What foods should you avoid while taking metformin for type 2 diabetes? Discover the key interactions between metformin and certain foods, as well as tips for a balanced diet to get the most benefits from your diabetes medication.

Understanding Metformin and Its Interactions

Metformin is a widely prescribed medication for individuals with type 2 diabetes, as it effectively lowers blood sugar levels. Unlike some other diabetes medications, metformin does not require patients to avoid specific foods. However, there are certain interactions that individuals taking metformin should be aware of, particularly when it comes to alcohol consumption.

The Relationship Between Metformin and Alcohol

People with diabetes should generally moderate their alcohol intake, as alcohol can impair the liver’s ability to manage blood glucose levels. This is particularly important for those taking metformin, as the combination of metformin and alcohol can lead to a condition known as metformin-associated lactic acidosis (MALA).

MALA is a rare but potentially life-threatening condition that occurs when there is a buildup of lactic acid in the blood. This can happen when someone with a thiamine (vitamin B1) deficiency consumes too much alcohol while also taking metformin. To avoid this complication, it’s best to discuss your alcohol consumption with your doctor, who may recommend limiting or avoiding alcohol altogether while taking metformin.

Optimizing Your Diet with Metformin

While metformin does not require specific food avoidance, it is important to maintain a balanced, healthy diet to get the most benefit from the medication. This means limiting or avoiding foods that can cause spikes in blood sugar, such as those high in simple carbohydrates and refined carbs.

Foods to Prioritize

• Complex carbohydrates (whole grains, brown rice, quinoa)
• Lean proteins (turkey, fish, tofu)
• Nonstarchy vegetables (broccoli, leafy greens)

Foods to Limit or Avoid

1. Sugary sodas, candies, and desserts
2. White bread, white rice, and pasta

Achieving the Best Outcomes with Metformin

To get the most benefits from your metformin treatment, it’s important to follow a balanced, healthy diet and discuss any concerns about alcohol consumption with your healthcare provider. By making these adjustments, you can optimize your diabetes management and improve your overall health.

Frequently Asked Questions

Can I drink alcohol while taking metformin?

It’s generally advisable to discuss your alcohol consumption with your doctor if you are taking metformin. While moderate drinking may be acceptable for some individuals, the combination of metformin and alcohol can increase the risk of a serious condition called metformin-associated lactic acidosis (MALA), particularly in those with thiamine deficiency or impaired liver or kidney function.

What foods should I avoid with metformin?

Unlike some other diabetes medications, metformin does not require the avoidance of specific foods. However, it is important to maintain a balanced, healthy diet that limits foods high in simple carbohydrates and refined carbs, as these can cause spikes in blood sugar. Focus on complex carbs, lean proteins, and nonstarchy vegetables to get the most benefit from your metformin treatment.

How does metformin interact with alcohol?

Metformin can interact with alcohol in a way that increases the risk of a serious condition called metformin-associated lactic acidosis (MALA). This can occur when someone with a thiamine deficiency consumes too much alcohol while also taking metformin. To avoid this complication, it’s important to discuss your alcohol consumption with your healthcare provider.

Conclusion

While metformin does not require avoiding specific foods, it is important for individuals taking this medication to be mindful of their diet and alcohol consumption. By maintaining a balanced, healthy diet and discussing any concerns about alcohol with their healthcare provider, people with type 2 diabetes can get the most benefit from their metformin treatment and optimize their overall health and diabetes management.

Foods to Avoid While Taking Metformin

If you’re on metformin for type 2 diabetes, here’s what you need to know about what to avoid while taking metformin.

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Metformin is a first-choice medication primarily prescribed to people with type 2 diabetes to lower their blood sugar. It is both highly effective and generally well-tolerated, and it is the first-line treatment recommended by the American Diabetes Association.

Unlike other medications, metformin doesn’t require a person to avoid any particular foods and it is also not associated with weight gain, like some other diabetes medicines, Elizabeth Halprin, MD, clinical director of adult diabetes at Harvard’s Joslin Diabetes Center, tells LIVESTRONG.com.

However, metformin does interact with alcohol, so it’s best to discuss with your doctor before drinking while taking the drug.

Read more: 7 Foods That Won’t Cause Blood Sugar Spikes

Metformin and Alcohol

As a general rule, people with diabetes should moderate their alcohol intake, because alcohol impairs the liver’s ability to store and release glucose (aka blood sugar). This is a problem for people with diabetes because their bodies already struggle to manage blood glucose.

In addition, drinking alcohol on an empty stomach can lead to low blood sugar (hypoglycemia), per the University of California, San Francisco. This alcohol-related complication is more common in people taking insulin or diabetes meds that increase insulin levels. Metformin does not increase insulin levels, so alcohol-induced hypoglycemia is less likely to occur in people who take it.

Metformin-Associated Lactic Acidosis

When the body uses glucose as energy, it generates lactic acid. Metformin increases the amount of lactate — the underlying compound of lactic acid — in the blood, as described by a study published in the February 2016 issue of Metabolism.

This is typically a benign effect, but according to a small study published in Scientific Reports in October 2017, too much alcohol coupled with a thiamine (vitamin B1) deficiency can lead to a buildup of lactate. This combination of metformin and alcohol can result in too much lactic acid in the blood, a toxic condition that can lead to lactic acidosis, in people with acute or chronic alcohol abuse.

Metformin-associated lactic acidosis (MALA) is rare but potentially life-threatening. Per the Metabolism study, it occurs in fewer than 10 out of every 100,000 people per year. While the risk of lactic acidosis for people with diabetes is low, your risk is higher if you have impaired liver or kidney function or congestive heart failure.

Read more: How Bad Is Alcohol for Weight Loss?

If you’re taking metformin, it might still be OK for you to drink in moderation. According to the Mayo Clinic, “moderation” means one drink per day for women (and men over 65), and two drinks per day for men under 65. But discuss your alcohol consumption with your doctor because a no-alcohol lifestyle might be healthiest for you.

Look at Your Overall Diet

Metformin is designed to lower blood sugar levels. But it is much less effective when it’s not accompanied by a balanced, healthy diet. To get the most benefit from your diabetes medication (and to improve your overall health), try to limit or avoid foods that cause high blood sugar in the first place.

Foods containing simple carbs (sodas, candies, desserts) and refined carbs (white bread, white rice, pasta) are the biggest culprits when it comes to high blood sugar. Instead, opt for complex carbs like brown rice and whole-grain bread: These carbs have more dietary fiber and are therefore harder for the body to metabolize, which slows the release of glucose into the bloodstream.

Also, be sure to include lean proteins (such as turkey, fish and tofu) and fill half of your plate with nonstarchy vegetables (such as broccoli and leafy greens) at each meal, as that will also slow your carb metabolization.

Read more: The Best Nuts for People With Diabetes

5 Foods To Eat and 6 You Should Avoid

There are many medications out there that can interact with other medications and supplements.

But did you know that medications can also interact with the food you eat? 

Metformin is no exception. If you are taking metformin, you may want to adjust your diet accordingly. Read on to find out why.

What is metformin?

Metformin is a drug that treats type 2 diabetes. In fact, it is one of the first choices recommended by the American Diabetes Association. 

People with type 2 diabetes cannot use insulin properly. They usually have insulin resistance or decreased insulin sensitivity. This means that they have a difficult time controlling how much sugar is in their blood. Metformin treatment increases the amount of lactate. This is the underlying compound of lactic acid in the blood.

Metformin is a diabetes drug in a class called biguanides. These are medications that prevent your liver from producing glucose. Therefore, metformin lowers the amount of glucose your body absorbs from what you eat. It also improves your body’s response to insulin.

Metformin can be used alone. You can also combine it with insulin treatment or with an oral antidiabetic medicine called sulfonylurea. Metformin is only available with a prescription from a doctor. 

What is it used for?

Metformin is used in type 2 diabetes. It’s also used in diabetes prevention for prediabetes. Metformin does not help in type 1 diabetes because these people cannot produce insulin from their pancreas. Patients with type 2 diabetes usually control their blood glucose with insulin injections.

Metformin is also used in the treatment of PCOS. PCOS stands for polycystic ovary syndrome. This is a hormonal condition that affects ovulation and may increase androgen production. Androgens are male hormones responsible for facial hair growth and male pattern baldness.

PCOS increases the risk of developing obesity, depression, infertility, and type 2 diabetes. Health care providers sometimes use metformin in people with polycystic ovarian syndrome who are struggling with infertility. The goal is to use metformin to improve ovulation and chances of conceiving. 

In the past, metformin has also been used to help women with PCOS with bodyweight loss maintenance. This is because metformin may decrease adipose tissue mass. Metformin may also help to reduce waist circumference and help with long-term weight loss.

Metformin can also be used in the treatment of metabolic syndrome.

Foods you should avoid while taking metformin

Below are six foods you should avoid while taking metformin.

Fats

Healthy fats are fine and should be included as part of a healthy diet if you’re on metformin. However, you should avoid foods high in trans and saturated fats. 

Sodium

You should avoid having too much sodium while you’re on metformin. Keep your sodium intake under 2300 milligrams per day.

Simple and refined carbs

Simple and refined carbs increase your blood sugar levels. Avoid simple carbs such as soda, candy, and desserts. Stay away from refined carbs such as white bread, pasta, and white rice.

High fiber foods

Fiber can absorb certain drugs and lower their concentration in your bloodstream. If you eat large amounts of fiber, your metformin levels may decrease. Keep your fiber intake under 30 grams per day.

Alcohol

You’ll want to avoid large amounts of alcohol since it increases your risk of developing low blood sugar and lactic acidosis. Alcohol prevents the liver from storing and releasing glucose. Since people with diabetes already struggle to manage blood glucose levels, minimizing the risk factor of alcohol consumption is worth consideration.

Drinking alcohol with an empty stomach can cause low blood sugar. This is even more true for people taking insulin or other diabetes medications that increase insulin levels.

Metformin increases the amount of lactate. Lactate is the underlying compound of lactic acid. This isn’t of too much concern, but research shows that too much alcohol, along with a thiamine deficiency, can lead to a buildup of lactate.

Alcohol and metformin together can lead to too much lactic acid in the blood. This can lead to lactic acidosis, a serious condition.

In general, drinking in moderation is safe. Safe levels are one drink per day for women and two drinks per day for men. Discuss this with your doctor, as it’s possible that abstaining from alcohol may be the best choice for you as an individual.

Grapefruit

One study looked at the effects of grapefruit on metformin in rats. Some rats were exposed to grapefruit juice and metformin. The others were given metformin on its own. 

Researchers found that the rats that had both grapefruit juice and metformin had a higher amount of lactic acid production than the just metformin group. They may also have more weight gain.

Researchers postulated that grapefruit juice increased the accumulation of metformin in the liver. This then caused an increase in lactic acid production. Researchers concluded that drinking grapefruit juice might lead to a higher risk of lactic acidosis in patients taking metformin.

Foods to include in your metformin diet

Below are five foods you should include in your metformin diet.

Complex carbohydrates

Complex carbohydrates come from vegetables, fruits, and whole grains such as brown rice and whole-grain bread. These carbs have more fiber. This makes them more difficult for the body to metabolize. This then slows the release of glucose into the bloodstream.

If you are consuming complex carbs, keep an eye on your overall carb intake. This is important because carbohydrates do directly affect blood sugar levels.

Nonstarchy vegetables

Nonstarchy vegetables can help to slow your carb metabolism. Examples of nonstarchy vegetables include broccoli and leafy greens.

Healthy fats

You can get healthy fats from sources such as fish, nuts, and olive oil.

Moderate fiber intake

Although lots of fiber is not recommended, moderate fiber intake can actually be helpful. This is because fiber can help to control blood glucose levels. An average intake of fiber is between 25 and 30 grams per day.

Lean protein

Encourage the consumption of lean proteins such as turkey, fish, and tofu.

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Any other safety concerns?

Metformin has been associated with lactic acidosis. Although this is a rare situation, it is potentially life-threatening and therefore worth mentioning here. 

Less than ten out of every 10,000 people on metformin experience lactic acidosis. You are at higher risk if you have impaired liver or kidney function. You are also at higher risk of lactic acidosis if you have congestive heart failure.

If you have ever had an allergic reaction to a medicine, you must tell your doctor this. Any other allergies to foods, preservatives, animals, or dyes are worth mentioning as well. Metformin is contraindicated if you have diabetic ketoacidosis.

Other potential side effects of metformin include the following:

Of the above side effects, the most common are nausea and diarrhea. These gastrointestinal symptoms happen most often if you take metformin without food. 

Since metformin therapy impairs your body’s ability to absorb glucose (through its effects on the gut microbiota), you may have diarrhea after eating carbs if you are on metformin.

Your dose of metformin needs to be balanced out with the foods you eat and the exercise you do. If you change your diet, exercise habits, or make other lifestyle interventions, you will want to test your blood sugar to ensure it doesn’t go too low. If this does happen, your health care provider will be able to help you out.

At Ben’s Natural Health, we believe that natural options are the way to go. Given the above side effects of metformin, many people prefer natural alternatives such as herbs and supplements which can treat type 2 diabetes without side effects. Talk to your healthcare provider about natural diabetes treatments to see which ones may be suitable for you.

Conclusion

If you’re taking metformin, avoid alcohol, high fiber foods, trans and saturated fats, grapefruit, sodium, and simple and refined carbs. Get most of your carbs from vegetables, fruits, and whole grains. 

Eat nonstarchy vegetables, healthy fats, lean proteins, and a moderate amount of fiber. If you’re taking metformin, it’s worth talking with your health care provider about a metformin diet.

Next Up

5 Natural Alternatives to Metformin for Diabetes & Insulin Resistance.

Metformin side effects and interactions, and how to avoid them

Metformin is an anti-diabetic medication (technically classified as a biguanide) that doctors commonly prescribe to treat type 2 diabetes and prediabetes. It helps control blood glucose levels and restore the body’s response to insulin. Metformin can also treat polycystic ovary syndrome (PCOS). Popular brand names of metformin include Glucophage, Fortamet, Glumetza, and Riomet.

Both type 2 diabetes and PCOS are common health conditions, each with more than 200,000 new cases in the U.S. every year. Millions of adults are at risk for type 2 diabetes, according to a CDC public health notice. 

If you’ve been diagnosed with either condition, chances are, metformin is a treatment option for you. Learning about metformin side effects, warnings, and interactions is a helpful first step toward gaining a better understanding of the drug.

What is metformin?

Metformin is most commonly prescribed to help people with type 2 diabetes. Type 2 diabetes is caused by insulin resistance or decreased insulin sensitivity, which means that the body doesn’t properly respond to insulin. People with type 2 diabetes or prediabetes have hyperglycemia (high blood sugar). Metformin works by slowing the release of glucose from the liver and by slowing the body’s absorption of glucose, both of which help lower blood sugar levels. It is also believed that metformin increases insulin sensitivity, which helps with lowering glucose levels. 

Metformin can also be prescribed off-label to treat polycystic ovary syndrome (PCOS), a condition that can cause elevated insulin levels that increases risk for diabetes. This medication helps normalize insulin levels and may improve fertility.

Common side effects of metformin

Learning about the potential side effects of metformin is just as important as learning about the benefits. As with any medication, there are always possible risks. These are some of the most common metformin side effects: 

• Diarrhea
• Nausea
• Upset stomach
• Metallic taste in the mouth
• Vomiting
• Flatulence 
• Weight loss
• Loss of appetite
• Heartburn 
• Bloating
• Cough
• Sleepiness
• Constipation
• Headache 
• Painful or difficult urination 
• Asthenia 
• Decreased levels of vitamin B12

Does metformin cause weight loss?

A common concern about metformin is that it causes weight loss. While it can cause weight loss by changing the way the body stores fat, this doesn’t mean that everyone who takes the drug will lose weight, or that you should use it to lose weight.

How long do metformin side effects last?

Side effects may start when you first start taking metformin. For some people, side effects will go away soon after their body adjusts to the medication. For others, side effects may linger or become worse. Most people take metformin for long periods of time, so if side effects don’t go away, they could potentially cause long-term damage. Some metformin side effects may go unnoticed, so regular checkups are essential. 

Serious side effects of metformin

Metformin is associated with some severe, long-term side effects. Some serious side effects caused by metformin are dangerous and require immediate medical attention. If you experience any of the following, consult with a healthcare professional right away: 

• Tiredness
• Unusual sleepiness
• Trouble breathing
• A slow or irregular heart rate
• Lightheadedness or dizziness

Taking metformin for extended amounts of time may result in long-term side effects. Metformin can affect the body’s ability to absorb vitamin B12 and cause a vitamin B12 deficiency. It’s often necessary for people taking metformin to get regular blood tests to check their vitamin B12 levels. 

Although it’s rare, metformin may cause allergic reactions. Signs of an allergic reaction include difficulty breathing, swelling of the face or hands, and a skin rash. You should seek immediate medical attention if you believe you’re experiencing an allergic reaction. 

Lactic acidosis

Taking metformin may cause a serious condition called lactic acidosis, which is a buildup of lactic acid in the bloodstream. Lactic acidosis can cause serious side effects and almost always requires hospitalization. Drinking excessive amounts of alcohol while on metformin can significantly increase the risk of getting lactic acidosis. Signs of lactic acidosis include:

• Dizziness or lightheadedness
• Muscle pain
• Extreme weakness or tiredness
• Trouble breathing 
• A fast or slow heart rate
• Flushing of the skin
• Decreased appetite
• Severe stomach pain

If you’re experiencing serious side effects from taking metformin, it’s best to call your doctor immediately. He or she will give you advice on what to do next, and may tell you to stop taking metformin. 

Metformin warnings

Metformin is not the right medication for people with type 1 diabetes. It’s generally considered okay for children and adults with type 2 diabetes or prediabetes, as long as a doctor approves it, but dosages will vary. For adults over the age of 80, metformin is prescribed with caution on a case-by-case basis.

People with certain health conditions have an increased risk of experiencing side effects from taking metformin. Anyone with congestive heart failure, compromised kidney function, poor liver function, or diabetic ketoacidosis should not take metformin.

People with blood problems, kidney problems, kidney disease, liver disease, or breathing problems should be cautious of taking metformin. Having any of these conditions and taking metformin may cause metformin to be less effective or cause additional health complications, such as lactic acidosis. This condition causes a buildup of lactic acid in the blood and can potentially be fatal.

Some studies suggest that metformin may have risk factors that go beyond common side effects. The Food and Drug Administration (FDA) is investigating whether metformin contains carcinogens, and a 2018 study suggests that metformin may reduce some of the positive benefits of aerobic exercise for older adults.

Meanwhile, some metformin myths have been busted. Some hypothesized that metformin caused dementia but a study published in February 2019 found that “metformin use is associated with a reduced risk of dementia.”

Although metformin doesn’t work for some people, these warnings shouldn’t negate the fact that it still helps many people around the world manage their health conditions.

Metformin interactions

Certain medications may make metformin less effective or worsen side effects.

For example, taking metformin with insulin releasing pills or insulin can cause hypoglycemia (low blood sugar), according to the Diabetes Teaching Center at the University of California. Many people who take metformin will need to monitor their blood levels closely. Signs of hypoglycemia include dizziness, shaking, confusion, fatigue, and fainting.

“Metformin can interact with other medications, including diuretic medications, steroid medications, certain thyroid drugs, oral contraceptives, and calcium channel blocking drugs like nifedipine,” says Chirag Shah, MD, and co-founder of Push Health, an online healthcare platform. “Due to a wide range of medication interactions, it is important to review a patient’s current medications before prescribing metformin.”

Creating a list of all the supplements and prescription drugs you take and sharing it with your doctor will help you avoid side effects that might come from taking metformin with something else.

The following medications may interact negatively with metformin: 

• Quinolone antibiotics
• Thiazide diuretics
• Verapamil 
• Medicines administered before MRIs, X-Rays, or CT scans 
• Ethanol
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Steroid medicines
• Thyroid medicines 

A doctor or other medical professional can give you a complete list of drugs that interact negatively with metformin. 

How to avoid metformin side effects

1. Take consistent dosages

It’s best to follow the manufacturer’s instructions on how to use the drug to reduce your chances of experiencing metformin side effects. Most patients take metformin every 12 hours. Consistently taking the appropriate dose at the right time can help reduce side effects.

The standard dosage of metformin for adults is 1000 mg taken twice daily with meals. Taking metformin with food can help eliminate or reduce stomach-related side effects. Missing or skipping a dose of metformin can make side effects worse.  

2. Make lifestyle and diet changes

Lifestyle changes are another key component of managing type 2 diabetes or prediabetes. Exercising regularly can positively affect blood pressure and blood glucose levels for people with type 2 diabetes. Certain foods like refined sugar, alcohol, and hydrogenated oils can cause high blood sugar, so avoiding them can be very beneficial.

Diet and exercise may not serve as complete alternatives to metformin, but they can still improve quality of life. The best way to reduce your chances of experiencing side effects while taking metformin is to talk to your doctor. 

3. Seek alternatives

There are alternative options to metformin for people with health conditions that prevent them from taking metformin, or for those who can’t take metformin because of its side effects. Those with type 2 diabetes may benefit from SGLT2 inhibitors, GLP1 medications, alpha-glucosidase inhibitors, gliptins, or pioglitazone.

Talking with your doctor is the best way to learn about other medications that may be a good fit for you based on your medical history and individual symptoms.

Metformin vs. metformin ER

Metformin and metformin extended-release (ER) are essentially the same medication, but patients don’t take metformin ER as frequently. ER stands for extended-release, meaning the body absorbs metformin ER more slowly than regular metformin. Both drugs help people with type 2 diabetes and prediabetes control their blood sugar levels.

Metformin, sometimes called metformin immediate-release (IR), is often taken twice a day. Metformin ER is taken less frequently, typically once per day. The standard dosage of metformin ER for adults with type 2 diabetes is 1000–2000 mg. Some people may need to take metformin ER twice daily. A healthcare professional can determine this on a case-by-case basis. 

Metformin ER is the generic version of the brand name Glucophage XR. Patients who have stomach upset with regular metformin may switch to Metformin ER, which is better tolerated. Take metformin ER as instructed by your doctor. Some doctors may recommend taking metformin ER once in the morning with breakfast or in the evening with dinner. Taking metformin ER with food can help reduce the risk of side effects like upset stomach and diarrhea.

Metformin vs. metformin ER side effects

Similarly to metformin, metformin ER side effects may include:

• Nausea
• Diarrhea
• Heartburn
• Headache 
• Metallic taste in the mouth
• Tiredness
• Lightheadedness
• Muscle aches or pains
• Slow or irregular heartbeat 

Like metformin, metformin ER can increase the risk of lactic acidosis. 

A medical professional can give a complete list of side effects. The best way to learn more about metformin and metformin ER side effects is to talk with your healthcare provider.  

Metformin decreases food consumption and induces weight loss in subjects with obesity with type II non-insulin-dependent diabetes

Metformin often promotes weight loss in patients with obesity with non-insulin-dependent diabetes mellitus (NIDDM). The mechanism may be attributed to decreased food intake. This study has tested the effect of metformin on satiety and its efficacy in inducing weight loss. Twelve diet-treated NIDDM women with obesity were randomly given two dose levels (850 mg or 1700 mg) of metformin or placebo at 0800 for three consecutive days followed by a meal test on the third day on three occasions using a 3×3 Latin square design. The number of sandwich canapes eaten in three consecutive 10-minute periods beginning at 1400 hours was used to quantitate food intake, and the level of subjective hunger was rated just before the sandwich meal with a linear analogue hunger rating scale at 1400 after a 6-hour fast. The prior administration of metformin produced a reduction in calorie intake after each of the two doses of metformin treatment. The 1700-mg metformin dose had the most marked appetite suppressant action. Similarly, hunger ratings were significantly lowered after metformin, and the effect was most pronounced after the administration of 1700 mg of metformin. To assess the efficacy of metformin in reducing bodyweight, 48 diet-treated NIDDM women with obesity who had failed to lose weight by diet therapy were first placed on a 1200-kcal ADA (American Diabetes Association) diet before being randomized to receive either metformin (850 mg) or placebo twice daily in a double-blind fashion for 24 weeks. A 4-week single-blind placebo lead-in period preceded and a 6-week single-blind placebo period followed the 24-week double-blind treatment period. Subjects treated with metformin continued to lose weight throughout 24 weeks of treatment; their mean maximum weight loss was 8 kg greater than that of the placebo group, with corresponding lower HbA1C and fasting blood glucose levels at the end of the active treatment period. These results indicate that metformin decreases calorie intake in a dose-dependent manner and leads to a reduction in bodyweight in NIDDM patients with obesity.

Effect of Long-Term Treatment with Metformin Added to Hypocaloric Diet on Body Composition, Fat Distribution, and Androgen and Insulin Levels in Abdominally Obese Women with and without the Polycystic Ovary Syndrome | The Journal of Clinical Endocrinology & Metabolism

Abdominal obesity and hyperinsulinemia play a key role in the development of the polycystic ovary syndrome (PCOS). Dietary-induced weight loss and the administration of insulin-lowering drugs, such as metformin, are usually followed by improved hyperandrogenism and related clinical abnormalities. This study was carried out to evaluate the effects of combined hypocaloric diet and metformin on body weight, fat distribution, the glucose-insulin system, and hormones in a group of 20 obese PCOS women[ body mass index (BMI) > 28 kg/m²] with the abdominal phenotype (waist to hip ratio >0.80), and an appropriate control group of 20 obese women who were comparable for age and pattern of body fat distribution but without PCOS. At baseline, we measured sex hormone, sex hormone-binding globulin (SHBG), and leptin blood concentrations and performed an oral glucose tolerance test and computerized tomography (CT) at the L4-L5 level, to measure sc adipose tissue area (SAT) and visceral adipose tissue area. All women were then given a low-calorie diet (1200–1400 kcal/day) alone for one month, after which anthropometric parameters and CT scan were newly measured. While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (850 mg/os, twice daily) (12 and 8, respectively) or placebo (8 and 12, respectively), according to a double-blind design, for the following 6 months. Blood tests and the CT scan were performed in each woman at the end of the study while they were still on treatment.

During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance; and 2 PCOS women, both treated with metformin, were also excluded because they became pregnant. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo).

The treatment was well tolerated. In the PCOS group, metformin therapy improved hirsutism and menstrual cycles significantly more than placebo. Baseline anthropometric and CT parameters were similar in all groups. Hypocaloric dieting for 1 month similarly reduced BMI values and the waist circumference in both PCOS and control groups, without any significant effect on CT scan parameters. In both PCOS and control women, however, metformin treatment reduced body weight and BMI significantly more than placebo. Changes in the waist-to-hip ratio values were similar in PCOS women and controls, regardless of pharmacological treatment. Metformin treatment significantly decreased SAT values in both PCOS and control groups, although only in the latter group were SAT changes significantly greater than those observed during the placebo treatment. On the contrary, visceral adipose tissue area values significantly decreased during metformin treatment in both PCOS and control groups, but only in the former was the effect of metformin treatment significantly higher than that of placebo.

Fasting insulin significantly decreased in both PCOS women and controls, regardless of treatment, whereas glucose-stimulated insulin significantly decreased only in PCOS women and controls treated with metformin. Neither metformin or placebo significantly modified the levels of LH, FSH, dehydroepiandrosterone sulphate, and progesterone in any group, whereas testosterone concentrations decreased only in PCOS women treated with metformin. SHBG concentrations remained unchanged in all PCOS women; whereas in the control group, they significantly increased after both metformin and placebo. Leptin levels decreased only during metformin treatment in both PCOS and control groups.

In summary, this study shows that, in PCOS women with abdominal obesity, long-term treatment with metformin added to hypocaloric diet induced, in comparison with placebo, a greater reduction of body weight and abdominal fat, particularly the visceral depots, and a more consistent decrease of serum insulin, testosterone, and leptin concentrations. These changes were associated with a more significant improvement of hirsutism and menses abnormalities. Moreover, the effects on body weight, insulin, and leptin were similar to those observed in the group of comparable abdominally obese controls, in whom, however, a more pronounced reduction of sc fat in the abdominal region and an increase of SHBG concentrations were found. These findings, therefore, indicate that hyperinsulinemia and abdominal obesity may have complementary effects in the pathogenesis of PCOS.

THE METABOLIC syndrome is an integral part of the polycystic ovary syndrome (PCOS) in most affected women. In its typical form, it includes insulin resistance and hyperinsulinemia, obesity (predominantly the abdominal phenotype), and altered lipid profile (1–3). Both hyperinsulinemia and obesity may be intimately related to the development and maintenance of hyperandrogenism (1, 4, 5). In fact, hyperinsulinemia is directly involved in determining increased ovarian androgen secretion (1, 5), through the activation of the cytochrome P450c17 enzyme system (6), and in reducing sex hormone-binding globulin (SHBG) synthesis by the liver (7, 8), which allows greater free androgen fraction availability in peripheral target tissues (9). The role of obesity in the development of hyperandrogenism is still under debate. On the other hand, it is well established that, in women, the abdominal obesity phenotype is associated with a marked decrease of SHBG levels (10–14) and some increase in total and free testosterone (T) (10, 11, 13), which is consistent with a state of relative hyperandrogenism. Numerous clinical and experimental data, in fact, indicate that obese women with PCOS, particularly those with the abdominal body fat distribution, may have a worse clinical condition and higher circulating androgen levels than their normal-weight counterparts (14). However, hyperandrogenism per se may favor enlargement of visceral fat in women (15). In fact, androgen administration to postmenopausal women has been shown to increase visceral fat (16). In addition, there are theoretical possibilities that increased androgen levels may directly affect insulin sensitivity in the target tissues, particularly muscles, therefore contributing to the development of the insulin resistance state (15).

Dietary-induced weight loss is usually followed by reduced hyperandrogenism and hyperinsulinemia and improved clinical status (such as fewer menses abnormalities, less hirsutism, and increased fertility rate) in many obese women with PCOS (17–19). On the other hand, with the exception of one study (20), the administration of insulin-lowering drugs, such as diazoxide (21), metformin (6, 22, 23), troglitazone (24), and (more recently) D-chito-inositol (25), has been proved to obtain the same results, regardless of significant changes in body weight, thus emphasizing the role of hyperinsulinemia in the pathophysiology of PCOS. Whether these effects may be mediated, at least in part, by selective reduction of visceral fat is still unknown. In addition, studies performed so far in obese PCOS women failed to investigate the effect of long-term hypocaloric dieting with or without the association of insulin sensitizers on body composition and fat distribution.

Therefore, we carried out this study to evaluate the effects of combined hypocaloric diet and metformin, an insulin-sensitizer agent, on body weight and fat distribution in a group of PCOS women with the abdominal obesity phenotype. The fasting insulin and glucose-stimulated insulin levels and androgen and leptin blood concentrations were also investigated. Moreover, to evaluate whether the effects of such a treatment were specifically conditioned by the presence of PCOS or by the presence of abdominal obesity, a control group of women, comparable for age and pattern of body fat distribution but without PCOS, was also investigated.

Subjects and Methods

Subjects

A group of 20 women with PCOS and a group of 20 controls, comparable for age and weight, were included in the study. They were recruited as outpatients attending the Endocrine Unit of the Department of Internal Medicine and Gastroenterology of the S. Orsola-Malpighi Hospital of Bologna. All PCOS and control women were obese, with body mass index (BMI; kg/m²) values greater than 28, and had abdominal body fat distribution defined by waist-to-hip ratio (WHR) values greater than 0.80 (26). The diagnosis of PCOS was made according to the presence of oligomenorrhea (less than four cycles in the last 6 months) or amenorrhea (no menses in the last 6 months) and hyperandrogenism, defined by supranormal total and free T concentrations, according to normal reference values in our laboratory (27). All women with PCOS had ovarian ultrasonic findings consistent with the diagnosis (28). None of the PCOS or control women had thyroid dysfunction, type II diabetes, or concomitant cardiovascular, renal, and liver dysfunction, based on clinical examination and routine laboratory findings. Other causes of hyperandrogenisms, such as Cushing syndrome and disease and congenital adrenal hyperplasia, were excluded by normal cortisol suppression after an overnight 1-mg dexamethasone test and normal fasting and stimulated (250 mg Synacthen iv) 17-hydroxyprogesterone concentrations. All PCOS women also had normal PRL levels. None of the PCOS or control women had taken any medication for at least 3 months before the study, nor were they dieting. Women of the control group had regular monthly menses and no clinical or laboratory evidence of androgen excess.

The protocol was approved by the Ethics Committee of S. Orsola-Malpighi Hospital, and all women gave their informed consent.

Anthropometry and measurement of body fat distribution

Body height was measured (without shoes) to the nearest 0.5 cm, and body weight (without clothes). According to the recommendation of the World Health Organization (29), waist circumference was obtained as the minimum value between the iliac crest and the lateral costal margin, whereas hip circumference was determined as the maximum value over the buttocks, using a 1-cm-wide metal measuring tape. Body fat distribution was also defined by a standardized measurement of body fat at the L4-L5 level, by computerized tomography (CT), which was performed on a scanner (Siemens, Erlangen, Germany). Total adipose tissue area (TAT), visceral adipose tissue area (VAT), and sc adipose tissue area (SAT) were calculated as previously described (30). Previous studies (reviewed in Ref. 31) have shown that visceral fat areas from a single scan taken at the level L4-L5 were highly correlated to total visceral fat (r > 95%), measured by multiple CT scans.

Protocol study

At baseline, PCOS women were studied within the first 10 days after the last menstruation if they had mild oligomenorrhea, or randomly if they had severe oligomenorrhea or amenorrhea, whereas all control women were studied during the early follicular phase of the menstrual cycle, except 2 women who were studied during the luteal phase. All women were following their usual diet, providing at least 250–300 g of carbohydrates were ingested. Blood samples for baseline hormone were drawn in the morning, at 0800–0830 h, after an overnight fast. An oral glucose tolerance test (OGTT) (75 g Curvosio, Sclavo, Cinisello Balsamo, Italy) was then performed, and blood samples were collected after 30, 60, 90, 120, and 180 min for glucose determination and after 60, 120, and 180 min for insulin determination. In the afternoon of the same day, the CT scans were performed. The day after, all women were then placed, for a month, on a standardized hypocaloric diet consisting of 1200–1400 kcal daily and containing 50% carbohydrates, 30% total lipids, and 20% proteins. The women returned after 1 month for a checkup, when body weight and body circumferences were newly measured and the CT scan was repeated. Apart from anthropometric and CT scan parameters, the OGTT and sex hormone blood samples were not performed after the first month of dietary therapy. In fact, it is well known that early reduction in body weight may mainly reflect a large loss of body water and that the changes in metabolic and hormonal parameters observed in these conditions may be caused by the effects of undernutrition rather than by changes in body composition (32). While continuing dietary treatment, PCOS women and obese controls were subsequently placed, in a random order, on metformin (Laboratori Guidotti Spa, Pisa, Italy; 850 mg/os, twice daily) (12 PCOS and 8 controls, respectively) or placebo (8 PCOS and 12 controls, respectively), according to a double-blind design, for the following 6 months. The randomization schedule was generated in blocks of 4, and the drug and placebo were packaged and labeled according to subject number. Dietary and pharmacological treatment were maintained for the following 6 months, during which the women were regularly checked, at monthly intervals, to evaluate compliance with the diet and pharmacological treatment and any side effects. Each woman was given 1 fresh 1-month pack of metformin or placebo at the start of the treatment and again at each monthly visit. Compliance with the treatment was evaluated by counting the number of pills remaining to each woman at each control visit. At the end of the trial, the women returned for the final study, which included the same protocol performed at baseline. In this case, blood testing was performed, regardless of the menstrual cycle, in both the women with PCOS and the controls. During the treatment period, 3 women of the control group (all treated with placebo) were excluded because of noncompliance with the diet. Another 2 PCOS women, both treated with metformin, were also excluded from the trial because they became pregnant while they were on month 1 and 4 of the treatment, respectively. Therefore, the women cohort available for final statistical analysis included 18 PCOS (10 treated with metformin and 8 with placebo) and 17 control women (8 treated with metformin and 9 with placebo).

Assays

Plasma glucose levels were determined by the glucose-oxidase method immediately after blood samples had been obtained. Blood samples for hormones were centrifuged immediately, and serum was stored at −20 C° until assayed. To avoid variation between assays, all the samples from an individual woman were analyzed in duplicate in a single assay for each hormone. Insulin and C-peptide were measured by reagents purchased from Eiken Chemical Corporation (Tokyo, Japan) and Sclavo (Cinisello Balsamo, Italy), respectively. Gonadotropin LH and FSH, T, dehydroepiandrosterone sulphate (DHEA-S), estradiol (E2), progesterone (P), SHBG, and leptin levels were measured as previously described (27, 30, 33). The intraassay coefficient of variation in our laboratory was 3.0% for insulin, 3.7% for C-peptide, 7.0% for T, 5.9% for DHEA-S, 5.6% for E2, 4.1% for P, 6.5% for SHBG, 3.0% for leptin, 4.8% for LH, and 1.9% for FSH.

Statistical analysis

Results are reported as the mean values ± sd, unless otherwise indicated. The response of glucose, insulin, and C-peptide to the OGTT was analyzed by calculating the (AUC) by the trapezoidal method. Normal distribution and homoscedasticity of continuous variables were tested by means of the Kolmogorov-Sminorv (34) and the Levene tests (35). Variables that did not fulfill these tests were log-transformed before analysis. To avoid multiple comparisons, the data at the different times of the study were evaluated by means of two-way ANOVA, applying a within-treatment and group design, while the within-subject ANOVA, with the same design, was used to compare the modifications observed during the course of the study. The scores of clinical parameters were analyzed by means of the Wilcoxon matched-pairs and the Mann-Whitney tests (34). Statistical evaluations were performed by running the SPSS, Inc.(Chicago, IL)/PC+ software package on a personal computer (36). Two-tailed P values less than 0.05 were used to define statistical significance.

Results

Tolerance and side effects

The treatment was well tolerated by all women. No women suspended the therapy because of side effects, although some of them (one PCOS and one control woman, both treated with metformin) experienced transient mild diarrhea and flatulence during the first 2 weeks of treatment.

Clinical parameters

At baseline, 13 PCOS women were hirsute (9 in the metformin group and 4 in the placebo group). During treatment, the Ferriman-Gallway score decreased significantly in those treated with metformin (basal, 14.8 ± 7.5; after, 12.9 ±.7.6; P < 0.05) but not in those taking placebo [basal, 11.5 ± 10.7; after, 10.3 ± 10.5; P = NS (not significant)]. None of the control women were hirsute.

At baseline, nine PCOS and six control women had acanthosis nigricans. Although several of them who were included in both treatments improved, no significant difference was found in either group between metformin and placebo.

Both PCOS groups improved the frequency of their menstrual cycles (metformin group: basal, 1.2 ± 1.6; after, 4.7 ± 2.1; P < 0.01) (placebo group: basal, 1.3 ± 1.5; after, 3.5 ± 2.3; P < 0.05), but the effects of metformin were significantly higher than those of placebo (P < 0.05).

Anthropometry and fat distribution

Baseline anthropometric and CT scan parameters and their changes during treatment are reported in Table 1. In basal conditions, there was no difference in any of them between PCOS and controls within each group, between women treated with metformin or placebo. Changes in body weight and BMI during the first month of hypocaloric dieting were similar in PCOS and control women and were not significantly different in subgroups treated with metformin or placebo. However, during the 6-month pharmacological treatment, both PCOS and controls treated with metformin similarly and significantly decreased body weight (PCOS, P < 0.05; controls, P < 0.001) and BMI (PCOS, P < 0.05; controls, P < 0.01) more than women treated with placebo. In all groups, there was a significant reduction in waist circumference after the first month of hypocaloric diet. Metformin therapy further significantly reduced waist circumference values during the 6-month treatment in both PCOS and controls, but only in the latter was a significant difference vs. placebo treatment found (P < 0.05). On the contrary, metformin and placebo induced a similar decrease in hip circumference in both PCOS and control women. Neither grouping nor treatment had a significant effect on WHR values.

Table 1.

Anthropometric parameters (m ± sd) and indices of body fat distribution (measured by CT scan) in PCOS women and control women (Obese) with abdominal obesity at baseline, after 1-month hypocaloric dieting and after 6-month combined treatment with hypocaloric diet plus metformin or placebo

Table 1.

Anthropometric parameters (m ± sd) and indices of body fat distribution (measured by CT scan) in PCOS women and control women (Obese) with abdominal obesity at baseline, after 1-month hypocaloric dieting and after 6-month combined treatment with hypocaloric diet plus metformin or placebo

TAT and SAT values were not significantly influenced by the first month of hypocaloric diet in any group, whereas those of VAT were weakly (but significantly) reduced only in the PCOS women included in the metformin group, and in the controls included in the placebo group. During the pharmacological treatment, TAT values significantly decreased in both PCOS and controls taking metformin and in the controls taking placebo. However, no differences in TAT changes between metformin and placebo were found in the PCOS groups; whereas, in the control group, they were significantly greater in those taking metformin than placebo (P < 0.05). The SAT values significantly decreased only in the PCOS and control metformin-treated groups. However, a significantly greater effect of metformin treatment was evident in controls (P < 0.05) but not in PCOS women. The opposite was found in VAT values. In fact, they significantly decreased in both PCOS and control groups treated with metformin, but only in the PCOS women was the effect of metformin significantly higher (P < 0.05) than that of placebo. Finally, after 1-month hypocaloric dieting, a significant reduction of the VAT/SAT ratio was found only in the PCOS women included in the metformin group. However, compared with baseline values, no significant changes were found in either PCOS or controls during either treatment; but in placebo-treated groups, values of the VAT/SAT ratio during treatment were significantly higher in controls than in PCOS women.

Glucose, insulin, and C-peptide

Fasting and glucose-stimulated values of glucose, insulin, and C-peptide before and at the end of the study are reported in Table 2. At baseline, there were no differences in any parameters between PCOS and controls or between metformin and placebo within each subgroup.

Table 2.

Fasting and glucose-stimulated (as AUC) values (m ± sd) of glucose, insulin, and C-peptide blood concentrations in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo

Table 2.

Fasting and glucose-stimulated (as AUC) values (m ± sd) of glucose, insulin, and C-peptide blood concentrations in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo

Fasting glucose levels decreased significantly only in the metformin-treated PCOS group, without any significant changes in the control metformin group and in either PCOS or controls treated with placebo. On the contrary, no significant difference was found in glucose_AUC in either PCOS or controls during either treatment.

At baseline, mean fasting insulin levels and insulin_AUC tended to be higher, although not significantly, in PCOS than in controls. In both groups, however, they significantly decreased during the treatment, regardless of therapy. On the contrary, insulin_AUC significantly decreased only in the PCOS group and in the controls treated with metformin, whereas no significant variation was found in the placebo-treated groups. As a consequence, changes in insulin_AUC after metformin seemed to be higher than those observed after placebo, in both PCOS (P < 0.06) and control women (P < 0.01).

Fasting C-peptide decreased significantly only in the metformin-treated PCOS group. Conversely, C-peptide_AUC significantly decreased in both PCOS and controls treated with metformin, but not in the placebo-treated groups. However, within each group, no significant differences in C-peptide_AUC values were found between metformin and placebo treatment.

Sex hormones and SHBG

Baseline and posttreatment sex hormone and SHBG values are reported in Table 3. At baseline, PCOS women had significantly higher LH and T levels than controls, whereas no significant difference was found in FSH, DHEA-S, and E2 values. However, because, in two control women included in the placebo group, baseline blood samples were collected in the luteal phase, this group had significantly higher P levels than the PCOS group treated with placebo.

Table 3.

Sex hormones and SHBG blood concentrations (m± sd) in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo

Table 3.

Sex hormones and SHBG blood concentrations (m± sd) in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo

Neither metformin nor placebo modified blood levels of LH, FSH, DHEA-S, and P in any group. Testosterone levels significantly decreased only in the metformin-treated PCOS group but not in those taking placebo. On the other hand, approximately half of them (five included in the metformin treatment and four in the placebo treatment) still had higher T and insulin [fasting and areas under the response curve (AUC)]rsqb] values than those observed in the control group after treatment.

Treatment did not significantly modify SHBG levels in PCOS groups; whereas, in the controls, SHBG significantly increased after both metformin and placebo. Therefore, posttreatment SHBG levels were significantly higher in controls than in PCOS women, regardless of treatment. E2 concentrations increased significantly only in the metformin-treated PCOS women, without any changes in those taking placebo and in the control groups. However, no significant difference was present in the PCOS group between metformin and placebo treatment.

Leptin

There were no differences in baseline leptin concentrations between PCOS women and controls. Both PCOS women and controls treated with metformin significantly decreased their leptin concentrations, whereas no significant variation after placebo was found in either group (Fig. 1). However, in both PCOS women and controls, mean changes observed during metformin or placebo were not significantly different.

Figure 1.

Leptin serum concentrations (mean ± sem) in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo. To convert leptin to pmol/L, multiply by 167. Reference values for fasting values in our laboratory are 5.9± 4.3 ng/mL.

Figure 1.

Leptin serum concentrations (mean ± sem) in PCOS women and control women (Obese) with abdominal obesity at baseline and after combined treatment with hypocaloric diet plus metformin or placebo. To convert leptin to pmol/L, multiply by 167. Reference values for fasting values in our laboratory are 5.9± 4.3 ng/mL.

Discussion

Dietary-induced weight loss may represent an appropriate means of improving hyperandrogenism and all parameters of the metabolic syndrome in many obese PCOS women (17–19). The amelioration of hyperinsulinemia and insulin sensitivity may explain these biological effects, together with the concomitant improvement of related clinical manifestations. However, available studies agree in suggesting that, even without changes in body weight, the reduction of insulin levels, which can be achieved by administering insulin-sensitizing agents, may be sufficient, in many cases, to reduce increased androgen levels, even after short-term administration (6, 21, 22–25). These findings clearly emphasize the independent role of hyperinsulinemia as a key factor in the development of hyperandrogenism in PCOS.

What the role of a reduction in adipose tissue, particularly visceral fat, is in determining these modifications is not yet clearly established. Our study was specifically conducted to determine whether the long-term administration of metformin, which can improve insulin resistance and reduce hyperinsulinemia, may have effects that supplement hypocaloric diet in reducing circulating insulin and androgen blood levels in obese PCOS women and to investigate whether these effects may be related, at least in part, to changes in body weight and fat distribution. To avoid confounding factors, only PCOS women with the abdominal obesity phenotype were included in the study, together with an age- and fat distribution-matched group of women with obesity but without PCOS. Both conditions are, in fact, associated with moderate-to-severe hyperinsulinemia and insulin resistance (1, 37). An apparent limitation of the study is that we did perform hormone blood levels and OGTT after 1 month of hypocaloric dieting. On the other hand, this was done to avoid the counterproductive effects of hypocaloric diet on hormones and metabolism. However, as was to be expected, the loss of weight after such a short time was similar in the PCOS women and in controls, regardless of the pharmacological treatment. This makes it unlikely that not having repeated these measurements after 1 month lead-in period could have affected the interpretation of the results. However, even if the above is taken into account, our data indicate that obese PCOS women and obese controls lost more weight while on metformin than on placebo. Compared with other studies, the weight loss in PCOS women and controls treated with metformin seems to have been greater than expected. In effect, our findings are in agreement with those reported by Crave et al. (38), who treated a group of obese hirsute PCOS women with hypocaloric diet (1500 kcal/day) and metformin (1500 mg/day) or placebo for 4 months and found a tendency toward greater weight loss in the metformin-treated group than in those receiving placebo. Unfortunately, any further comparison regarding the effects of metformin on weight loss in PCOS is difficult because, in most of the studies carried out (6, 20, 22, 23), metformin was administered without dietary restriction and, therefore, changes in body weight were negligible. It is also important to consider that, in our study, we only included PCOS and control women with abdominal obesity, whereas all other cited studies examined obese PCOS women regardless of their body fat distribution pattern. Because, during hypocaloric dieting, women with the abdominal obesity phenotype respond better than those with the peripheral (or sc) phenotype (39), it could have been expected that, when metformin is combined with a hypocaloric diet, the weight loss could be greater than that observed in the majority of studies carried out in nonselected obese subjects (with or without PCOS). In addition, metformin therapy favored a greater reduction of the waist circumference in both groups, which suggests a significant modification of the pattern of fat distribution, particularly at the abdominal level. However, whereas obese PCOS lost significantly more VAT in the abdomen area during metformin than during placebo treatment, without any significant difference in changes of SAT, the opposite was observed in the control obese group. These findings, therefore, suggest disparate effects of metformin added to the diet on visceral fat in PCOS, with respect to control women, in spite of the fact that they were characterized by similar obesity phenotype. They clearly seem to be related to changes in the hormonal environment that occurred during treatment in PCOS and in controls.

As expected, treatment significantly reduced fasting insulin levels; but, unlike placebo, metformin significantly decreased insulin and C-peptide response to oral glucose administration, which indicates a contemporary improvement of both insulin resistance and β-cell function. The extent of these effects was similar in PCOS and control metformin-treated women, which means that the responsiveness of the insulin-glucose system was not affected by the presence of PCOS per se, but rather by the reduction of abdominal obesity.

The pathogenetic role of obesity and body fat distribution in PCOS is still a matter of intensive debate. Available data seem to support the concept that PCOS and obesity may have an additive effect, or a synergistic, negative impact on insulin sensitivity (1). However, in a study performed in a cohort of normal-weight and obese women with and without PCOS and different patterns of body fat distribution, we previously showed that hyperinsulinemia was more consistently correlated with abdominal fat distribution, regardless of the presence of PCOS (40). In addition, others found that women with PCOS may not be insulin-resistant in the absence of increased abdominal fatness, in spite of significant hyperandrogenism (3). In addition, our present and previous intervention data (41) indicate that hyperinsulinemia and insulin resistance may be largely reversible with reduction or normalization of abdominal fat depots. Therefore, it is hypothesized that abdominal (visceral) fatness may have a dominant role in determining these abnormalities in most women with PCOS, regardless of other factors, including genetic predisposition (1).

A reduction in serum T levels occurred only in the metformin-treated PCOS group but not in the control group or in the PCOS taking placebo in addition to hypocaloric diet. Some previous studies had, in fact, shown that weight reduction obtained with hypocaloric diet alone was associated with a significant decrease in serum T levels (17–19). At variance, Crave et al. (38) found no difference between metformin and placebo added to hypocaloric diet after 4 months treatment in a group of obese hirsute women, most of whom probably had PCOS. The most likely explanation seems to be that all these studies included PCOS women based on the presence of obesity but with a wide range of body fat distribution. Contrary to what is reported by other studies (19, 21, 38), we found no significant variations in SHBG concentrations in PCOS women, whereas they were significantly increased in both metformin- and placebo-treated control women. The lack of SHBG increase in the PCOS group, particularly in those treated with metformin, was an unexpected finding. On the other hand, the fact that SHBG levels increased in the controls (both during metformin and placebo treatment) makes it improbable that the data depend on the size of the sample, unreliable assay systems, or statistical inadequacy. Other factors may probably be involved. In fact, at variance with previous studies, all women included in the study had abdominal obesity, a condition always associated with reduced SHBG concentrations (12). However, among PCOS women, lowered SHBG concentrations can also be found in those with the peripheral obesity phenotype, regardless of whether they may be relatively less hyperandrogenic and hyperinsulinemic, with respect to those with abdominal obesity (14). Moreover, the fact that approximately half the PCOS women were still relatively hyperinsulinemic and hyperandrogenic, although sia mean values of both T and insulin (fasting and glucose-stimulated) were significantly lower during treatment, particularly in the metformin-treated group, may further explain the nonincrease of the SHBG concentrations during treatment. Therefore, further studies are needed in this area, focusing on the effects of weight loss and insulin-lowering drugs in PCOS women according to specific obesity phenotype.

Finally, we found a significant effect of metformin treatment on leptin levels, which was identical in PCOS women and in controls. Because leptin levels are dependent on the amount of total body fat (42), these findings can be explained by the greater weight reduction found in both groups treated with metformin, compared with those treated with placebo. In addition, they may be dependent on the greater reduction of insulin levels induced by the metformin treatment. In fact, metformin administration has been found to decrease serum leptin in obese PCOS women, even in the absence of changes in body weight (43). Therefore, these findings confirm the regulatory role of insulin on leptin synthesis and secretion (44).

In summary, this study shows that, in PCOS women with abdominal obesity, long-term treatment with metformin, added to hypocaloric diet, induced (in comparison with placebo) a greater reduction of body weight and visceral fat and a more consistent decrease of serum insulin, T, and leptin concentrations. These changes were associated with a more significant improvement of menses abnormalities. The effects on body weight, insulin, and leptin were similar to those observed in the group of comparable abdominally obese controls in whom, however, a more pronounced reduction of sc fat in the abdominal region and an increase of SHBG concentrations were found. These findings, therefore, indicate that hyperinsulinemia and abdominal obesity may have complementary effects in the pathogenesis of PCOS.

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Linagliptin; Metformin extended-release tablets

What is this medicine?

LINAGLIPTIN; METFORMIN (lin a GLIP tin; met FOR min) is a combination of 2 medicines used to treat type 2 diabetes. This medicine lowers blood sugar. Treatment is combined with a balanced diet and exercise.

This medicine may be used for other purposes; ask your health care provider or pharmacist if you have questions.

COMMON BRAND NAME(S): Jentadueto XR

What should I tell my health care provider before I take this medicine?

They need to know if you have any of these conditions:

• anemia
• dehydration
• gallbladder disease
• heart disease
• heart failure
• high levels of triglycerides in the blood
• history of diabetic ketoacidosis
• if you often drink alcohol
• kidney disease
• liver disease
• low levels of vitamin B12 in the blood
• pancreatitis
• polycystic ovary syndrome
• previous swelling of the tongue, face, or lips with difficulty breathing, difficulty swallowing, hoarseness, or tightening of the throat
• serious infection or injury
• thyroid disease
• type 1 diabetes
• an unusual or allergic reaction to linagliptin, metformin, other medicines, foods, dyes, or preservatives
• pregnant or trying to get pregnant
• breast-feeding

How should I use this medicine?

Take this medicine by mouth with a glass of water. Take this medicine with food. Swallow whole, do not crush or chew. Follow the directions on the prescription label. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking except on your doctor’s advice.

A special MedGuide will be given to you by the pharmacist with each prescription and refill. Be sure to read this information carefully each time.

Talk to your pediatrician regarding the use of this medicine in children. Special care may be needed.

Overdosage: If you think you have taken too much of this medicine contact a poison control center or emergency room at once.

NOTE: This medicine is only for you. Do not share this medicine with others.

What if I miss a dose?

If you miss a dose, take it as soon as you can. If it is almost time for your next dose, take only that dose. Do not take double or extra doses.

What may interact with this medicine?

Do not take this medicine with any of the following medications:

• certain contrast medicines given before X-rays, CT scans, MRI, or other procedures
• dofetilide

This medicine may also interact with the following medications:

• acetazolamide
• alcohol
• bosentan
• certain antivirals for HIV or hepatitis
• certain medicines for blood pressure, heart disease, irregular heart beat
• certain medicines for seizures like carbamazepine, phenobarbital, phenytoin
• cimetidine
• dichlorphenamide
• digoxin
• diuretics
• female hormones, like estrogens or progestins and birth control pills
• glycopyrrolate
• isoniazid
• lamotrigine
• memantine
• methazolamide
• metoclopramide
• midodrine
• niacin
• phenothiazines like chlorpromazine, mesoridazine, prochlorperazine, thioridazine
• phenytoin
• ranolazine
• rifabutin
• rifampin
• St. John’s Wort
• steroid medicines like prednisone or cortisone
• stimulant medicines for attention disorders, weight loss, or to stay awake
• thyroid medicines
• topiramate
• trospium
• vandetanib
• zonisamide

This list may not describe all possible interactions. Give your health care provider a list of all the medicines, herbs, non-prescription drugs, or dietary supplements you use. Also tell them if you smoke, drink alcohol, or use illegal drugs. Some items may interact with your medicine.

What should I watch for while using this medicine?

Visit your doctor or health care professional for regular checks on your progress.

A test called the HbA1C (A1C) will be monitored. This is a simple blood test. It measures your blood sugar control over the last 2 to 3 months. You will receive this test every 3 to 6 months.

Learn how to check your blood sugar. Learn the symptoms of high or low blood sugar and how to manage them.

Always carry a quick-source of sugar with you in case you have symptoms of low blood sugar. Examples include hard sugar candy or glucose tablets. Make sure others know that you can choke if you eat or drink when you develop serious symptoms of low blood sugar, such as seizures or unconsciousness. They must get medical help at once.

Tell your doctor or health care professional if you have high blood sugar. You might need to change the dose of your medicine. If you are sick or exercising more than usual, you might need to change the dose of your medicine.

Do not skip meals. Ask your doctor or health care professional if you should avoid alcohol. Many nonprescription cough and cold products contain sugar or alcohol. These can affect blood sugar.

This medicine may cause ovulation in premenopausal women who do not have regular monthly periods. This may increase your chances of becoming pregnant. You should not take this medicine if you become pregnant or think you may be pregnant. Talk with your doctor or health care professional about your birth control options while taking this medicine. Contact your doctor or health care professional right away if you think you are pregnant.

If you are going to need surgery, a MRI, CT scan, or other procedure, tell your doctor that you are taking this medicine. You may need to stop taking this medicine before the procedure.

Wear a medical ID bracelet or chain, and carry a card that describes your disease and details of your medicine and dosage times.

This medicine may cause a decrease in folic acid and vitamin B12. You should make sure that you get enough vitamins while you are taking this medicine. Discuss the foods you eat and the vitamins you take with your health care professional.

What side effects may I notice from receiving this medicine?

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• breathing problems
• feeling faint or lightheaded, falls
• joint pain
• muscle aches or pains
• redness, blistering, peeling or loosening of the skin, including inside the mouth
• signs and symptoms of low blood sugar such as feeling anxious, confusion, dizziness, increased hunger, unusually weak or tired, sweating, shakiness, cold, irritable, headache, blurred vision, fast heartbeat, loss of consciousness
• signs and symptoms of heart failure like breathing problems, fast, irregular heartbeat, sudden weight gain; swelling of the ankles, feet, hands; unusually weak or tired
• slow or irregular heartbeat
• unusual stomach pain or discomfort
• unusually tired or weak
• vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• diarrhea
• gas
• headache
• heartburn
• metallic taste in mouth
• nausea
• runny or stuffy nose
• sore throat
• upset stomach

This list may not describe all possible side effects. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Where should I keep my medicine?

Keep out of the reach of children.

Store at room temperature between 15 and 30 degrees C (59 and 86 degrees F). Throw away any unused medicine after the expiration date.

NOTE: This sheet is a summary. It may not cover all possible information. If you have questions about this medicine, talk to your doctor, pharmacist, or health care provider.

Vitamins & Diabetes | ADA

Daily Dose

Many think that a supplement contains the same vitamins and minerals as whole foods, so why not just pop a pill? It’s because vitamins and minerals are best absorbed through food.

Think of it like this—whole foods contain a mix of minerals, enzymes, fiber, and other substances that may help your body absorb and use these nutrients. Eating a well-balanced meal is much healthier than a multivitamin. It’s not clear whether vitamins and minerals have the same effect in the body when taken in supplement form.

If you have a true vitamin deficiency, however, a supplement may be helpful. Americans are most commonly deficient in vitamins D and B12, calcium, and iron. The only way to know whether you’re deficient is through blood work, but you might see some signs. If you’re experiencing symptoms you think a supplement could fix, consult your doctor before trying to remedy the problem yourself.  

Supplements that impact blood sugar

Supplements may cause unwelcome—or dangerous—side effects, especially if they interact with your medications. While some ingredients could intensify the effects of your diabetes meds, causing hypoglycemia (low blood sugar, also called blood glucose), others may have the opposite effect, leading to hyperglycemia (high blood sugar).

Research on many supplements is inconclusive. Talk to your health care provider before you start taking chromium, vitamin E, St. John’s wort, or niacin.

• Chromium
  A chromium deficiency may lead to high blood sugar levels. It may be worth a try if you’re deficient in chromium, but that’s very rare. Steer clear if you’ve been diagnosed with kidney disease. Chromium supplements might further damage the kidneys and worsen the disease.
• Vitamin E & St. John’s Wort
  Both vitamin E and the herb St. John’s wort can have dangerous interactions with blood-thinning drugs used to treat heart disease—increasing your bleeding risk. Among people with heart disease being treated with the blood thinner warfarin, those most likely to experience bleeding events have higher levels of vitamin E in their bodies. Other studies have found that St. John’s wort amplifies the effect of blood thinners. Avoid these supplements if you’re taking a blood-thinning medication. Besides warfarin, those include apixaban, dabigatran, heparin, and rivaroxaban.
• Niacin
  Some people take niacin to raise HDL (“good”) cholesterol, but it can also affect your diabetes management. Niacin raises fasting glucose levels (your blood sugar levels when you are not eating) for people with diabetes, meaning the risks may outweigh the benefits. And while niacin can raise HDL cholesterol, there’s no evidence that this leads to a lower risk of cardiovascular disease. A chat with your health care provider can help you determine if this is safe for you to take.

Confused about what to take? Unless your health care provider recommends a specific vitamin or supplement, it’s probably not all that helpful—or economical—to add another pill to your regimen. 

Other common supplements

Here’s what you need to know about other common supplements:

• A B12 supplement can be helpful if you have type 2 diabetes and are deficient in the vitamin. People who take metformin for type 2 diabetes have lower levels of vitamin B12. If you’re on metformin, talk to your health care provider about periodically being tested for a B12 deficiency. 
• Vitamin C and E supplements won’t ward off diabetes and diabetes complications. Until the research shows a clear benefit, it’s best to pass on these.
• The jury’s still out on vitamin D. There is an association between higher concentrations of vitamin D in the blood during childhood and a lower risk of type 1 diabetes. More research is needed to understand the link, but here’s one thing experts can agree on: if you’re deficient in vitamin D, a supplement can help.
• Cinnamon isn’t as effective as your type 2 diabetes medication. Cinnamon supplements do nothing to help people with type 2 achieve treatment goals or provide a reliable drop in blood sugar. However, since cinnamon is fragrant seasoning, you can use it flavor your food instead of sugary condiments. Enjoy a sprinkling of cinnamon on oatmeal instead of taking supplements.
• Alpha-lipoic acid (ALA) reduces pain from diabetic neuropathy. ALA injections, which are available only in Europe, improve symptoms of neuropathy in the short term. Results are mixed with oral supplements, which are available in the United States. 

The takeaway

At the end of the day, be sure to talk with your diabetes team before making changes—your health care provider can help you figure out if it’s a good idea to add a vitamin or supplement to your routine.

Sitagliptin and Metformin | Memorial Sloan Kettering Cancer Center

This document, provided by Lexicomp ^® , contains all the information you need to know about the drug, including the indications, route of administration, side effects and when you should contact your healthcare provider.

Trade names: USA

Janumet; Janumet XR

Trade names: Canada

Janumet; Janumet XR

Warning

• In rare cases, metformin may cause an increase in blood lactic acid levels (lactic acidosis).The risk is increased in people who have kidney disease, liver disease, heart failure, who drink alcohol or take other drugs such as topiramate. This risk is also increased in the elderly 65 years of age and older, as well as in patients undergoing surgery, contrast media examinations, or other procedures. If it occurs, lactic acidosis can lead to other health problems and be fatal.Kidney function tests may be done while this drug is used.
• This drug should not be used if you have a severe infection, low blood oxygen, or severe dehydration (dehydration).
• When signs of high lactic acid in the blood (lactic acidosis) appear, such as rapid breathing, tachycardia or bradycardia, a feeling of irregular heartbeat, very severe nausea or vomiting, severe drowsiness, shortness of breath, feeling very tired or weak, very dizzy, feeling cold, muscle pain or cramps, see a doctor immediately.

What is this drug used for?

• The drug is used to lower blood sugar in diabetics.

What should I tell my doctor BEFORE taking this drug?

• If you are allergic to this drug, any of its ingredients, other drugs, foods or substances. Tell your doctor about your allergy and how it manifested itself.
• For the following conditions: Blood acidosis, kidney disease, liver disease or type 1 diabetes.
• If you have recently had a myocardial infarction or stroke.
• If you are unable to eat or drink normally, including before certain procedures or surgery.
• Consult your doctor if you are currently undergoing or have had a contrast test or test within the past 48 hours.

This list of drugs and diseases that may be adversely associated with the use of this drug is not exhaustive.

Tell your doctor and pharmacist about all the medicines you take (prescription and over-the-counter, natural products and vitamins) and your health problems. You need to make sure that this drug is safe for your medical condition and in combination with other drugs you are already taking. Do not start or stop taking any drug or change the dosage without your doctor’s approval.

What do I need to know or do while taking this drug?

• Tell all healthcare providers that you are taking this drug. These are doctors, nurses, pharmacists and dentists.
• Consult a physician before drinking alcohol.
• Do not drive a car if your blood sugar is low. The risk of an accident increases.
• Check your blood sugar as directed by your doctor.
• Perform blood tests as directed by your healthcare practitioner.Please consult your doctor.
• Blood sugar levels may decrease. This effect may be increased when this drug is used with other diabetes drugs. Symptoms may include dizziness, headache, drowsiness, feeling weak, tremors, tachycardia, confusion, hunger, or sweating. Call your doctor right away if any of these signs occur. If your blood sugar drops, follow the directions for that condition.Such directions may include taking tablets or glucose solution and some fruit juices.
• It may be difficult to control blood sugar levels during times of stress, such as fever, infection, injury, or surgery. Blood sugar levels can also be affected by changes in physical activity or exercise and diet.
• Exercise caution in hot weather and during vigorous activity. Drink plenty of fluids to stay hydrated.
• Follow your doctor’s recommended diet and exercise program.
• The use of drugs of this kind has been accompanied by the development of a skin reaction called bullous pemphigoid. In some cases, hospitalization was required. If you develop blisters or your skin begins to crack, see your doctor immediately.
• Heart failure has been reported in patients taking similar drugs. Tell your doctor if you have ever had heart failure or kidney problems.If you experience extreme fatigue, shortness of breath, sudden weight gain, or swelling in your arms or legs, see your doctor immediately.
• Kidney problems have occurred. In some cases, hospitalization or dialysis may be required to treat these disorders.
• If you are unable to drink fluids, or if you have nausea, vomiting, or diarrhea that persists, you should avoid dehydration. Contact your doctor and find out what to do. Dehydration can cause or worsen existing kidney disease.
• Long-term treatment with metformin may result in decreased vitamin B-12 levels. If you have ever had low vitamin B-12 levels, consult your doctor.
• If you are 65 years of age or older, use this drug with caution. You may have more side effects.
• There is a risk of pregnancy in people of childbearing age who have not ovulated. If you want to avoid pregnancy, use birth control while taking this drug.
• Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. The benefits and risks for you and your child will need to be discussed.

What side effects should I report to my doctor immediately?

WARNING. In rare cases, some people with this drug can have serious and sometimes deadly side effects. Call your doctor right away or get medical help if you have any of the following signs or symptoms, which may be associated with serious side effects:

All forms of issue:

• Signs of an allergic reaction, such as rash, hives, itching, reddened and swollen skin with blisters or scaling, possibly associated with fever, wheezing or wheezing, tightness in the chest or throat, difficulty breathing, swallowing or speaking, unusual hoarseness, swelling in the mouth, face, lips, tongue, or throat.
• Signs of kidney problems, including lack of urination, change in urine volume, blood in the urine, or rapid weight gain.
• A serious and sometimes deadly pancreas problem (pancreatitis) has happened with this drug. Such a violation can occur at any stage of treatment. Signs of pancreatitis include very severe abdominal pain, very severe back pain, very severe stomach upset, or vomiting. Call your doctor right away if any of these signs occur.
• Digestive problems such as upset stomach, vomiting, and diarrhea often happen after this drug is started. If stomach disorders occur in the later stages of treatment, see your doctor immediately. This may be a sign of blood acidity disorder (lactic acidosis).
• Possible severe skin reaction (Stevens-Johnson syndrome / toxic epidermal necrolysis). This can lead to serious and permanent health problems and sometimes death.Get immediate medical attention if you experience symptoms such as redness, skin swelling with blistering or scaling (with or without a high fever), eye redness or irritation, or ulceration in the mouth, throat, nose, or eyes.
• Drugs of this nature can cause joint pain, which can be very severe and disabling. See your doctor right away if you have very severe joint pain or any joint pain that does not go away.

Extended release tablets:

• Something that looks like a pill can be seen in the stool. If you find that you have a lot of pills in your stool, talk to your doctor.

What are some other side effects of this drug?

Any medicine can have side effects. However, many people have little or no side effects. Call your doctor or get medical help if these or any other side effects bother you or do not go away:

• Abdominal pain or heartburn.
• Diarrhea, indigestion or vomiting.
• Gas.
• Feeling tired or weak.
• Headache.
• Signs of a cold.
• Nose or throat irritation.

This list of potential side effects is not comprehensive. If you have any questions about side effects, please contact your doctor. Talk to your doctor about side effects.

You can report side effects to the National Health Office.

You can report side effects to the FDA at 1-800-332-1088. You can also report side effects at https://www.fda.gov/medwatch.

What is the best way to take this drug?

Use this drug as directed by your healthcare practitioner. Read all the information provided to you. Follow all instructions strictly.

Immediate-release tablets of active ingredient:

• Take this medication with food.
• Do not break or crush the tablet.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.

Extended release tablets:

• Take with meals.
• Take in the evening unless instructed otherwise by your doctor.
• Swallow whole. Do not chew, break, or crush.
• Continue taking this drug as directed by your doctor or other healthcare professional, even if you feel well.

What should I do if a dose of a drug is missed?

• Take the missed dose as soon as you can.
• If it’s time to take your next dose, do not take the missed dose and then return to your normal dose.
• Do not take 2 doses at the same time or an additional dose.

How do I store and / or discard this drug?

• Store at room temperature in a dry place. Do not store in the bathroom.
• Store all medicines in a safe place. Keep all medicines out of the reach of children and pets.
• Dispose of unused or expired drugs. Do not empty into toilet or drain unless directed to do so.If you have any questions about the disposal of your medicinal products, consult your pharmacist. There may be drug recycling programs in your area.

General information on medicinal products

• If your health does not improve or even worsens, see your doctor.
• You should not give your medicine to anyone and take other people’s medicines.
• Some medicines may come with other patient information sheets.If you have questions about this drug, talk with your doctor, nurse, pharmacist, or other healthcare professional.
• A separate patient instruction sheet is attached to the product. Please read this information carefully. Reread it every time you replenish your supply. If you have questions about this drug, talk with your doctor, pharmacist, or other healthcare professional.
• If you think an overdose has occurred, call a Poison Control Center immediately or seek medical attention.Be prepared to tell or show which drug you took, how much and when it happened.

Use of information by the consumer and limitation of liability

This summary information includes a summary of the diagnosis, treatment, and / or drug. It is not a comprehensive data source and should be used as a tool to help the user understand and / or evaluate potential diagnostic and treatment options.It does NOT include all information about conditions, treatments, medications, side effects or risks that may apply to a particular patient. It should not be considered medical advice or a substitute for medical advice, diagnosis or treatment provided by a physician based on a medical examination and assessment of the patient’s specific and unique circumstances. Patients should consult a physician for complete information about their health, medical issues and treatment options, including any risks or benefits in relation to the use of the medication.This information does not guarantee that a treatment or drug is safe, effective, or approved for specific patients. UpToDate, Inc. and its subsidiaries disclaim any warranties or obligations related to this information or its use. Use of this information is governed by the Terms of Use found at https://www.wolterskluwer.com/en/solutions/lexicomp/about/eula.

Copyright

© UpToDate, Inc.and its affiliates and / or licensors, 2021. All rights reserved.

90,000 If old age is just a disease, can it be cured?

• Britt Ray
• BBC Future

March 25, 2018

Photo Credit, Getty Images

As we learn more about disease, science is finding more ways to deal with it. Will we ever learn to cope with a disease that until now was considered incurable – old age? Some experts answer in the affirmative.

The list of diseases that humans have learned to treat is truly impressive: polio, typhoid, measles, tetanus, yellow fever, smallpox, diphtheria, chickenpox – many regions of the planet are almost completely free from these diseases.

Vaccines and powerful medications help humans fight dangerous and often deadly bacteria and viruses.

However, as long as humanity can remember itself, people have always been susceptible to a disease that not a single most talented doctor is able to cope with.Aging cannot be avoided by any of us, and no one has yet managed to cure old age.

As we age, our cells stop working as before, leading to cancer, heart disease, arthritis, Alzheimer’s disease, etc.

Diseases associated with age, every day claim the lives of 100 thousand people, and huge amounts of money are spent all over the world to somehow slow down the aging process of our immortal bodies.

Nevertheless, some researchers believe that our view of old age is fundamentally wrong.In their opinion, we must begin to treat the aging of the body in the same way as we treat diseases. Old age, they say, is something that can be avoided, something that can be cured.

We spoke to some of these scientists who are trying to find ways to slow down or even stop aging.

Photo author, Getty Images

Photo caption,

Will we ever learn to stop aging?

The hopes of these specialists are based on the latest discoveries, based on which it can be assumed that biological aging is curable.

From a biological point of view, the body, depending on genetic and environmental factors, can age at different rates. Small glitches build up in our DNA, and cells begin to function with errors, which also accumulate, leading to tissue damage.

The degree of such changes occurring in the body results in either what we call healthy old age, or old age burdened with chronic diseases.

Scientists hoping to slow down and even cure people of old age are still on the fringes of the medical scientific landscape.

However, there are already a sufficient number of research centers in the world where this task has been made a priority. Experiments on animals have shown that life expectancy can be significantly increased. There was a hope that this is possible with a person.

For example, the well-known diabetes drug metformin has been shown to prolong life in rodents during research.

In the early 1990s, Cynthia Kenyon is currently vice president of research at Calico Labs, a division of Google’s Alphabet, which is trying to apply the latest technology to understand how human biology controls life expectancy.- Approx. Translator ), her experiments demonstrated that roundworms, if they change only one letter in the genetic code, begin to live twice as long (six weeks instead of the usual three).

One of the most famous experts in the world studying the possibility of life extension, British gerontologist Aubrey Dee Gray told the BBC how such an increase in life expectancy could be possible for humans.

Photo author, Sens Foundation / Wikipedia

Caption,

British gerontologist Aubrey de Gray is confident that he can cope with old age

De Gray is chairman and director of science of the SENS Foundation (Strategies for Engineered Negligible Senescence, “strategies for aging by engineering methods “).As he explains, the goal of the foundation is to develop a therapeutic complex for middle-aged and elderly people that will help them return to the physical and mental state of a person who is not even 30.

“Naturally, without erasing memory,” he adds.

Dee Gray says “I want to get rid of what we don’t like about the changes that occur as we age – between the ages of 30 and 70”.

According to Dee Gray, there are seven major biological factors responsible for cellular damage associated with aging and underlying diseases that develop with age.

One of these factors is when cells in tissues stop regenerating quickly enough. Another is when cells start dividing uncontrollably (as in the case of cancer). The third is when cells do not die when they are supposed to (also related to cancer).

Fourth – damage to the DNA of mitochondria, the tiny power plants of our cells. Fifth – the accumulation of decay products inside cells. Sixth – decay products that accumulate outside the cells. And seventh – an increase in the rigidity of the intercellular substance, the extracellular matrix, which is responsible for the ability of tissues to stretch and bend.

Dee Gray and the SENS research team say they have discovered ways in which each of these factors can be overcome – with therapies they have developed.

“The first problem can be overcome with stem cell therapy,” says De Gray.

The body tissue receives fresh, young cells, which replace old ones that die as a result of aging.

In other cases – for example, when cells do not die when they should – more complex solutions are required.

“In principle, we could apply such a targeted effect on genes, after which the body will have ‘suicide genes’ – those that will produce proteins that simply kill the cell,” explains De Gray.

The problem, however, is to obtain genes that would create a lethal protein only for those cells that the body no longer needs.

According to Dee Gray, these methods are not enough to completely stop aging, but they can extend life by 30 years.

He well foresees a future in which the use of “rejuvenating technologies” will be prescribed to older people to restore their cells to the ability to function as in youth.

For example, a 60-year-old person can be returned to the biological age of 30 years. However, the cells of this person will still return to 60 years of age in 30 years.

But by then, De Gray hopes, the therapy can be repeated. As a result of this approach, the cells of this person will not reach the state of a 60-year-old organism until the person turns 150 years old.

However, such promises should be treated with great caution. There is no evidence, confirmed by experiments, that our body will accept such a “software update” positively and without complications.

As is the case with computers, too many updates can cause the entire system to freeze.

But Dee Gray believes that such a way of thinking (which he calls hypnosis of the inevitability of aging) only hinders the development of technology.

The problem, he says, is that we humans traditionally perceive aging as inevitable.And therefore, all attempts to prevent old age, to defeat it are often perceived as unscientific, as quackery.

De Gray is not the only one who believes that diseases associated with aging can be defeated. George Church, a geneticist at Harvard, considers the approach of some of his colleagues, who speak of the impossibility of curing many of these diseases, to be wrong, because it is allegedly too difficult.

“If you learn to manage ecology and genetics, then as a result you will have people living their lives healthy and young, and this life will be much longer than now,” he says.

Photo author, Getty Images

Caption,

Blood transfusions from young donors can slow aging

One way to prolong a healthy life is known as “vampire therapy”. Patients suffering from senile dementia receive blood transfusions from donors between the ages of 18 and 30.

Recent studies have shown that the condition of older people improves as a result. A patient with early Alzheimer’s has regained the ability to dress and wash independently, as well as perform simple household chores.

These studies are still ongoing, but the American startup Ambrosia is already offering elderly patients donor blood transfusions between the ages of 16 and 25. The cost of one such procedure is 8 thousand dollars.

The company says the transfusions can “wake up” cells that have fallen asleep in an elderly body, improve the condition of a patient with early-onset Alzheimer’s, and even make a 60-year-old’s hair look less gray.

The Ambrosia research report, however, has yet to be published in a peer-reviewed scientific journal.Skeptics are already criticizing him for not considering the placebo effect.

However, there are a number of animal studies that suggest that such therapies may well have a biological rationale.

In 2013, experiments by scientists at the Harvard Institute for Stem Cell Research demonstrated that muscle strength in mice can be increased using the GDF11 component found in the blood of a young individual, but this result has not yet been reproduced.

In contrast to laboratory approaches, some researchers argue that life expectancy can be increased simply by consuming fewer calories.

How about curing … death? As you know, some resort to cryogenic freezing of a newly deceased body – in the hope that one day science will learn to resurrect the dead. It is clear that today none of the clients of companies offering freezing services have yet returned to life.

The famous American inventor and futurist Ray Kurzweil proposes another version of immortality, predicting the emergence of a “posthuman”: “We will have non-biological bodies.We will be able to create bodies with the help of nanotechnology, we will be able to create virtual bodies and virtual reality that will be completely realistic due to the fact that virtual bodies will be as detailed and convincing as real ones. “

Photo caption,

What will be the” posthuman “? And what kind of world will he create around him?

Such ideas are very easy to consider insane, refer them to (not) science fiction.But no matter how humanity comes to the ability to prolong life (or even to the immortality of an individual), for society it is can turn into a big problem.

The increase in life can lead to serious overpopulation of our planet. De Gray says he is often asked whether life extension technology will become a tool in the hands of the rich and tyrant rulers. Or a too long life may simply bore the people who are happy with it …

De Gray believes that other technologies will come to the rescue in all these cases, with the help of which artificial products (for example, meat) will be created, humanity will learn to use solar energy much more efficiently and all other natural reserves, which will allow more people to live long and safely on our small planet.

However, the weakness of De Gray’s arguments is that he relies on technological breakthroughs in his forecasts, the future effectiveness of which we can only guess – whether they will actually help, we do not know.

True, it should be remembered that if we were always guided by such fears and because of this blocked the research of scientists who invented vaccinations and antibiotics, then the average life expectancy of a modern person would not exceed 40 years.

The advances in medicine of the last two centuries have taught us that we are able to defeat diseases that threaten humanity.Perhaps we will be able to do this with old age.

To read the original of this article in English, please visit BBC Future .

90,000 PRODUCTS TO AVOID FOR BORDER DIABETES PATIENTS – MEDICAL

Contents:

In borderline diabetes or prediabetes, blood sugar levels are higher than normal, but not as high as in type 2 diabetes (T2DM). Prediabetes is based on a condition called insulin resistance.In this condition, the body stops responding normally to insulin, a hormone that allows cells to absorb and use blood sugar or glucose.

Prediabetes occurs when muscle, fat, and liver cells become so resistant to insulin that glucose builds up in the blood.

The good news for people with prediabetes is that dietary changes, along with exercise and weight loss, can delay or prevent the progression of T2DM. Knowing which foods to avoid will help you formulate a healthy diet for borderline diabetes.

Sweet foods

Carbohydrates include sugar, starch and fiber. While fiber passes through the digestive system largely unchanged, sugar is rapidly digested and absorbed into the bloodstream. This leads to an increase in blood sugar levels, which varies depending on the food source.

Fruits, vegetables, dairy products and whole grains are beneficial sources of carbohydrates for people with prediabetes as they provide essential fuel for the body along with various other beneficial nutrients.But sugary foods like desserts, candy, and sugar-sweetened drinks are high in calories and not very nutritious.

A large BMJ review of 17 studies in July 2015 of 189.1 million US adults found that regular consumption of sugar-sweetened beverages increased the risk of developing T2DM by 13 percent for each daily serving. Initial risk estimates were higher, but were revised to exclude obesity as a contributing factor, as it could skew the results.

While you don’t have to skip these foods, the ADA suggests keeping them for special occasions and eating a small portion. It helps control weight, which is important for reducing the risk of developing T2DM.

• Carbohydrates include sugar, starch and fiber.
• Fruits, vegetables, dairy products and whole grains are beneficial sources of carbohydrates for people with prediabetes as they provide essential fuel for the body along with various other beneficial nutrients.

Refined grain products

Cereals contain varying amounts of starch and fiber.

Starch is digested into glucose, which affects blood sugar levels. Fiber is the indigestible part of plant foods, including fruits, vegetables, beans, and grains.

Since fiber is not digested, it does not raise blood sugar levels. In fact, foods high in fiber can help control blood sugar levels by slowing down and reducing the absorption of sugar from the digestive system.

Refined grains are ground, which removes most of the fiber, as well as some useful vitamins and minerals. Examples include white rice and white flour. As reported in December 2008 American Journal of Clinical Nutrition article 3, foods made with refined grains tend to cause a larger spike in blood sugar than whole grains.

This is important because large swings in blood sugar trigger the release of chemicals called free radicals, note the authors of the April 2006 JAMA study report.High levels of free radicals can contribute to the progression of prediabetes to T2DM.

ADA recommends choosing high fiber whole grains instead of refined grains.

* * Examples of foods to avoid or limit: – White flour bread, pasta and crackers.

* * – Cereals such as cornflakes, puffed rice and instant oatmeal. – White rice and couscous.

• Cereals contain varying amounts of starch and fiber.
• As reported in December 2008 article 3 of the American Journal of Clinical Nutrition, foods made with refined grains tend to cause a larger spike in blood sugar than whole grains.

Foods high in unhealthy fats

Fat intake does not directly affect blood sugar levels.

But a high-calorie, high-fat diet increases the risk of prediabetes and T2DM.Plus, prediabetes increases the risk of heart disease. For these reasons, it is important for people with borderline diabetes to limit their intake of foods high in saturated fat and avoid any trans fats. ADA recommends that people with prediabetes follow the same guidelines as the general population for fat intake.5 The American Heart Association recommends limiting saturated fat to 5-6 percent of daily calories 257. On a 2,000 calorie diet, this is no more than 13 g per day.Saturated fat comes from animal foods, including meat, eggs, and dairy products.

Examples of foods high in saturated fat that should be limited or avoided in prediabetes: – Fatty cuts of beef, pork, lamb and other red meats.

– Processed meats such as sausage, bacon and deli meats. – Bird in the skin. – Butter, full-fat milk and cheese.

Trans fats are more harmful than saturated fat in terms of an increased risk of heart disease. A small amount of trans fat is found in some animal products. Artificial trans fats, also known as partially hydrogenated oils, are formulated to harden vegetable oils. Trans fats have historically been used in many processed foods and fast foods. However, due to health risks, the FDA is mandating that trans fats be eliminated from all foods manufactured by 2018.While many manufacturers have already eliminated trans fats from their products, check the food label and ingredients to make sure the food is free. trans fats.

According to the Cleveland Clinic, foods to avoid that may still contain trans fats include: – Ready-to-eat cakes, pastries, cookies and breakfast sandwiches. – Chips, microwave popcorn and other snacks.

* * – Frozen foods with a crust such as pizza and pies.

* * – Mixes for baking and ready-made glaze. – Margarine.

• Fat intake does not directly affect blood sugar levels.
• Examples of foods high in saturated fat that should be limited or avoided in prediabetes: – Fatty cuts of beef, pork, lamb and other red meats.
• – Although many manufacturers have already eliminated trans fats from their products, check the food label and ingredients to make sure they are free of trans fats.

The National Institutes of Health (NIH) reports that prediabetes usually progresses to T2DM within 10 years unless lifestyle changes. However, with proper diet, exercise, and moderate weight loss, people with prediabetes can significantly delay or prevent the onset of T2DM. A large study, sponsored by the National Institutes of Health (NIH) in 3234 overweight and pre-diabetic people, found that losing as little as 7 percent of body weight along with 150 minutes of exercise per week reduced the rate of T2DM progression by 34 percent over 10 years compared with lack of treatment.In addition, treatment with an oral diabetes drug called metformin (Glucophage, Glumetza, Fortamet) reduced the rate of T2DM by 18 percent.

ADA recommends a personalized diet for people with prediabetes, so it is important to talk with your doctor and dietitian about the best meal plan for you and what foods to avoid or limit.

• The National Institutes of Health (NIH) reports that prediabetes usually progresses to T2DM within 10 years unless lifestyle changes.
• In addition, treatment with an oral diabetes drug called metformin (Glucophage, Glumetza, Fortamet) reduced the rate of T2DM by 18 percent.