How does insulin therapy work for type 2 diabetes. What are the different types of insulin routines. How to adjust insulin dosage for optimal blood glucose control. What factors affect blood glucose levels in diabetic patients. How to choose the right insulin delivery method. Why is proper insulin injection technique important. How to time insulin doses with meals for effective glucose management.

Understanding Insulin Therapy in Type 2 Diabetes

Insulin therapy plays a crucial role in managing type 2 diabetes when other treatment options become insufficient. While not all individuals with type 2 diabetes require insulin, it becomes necessary for many as the disease progresses. This comprehensive guide explores the intricacies of insulin initiation, titration, and management for patients with type 2 diabetes.

Why is insulin therapy needed in type 2 diabetes?

In type 2 diabetes, the body either doesn’t produce enough insulin or becomes resistant to its effects. As the condition progresses, the pancreas may struggle to produce sufficient insulin to maintain normal blood glucose levels. At this stage, exogenous insulin therapy becomes essential to regulate blood sugar and prevent complications.

Types of Insulin and Insulin Regimens

Insulin therapy for type 2 diabetes can involve various types of insulin and regimens, tailored to individual needs and lifestyle factors.

What are the main types of insulin used in type 2 diabetes treatment?

• Rapid-acting insulin
• Short-acting (regular) insulin
• Intermediate-acting insulin
• Long-acting insulin
• Ultra-long-acting insulin
• Premixed insulin combinations

Each type of insulin has a specific onset, peak, and duration of action, allowing for customized treatment plans. Healthcare providers consider factors such as the patient’s blood glucose patterns, lifestyle, and individual response when selecting the appropriate insulin type and regimen.

Common insulin regimens for type 2 diabetes

1. Basal insulin only: A single daily injection of long-acting insulin
2. Basal-bolus regimen: Long-acting insulin combined with mealtime rapid-acting insulin
3. Premixed insulin: Fixed combinations of intermediate- and short-acting insulins
4. Intensive insulin therapy: Multiple daily injections or insulin pump therapy

The choice of regimen depends on various factors, including the severity of diabetes, lifestyle considerations, and individual glucose control needs.

Initiating Insulin Therapy in Type 2 Diabetes

Starting insulin therapy can be a significant step for patients with type 2 diabetes. The process requires careful consideration and close monitoring to ensure optimal outcomes.

When should insulin therapy be initiated in type 2 diabetes?

Insulin therapy is typically considered when oral medications and lifestyle modifications fail to achieve adequate glycemic control. Specific indicators for insulin initiation may include:

• HbA1c levels persistently above target despite maximum oral therapy
• Fasting blood glucose levels consistently above 250 mg/dL
• Presence of significant hyperglycemia symptoms
• Acute illness or surgery necessitating tight glucose control

Healthcare providers assess individual patient factors, including comorbidities, risk of hypoglycemia, and patient preferences, when deciding to initiate insulin therapy.

How is insulin therapy typically started in type 2 diabetes?

Insulin initiation often begins with a single daily injection of basal insulin, usually administered at bedtime. The starting dose is calculated based on the patient’s weight, typically around 0.1-0.2 units per kilogram of body weight. This conservative approach helps minimize the risk of hypoglycemia while allowing for gradual dose titration.

Insulin Titration and Dose Adjustment

Proper insulin titration is crucial for achieving optimal glycemic control while minimizing the risk of hypoglycemia. The process involves regular monitoring and adjustment of insulin doses based on blood glucose readings and individual patient factors.

What is the recommended approach for insulin dose titration?

A common titration approach involves adjusting the basal insulin dose every 3-7 days based on fasting blood glucose levels. Patients are typically instructed to increase their dose by 2-4 units if fasting glucose remains above target for 2-3 consecutive days. Conversely, doses may be reduced if hypoglycemia occurs or fasting glucose drops too low.

For patients on multiple daily injections, mealtime insulin doses are adjusted based on pre-meal and post-meal glucose readings. Carbohydrate counting and insulin-to-carb ratios may be employed to fine-tune mealtime insulin doses.

How often should insulin doses be reviewed and adjusted?

Initially, insulin doses should be reviewed frequently, often weekly or bi-weekly, until stable glycemic control is achieved. Once stability is reached, less frequent reviews (every 1-3 months) may be sufficient. However, dose adjustments may be needed more frequently during times of illness, significant weight changes, or alterations in physical activity levels.

Monitoring Blood Glucose and HbA1c Levels

Regular monitoring of blood glucose and HbA1c levels is essential for effective insulin management in type 2 diabetes. These measurements provide valuable information for dose adjustments and overall treatment efficacy.

How often should blood glucose be monitored in patients on insulin therapy?

The frequency of blood glucose monitoring depends on the insulin regimen and individual patient factors. Generally, patients on basal insulin alone may need to check fasting glucose daily. Those on multiple daily injections or insulin pump therapy typically require more frequent monitoring, including pre-meal and occasional post-meal checks.

Continuous glucose monitoring (CGM) systems can provide more comprehensive data, allowing for better insulin dose optimization and improved glycemic control.

What is the target HbA1c for patients with type 2 diabetes on insulin therapy?

The target HbA1c for patients with type 2 diabetes on insulin therapy is typically below 7% (53 mmol/mol). However, this target may be individualized based on factors such as age, comorbidities, hypoglycemia risk, and patient preferences. In some cases, a less stringent target of 7.5-8% (58-64 mmol/mol) may be appropriate for older adults or those with multiple comorbidities.

Insulin Delivery Methods and Techniques

Various insulin delivery methods are available for patients with type 2 diabetes, each with its own advantages and considerations. Proper injection technique is crucial for ensuring optimal insulin absorption and efficacy.

What are the main insulin delivery methods available?

• Insulin syringes: Traditional method offering precise dosing
• Insulin pens: Convenient, pre-filled devices for easier administration
• Insulin pumps: Continuous subcutaneous insulin infusion devices
• Inhaled insulin: Rapid-acting insulin delivered via inhalation

The choice of delivery method depends on factors such as patient preference, dexterity, lifestyle, and specific insulin requirements.

Why is proper insulin injection technique important?

Correct insulin injection technique ensures consistent and predictable insulin absorption, leading to better glycemic control. Key aspects of proper technique include:

• Rotating injection sites to prevent lipohypertrophy
• Using the correct needle length and injection angle
• Proper storage and handling of insulin
• Adhering to recommended injection-to-meal timing

Healthcare providers should regularly review and reinforce proper injection technique with patients to optimize insulin therapy outcomes.

Managing Insulin-Related Complications and Challenges

While insulin therapy is effective for managing type 2 diabetes, it can present certain challenges and potential complications. Understanding and addressing these issues is crucial for successful long-term management.

How can the risk of hypoglycemia be minimized in patients on insulin therapy?

Hypoglycemia is a significant concern for patients on insulin therapy. Strategies to reduce hypoglycemia risk include:

• Regular blood glucose monitoring and appropriate dose adjustments
• Patient education on recognizing and treating hypoglycemia
• Matching insulin doses to carbohydrate intake and activity levels
• Using insulin analogs with lower hypoglycemia risk when appropriate
• Considering the use of continuous glucose monitoring systems

Healthcare providers should work closely with patients to develop individualized strategies for hypoglycemia prevention and management.

What are common barriers to insulin therapy adherence?

Adherence to insulin therapy can be challenging for many patients. Common barriers include:

• Fear of injections or needles
• Concerns about weight gain
• Complex regimens interfering with daily routines
• Cost and access issues
• Stigma associated with insulin use

Addressing these barriers through patient education, psychological support, and tailored treatment plans can improve adherence and outcomes.

Optimizing Insulin Therapy Through Lifestyle Modifications

While insulin therapy is a cornerstone of type 2 diabetes management, its effectiveness can be significantly enhanced through lifestyle modifications. Integrating diet, exercise, and stress management strategies can lead to improved glycemic control and overall health outcomes.

How does diet impact insulin requirements and glycemic control?

Dietary choices play a crucial role in managing blood glucose levels and insulin requirements. Key dietary considerations for patients on insulin therapy include:

• Carbohydrate counting and consistent carbohydrate intake
• Choosing low glycemic index foods to minimize blood glucose spikes
• Balancing macronutrients for sustained energy and glucose control
• Timing meals and snacks in relation to insulin doses
• Monitoring portion sizes to prevent overfeeding and excessive insulin needs

Working with a registered dietitian can help patients develop personalized meal plans that complement their insulin regimen and support overall health goals.

What role does physical activity play in insulin management?

Regular physical activity can significantly impact insulin sensitivity and glucose utilization. Benefits of exercise for patients on insulin therapy include:

• Improved insulin sensitivity, potentially leading to lower insulin requirements
• Enhanced glucose uptake by muscles, helping to lower blood glucose levels
• Better overall glycemic control and reduced HbA1c levels
• Improved cardiovascular health and weight management

However, it’s crucial to adjust insulin doses and timing in relation to exercise to prevent hypoglycemia. Patients should work closely with their healthcare team to develop safe and effective strategies for incorporating physical activity into their diabetes management plan.

How can stress management techniques support insulin therapy?

Stress can have a significant impact on blood glucose levels, often leading to increased insulin resistance and higher glucose readings. Incorporating stress management techniques can help optimize insulin therapy by:

• Reducing stress-induced glucose fluctuations
• Improving overall glycemic control
• Enhancing adherence to diabetes management routines
• Promoting better sleep, which can positively impact insulin sensitivity

Effective stress management strategies may include mindfulness meditation, deep breathing exercises, regular physical activity, and adequate sleep hygiene. Encouraging patients to explore and adopt stress-reduction techniques can complement their insulin therapy and improve overall diabetes management.

Insulin Routines | ADA

• Insulin is required for people with type 1 diabetes and sometimes necessary for people with type 2 diabetes.
• Syringe is the most common form of insulin delivery, but there are other options, including insulin pens and pumps.
• Insulin should be injected in the same general area of the body for consistency, but not the exact same place.
• Insulin delivery should be timed with meals to effectively process the glucose entering your system.

Insulin therapy

With the help of your health care team, you can find an insulin routine that will keep your blood glucose (blood sugar) near normal, help you feel good, and fit your lifestyle.

Type 1

People diagnosed with type 1 diabetes usually start with two injections of insulin per day of two different types of insulin and generally progress to three or four injections per day of insulin of different types. The types of insulin used depend on their blood glucose levels. Studies have shown that three or four injections of insulin a day give the best blood glucose control and can prevent or delay the eye, kidney, and nerve damage caused by diabetes.

Type 2

Most people with type 2 diabetes may need one injection per day without any diabetes pills. Some may need a single injection of insulin in the evening (at supper or bedtime) along with diabetes pills. Sometimes diabetes pills stop working, and people with type 2 diabetes will start with two injections per day of two different types of insulin. They may progress to three or four injections of insulin per day.

Fine-tuning your blood glucose

Many factors affect your blood glucose levels, including the following:

• What you eat
• How much and when you exercise
• Where you inject your insulin
• When you take your insulin injections
• Illness
• Stress

Self-monitoring

Checking your blood glucose and looking over results can help you understand how exercise, an exciting event, or different foods affect your blood glucose level. You can use it to predict and avoid low or high blood glucose levels. You can also use this information to make decisions about your insulin dose, food, and activity.

For more information, see our Blood Glucose Control section.

Insulin delivery

Many people who take insulin use a syringe, but there are other options as well.

Insulin pens

Some insulin pens contain a cartridge of insulin that is inserted into the pen and some are pre-filled with insulin and discarded after all the insulin has been used. The insulin dose is dialed on the pen, and the insulin is injected through a needle, much like using a syringe. Cartridges and pre-filled insulin pens only contain one type of insulin. Two injections must be given with an insulin pen if using two types of insulin.

Pump therapy

Insulin pumps help you manage diabetes by delivering insulin 24 hours a day through a catheter placed under the skin. Read more about insulin pumps.

Site rotation

The place on your body where you inject insulin affects your blood glucose level. Insulin enters the blood at different speeds when injected at different sites. Insulin shots work fastest when given in the abdomen. Insulin arrives in the blood a little more slowly from the upper arms and even more slowly from the thighs and buttocks. Injecting insulin in the same general area (for example, your abdomen) will give you the best results from your insulin. This is because the insulin will reach the blood with about the same speed with each insulin shot.

Don’t inject the insulin in exactly the same place each time, but move around the same area. Each mealtime injection of insulin should be given in the same general area for best results. For example, giving your before-breakfast insulin injection in the abdomen and your before-supper insulin injection in the leg each day give more similar blood glucose results. If you inject insulin near the same place each time, hard lumps or extra fatty deposits may develop. Both of these problems are unsightly and make the insulin action less reliable. Ask your health care provider if you aren’t sure where to inject your insulin.

Timing

Insulin shots are most effective when you take them so that insulin goes to work when glucose from your food starts to enter your blood. For example, regular insulin works best if you take it 30 minutes before you eat.

Too much insulin or not enough?

High morning blood glucose levels before breakfast can be a puzzle. If you haven’t eaten, why did your blood glucose level go up? There are two common reasons for high before-breakfast blood glucose levels. One relates to hormones that are released in the early part of sleep (called the Dawn Phenomenon). The other is from taking too little insulin in the evening. To see which one is the cause, set your alarm to self-monitor around 2 or 3 a.m. for several nights and discuss the results with your health care provider.

10 Tips for Starting Insulin Therapy

Finding out that you need to start taking insulin for your type 2 diabetes may cause you to become concerned. Keeping your blood sugar levels within target range takes a bit of effort, including eating a healthy diet, exercising, and taking your medications and insulin as prescribed.

But while it may sometimes seem like a hassle, insulin can help you properly manage your blood sugar, improve your diabetes management, and delay or prevent long-term complications such as kidney and eye disease.

Here are 10 tips for how to make your transition to using insulin easier.

Working closely with your healthcare team is the first step to starting on insulin. They’ll discuss the importance of taking your insulin exactly as prescribed, address your concerns, and answer all of your questions. You should always be open with your doctor about all aspects of your diabetes care and overall health.

Starting to use insulin isn’t as challenging as you might think. Methods for taking insulin include pens, syringes, and pumps. Your doctor can help you decide what’s best for you and your lifestyle.

You might need to start on long-acting insulin. Your doctor may also recommend mealtime insulin to help manage your blood sugar levels. It’s possible that you may switch to a different insulin delivery device. For example, you may start out using an insulin pen and eventually begin to use an insulin pump.

When it comes to your insulin or your insulin delivery system, a one-size-fits-all plan doesn’t exist. If your current insulin regimen doesn’t work for you, discuss your concerns with your healthcare team.

Your healthcare team can help you learn different aspects of diabetes self-care management. They can teach you how your insulin works, how to administer it, and what side effects to anticipate.

Talk to your doctor, certified diabetes educator, and other members of your healthcare team about your blood sugar testing schedule, including what to do when you’re at home, school, or away on a vacation. They may ask you to check your blood sugar more often when you first start on insulin to make sure you’re within target range.

They may adjust your insulin dose over time depending on blood sugar readings. They may also adjust your dosing schedule depending on your:

• needs
• weight
• age
• physical activity level

Your doctor and other members of your healthcare team can help you and answer any questions you have about your insulin and diabetes management. Try keeping an updated, written list of questions to discuss during your next visit. Store this list in the notes section of your smartphone or on a small pad of paper that you can easily access during the day.

Keep detailed logs of your blood sugar levels, including your fasting, premeal and post-meals levels.

Hypoglycemia, or low blood sugar, occurs when too much insulin is in your bloodstream and not enough sugar is reaching your brain and muscles. The symptoms may occur suddenly. They can include:

• feeling cold
• shakiness
• dizziness
• a rapid heartbeat
• hunger
• nausea
• irritability
• confusion

Make sure you keep a fast-acting source of carbohydrate with you at all times in case you experience low blood sugar. This may be glucose tablets, hard candies, or juice. Work closely with your doctor to develop an action plan in case an insulin reaction occurs.

Hyperglycemia, or high blood sugar, can also happen. This condition develops slowly over several days when your body doesn’t have enough insulin, which causes blood sugar levels to increase. The symptoms include:

• increased thirst and urination
• weakness
• difficulty breathing
• nausea
• vomiting

If your blood sugar is well above your target range, call your doctor.

Your doctor, nurse, or certified diabetes educator can teach you and your family about the symptoms of low or high blood sugar, and what to do about them. Being prepared can make it easier to manage your diabetes and enjoy life.

It’s very important to continue to eat a healthy diet and stay physically active when you start taking insulin. Having a nutritious meal plan along with getting regular exercise will help keep your blood sugar levels within your target range. Make sure to discuss any changes in your physical activity level with your healthcare team. You may need to check your blood sugar level more often and adjust your meal or snack schedule if you have a significant increase in your physical activity level.

Learn how to properly inject insulin from your doctor or another member of your healthcare team. You should inject insulin into the fat just underneath the skin, not into the muscle. This will help prevent differing absorption rates each time you inject. Common places to inject include the:

• stomach
• thighs
• buttocks
• upper arms

In general, you can store insulin at room temperature, either opened or unopened, for ten to 28 days or more. This depends on the type of package, the brand of insulin, and how you inject it. You can also keep insulin in the refrigerator, or between 36 to 46°F (2 to 8°C). You can use unopened bottles that you’ve kept refrigerated until the printed expiration date. Your pharmacist will probably be the best source of information about how to store your insulin correctly.

Here are some tips for proper storage:

• Always read the labels and use opened containers within the time period recommended by the manufacturer.
• Never store insulin in direct sunlight, in the freezer, or near heating or air-conditioning vents.
• Don’t leave insulin in a hot or cold car.
• Use insulated bags to moderate temperature changes if you’re traveling with insulin.

Always be prepared to test your blood sugar. Make sure that your testing strips aren’t expired and that you’ve properly stored them along with a control solution. Wear diabetes identification, such as a medical alert bracelet, and keep a card in your wallet with emergency contact information at all times.

The main goal in treating type 2 diabetes is to manage your blood sugar levels properly to reduce your risk of complications. Using insulin is in no way a failure. It’s simply part of your overall treatment plan to improve your diabetes management. By learning about all aspects of insulin therapy, you’re ready to take the next step to control your diabetes.

Insulin secretion in normal and type 2 diabetes mellitus | Ametov

According to the International Diabetes Federation (IDF), more than 246 million people currently suffer from diabetes. It has been found that every 21 seconds a new patient with this disease appears on our planet.

The bulk of these patients are patients with type 2 diabetes mellitus. It should be emphasized that for a long time in relation to this disease there was an erroneous opinion. It was thought that it was a milder form of diabetes that might not have complications, that treatment goals might not be as stringent, and that obesity was best ignored because we weren’t very good at treating it. At present, scientists are firmly convinced that this is a severe, chronic and constantly progressive disease, amounting to 85–90% of the total number of patients with diabetes. A disease in which, at the time of diagnosis, more than 50% of patients already have late complications of diabetes.

It is well known that type 2 diabetes mellitus is characterized by the presence of two fundamental defects, insulin resistance and dysfunction of pancreatic β-cells. In this regard, it is appropriate to recall the definition of the World Health Organization (WHO) and the American Diabetes Association (ADA) in relation to type 2 diabetes mellitus based on phenotypes:

Speaking about the possible mechanisms involved in the development of glucose homeostasis disorders in this disease, at least three different levels should be distinguished:

• level 1 – the pancreas, where β-cells, for various reasons, may not “recognize” glucose, and therefore insulin secretion is impaired;

• Level 2 – the liver, where the rate of glucose production can increase, either due to insufficient suppression of this process by insulin or glucose, or due to stimulation – by glucagon or catecholamines;

• Level 3 – peripheral target cells – muscle and adipose tissue, where, for various reasons, insulin sensitivity decreases and a condition known as insulin resistance develops.

It is known that glucose from food is initially distributed in the human body as follows:

• 50% of glucose enters the brain cells;

• 50% of glucose is utilized by muscle and, to a lesser extent, adipose tissue.

It should be noted that, in order to enter the brain, glucose, with the help of a special transport protein, GLUT-1, first penetrates the blood-brain barrier. Moreover, this process is controlled with the help of special sensors, by the way, which are KATP-dependent channels. In this regard, it is important to recall that these sensors clearly control the level of glucose entering the brain. Its decrease will cause the development of neuroglycopenia, and an increase in the level of glucose entering the brain will contribute to the development of neuroglucotoxicity. This process is called plasticity, in which case this term refers to memory for certain desired levels of glucose. Thus, recent studies really expand our understanding of the role of KATP-dependent channels in the regulation of glucose homeostasis (Fig.  1) (S.Slino, T.Miki, 2005).

In turn, the regulation of the flow of glucose into the muscle tissue is carried out, along with insulin, by the specialized transport protein GLUT 4. Thus, it is necessary to pay attention to the fact that the specialized transport proteins known to us carry out not only the transport of glucose into the cell, but also regulate the distribution of glucose between various organs. and tissues, as well as the distribution of glucose between the extracellular and intracellular spaces.

In healthy individuals, insulin is known to regulate three key processes:

• uptake of glucose by target tissues;

• release of endogenous glucose from the liver;

• the release of free fatty acids from adipose tissue through the processes of lipolysis.

It should be especially noted that the secretion of insulin from pancreatic β-cells is controlled by a multilevel system that ensures the level of secretion of this hormone is adequate and proportional to the daily fluctuations in glucose levels.

The best and simplest illustration of such tight control over 24-hour glycemic fluctuations by insulin, obviously, can be data on the concentration of glucose during the day in healthy volunteers, when the glucose level was measured at least 18 times during the day. Thus, the average glucose level was 4.22 ± 0.8 mmol / l, the lowest level was, on average, 3.88 ± 0.6 mmol / l, and the highest glucose level during the day was, on average, 4 .88±1.0 mmol/l.

Returning to the pathophysiological defects underlying the pathogenesis of type 2 diabetes mellitus, it is necessary to draw the attention of readers to the enhancement hypothesis (Fig. 2) (R.P. Robertson, 2005). As can be seen from the data presented in Fig. 2, insulin resistance and dysfunction of pancreatic β-cells, developing independently from each other at the start, at some stage combine and contribute to the development of hyperglycemia and associated acute and chronic glucose toxicity.

It is known that ensuring normal glucose metabolism requires careful coordination and control over the secretion and action of insulin (Table 1).

Speaking about the action of insulin, one should also pay attention to the results of research by Professor H.Yki-Yarvinen, 2004, who studied the causes leading to changes in the action of insulin (Table 2). Attention is drawn to the fact that only physical activity and an increase in muscle mass lead to an improvement in insulin sensitivity, while the rest suppressed the action of insulin.

In recent years, much attention of scientists has been attracted by studies on the stages of development of the pathological process in type 2 diabetes mellitus. In this regard, the publication of Gordon S. Weir, Susan Bonner-Weir, 2004, which addresses this problem, deserves some interest. These authors believe that the development and progression of diabetes can be viewed through the prism of certain factors characterized by changes in various metabolic parameters and β-cell function (Fig. 3). In particular, at stage 0, at the very beginning of the disease, the glucose level begins to rise from the “perfectly” normal values ​​of ~4. 5 mmol/l to higher values ​​that are in the range of ~5.0 mmol/l. These changes, of course, cannot be recognized as clinically pathological, as they do not reach the official category of impaired fasting glycemia (ULN ≥ 5.6 mmol/l or 100 mg%) or impaired glucose tolerance (IGT, 2-hour postglucose level ≥ 7.8 mmol/l or 140 mg%).

Thus, persons predisposed to the development of type 2 diabetes mellitus initially progress towards the development of impaired fasting glycemia, and then impaired glucose tolerance develops. Moreover, the stages of NGN and IGT can continue for a long period of time, until a pronounced clinic of diabetes mellitus develops.

Although we specifically discuss this progression in the context of type 2 diabetes, very similar changes occur in type 1 diabetes mellitus or when transplantation of β-cell culture or the pancreas in general fails.

In stage 1, which is called compensation, the most common example is found in insulin resistance (IR) associated with obesity associated with higher insulin secretion and increased acute glucose-stimulated insulin secretion in response to an intravenous glucose load. In this case, most of the increased insulin secretion is undoubtedly due to the increase in β-cell mass, which has been shown at autopsy in humans in a number of experimental models. It should be noted that the mass of β-cells under physiological conditions is clearly controlled and regulated through the balance between the birth of β-cells (β-cell replication and islet neogenesis), on the one hand, and the death of β-cells (apoptosis), on the other.

There are data in the literature that indicate that an increase in the function of pancreatic β-cells, which develops against the background of insulin resistance, can be associated with both an increase in the mass of functioning β-cells and the development of hypertrophy of pancreatic β-cells.

Although it is still unknown whether the elevated insulin level at the compensation stage is associated with an increase in the mass of β-cells or an increase in secretion per unit mass of β-cells. Although compensation is primarily thought and spoken of as a situation during insulin resistance, similar changes may positively occur in the early stages of autoimmune destruction that occurs during the development of type 1 diabetes mellitus.

At this stage (compensation), it is also possible to develop a decrease in the mass of pancreatic β-cells, which may be a signal for an increase in the mass of functioning β-cells and insulin secretion capacity, which, presumably, may lengthen the pre-diabetic period, which in fact can last for many years. !

In this regard, it should be noted that at present there is great interest in studying the signals leading to an increase in the mass of β-cells at this stage of the development of the pathological process. Unfortunately, a poorly understood but plausible explanation for this fact is that there is a feedback mechanism between insulin resistance and pancreatic β-cell function. In this connection, against the background of a decrease in insulin sensitivity, hyperglycemia develops, which, in turn, will stimulate β-cell growth and create opportunities for insulin secretion adequate to this state. With relatively normal glucose levels, obviously the above explanation alone will not suffice, and more research is needed.

There are other versions of the explanation in the literature, in particular that there is a “closed loop” feedback that is carefully regulated, like a thermostat that maintains the temperature in a very narrow range. In this regard, even very small changes in glucose levels can lead to changes in the set point in glucose-stimulated insulin secretion, ultimately maintaining “normal” plasma glucose levels.

Also an important role in achieving and maintaining a rapid balance between extracellular and intracellular glucose is played by glucose transporters, in particular GLUT-2, which ensures normal levels of glucose in blood plasma.

It is difficult to determine the exact range of glucose levels for stage 2 – stable adaptation, however, fasting glucose levels between 5.0–7.3 mmol/L (89–130 mg%) are, in our opinion, a reasonable approximation.

At the stage of stable adaptation, β-cells can no longer provide a truly normal level of glucose. However, this stage is considered stable, because if it were not for the presence of certain processes, such as autoimmunity, which contributes to the rapid destruction of β-cells, patients could be in stage 2 for a long time, in the absence of progression of the pathological process.

In parallel with the increase in glucose levels during stage 2, important changes in β-cell differentiation and function occur. The best studied and most impressive change is the loss of glucose-stimulated insulin secretion (GSSI). In particular, it has been shown that normal GSIS remains as long as the level of glycemia remains <5.6 mmol/l (100 mg%). However, the decrease in GSIS begins to show dramatically at glucose levels higher than 5.6%, and at fasting glycemic levels higher than 6.4 mmol/L (114 mg%), GSIS completely disappears! At the same time, despite the loss of GSSI (1st phase), the 2nd phase in insulin secretion in response to glucose is preserved, and an acute response to the so-called non-glucose stimuli (for example, arginine) is also preserved.

Currently, the loss of glucose-stimulated insulin secretion is explained by either the glucose toxicity hypothesis or the lipotoxicity hypothesis. However, these hypotheses require further testing. Although in clinical practice, the normalization of carbohydrate and fat metabolism leads to the restoration of the 1st phase in insulin secretion, and to prandial regulation.

It should be noted that individuals who develop type 2 diabetes mellitus may be in stage 2 until plasticity loss develops and the mass of functioning β-cells ceases to adequately respond to the body’s increasing demand for insulin. It is assumed that stage 2 ends when the fasting glucose level becomes higher than 7.3 mmol / l (130 mg%) and can relatively quickly move from stage 3 – the stage of unstable early decompensation – to stage 4, characterized by glycemic levels of 16-20 mmol/l (285–350 mg%)!

A similar rapid progression of the pathological process can also occur in type 1 diabetes mellitus, however, in this type of diabetes, stage 2 lasts a very short time.

The stage of stable decompensation – stage 4 – can also be quite transient due to the continued loss of mass of functioning β-cells, which eventually leads to severe decompensation – stage 5.

Individuals who have progressed from stage 3 to clinical stage 4 diabetes typically have sufficient insulin secretion to allow them to remain at this stage, as evidenced by the absence of ketoacidosis in these patients. In most cases, this stage can remain throughout life in individuals with type 2 diabetes and, conversely, can rapidly progress to stage 5 in patients with type 1 diabetes, due to autoimmune destruction.

Morphometric studies of the postmortem pancreas in patients with type 2 diabetes mellitus indicate a decrease in the mass of functioning β-cells by ~ 50% compared with the control. In this regard, it should be noted that there is evidence that with a decrease in the mass of β-cells by 50%, the possibilities of insulin secretion also decrease by 50%! (Fig. 4).

At the stage of severe decompensation, there is a significant loss of β-cell mass, and to such an extent that these patients develop ketoacidosis, and insulin therapy is really necessary for them to save their lives.

Characteristically, in patients with severe decompensation, glycemic levels are usually > 22 mmol/l, although they may vary depending on the nature of nutrition and the degree of dehydration. A similar situation usually occurs in patients with type 1 diabetes mellitus or in patients after pancreatic transplantation or β-cell culture, when most of the cells are destroyed by the autoimmune process. This situation, however, is extremely rare in typical type 2 diabetes, but is possible in cases of exposure to certain toxins or in cases of severe pancreatitis.

Undoubtedly, the results of studies on the synthesis and the first minutes of life of insulin in the human body are also of some interest. Thus, to date, the general sequence of events occurring from the stage of transcription of the insulin gene to the stage of secretion has been studied (Fig. 5).

It was noted that disturbances are possible both at the stage of formation of the insulin molecule and at the stages of conversion of proinsulin into insulin.

Speaking of normal basal insulin secretion, it is known that β-cells convert proinsulin to insulin and C-peptide in equivalent amounts. However, not all insulin enters the peripheral circulation, as about 60% of it is removed (cleared) during the first passage through the liver. Thus, the concentration of insulin in the portal vein will be 2-3 times higher than in the peripheral circulation.

In addition, it should be remembered that insulin clearance also occurs in the kidneys, while the kidneys remove up to 40% of insulin. As a result, normal insulin concentrations in lean subjects are typically 18–90 pmol/L. And in order to maintain these values ​​of insulin, its secretion varies from 0.25 to 1.25 units / hour.

Also of fundamental importance were the results of studies in recent years, which were devoted to various disorders in insulin secretion in type 2 diabetes mellitus. So, the following most common defects were identified.

1. Decrease or loss of the first phase in glucose-stimulated insulin secretion.

2. Decrease or inadequacy (↓,↑) of insulin secretion and other stimuli (eg, food).

3. Changes in the oscillatory secretion of insulin (acceleration of the pulse, irregularity of the pulse, a decrease in amplitude and a mismatch with the daily, as well as the pulse pattern of glucose secretion).

4. Potentially reversible decrease in insulin secretion due to glucose toxicity and lipotoxicity.

5. Increased secretion of proinsulin.

From a practical point of view, it will be of some importance to compare the dynamics of glucose and insulin in response to an oral glucose tolerance test in individuals with impaired glucose tolerance and in patients with type 2 diabetes mellitus compared with healthy individuals (Fig. 6).

It should be emphasized that patients with type 2 diabetes mellitus were divided into two subgroups. In the first subgroup, fasting glycemia was < 8.3 mmol/L (~ 6.6–7.7 mmol/L), and in the second subgroup, fasting glycemia was > 8.3 mmol/L.

Attention is drawn to the fact of increased insulin secretion in the group of individuals with IGT, which indicates good compensatory capabilities at this stage of the development of events. It should also be borne in mind that people with type 2 diabetes mellitus and glucose concentration < 8.3 mmol/l give the impression of sufficient quantitative insulin secretion, but there is a delay in time, which already indicates problems in prandial regulation.

And, finally, the presence of a flat insulinemic curve indicates the absence of an adequate response of pancreatic β-cells in response to a glucose load in patients with type 2 diabetes mellitus, with fasting glycemia > 8.3 mmol/l. This fact indicates the need for more careful attention in terms of the choice of treatment tactics in these patients and, perhaps, the appointment of insulin therapy at earlier stages of treatment.

Continuing the theme of prandial regulation in patients with diabetes mellitus due to the loss of the first phase in insulin secretion, it should be especially noted that the first phase in insulin secretion normally appears in the portal vein after 60–120 seconds (!), and in the peripheral blood flow after 3– 4 minutes. This response lasts, as a rule, within 10 minutes and reflects the immediate secretion of insulin, which was already synthesized and was in the secretory granules in close proximity to the β-cell membrane.

It was shown (Kahn, 1993) that the magnitude of the first phase in insulin secretion depends on two factors:

1) speed and amount of glucose administered;

2) degree of insulin sensitivity.

It is interesting to note that the second phase in insulin secretion also begins immediately after the glucose bolus, but is masked by the first phase during the first 10 minutes. Starting from this time (10 minutes), the second phase begins to manifest itself and continues throughout the entire period of hyperglycemia. This phase is provided by both initially synthesized insulin and newly synthesized insulin. The second phase in insulin secretion increases linearly from glucose levels of 13.9mmol/l, and reaches its maximum at a glucose concentration higher than 25 mmol/l. Thus, when we talk about the depletion of pancreatic β-cells, we mean the loss of both the first and second phases in insulin secretion.

Concluding the material concerning insulin secretion in type 2 diabetes mellitus, it should be noted that other stimuli, including non-glucose ones, are currently being actively studied.

As can be seen from this material, a lot has already been done and studied, but the most important task today is to develop ways to correct various dysfunctions (plasticity) of pancreatic β-cells in type 2 diabetes mellitus.

Type 1 diabetes mellitus. Answers to the main questions from the endocrinologists of the Ilyinsky hospital.

Type 1 diabetes is the second
frequency form of diabetes (after type 2 diabetes), but it can be called
the most dramatic. The disease is also called “juvenile diabetes”, “diabetes
thin”, and previously used the term “insulin-dependent diabetes”.

Diabetes mellitus
Type 1 usually occurs in childhood
or adolescence. Sometimes the onset of the disease occurs at age
30-50 years, in which case it is milder, loss of pancreatic function
gland is slower. This form is called “slowly progressive
type 1 diabetes” or LADA (Late-onset Autoimmune Diabetes of Adults).

• Type 1 diabetes mechanism

Sugar
Type 1 diabetes belongs to a large group of autoimmune diseases. Cause of all
of these diseases is that the immune system accepts proteins from its own tissues
for the protein of another organism. Usually the causative factor is a viral
an infection in which the proteins of the virus appear to the immune system to “look like” proteins
own organism. In type 1 diabetes, the immune system
attacks pancreatic beta cells (producing insulin) until completely
will not destroy them. Insulin deficiency develops, a protein that is necessary for
supply of nutrients to cells.

• Type 1 diabetes treatment

Treatment
disease is based on the constant administration of insulin. Because insulin
is destroyed by ingestion, it must be administered as an injection. At first
XXI century, several American companies have developed drugs
inhaled insulin (for inhalation). However, their release was soon discontinued.
due to low demand. Apparently, the fact of the injection itself is not
the main difficulty in insulin therapy.

Discuss
questions that often arise in patients diagnosed with diabetes
type 1 diabetes.”

• Can type 1 diabetes be cured?

today, medicine cannot reverse autoimmune processes,
which destroyed pancreatic beta cells. Moreover, when the
symptoms of the disease usually remain no more than 10% of functioning beta cells.
New methods are being actively developed to save patients from
the need to constantly inject insulin before meals. To date, this
significant progress has been made in this direction.

Insulin pumps. Since the 1990s, the practice has been
insulin pumps are body-worn dispensers that deliver insulin through the subcutaneous
catheter. At first, the pumps were not automatic, all commands to deliver insulin
the patient had to give by pressing the buttons on the pump. Since the 2010s, the market has been
pump models with “partial feedback”: they are integrated with the sensor, constantly
measuring the level of sugar in the subcutaneous tissue, and are able to adjust the speed
insulin administration based on these data. But the patient is not yet completely spared
from the need to give commands to the pump. Promising models of insulin pumps
able to control blood sugar without human intervention. They will probably show up
on the market soon.

Insulin pump

Image source: shutterstock.com / Click and Photo

Beta cell or pancreas transplant
glands. Donor material can only be human. Basic condition
success in transplantation – the constant use of drugs that suppress the immune
system and preventing rejection. In recent years, drugs have appeared, selectively
affecting the immune system – suppressing rejection, but not immunity in general.
The technical problems of isolating and preserving beta cells have been largely solved. This
allows you to carry out transplant operations more actively. For example,
such an operation is possible simultaneously with a kidney transplant (which
often required by a patient with diabetic kidney disease – nephropathy).

• My blood sugar was high, I was given
  diagnosed with diabetes and prescribed insulin. But after 2 months sugar
  returned to normal, and does not rise, even if insulin is not injected. I’m cured
  Or is the diagnosis wrong?

K
unfortunately, neither. This phenomenon is called “diabetes honeymoon”.
The fact is that the symptoms of type 1 diabetes appear when the patient dies.
approximately 90% of beta cells, but some beta cells are still
lively. With the normalization of blood sugar (insulin), their function improves for a while,
and the insulin secreted by them may be enough to keep blood sugar normal. autoimmune
the process (which led to the development of diabetes) does not stop,
virtually all beta cells die within 1 year. After that hold
sugar is normal only with the help of insulin administered from the outside. “Honeymoon”
does not occur in 100% of patients diagnosed with diabetes mellitus 1
type, but this is a common occurrence. If it is observed, the endocrinologist should
time to reduce the dose of insulin administered.

B
In some cases, a patient with a diagnosis turns for help to
traditional healers and other alternative treatments. If reception
“folk remedies” falls at the time of the development of the “honeymoon”, this creates
the patient (and the healer, which is also bad) has the feeling that these remedies
help. But, unfortunately, this is not the case.

• If diabetes is incurable and I got sick at the age of 15
  Will I be able to live to at least 50?

Up to 50 and up to 70 – no doubt! American Joslin Foundation for a long time
established a medal for people who lived 50 years (and then 75 years) after
diagnosis of type 1 diabetes mellitus. Throughout
hundreds of people around the world received these medals, including in Russia. Such medalists
there would be more if it were not for a technical problem: not everyone has preserved
medical documents 50 years old confirming the fact of the diagnosis
exactly at that time.

But in order to
to receive the Joslin Foundation medal, you must learn how to manage well
own sugar level. The difficulty is that in a person without diabetes, each
a different amount of insulin is secreted per day – depending on the diet,
physical activity and many other factors. A healthy person has a natural
The “machine” that constantly regulates the level of sugar is the beta cells of the pancreas
glands and a number of other cells and hormones that are involved in this process. With sugar
type 1 diabetes, this machine is broken and has to be replaced by a “manual
management” – control blood sugar before each meal, take into account
all carbohydrates eaten according to the system of “bread units” and calculate the required amount
insulin before meals according to a not very complicated algorithm. It’s important not to trust your
well-being that can be misleading: high or low sugar levels
the body does not always feel.

Initially
blood sugar was measured by a glucometer – a portable device that
determines the level of sugar in a drop of blood from a finger. Later there were
special sensors have been developed that measure the level of sugar in the intercellular
fluid (in the subcutaneous tissue). In the past few years, the market has entered
such devices that allow you to quickly obtain information about the current level
Sahara. Examples are DexCom and FreeStyle Libre devices.

Continuous blood glucose monitoring system

Image Source: shutterstock.com / Nata Photo

But,
despite all the modern technology to master the “manual control”
sugar levels, training in a special structured program is necessary,
which is called “School of Diabetes”. How
As a rule, training is carried out in a group and takes at least 20 hours. Knowledge is
not the only condition for successful management. A lot depends on
putting this knowledge into practice: from the frequency of measuring blood sugar and introducing
correct doses of insulin. Therefore, it is very important that the endocrinologist regularly
assessed the patient’s condition and his blood sugar fluctuations (based on the “diary
self-control”, which is conducted by the patient), determined the correctness of the calculation of insulin
and corrected the treatment in a timely manner. Unfortunately, in Russia there are many
patients see a doctor just to get free insulin,
and for everything else, the doctor of the polyclinic simply does not have enough time …
a person with diabetes should find an endocrinologist who will correctly conduct
training, and will continue to be engaged in the operational control of the state
patient health and timely correction of treatment. Not always like this
an endocrinologist works in the compulsory health insurance system, and is not
it must be the same doctor who prescribes free insulin.

• I have type 1 diabetes. If I have
  If there are children, will they also have diabetes? Is diabetes hereditary?

No matter how
strangely, in type 2 diabetes, the hereditary predisposition is much
higher than in type 1 diabetes. Although type 2 diabetes usually occurs in
older age, a genetic predisposition to it is present from birth. At
type 1 diabetes mellitus hereditary predisposition is small: with
the presence of type 1 diabetes in one of the parents the likelihood of this disease in
child is from 2 to 6% (in the presence of type 1 diabetes in the father of the child, the probability
inheritance is higher than in maternal diabetes). If the family has diabetes 1
type one child, then the probability of the disease in any of his brother or sister
is 10%.

People with
diabetes is quite affordable happy motherhood and fatherhood. But for safe
pregnancy in a woman with type 1 diabetes is very important
stable sugar level before conception and observation by an endocrinologist according to a special
program throughout pregnancy.