoms of lichen planus are itchy polygonal erythematous papules and Wickham mesh. Typical localization is the skin of the wrist, ankles. The defeat of the oral mucosa is found in 30-70% of patients with lichen planus; represented by asymptomatic white mesh plaques.The first line of therapy is topical corticosteroids. Other therapeutic options are also possible – systemic corticosteroids, oral retinoids, phototherapy. Also, it is necessary to remember about the possibility of malignant transformation of lichen planus of the oral mucosa.

Itching

Xerosis accompanied by itching is observed in 25% of patients with diabetes mellitus and is one of the most common cutaneous manifestations of diabetes mellitus. One of the causes of hypohidrosis and dry skin is dysfunction of sympathetic nerve fibers (including sudomotor dysfunction).Also, itching can be caused by damage to sensitive c-fibers associated with diabetic polyneuropathy. Since itching often occurs with dry skin, regular use of emollients can partially prevent this complication.

Annular granuloma

Annular granuloma is most often localized on the extremities, mainly in the area of ​​the joints, dorsal surface of the hands and feet. It manifests itself as multiple erythematous-purple papules forming a ring with a resolution in the center, without atrophy.Lesions are usually asymptomatic. The etiology is not known, there may be a relationship between the generalized annular granuloma and malignant neoplasms, thyroid diseases, viral hepatitis B and C, HIV infection, and diabetes mellitus. However, the opinions of literary sources about the association of granuloma annular with diabetes mellitus remain controversial. Histologically, granulomatous infiltration is determined in the dermis, consisting of lymphocytes and histiocytes with the presence of degenerative collagen fibers and giant cells in the center.The effectiveness of topical corticosteroids, intralesional administration of corticosteroids, PUVA therapy, topical calcineurin inhibitors, and systemic drugs such as adalimumab and dapsone has been shown. Solitary lesions tend to resolve spontaneously.

Vitiligo

Vitiligo is a pigmentation disorder with a frequency of about 1%. The lower extremities are most often affected. The pathogenesis of the disease is not fully understood. The affected skin lacks normal, intact melanocytes. The relationship of vitiligo with other autoimmune diseases, for example, thyroid gland damage, diabetes mellitus, has been found.The autoimmune pathogenesis of vitiligo confirms the fact that only insulin-dependent diabetes mellitus is associated with vitiligo (there is no such relationship with insulin-independent diabetes mellitus). Therapeutic options for this disease are often unsatisfactory. It is very important to use photoprotective products. In the treatment of generalized vitiligo, UV-B phototherapy may be effective.

Acanthosis black

Skin lesions are represented by black-brown plaques.(Figure 4) Most of the folds and flexion surfaces are affected, most often the neck and axillary region. It is believed that the pathogenesis is based on excessive binding of elevated insulin levels to insulin-like growth factor receptors, which leads to proliferation of keratinocytes. Histologically, with acanthosis nigricans, the proliferation of epidermal keratinocytes and fibroblasts is determined, leading to a thickening of the stratum corneum. Acanthosis nigricans can also serve as a marker of malignant neoplasms, in particular, gastrointestinal adenocarcinoma.However, acanthosis nigricans are most often associated with obesity and insulin resistance. This is most likely due to the increasing number of patients with type 2 diabetes and metabolic syndrome. Acanthosis nigricans are an important indicator of diabetes mellitus. The presence of this syndrome should attract the attention of the doctor, suggest the exclusion of insulin resistance in the patient. The main thing in therapy is the correction of the underlying disease.

Lipoid necrobiosis in diabetes mellitus

Lipoid necrobiosis is a chronic inflammatory granulomatous skin disease.The most characteristic features are the presence of yellow-brown plaques with raised erythematous edges, an atrophic center and expanded telangiectatic vessels visible on the surface. The legs are often affected. (Figure 5) About two-thirds of cases are associated with diabetes mellitus, however, data on the correlation between the severity of diabetes and the activity of necrobiosis lipoidosis remain controversial. The pathogenesis of the disease is not known. Rashes can resolve on their own, however, they often become chronic or ulcerate with the addition of a secondary infection.Lipoid necrobiosis is, to a greater extent, a clinical diagnosis. Histologically, necrobiosis (collagen degeneration) of the entire dermis, atrophy of the epidermis with infiltration of inflammatory cells is determined. In several cases, the possibility of transformation into squamous cell carcinoma of the skin has been described. Treatment options include topical corticosteroids, intralesional corticosteroids, systemic corticosteroids, topical tacrolimus, phototherapy, cyclosporine, fumaric acid esters, TNF-a inhibitors.

Skleredema Adult Buschke

Adult Skleredema was first described by Buschke.The disease manifests itself as a symmetrical dense edema, localized, as a rule, in the upper back, on the neck and face. Many variants of the etiology of this disease have been proposed. Scleredema of adults Buschke can occur after infectious diseases (benign form), possible association with systemic diseases such as paraproteinemia, malignant neoplasms, as well as poorly controlled type 2 diabetes mellitus (chronic form). The adult Buschke scleredema associated with diabetes mellitus often has a slowly progressive course, without a tendency to resolve spontaneously.Slow collagen degradation and stimulation of collagen synthesis by fibroblasts in response to excess glucose are likely pathogenic factors. In rare cases, damage to internal organs, generalization of the process (respiratory failure) is possible. The histological picture is characterized by thickened bundles of collagen fibers, separated by areas of mucin deposition, which leads to a thickening of the dermis. The epidermis remains intact. Treatment is difficult. The use of physiotherapy, high doses of penicillin, phototherapy (PUVA baths, UVA1 phototherapy) can be successful.In severe cases, radiotherapy may be effective.

Diabetic blisters

Diabetic blisters – a rare phenomenon of diabetes mellitus on the skin, which occurs in 0.5% of cases. It is characterized by the formation of tense blisters localized on the acral areas of the limbs, often in the area of ​​\ u200b \ u200bthe feet. (Figure 6) The skin of the trunk is rarely affected. Diabetic blisters often appear suddenly, are located in isolation, their contents can be transparent or hemorrhagic.The pathogenesis has not been fully understood. It is believed that diabetic angiopathy leads to increased vulnerability of the skin, which provokes the formation of blisters. The predominant localization of lesions on the lower extremities is explained by the presence of diabetic polyneuropathy in patients. It is mandatory to take a patient’s history, as well as to exclude immunoassociated bullous dermatoses, such as pemphigus and pemphigoid. Spontaneous blistering, especially limited to the skin of the acral extremities, should alert the physician and require screening to rule out diabetes mellitus.Histologically, a subepidermal bladder is found at the level of the lamina lucida. Immunofluorescence study is negative. Diabetic blisters are usually a self-limiting process that tends to resolve spontaneously without scarring over several weeks. Adequate blood glucose levels must be maintained. Complications are possible in the form of secondary chronic ulcers, the addition of a bacterial infection. Most patients suffer from chronic recurrent episodes of diabetic bladder.

Acquired reactive perforating collagenosis

Acquired reactive perforating collagenosis is a rare skin disease associated with diabetes mellitus. In addition, the disease often accompanies chronic renal failure and other systemic diseases, as well as malignant neoplasms. The clinical picture is characterized by the appearance in patients of erythematous papules or plaques with a central keratotic plug. (Figure 7) Skin lesions are often accompanied by itching.The pathogenesis of the disease is unknown. The appearance of new loose elements can be provoked by the type of the Kebner phenomenon. It is believed that acquired reactive perforating collagenosis is caused by transepidermal collagen elimination. Histological features of the disease are defined by basophilic bundles of collagen fibers located in the upper part of the dermis, keratin and neutrophils, forming epidermal ulceration, which may be covered with a hyperkeratotic crust. Treatment is often difficult.Treatment of the underlying disease is required. It is possible to use topical GCS, antihistamines, phototherapy, doxycycline, systemic retinoids. Significant improvement has been reported with allopurinol. The key point remains the treatment of the underlying disease (diabetes mellitus, renal failure).

Yellow nails

Another complication of diabetes mellitus affecting the nail plate. Yellow nail staining occurs in 40% of patients with diabetes.(Figure 8) A possible cause of yellow nail discoloration is non-enzymatic glycation, which also results in yellow skin staining in diabetic patients. It is necessary to carry out differential diagnosis with onychomycosis.

Skin complications associated with the treatment of diabetes mellitus

Skin reactions to insulin

The classic side effect of insulin therapy is the development of lipoatrophy at the injection site, characterized by local loss of subcutaneous fat.The incidence of this complication was significantly reduced with the use of highly purified insulin. It is believed that the basis of the occurrence of lipoatrophy is an immunological reaction. In the immunofluorescence analysis of the affected skin, an increased accumulation of immunoglobulins and complement in the blood vessels of the dermis is determined, which leads to the activation of the signaling cascade and suppression of adipocyte differentiation. The likelihood of lipoatrophy is reduced by constantly changing the site of insulin injections.Lipohypertrophy, on the other hand, is characterized by excessive deposition of subcutaneous adipose tissue. This is the most common side effect of insulin therapy and occurs in 27% of patients with diabetes. Impaired insulin absorption in the area of ​​lipohypertrophy is of particular clinical importance, as it leads to impaired glycemic control. Local allergic reactions to insulin such as pruritus, erythema, induration are noted in less than 1% of cases. With the introduction of highly purified insulin and new delivery systems, local skin reactions to insulin have become a very rare complication.When treating an allergic reaction to insulin, it is possible to change the drug to insulin lispro as it is less allergic, desensitization, and the use of insulin pumps. In rare cases, adverse skin reactions have been reported to m-methylphenol, a preservative used in virtually all commercially available insulin variants. It is worth remembering the rare systemic IgE-dependent type I hypersensitivity reaction to insulin, which can lead to a life-threatening anaphylaxis reaction.

Skin reactions to oral antidiabetic drugs

Skin reactions to oral hypoglycemic drugs are a very rare complication.In the literature, there are cases of allergic reactions, leukocytoclastic vasculitis, erythema multiforme exudative when taking metformin biguanide. Moreover, have been described reactions such as vulgar peptic ulcer, psoriasiform drug reactions that occur when taking sulfonylurea glibenclamide. It must be remembered that most sulfonylurea preparations induce cutaneous photosensitivity. Previously, generalized exanthematous pustulosis and generalized exudative erythema multiforme have been described, most likely arising from acarbose.In several cases, the development of lichenoid drug reactions associated with sulfonylureas – chloropropamide, tolazamide, glimepiride – has been described.

Conclusion

Almost all patients with diabetes mellitus have skin symptoms associated with diabetes mellitus. The appearance of skin manifestations of diabetes mellitus is possible before the diagnosis and the onset of symptoms from the internal organs. Thus, certain skin reactions should be considered as warning markers of diabetes mellitus.Tight glycemic control is known to reduce the incidence of vasculopathy, neuropathy, and nephropathy. It is very likely that this has a positive effect on the cutaneous manifestations of diabetes mellitus. Thus, in the treatment of patients with diabetes mellitus, the interaction of a dermatologist and an endocrinologist is important.

Behm B, Schreml S, Landthaler M, Babilas P. Skin signs in diabetes mellitus.

Böhm B., Schreml S., Landthaler M., Babilas P., Department of Dermatology, University Hospital Regensburg

This material was taken from the dermatology site.ru

Dermatological manifestations of insulin resistance

Reduced biological response of tissue to normal insulin concentration is called insulin resistance (IR). The body makes insulin (usually in higher concentrations than healthy people) but does not use it efficiently. It is one of the key pathophysiological factors in the development of type 2 diabetes.

Insulin resistance can manifest in a wide range of dermatological manifestations.

These include: acanthosis nigricans, hirsutism (ovarian hyperandrogenism), fibroepithelial polyps and androgenetic alopecia. Skin manifestations of insulin resistance in real time help the doctor determine further therapy tactics, avoid diabetes, increase the effectiveness of treatment of metabolic syndrome, influence pathogenesis, and not fight symptoms.91% of patients with type 2 diabetes have at least one dermatologic symptom. 70-80% of obese patients will have insulin resistance.

Insulin resistance develops several years before the clinical diagnosis of diabetes mellitus. The biological rationale for the association of IR with cutaneous manifestations is based on the fact that hyperinsulinemia activates receptors for insulin-like growth factor-1 (IGF-1) located in fibroblasts and keratinocytes. Elevated insulin and IGF-1 levels increase androgen production in the ovaries through increased local 17-hydroxylase activity and inhibition of hepatic synthesis of sex hormone binding globulin (shbg), which increases the availability of free testosterone.

Androgenetic alopecia. One of the most common factors in androgenetic alopecia (AHA) is metabolic syndrome (including insulin resistance). Testosterone is metabolized in many tissues of the skin. It penetrates the cell membrane and is irreversibly converted by 5-alpha reductase (mainly type II) in the cytoplasm into the most powerful form: dihydrotestosterone (DHT). DHT is the main androgen involved in the pathogenesis of AGA. DHT binds to androgen receptors and is translocated to the nucleus, where it stimulates gene transcription.This activation is the key to the gradual transformation of terminal follicles into small vellus hairs, from a truncated anagen.

Female pattern hair loss.

Other cutaneous manifestations. Fibroepithelial polyps. IGF-1 binds to receptors in keratinocytes, causing epidermal hyperplasia. Clinically, these are small, soft, slightly hyperpigmented tumors of various sizes with a pedicle. Often multiple, but may appear as a single lesion.The neck, armpits and groin are the most common areas of involvement, however, the eyelids and in the chest folds can be affected.

Histological picture showing papillomatosis.

The clinical picture.

Black acanthosis. Most often it is a sign of insulin resistance, but there are other reasons for the development. The benign variant is congenital or develops in early childhood. Not associated with metabolic changes.The malignant form is associated with adenocarcinoma of the gastrointestinal tract. Associated with the use of drugs such as niacin, oral contraceptives, corticosteroids, and methyltestosterone. As a rule, it goes away spontaneously within 4-11 months after stopping the drug. Obesity-related is the most common variant and develops as a manifestation of insulin resistance. The pathogenesis is similar to papillomatosis (the result of IGF-1 stimulation of keratinocytes and fibroblasts in the dermis).Classic topography includes the neck, armpits and elbows. Possible manifestation in the periorbital and peri-umbilical regions, inner thighs, chest folds, knees.

Hirsutism, acne. The term “diabetes in bearded women” was first used by Archard and Thiers in the 1920s, when they first identified the relationship between impaired carbohydrate metabolism and hyperandrogenism. Polycystic ovary syndrome (PCOS) is a well-recognized metabolic change associated with an increased risk of diabetes mellitus and infertility.Regardless of obesity, a large percentage of women with PCOS have insulin resistance. The prevalence of obesity among them ranges from 25% to 70% (usually the central type) and contributes to insulin resistance. In vitro studies have shown that insulin enhances the effect of luteinizing hormone on ovarian androgen production. Hyperandrogenism is one of the key diagnostic features of PCOS and manifests itself clinically as hirsutism, acne, and AGA.

Diagnostics. The glucose tolerance test is considered the gold standard for the diagnosis of insulin resistance. It detects an increase in fasting sugar as well as after meals.
Note: However, IR can develop long before blood sugar rises. To detect it in the early stages, it is possible to conduct a glucose tolerance test with the determination of not only sugar, but also C-peptide, insulin. Increases in C-peptide and insulin indicate their increased production to overcome tissue resistance.

Treatment. Methods for overcoming insulin resistance include lifestyle modification, dietary modification, and drug therapy. Lifestyle changes should include exercise and weight loss. Insulin sensitizers such as metformin.
Note: When diagnosed with type 2 diabetes mellitus, the recommended dose of metformin is 2000-3000 mg per day. Start therapy with 500mg per day, with a further increase in the dose of 500mg in 1-2 weeks.When insulin resistance is detected without an increase in glycemia, the recommended dose is 1000 mg with insulin and C-peptide control. In the absence of normalization of these indicators, an increase in the dose is possible.

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90,000 Insulin resistance in obesity: causes and consequences | Lavrenova

INTRODUCTION

Obesity is a chronic recurrent heterogeneous disease that develops under the influence of genetic, physiological and environmental factors and is characterized by excessive accumulation of adipose tissue, the dysfunction of which leads to numerous negative consequences.

The number of overweight people in the modern world is increasing by 10% every 10 years. This made it possible to define obesity as a non-communicable epidemic. In English-language sources, you can often find the term “Globesity” (“global obesity”), which most accurately reflects the severity of the problem. According to the WHO, in 2016 about 2 billion people in the world are overweight and about 650 million of them are obese [1].

In Russia, the statistics are also disappointing.Every second Russian is overweight today. According to the multicenter epidemiological study ESSE-RF (2013), 29.7% of Russians are obese. At the same time, men gain weight much more rapidly than women. The percentage of obese men in our country for the period from 1993 to 2003 increased threefold and is 26.9% [2].

What are the main causes of obesity? The main reasons today are the wrong nutrition system and physical inactivity: excessive energy consumption against the background of low energy consumption inevitably leads to the development of exogenous constitutional obesity.Modern man consumes much more kilocalories than he can spend. The share of secondary obesity, that is, obesity in various diseases (genetic, endocrine, diseases of the central nervous system, etc.), including iatrogenic obesity, accounts for no more than 5% of cases.

Often, obese people perceive excess body weight as nothing more than an aesthetic problem, without realizing how serious the consequences can be. Thus, obesity is a risk factor for the development of a number of diseases – type 2 diabetes mellitus, arterial hypertension, ischemic heart disease, non-alcoholic fatty liver disease, gastroesophageal reflux disease, obstructive sleep apnea syndrome, various reproductive disorders in men and women, and some oncological diseases ( breast cancer, endometrial cancer, colorectal cancer), lesions of the musculoskeletal system, etc.

OBESITY AND CARBOHYDRATE EXCHANGE

Obesity is one of the main risk factors for the development of disorders of carbohydrate metabolism. Diabetes mellitus is another global disaster in the modern world. According to the International Diabetes Federation, at the end of 2019, about 463 million patients with diabetes mellitus were registered, of which more than 90% were patients with type 2 diabetes mellitus (T2DM) [3]. In 2016, the results of the first national epidemiological cross-sectional study to identify the prevalence of T2DM in the Russian Federation were announced, according to which, among the adult population of Russia 20–79 years old, 19.3% were diagnosed with prediabetes, 5.4% of the population was diagnosed with T2DM, with 54% of them not previously diagnosed with the disease.Moreover, among obese individuals (BMI ≥30 kg / m ² ), the prevalence of these disorders of carbohydrate metabolism was 33.3% and 12%, respectively [4].

Numerous epidemiological studies show that the risk of developing diabetes increases as the amount of adipose tissue in the body increases. It is also undeniable that the presence of visceral (central, abdominal, android) obesity indicates a high risk of developing various cardiometabolic consequences.Therefore, when assessing the patient’s status, it is important not only to calculate the BMI, but also to determine the waist circumference. The critical size, in terms of the development of complications, for representatives of the Caucasian race is a waist circumference of more than 84 cm in women and more than 90 cm in men.

The basis of the association of obesity and carbohydrate metabolism disorders is the development of secondary insulin resistance (IR) against the background of hypertrophy and dysfunction of fat cells. Over the past decades, many scientific research works have been devoted to the study of the mechanisms of the influence of excess adipose tissue on the development of systemic insulin resistance, but answers to all questions have not yet been received.Hyperinsulinemia, which inevitably develops against the background of IR, leads to an increase in body weight, closing a vicious circle and causing a whole range of other pathophysiological complications, including arterial hypertension, hyperlipidemia, atherosclerosis, etc. (Fig. 1).

Figure 1. Development of insulin resistance (IR)

Today, there are about ten different methods for diagnosing IR. Among them, there are direct and indirect methods for assessing IR. Each has its own advantages and disadvantages.The gold standard for diagnosing IR is the euglycemic hyperinsulinemic clamp test – the most informative direct diagnostic method with a high level of sensitivity and specificity. The essence of the method is to increase the concentration of insulin in the blood by infusion of insulin at a rate of 1 IU / min per 1 kg of body weight and simultaneous intravenous administration of glucose to maintain a glycemic level of about 5.5 mmol / L. The amount of glucose injected to maintain a specified glycemic level will reflect its insulin-mediated tissue metabolism.Accordingly, the more pronounced the IR, the less glucose will be needed. However, this method is rather laborious, is associated with the need for infusion of exogenous insulin, and is difficult to implement in everyday clinical practice. Indirect methods for assessing IR using special calculated indices based on the ratio of glucose and insulin concentrations both on an empty stomach and 2 hours after exercise during the oral glucose tolerance test are widely used in clinical practice.In our country, the most commonly used index is HOMA-IR (homeostasis model assessment), proposed in 1985 [5]: fasting insulin level (μU / L) × fasting plasma glucose level (mmol / L) / 22.5. A HOMA-IR index level of more than 2.7 indicates the presence of IR. There are no clear criteria for the interpretation of HOMA-IR, in studies one can find different indicators of the cut-off point (75th percentile of the cumulative population distribution), but it should always be taken into account – the higher this IR index, the more pronounced the IR.Another IR index is based on lipid spectrum indicators – triglyceride (TG) level (mg / dl) / high-density lipoprotein cholesterol (HDL-C) level (mg / dl). When using the indicated units of measurement, the calculated index of more than 3.5 indicates the presence of IR. The above mathematical models are widely used in practice, however, due to their variability, they cannot be used for routine screening.

In recent years, new approaches to the definition of IR have been actively studied.In particular, in 2007 the index of IR with the participation of adiponectin (HOMA-AD) was proposed – the ratio of HOMA-IR and adiponectin level. The HOMA-AD level of more than 0.95 is considered to be the threshold value indicating IR [6].

In 2014, data were published on the use of a new metabolic index (MI) to determine IR, which took into account not only indicators of carbohydrate metabolism, but also the level of TG and HDL-C on an empty stomach. MI = TG (mmol / L) × glucose (mmol / L) / HDL-C (mmol / L). IR is diagnosed at MI level of 7.0 or more [7].

INSULIN-INDUCED GLUCOSE METABOLISM IN NORMAL AND OBESITY

Insulin is a hormone that affects all types of metabolism, with a pronounced anabolic effect. In the framework of fat metabolism, insulin stimulates the flow of glucose into adipocytes, the formation of fatty acids, triglycerides and glycerophosphate; lipolysis is suppressed. The effects of insulin are mediated through a series of cascading reactions when insulin receptors are activated. The number of these receptors in cells is different, most of all insulin receptors are in hepatocytes, adipocytes and myocytes.The receptor consists of two alpha subunits with affinity for insulin and two catalytic beta subunits with tyrosine protein kinase activity. The activated insulin receptor interacts with cytoplasmic proteins – insulin-receptor substrates (IRS), the main of which are IRS-1 and IRS-2. The degree of cell sensitivity to insulin depends on the severity of substrate phosphorylation. By means of a substrate, insulin activates phosphatidylinositol-3-kinase, which, in turn, stimulates the translocation of the main glucose transporter – GLUT4 (Glucose transporter type 4) – from the cytoplasm to the membrane, with the participation of which the transmembrane transfer of glucose into cells is carried out (Fig.2). In addition, in adipose cells, activation of phosphatidylinositol 3-kinase by insulin leads to inhibition of lipolysis [8].

Figure 2. Transmembrane glucose transfer

A significant increase in the size and hyperplasia of adipocytes in obesity is accompanied by pronounced changes in their secretory activity: an imbalance in the secretion of adipokines, an increase in the secretion of pro-inflammatory cytokines, free fatty acids (FFA), reactive oxygen species and other metabolites.All this leads to the development of chronic slowly progressive inflammation, oxidative stress, endothelial dysfunction, etc. As a result, the risk of developing T2DM, atherosclerosis, and arterial hypertension increases (Fig. 3) [9–12].

Figure 3. Imbalance in the secretion of fat metabolites in obesity and its consequences

IR in obesity is manifested in a decrease in insulin-induced glucose transport and metabolism in adipocytes, skeletal muscles, and liver [13].These functional defects are partially caused by impaired transduction of the insulin signal in all target tissues, due to inhibition of translocation and regulation of GLUT4 action, a decrease in the number of insulin receptors in myocytes and adipocytes, impaired receptor autophosphorylation, decreased tyrosine kinase activity and IRS phosphorylation. Also, one of the mechanisms for the development of signaling defects in obesity may be the increased expression and activity of several protein tyrosine phosphatases, which increase against the background of chronic inflammation, which dephosphorylate the substrates of insulin receptors and, thus, stop signaling, which, in turn, contributes to the development of IR.

Some studies have shown the relationship between the level of adiponectin and the development of IR. In some, there was an inverse relationship between the adiponectin level and the HOMA-IR index, BMI and waist circumference [14]. In others, it has been demonstrated that in patients with impaired glucose tolerance (IGT) or T2DM, the adiponectin level is significantly lower [15]. In addition, there is evidence of the effect of leptin on insulin secretion in obesity and IR. The results of a number of studies demonstrate a positive correlation between the severity of hyperleptinemia and IR in individuals with different BMIs [16].The described results suggest that the imbalance of adipokine secretion makes a significant contribution to the development of IR in obesity.

Various mechanisms play a leading role in decreasing insulin sensitivity in different tissues. In adipocytes, a decrease in the density of insulin receptors prevails, in muscle tissue – a decrease in tyrosine kinase activity, which leads to a violation of glucose absorption, the antilipolytic effect of insulin is inhibited, the level of FFA increases; glycogenolysis and gluconeogenesis are significantly activated.

It is IR that is one of the most important links in the pathogenesis of a number of basic metabolic and hemodynamic disorders associated with obesity, in the pathogenesis of which adipose tissue dysfunction and IR are closely intertwined.

INSULIN RESISTANCE, DYSLIPIDEMIA AND CARDIOVASCULAR DISEASES

Currently, a broad evidence base has been collected for the close relationship of IR, hyperinsulinemia and arterial hypertension (AH). According to some authors, up to 58% of patients with hypertension have IR of varying severity [17].There is evidence that IR is an independent risk factor for the development of hypertension in people with normal body weight and may be the first predictor of its development [18]. In obesity, IR exacerbates the development of the inflammatory reaction, enhances the hyperactivation of the sympathoadrenal system, the renin-angiotensin-aldosterone system, increases the volume of circulating blood against the background of increased reabsorption of sodium ions in the renal tubules, which leads to an increase in cardiac output and an increase in total peripheral vascular resistance [19] …In conditions of developing endothelial dysfunction against the background of obesity, hyperinsulinemia leads to suppression of the synthesis of nitric oxide (NO), prostacyclin and an increase in the synthesis of vasoconstrictors.

Chronic inflammation, decreased NO synthesis, vasoconstriction, oxidative stress have a significant effect on the development of atherosclerosis. Many studies have demonstrated an increase in the frequency and severity of atherosclerotic lesions of the coronary arteries against the background of IR and hyperinsulinemia. Research results show that IR promotes the development of coronary heart disease and complications, in particular, acute myocardial infarction, influencing their outcome [20].It is known that an imbalance in the secretion of active metabolites of adipose tissue significantly affects blood coagulation. The developed IR and hyperinsulinemia aggravate these disorders, lead to an increase in the level of fibrinogen and an increase in the activity of the tissue plasminogen activator inhibitor-1 [21]. A decrease in fibrinolytic activity contributes to the development of thrombosis and the formation of atherosclerotic plaque, which significantly increases cardiovascular risks in such patients.

Decrease in the sensitivity of myocytes to insulin captures all types of muscle tissue, including cardiomyocytes.The progression of IR in the myocardium aggravates dysfunction and changes in mitochondrial morphology in obesity, leads to a decrease in the energy reserve in cardiomyocytes, to an increased risk of left ventricular dysfunction against the background of an increase in circulating blood volume and chronic stimulation of the sympathetic nervous system [22]. It was noted that IR exacerbates the development of dyslipidemia in obesity. With IR, the level of triglycerides (TG), very low density lipoproteins (VLDL) increases, the level of high density lipoproteins (HDL) decreases, and the level of low density lipoproteins (LDL) rises moderately.The substrate for the excess formation of TG is FFA, the synthesis of which is increased in obesity and IR. In addition to the excessive synthesis of FFA against the background of excess adipose tissue and IR, these changes are also associated with a violation of the regulatory effects of insulin on lipid metabolism. In conditions of IR and hyperinsulinemia, there is a change in the activity of enzymes – lipoprotein lipase and hepatic triglyceride lipase, leading to an increase in the synthesis and secretion of VLDL and a slowdown in their removal from the bloodstream. In addition, the inhibitory effect of insulin on the release of VLDL in the liver is suppressed, as a result of which the balance between the synthesis and elimination of VLDL is disturbed.In turn, dyslipidemia increases insulin resistance. It is known that a high level of LDL helps to reduce the number of insulin receptors [23].

INSULIN RESISTANCE AND NON-ALCOHOLIC FATTY LIVER DISEASE

As already mentioned, the liver is also one of the main target organs for the action of insulin, the function of which is significantly impaired in the development of obesity and IR. And another disease associated with obesity, which in its pathogenesis is closely related to IR and has the character of a global epidemic, is non-alcoholic fatty liver disease (NAFLD).Epidemiological data vary significantly depending on the diagnostic method used. According to the data of the first Russian epidemiological surveillance study DIREG L 01903, the prevalence of NAFLD in the Russian Federation in 2007 was 27%, including 80.3% of cases were hepatic steatosis, 16.8% – non-alcoholic steatohepatitis and 2.9 % – for cirrhosis of the liver. An increase in the frequency of detection of NAFLD with age has been shown, with the maximum prevalence among people 50–59 years old – 31.1% [24].Other studies demonstrate that among obese individuals, the detection rate of NAFLD is up to 100% [25]. There are three main forms of NAFLD, which also reflect the staging of the development of the disease: liver steatosis, non-alcoholic steatohepatitis, liver cirrhosis. Often, NAFLD is asymptomatic or accompanied by nonspecific complaints. If cirrhosis of the liver develops, the symptoms of liver failure, portal hypertension come to the fore.

The pathogenesis of NAFLD is a complex multicomponent process, which is based on the development of IR, the accumulation of triglycerides and other cholesterol derivatives in hepatocytes.Obesity and IR promote the formation of an excess amount of FFAs, slowing down their release and utilization from the liver, which leads to their excessive accumulation in the liver. Due to the high level of FFA, the processes of peroxidation are activated, which leads to the accumulation of reactive oxygen species, damage to mitochondria, ATP deficiency, excessive production of tumor necrosis factor alpha, the development of a chronic inflammatory process and hepatic IR. As a result, the death of hepatocytes is initiated and the production of glucose by the liver paradoxically increases, despite the existing hyperinsulinemia.To date, a correlation has been proven between IR indicators and signs of liver damage: serum insulin levels and the presence of signs of cytolysis; an increase in the HOMA-IR index and the severity of liver fibrosis, which has been demonstrated in many clinical studies [26]. In addition, it is known that a running cycle of pathological processes in NAFLD stimulates the development of IR, promotes atherogenesis, and significantly increases cardiovascular risks (Fig. 4).

Figure 4.Formation of a vicious circle of metabolic and hemodynamic disorders in obesity.

INSULIN RESISTANCE AND REPRODUCTIVE FUNCTION DISORDERS IN OBESITY

Another acute problem is impaired reproductive function in both women and men with obesity and IR. Various menstrual irregularities, including anovulatory menstrual cycle, occur 3-5 times more often in obese women than in women with normal body weight. In addition to the well-known dyshormonal disorders against the background of excess adipose tissue, IR exacerbates the development of hyperandrogenism in obese women, contributes to the progression of polycystic ovary syndrome (PCOS), which can cause violations of the ovulatory cycle and lead to infertility.The prevalence of obesity and IR among women with PCOS is 65% [27]. Hyperinsulinemia stimulates the synthesis of ovarian androgens, and also inhibits the secretion of sex hormone binding globulins (SHBG) in the liver, which leads to an increase in the circulation of free androgens in the bloodstream. Pathological IR during pregnancy can cause the development of gestational diabetes mellitus, arterial hypertension, and lead to termination of pregnancy. The risk of complications in the neonatal period also increases, which is associated with fetal developmental disorders — fetal hypertrophy and malnutrition occurs in women with pathological IRR 2 and 3 times more often, respectively, than in healthy women [28].

Obesity also has a significant negative effect on the reproductive potential of men. Due to hyperleptinemia, an increase in aromatase levels and, accordingly, the conversion of androgens to estrogens in adipose tissue, androgen deficiency develops in obese men. In addition, chronic slowly progressive systemic inflammation, oxidative stress, in turn, have a direct effect on the morphology, number and motility of spermatozoa. These processes are the main key mechanisms in the development of infertility in obese men.The relationship between high BMI and the frequency of infertility in men has been demonstrated in a large number of studies [29, 30] and to date, there is no doubt. Hypogonadism in obese men aggravates IR, increases the risk of developing diabetes, and makes a significant contribution to the development of metabolic disorders and weight gain, thereby closing the pathological vicious circle.

BASIC PRINCIPLES OF THERAPY FOR INSULIN RESISTANCE SYNDROME

Weight loss is a key aspect of IR treatment in obesity.The therapy is based on balanced nutrition, individual selection of the calorie content of the daily diet and the fight against physical inactivity. It is important that the energy consumption exceeds the energy consumption while maintaining a nutritious and varied diet. In combination with non-drug methods, with a BMI ≥30 kg / m ² , as well as in patients with a BMI ≥27 kg / m ² in the presence of complications, it is possible to use drugs to reduce body weight. Three such drugs are currently registered in the Russian Federation – orlistat, sibutramine and liraglutide 3.0 mg.Each of the drugs has its own mechanism of action, should be used strictly in accordance with the instructions and taking into account contraindications. With morbid obesity and in the case of BMI ≥35 kg / m ² in the presence of complications, surgical treatment is possible using various methods of bariatric surgery. Drugs that reduce IR (biguanides, thiazolidinediones, angiotensin-converting enzyme inhibitors) are used only in the case of diagnosed prediabetes, diabetes mellitus, hypertension, and in case of isolated IR against the background of obesity without these manifestations, they are not recommended.

CONCLUSION

Thus, IR that develops against the background of overweight and obesity is, on the one hand, an independent, and on the other, an aggravating factor in the development of such obesity-associated diseases as diabetes mellitus, coronary heart disease, AH, NAFLD, etc., being in close pathogenetic relationship with each other. A vicious circle is formed, which must be broken in the early stages of manifestations. And, despite the fact that currently well-developed drug treatment methods, it is important to understand that the basis of therapy and the basis for the prevention of obesity and carbohydrate metabolism disorders is lifestyle modification (changing the diet and expanding the mode of physical activity).The development of a food culture is of great importance at all levels of prevention and treatment of these diseases. Therefore, today all the forces of world health are aimed at realizing this goal, forming a commitment to a healthy lifestyle among the population and responsibility for their own health.

ADDITIONAL INFORMATION

Funding source. Preparation and publication of the manuscript were financed by the personal funds of the group of authors.

Conflict of interest. The authors of the work report that there are no potential and obvious conflicts of interest (financial relations, service or work in institutions with a financial or political interest in the published materials, official duties, etc.) related to the manuscript.

Contribution of authors. All authors made a significant contribution to the preparation of the article, read and approved the final version of the article before publication.

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Symptoms and signs of diabetes mellitus in men and women

Diabetes mellitus is perhaps the most common disease in the world: according to official statistics, about 6% of the world’s population suffers from it. And most doctors agree that these data do not reflect reality: more than half of the cases have not been diagnosed.Meanwhile, early detection of diabetes can significantly increase the life expectancy of patients and prevent the development of many complications. We will talk about what signs indicate an elevated blood glucose level and what tests should be done to be sure that there is no disease.

Diabetes manifests itself, regardless of its type, is always the same – the cells stop “extracting” energy from glucose and the substance accumulates in the body in an undivided form.Disruption of metabolic processes is due to a lack of the hormone insulin, which is responsible for the absorption of sugars. However, the causes, features, and symptoms differ for different types of diabetes.

With type 1 diabetes insulin is not produced by the body due to significant damage to the beta cells of the pancreas during an autoimmune attack. The onset of the disease is often preceded by viral infections. Typically, this type of diabetes does not depend on the patient’s physique and occurs at an early age – in children, adolescents and young people under the age of 25.

To Type 2 , according to various sources, up to 95% of all cases of diabetes are related. Unlike type 1, the body continues to produce insulin, but it is not properly absorbed by the cells and is not absorbed. Obesity provokes the development of the disease (especially the accumulation of fat in the abdomen and waist), hereditary factors, an inactive lifestyle, unhealthy diet. Type 2 diabetes is a disease of mature age, and it is more susceptible to citizens over 45 years of age.

Gestational diabetes is a rather rare and, fortunately, temporary type that develops exclusively during pregnancy and disappears with its end. The development of the disease can be considered an individual reaction of the body: the hormones produced block the perception of insulin by the cells of the expectant mother. In some cases, the pancreas simply cannot cope with the double production of insulin – the result is gestational diabetes. Risk factors include the late age of the woman in labor (over 40 years), smoking, overweight, heredity.

Reference
The term “diabetes” dates back to the 2nd century BC. NS. in Ancient Greece. Initially, this name united a group of diseases manifested in patients by constant thirst, water incontinence in the body and frequent urination.

Clinical signs of diabetes

Diabetes is one of the most insidious diseases, according to doctors: its early stages are rarely accompanied by painful sensations and do not always have pronounced symptoms.To notice the first signs of diabetes, you need to listen carefully to your body and, of course, know what disorders you should pay attention to.

In general, the symptoms of all types of diabetes mellitus are similar and do not depend on gender and age: the occurrence of certain signs of the disease in men, women and children is purely individual.

Symptoms of type 1 diabetes

Type 1 diabetes develops rapidly and has pronounced manifestations. The patient, despite the increased appetite, quickly loses weight, feels constant fatigue, drowsiness, thirst.Frequent urge to urinate makes him wake up in the middle of the night several times, the amount of urine excreted significantly exceeds the norm. Symptoms come on suddenly and do not go unnoticed with careful attention.

Symptoms of type 2 diabetes mellitus

The second type of diabetes mellitus is the most common and at the same time the most difficult to recognize. The disease progresses slowly, and, despite the large number of possible symptoms, they are usually mild.

Type II diabetes is characterized by:

• dry mouth and thirst, the patient can consume up to three to five liters of fluid daily;
• weight loss;
• profuse urination;
• Constant fatigue, drowsiness, feeling of weakness, irritability;
• tingling sensation in the fingers, numbness of the limbs;
• significant sudden weight loss despite high appetite;
• nausea, sometimes vomiting;
• the skin is dry, severe itching is possible, long healing of wounds and abrasions;
• urinary tract infections;
• high pressure.

Both of these types of diabetes are fraught with serious complications. So, hyperosmolar and lacticidotic coma, hypoglycemia, ketoacidosis can develop literally within two to three hours and in some cases lead to death.

Diabetes is also the cause of vision problems (up to complete blindness), heart, kidney, nervous system, skin, blood vessels. Thrombosis, atherosclerosis, renal failure, myocardial infarction, stroke – these are just a small part of the list of dangerous diseases that can be observed with late diagnosis and improper treatment of diabetes.

Symptoms of gestational diabetes

This type of disease very rarely has external symptoms: it is usually found only during routine examinations, including urine and blood tests. In cases where the manifestations are still noticeable, they are similar to signs of type 1 and 2 diabetes: weakness, nausea, thirst, urinary tract infections.

Gestational diabetes, although it does not pose a direct threat to the child’s life, still negatively affects the condition of the mother and baby: the higher the blood glucose levels, the stronger the effect of the disease.As a rule, a baby is born with a weight exceeding the norm; in the future, he remains prone to obesity, diabetes. There is a small risk of fetal growth retardation, as well as hypoglycemia, jaundice and other diseases in the first weeks of a child’s life.

Laboratory signs of diabetes mellitus in men, women and children

Reliable confirmation of the diagnosis is possible only after a series of laboratory tests to assess the level of sugar (glucose) in the blood:

• Random analysis of glucose in blood plasma is usually carried out during mass examinations and clinical examination, as well as, if necessary, conduct an emergency study of indicators.A critical value can be considered an indicator of 7 mmol / l or more.
• Fasting blood glucose test – the most common type of analysis, albeit not distinguished by absolute accuracy, but simple to perform. As a rule, it is carried out in the morning, while the patient should not eat for 8-12 hours before the study. As with any blood test, you should not drink alcoholic beverages the day before, and also smoke an hour before taking the material. A good indicator is considered if the glucose level does not exceed 5.5 mmol / l.At 7 mmol / L or more, the patient will be referred for additional examination.
• Glucose Tolerance Test is usually prescribed to clarify the results of the tests described above. The test allows not only to accurately answer the question of the presence of diabetes, but also to diagnose impaired glucose tolerance. To do this, blood is taken from the patient on an empty stomach, then he must drink a glass of water with sugar dissolved in it (75 g for adults; 1.75 g per 1 kg of the child’s weight), and after two hours he must be tested again.In the normal state of the body, the first indicator is below 5.5 mmol / l, and the second is less than 7.8 mmol / l. Values ​​from 5.5 to 6.7 mmol / L and from 7.8 to 11.1 mmol / L, respectively, indicate the presence of prediabetes. Values ​​above these numbers indicate diabetes.
• Glycated Hemoglobin Test is a modern, reliable test recommended by the World Health Organization for the detection of diabetes. Its results show the average blood glucose value over the past 90 days, and accuracy is not affected by food intake, sampling time, or many other external factors.Normally, the indicator will be less than 6.5% HbA1C, which corresponds to a glucose level of 7.8 mmol / l, a value above this is a clear sign of the disease. At 6% (7 mmol / L), the risk of diabetes is considered increased, but the situation can still be corrected by changing the lifestyle.

Modern methods of treatment in combination with the prescribed diet can make the life of a diabetic patient full and comfortable, as well as avoid many complications. The biggest problem is the timely diagnosis of this disease: many patients go to clinics only in the late stages of diabetes.To avoid irreversible consequences for the body, doctors recommend to undergo an examination at least once a year, especially if there are “risk factors” in the anamnesis, and even more so when the first signs of diabetes appear.

90,000 causes, symptoms, diagnosis and treatment

Insulin resistance is a decrease in the susceptibility of insulin-sensitive tissues to the action of insulin when it is sufficiently concentrated in the blood. Insulin resistance has no specific symptoms.Frequent accompanying signs are: visceral obesity, arterial hypertension, fatty hepatosis, atherosclerosis, acanthosis nigricans (pigmented wrinkled areas of the skin). Laboratory tests are used for diagnostics: oral glucose tolerance test, intravenous glucose tolerance test, calculation of the HOMA-IR index. The main methods for correcting insulin resistance are compliance with the rules of a balanced diet, systemic physical training.

General information

The term “insulin resistance syndrome” was introduced into medicine in 1992 to denote a factor causing a complex of metabolic disorders, which include hypertension, diabetes mellitus, hypertriglyceridemia and visceral obesity.Since 1999, the concept of “metabolic syndrome” has been used in the same sense. According to 2001 studies, the prevalence of pathological insulin resistance among healthy women is 10%, among men – 15%. In individuals with impaired glucose tolerance, the indicators are 42% and 64%, in patients with diabetes – 78% and 84%, respectively. High epidemiological data indicate the need for the development of rapid diagnostic methods and their introduction into clinical endocrinology.

Insulin resistance

Causes of insulin resistance

Decreased insulin reactivity of tissues can be triggered by many factors – age-related changes, pregnancy, hypodynamia, puberty, weight gain, infectious process, stress, cirrhosis, liver disease, liver cancerThe most common causes of insulin resistance include:

• Excess sugar intake. When you eat foods that contain a large amount of refined sugar, the body begins to produce more insulin. The sensitivity of cells to its effects decreases, and the amount of glucose remains elevated.
• Obesity. Adipose tissue has an endocrine and paracrine function – it produces substances that affect the insulin sensitivity of cells.In obesity, the interaction of the hormone with receptors and intracellular glucose transport are disrupted.
• Genetic burden. Heredity is a factor in susceptibility to insulin resistance. Disorders of carbohydrate metabolism are found in people whose direct relatives are diagnosed with diabetes mellitus, obesity or arterial hypertension.

Pathogenesis

Insulin resistance develops when the most insulin-sensitive tissues – the liver, adipose and muscle tissue – lose their ability to perceive the action of this hormone.Several leading pathological mechanisms have been identified: increased levels of free fatty acids, chronic hyperglycemia, chronic inflammation of adipose tissues, oxidative metabolic stress, changes in gene expression, and mitochondrial dysfunction.

Free fatty acids (FFA) are a substrate for the synthesis of triglycerides, which are insulin antagonists. When the concentration of FFA increases and the metabolism of triglycerides in myocytes changes, the amount of glucose transporters decreases, glucose is broken down more slowly.In the liver, an excessive intake of FFA inhibits the processes of transfer and phosphorylation of glucose. Insulin does not inhibit gluconeogenesis, and the production of glucose by hepatocytes is increased. With insulin resistance, the synthesis and secretion of VLDLP increases, the concentration of HDLP decreases. Due to the high level of FFA, lipids accumulate in the cells of the pancreas, disrupting their hormonal function. In adipose tissue, the anti-lipolytic effect of insulin is reduced. Obesity is characterized by an aseptic inflammatory process in adipocytes, oxidative stress and hyperglycemia are formed.

Classification

The sensitivity of body tissues to the effects of insulin is determined by various factors – age, body weight, fitness of the body, the presence of bad habits and diseases. Insulin resistance is detected in type 2 diabetes and a number of other diseases and functional conditions, which are based on metabolic disorders. Depending on this factor, four types of insulin resistance are distinguished in endocrinology:

1. Physiological. Is a mechanism for adapting to periods of changing energy input and release. It occurs during nighttime sleep, pregnancy, puberty, in old age, with frequent consumption of fatty foods.
2. Metabolic. Diagnosed with dysmetabolic disorders. It is characteristic of type 2 diabetes, decompensated type 1 diabetes, diabetic ketoacidosis, prolonged nutritional deficiency, alcohol intoxication, and obesity.
3. Endocrine. It is caused by pathologies of the endocrine glands. It is determined with thyrotoxicosis, hypothyroidism, Cushing’s syndrome, acromegaly, pheochromocytoma.
4. Pathological non-endocrine. Aimed at maintaining homeostasis in diseases and some emergency conditions. Accompanies arterial hypertension, chronic renal failure, cirrhosis of the liver, oncological cachexia, burn disease, blood poisoning, surgery.

Symptoms of insulin resistance

Insulin resistance is not clinically manifested, but it develops on the basis of certain characteristics of the body, provokes metabolic disorders, changes the functioning of internal organs.Therefore, in relation to insulin resistance, it is worth talking not about the symptoms, but about the signs accompanying it. Excessive fat deposition is observed, especially in the waist area. This type of obesity is called abdominal obesity. Visceral fat accumulates around the organs and affects their function. Another common symptom is high blood pressure, manifested by a headache in the back of the head, dizziness, confusion, heart palpitations, sweating, and facial flushing.

Fluctuations in blood sugar levels lead to the fact that patients feel tired, weak, depressed, irritable, experience increased thirst and hunger. The skin may have a specific pigmentation – black keratosis (acanthosis). Areas of the skin on the neck, sides, in the armpits, under the mammary glands darken, become rough and wrinkled, sometimes peeling. In women, insulin resistance is often accompanied by symptoms of hyperandrogenism, which have arisen on the basis of polycystic ovary syndrome.Typical signs are oily seborrhea, acne vulgaris, menstrual irregularities, excess hair on the arms, legs and face.

Complications

The most common consequences of insulin resistance are cardiovascular disease and diabetes. With insulin resistance and obesity, the function of insulin to cause vasodilation is reduced, and the inability of the arteries to dilate is the initial stage in the development of angiopathies (circulatory disorders). Also, insulin resistance contributes to the formation of atherosclerosis, as it changes the activity of blood coagulation factors and the process of fibrinolysis.The mechanism of development of type II diabetes as a complication of insulin resistance is long-term compensatory maintenance of hyperinsulinemia and subsequent depletion of beta cells, a decrease in insulin synthesis, and the formation of persistent hyperglycemia.

Diagnostics

Identification of insulin resistance is a difficult diagnostic task due to the fact that this condition does not have specific clinical manifestations, does not induce patients to seek medical help. As a rule, it is found during examination by an endocrinologist for diabetes or obesity.The most common diagnostic methods are:

• Insulin suppression test. The method is based on prolonged glucose administration, simultaneous suppression of β-cell response and endogenous glucose production. Insulin sensitivity is measured by the level of glucose at steady state. When the MI value is ≥7.0, insulin resistance is confirmed.
• Oral glucose tolerance test. Widely used in screening, determines the presence and severity of hyperinsulinemia.Serum glucose, C-peptide, fasting and post-carbohydrate insulin levels are measured. Two hours after the carbohydrate load in hyperinsulinemia, the insulin indicator is more than 28.5 μIU / ml, in the metabolic syndrome, the C-peptide indicator is more than 1.4 nmol / l, in diabetes mellitus, the glucose indicator is more than 11.1 mmol / l.
• Intravenous glucose tolerance test. Allows you to assess the phases of insulin secretion, to reproduce the physiological model of its action.During the procedure, glucose and insulin are injected intravenously according to the scheme, the results reflect changes in glucose regardless of insulin and under its influence. Insulin resistance is determined by the index SI -4 min ^-1 .
• HOMA-IR Index . Before calculating the coefficient, a blood test is performed, indicators of the amount of insulin, sugar (glucose) in fasting blood plasma are used. The presence of insulin resistance is indicated by an index above 2.7.

Treatment of insulin resistance

Medical care for patients is provided in a comprehensive manner.It is aimed not only at enhancing the insulin response of tissues, but also at normalizing the concentration of glucose, cholesterol, blood insulin, eliminating excess weight, preventing obesity, diabetes, heart and vascular diseases. Treatment is carried out by an endocrinologist, nutritionist, exercise therapy instructor. Patients are shown:

• Drug therapy. Medicines are prescribed for patients with a body mass index over 30 who have a high risk of cardiovascular disease. To reduce weight and increase insulin sensitivity, biguanides, alpha-glucosidase blockers, thiazolidinediones are used.
• Low carb diet. For people with insulin resistance, a low carbohydrate diet but no fasting periods is indicated. The fractional diet – from 5 to 7 meals a day in small portions. This scheme allows you to maintain a stable sugar level, relatively uniform insulin activity.
• Regular physical activity. Exercise activates glucose transport and insulin’s ability to stimulate glycogen synthesis.The training regimen is selected individually for patients: from walking and light gymnastics to strength and aerobic training. The main condition is the regularity of classes.