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What does metformin do for type 2 diabetes

Type 2 diabetes - Diagnosis and treatment


Type 2 diabetes is usually diagnosed using the glycated hemoglobin (A1C) test. This blood test indicates your average blood sugar level for the past two to three months. Results are interpreted as follows:

  • Below 5.7% is normal.
  • 5.7% to 6.4% is diagnosed as prediabetes.
  • 6.5% or higher on two separate tests indicates diabetes.

If the A1C test isn't available, or if you have certain conditions that interfere with an A1C test, your doctor may use the following tests to diagnose diabetes:

Random blood sugar test. Blood sugar values are expressed in milligrams of sugar per deciliter (mg/dL) or millimoles of sugar per liter (mmol/L) of blood. Regardless of when you last ate, a level of 200 mg/dL (11.1 mmol/L) or higher suggests diabetes, especially if you also have signs and symptoms of diabetes, such as frequent urination and extreme thirst.

Fasting blood sugar test. A blood sample is taken after an overnight fast. Results are interpreted as follows:

  • Less than 100 mg/dL (5.6 mmol/L) is normal.
  • 100 to 125 mg/dL (5.6 to 6.9 mmol/L) is diagnosed as prediabetes.
  • 126 mg/dL (7 mmol/L) or higher on two separate tests is diagnosed as diabetes.

Oral glucose tolerance test. This test is less commonly used than the others, except during pregnancy. You'll need to fast overnight and then drink a sugary liquid at the doctor's office. Blood sugar levels are tested periodically for the next two hours. Results are interpreted as follows:

  • Less than 140 mg/dL (7.8 mmol/L) is normal.
  • 140 to 199 mg/dL (7.8 mmol/L and 11.0 mmol/L) is diagnosed as prediabetes.
  • 200 mg/dL (11.1 mmol/L) or higher after two hours suggests diabetes.

Screening. The American Diabetes Association recommends routine screening with diagnostic tests for type 2 diabetes in all adults age 45 or older and in the following groups:

  • People younger than 45 who are overweight or obese and have one or more risk factors associated with diabetes
  • Women who have had gestational diabetes
  • People who have been diagnosed with prediabetes
  • Children who are overweight or obese and who have a family history of type 2 diabetes or other risk factors

After a diagnosis

If you're diagnosed with diabetes, your doctor or health care provider may do other tests to distinguish between type 1 and type 2 diabetes — since the two conditions often require different treatments.

Your health care provider will repeat the test A1C levels at least two times a year and when there are any changes in treatment. Target A1C goals vary depending on your age and other factors. For most people, the American Diabetes Association recommends an A1C level below 7%.

You will also receive regular diagnostic tests to screen for complications of diabetes or comorbid conditions.

More Information

  • A1C test
  • Glucose tolerance test


Management of type 2 diabetes includes:

  • Healthy eating
  • Regular exercise
  • Weight loss
  • Possibly, diabetes medication or insulin therapy
  • Blood sugar monitoring

These steps will help keep your blood sugar level closer to normal, which can delay or prevent complications.

Healthy eating

Contrary to popular perception, there's no specific diabetes diet. However, it's important to center your diet around:

  • A regular schedule for meals and healthy snacks
  • Smaller portion sizes
  • More high-fiber foods, such as fruits, nonstarchy vegetables and whole grains
  • Fewer refined grains, starchy vegetables and sweets
  • Modest servings of low-fat dairy, low-fat meats and fish
  • Healthy cooking oils, such as olive oil or canola oil
  • Fewer calories

Your health care provider may recommend seeing a registered dietitian, who can help you:

  • Identify healthy choices among your food preferences
  • Plan well-balanced, nutritional meals
  • Develop new habits and address barriers to changing habits
  • Monitor carbohydrate intake to keep your blood sugar levels more stable

Physical activity

Exercise is important for losing weight or maintaining a healthy weight. It also helps with regulating blood sugar levels. Talk to your primary health care provider before starting or changing your exercise program to ensure that activities are safe for you.

Aerobic exercise. Choose an aerobic exercise that you enjoy, such as walking, swimming, biking or running. Adults should aim for 30 minutes or more of moderate aerobic exercise on most days of the week, or at least 150 minutes a week. Children should have 60 minutes of moderate to vigorous aerobic exercise daily.

Resistance exercise. Resistance exercise increases your strength, balance and ability to perform activities of daily living more easily. Resistance training includes weightlifting, yoga and calisthenics.

Adults living with type 2 diabetes should aim for two to three sessions of resistance exercise each week. Children should engage in activities that build strength and flexibility at least three days a week. This can include resistance exercises, sports and climbing on playground equipment.

Limit inactivity. Breaking up long bouts of inactivity, such as sitting at the computer, can help control blood sugar levels. Take a few minutes to stand, walk around or do some light activity every 30 minutes.

Weight loss

Weight loss results in better control of blood sugar levels, cholesterol, triglycerides and blood pressure. If you're overweight, you may begin to see improvements in these factors after losing as little as 5% of your body weight. However, the more weight you lose, the greater the benefit to your health and disease management.

Your health care provider or dietitian can help you set appropriate weight-loss goals and encourage lifestyle changes to help you achieve them.

Monitoring your blood sugar

Your health care provider will advise you on how often to check your blood sugar level to make sure you remain within your target range. You may, for example, need to check it once a day and before or after exercise. If you take insulin, you may need to do this multiple times a day.

Monitoring is usually done with a small, at-home device called a blood glucose meter, which measures the amount of sugar in a drop of your blood. You should keep a record of your measurements to share with your health care team.

Continuous glucose monitoring is an electronic system that records glucose levels every few minutes from a sensor placed under your skin. Information can be transmitted to a mobile device such as your phone, and the system can send alerts when levels are too high or too low.

Diabetes medications

If you can't maintain your target blood sugar level with diet and exercise, your doctor may prescribe diabetes medications that help lower insulin levels or insulin therapy. Drug treatments for type 2 diabetes include the following.

Metformin (Fortamet, Glumetza, others) is generally the first medication prescribed for type 2 diabetes. It works primarily by lowering glucose production in the liver and improving your body's sensitivity to insulin so that your body uses insulin more effectively.

Some people experience B-12 deficiency and may need to take supplements. Other possible side effects, which may improve over time, include:

  • Nausea
  • Abdominal pain
  • Bloating
  • Diarrhea

Sulfonylureas help your body secrete more insulin. Examples include glyburide (DiaBeta, Glynase), glipizide (Glucotrol) and glimepiride (Amaryl). Possible side effects include:

  • Low blood sugar
  • Weight gain

Glinides stimulate the pancreas to secrete more insulin. They're faster acting than sulfonylureas, and the duration of their effect in the body is shorter. Examples include repaglinide and nateglinide. Possible side effects include:

  • Low blood sugar
  • Weight gain

Thiazolidinediones make the body's tissues more sensitive to insulin. Examples include rosiglitazone (Avandia) and pioglitazone (Actos). Possible side effects include:

  • Risk of congestive heart failure
  • Risk of bladder cancer (pioglitazone)
  • Risk of bone fractures
  • High cholesterol (rosiglitazone)
  • Weight gain

DPP-4 inhibitors help reduce blood sugar levels but tend to have a very modest effect. Examples include sitagliptin (Januvia), saxagliptin (Onglyza) and linagliptin (Tradjenta). Possible side effects include:

  • Risk of pancreatitis
  • Joint pain

GLP-1 receptor agonists are injectable medications that slow digestion and help lower blood sugar levels. Their use is often associated with weight loss, and some may reduce the risk of heart attack and stroke. Examples include exenatide (Byetta, Bydureon), liraglutide (Saxenda, Victoza) and semaglutide (Rybelsus, Ozempic). Possible side effects include:

  • Risk of pancreatitis
  • Nausea
  • Vomiting
  • Diarrhea

SGLT2 inhibitors affect the blood-filtering functions in your kidneys by inhibiting the return of glucose to the bloodstream. As a result, glucose is excreted in the urine. These drugs may reduce the risk of heart attack and stroke in people with a high risk of those conditions. Examples include canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance). Possible side effects include:

  • Risk of amputation (canagliflozin)
  • Risk of bone fractures (canagliflozin)
  • Risk of gangrene
  • Vaginal yeast infections
  • Urinary tract infections
  • Low blood pressure
  • High cholesterol

Other medications your doctor might prescribe in addition to diabetes medications include blood pressure and cholesterol-lowering medications, as well as low-dose aspirin, to help prevent heart and blood vessel disease.

Insulin therapy

Some people who have type 2 diabetes need insulin therapy. In the past, insulin therapy was used as a last resort, but today it may be prescribed sooner if blood sugar targets aren't met with lifestyle changes and other medications.

Different types of insulin vary on how quickly they begin to work and how long they have an effect. Long-acting insulin, for example, is designed to work overnight or throughout the day to keep blood sugar levels stable. Short-acting insulin might be used at mealtime.

Your doctor will determine what type of insulin is appropriate for you and when you should take it. Your insulin type, dosage and schedule may change depending on how stable your blood sugar levels are. Most types of insulin are taken by injection.

Side effects of insulin include the risk of low blood sugar (hypoglycemia), diabetic ketoacidosis and high triglycerides.

Weight-loss surgery

Weight-loss surgery changes the shape and function of your digestive system. This surgery may help you lose weight and manage type 2 diabetes and other conditions related to obesity. There are various surgical procedures, but all of them help you lose weight by limiting how much food you can eat. Some procedures also limit the amount of nutrients you can absorb.

Weight-loss surgery is only one part of an overall treatment plan. Your treatment will also include diet and nutritional supplement guidelines, exercise and mental health care.

Generally, weight-loss surgery may be an option for adults living with type 2 diabetes who have a body mass index (BMI) of 35 or higher. BMI is a formula that uses weight and height to estimate body fat. Depending on the severity of diabetes or comorbid conditions, surgery may be an option for someone with a BMI lower than 35.

Weight-loss surgery requires a lifelong commitment to lifestyle changes. Long-term side effects include nutritional deficiencies and osteoporosis.


Women with type 2 diabetes will likely need to change their treatment plans and adhere to diets that carefully controls carbohydrate intake. Many women will need insulin therapy during pregnancy and may need to discontinue other treatments, such as blood pressure medications.

There is an increased risk during pregnancy of developing diabetic retinopathy or a worsening of the condition. If you are pregnant or planning a pregnancy, visit an ophthalmologist during each trimester of your pregnancy, one year postpartum or as advised.

Signs of trouble

Regularly monitoring your blood sugar levels is important to avoid severe complications. Also, be aware of signs and symptoms that may suggest irregular blood sugar levels and the need for immediate care:

High blood sugar (hyperglycemia). Eating certain foods or too much food, being sick, or not taking medications at the right time can cause high blood sugar. Signs and symptoms include:

  • Frequent urination
  • Increased thirst
  • Dry mouth
  • Blurred vision
  • Fatigue
  • Headache

Hyperglycemic hyperosmolar nonketotic syndrome (HHNS). This life-threatening condition includes a blood sugar reading higher than 600 mg/dL (33.3 mmol/L). HHNS may be more likely if you have an infection, are not taking medicines as prescribed, or take certain steroids or drugs that cause frequent urination. Signs and symptoms include:

  • Dry mouth
  • Extreme thirst
  • Drowsiness
  • Confusion
  • Dark urine
  • Seizures

Diabetic ketoacidosis. Diabetic ketoacidosis occurs when a lack of insulin results in the body breaking down fat for fuel rather than sugar. This results in a buildup of acids called ketones in the bloodstream. Triggers of diabetic ketoacidosis include certain illnesses, pregnancy, trauma and medications — including the diabetes medications called SGLT2 inhibitors.

Although diabetic ketoacidosis is usually less severe in type 2 diabetes, the toxicity of the acids can be life-threatening. In addition to the signs and symptoms of hypoglycemia, such as frequent urination and increased thirst, ketoacidosis may result in:

  • Nausea
  • Vomiting
  • Abdominal pain
  • Shortness of breath
  • Fruity-smelling breath

Low blood sugar. If your blood sugar level drops below your target range, it's known as low blood sugar (hypoglycemia). Your blood sugar level can drop for many reasons, including skipping a meal, unintentionally taking more medication than usual or being more physical activity than usual. Signs and symptoms include:

  • Sweating
  • Shakiness
  • Weakness
  • Hunger
  • Irritability
  • Dizziness
  • Headache
  • Blurred vision
  • Heart palpitations
  • Slurred speech
  • Drowsiness
  • Confusion

If you have signs or symptoms of low blood sugar, drink or eat something that will quickly raise your blood sugar level — fruit juice, glucose tablets, hard candy or another source of sugar. Retest your blood in 15 minutes. If levels are not at your target, repeat the sugar intake. Eat a meal after levels return to normal.

If you lose consciousness, you will need to be given an emergency injection of glucagon, a hormone that stimulates the release of sugar into the blood.

More Information

  • Medications for type 2 diabetes
  • GLP-1 agonists: Diabetes drugs and weight loss
  • Bariatric surgery
  • Endoscopic sleeve gastroplasty
  • Gastric bypass (Roux-en-Y)

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Lifestyle and home remedies

Careful management of type 2 diabetes can reduce your risk of serious — even life-threatening — complications. Consider these tips:

  • Commit to managing your diabetes. Learn all you can about type 2 diabetes. Make healthy eating and physical activity part of your daily routine.
  • Work with your team. Establish a relationship with a diabetes educator, and ask your diabetes treatment team for help when you need it.
  • Identify yourself. Wear a necklace or bracelet that says you are living with diabetes, especially if you take insulin or other blood sugar-lowering medication.
  • Schedule a yearly physical exam and regular eye exams. Your regular diabetes checkups aren't meant to replace regular physicals or routine eye exams.
  • Keep your vaccinations up to date. High blood sugar can weaken your immune system. Get a flu shot every year. Your health care provider may also recommend the pneumonia vaccine. The Centers for Disease Control and Prevention (CDC) also recommends the hepatitis B vaccination if you haven't previously received this vaccine and you're 19 to 59 years old.
  • Take care of your teeth. Diabetes may leave you prone to more-serious gum infections. Brush and floss your teeth regularly and schedule recommended dental exams. Consult your dentist right away if your gums bleed or look red or swollen.
  • Pay attention to your feet. Wash your feet daily in lukewarm water, dry them gently, especially between the toes, and moisturize them with lotion. Check your feet every day for blisters, cuts, sores, redness and swelling. Consult your health care provider if you have a sore or other foot problem that isn't healing.
  • Keep your blood pressure and cholesterol under control. Eating healthy foods and exercising regularly can go a long way toward controlling high blood pressure and cholesterol. Take medication as prescribed.
  • If you smoke or use other types of tobacco, ask your health care provider to help you quit. Smoking increases your risk of various diabetes complications. Talk to your health care provider about ways to stop smoking tobacco.
  • Use alcohol sparingly. Depending on the type of drink, alcohol may lower or raise blood sugar levels. If you choose to drink alcohol, only do so with a meal. The recommendation is no more than one drink daily for women and no more than two drinks daily for men. Check your blood sugar frequently after consuming alcohol.

More Information

  • Caffeine: Does it affect blood sugar?

Alternative medicine

Many alternative medicine treatments claim to help people living with diabetes. According to the National Center for Complementary and Integrative Health, studies haven't provided enough evidence to recommend any alternative therapies for blood sugar management. Research has shown the following results about popular supplements for type 2 diabetes:

  • Chromium supplements have been shown to have few or no benefits. Large doses can result in kidney damage, muscular problems and skin reactions.
  • Magnesium supplements have shown benefits for blood sugar control in some but not all studies. Side effects include diarrhea and cramping. Very large doses — more than 5,000 mg a day — can be fatal.
  • Cinnamon, in some studies, has lowered fasting glucose levels but not A1C levels. Therefore, there's no evidence of overall improved glucose management. Most cinnamon contains a substance called coumarin that may cause or worsen liver disease.

Talk to your doctor before starting a dietary supplement or natural remedy. Do not replace your prescribed diabetes medication with alternative medicines.

Coping and support

Type 2 diabetes is a serious disease, and following your diabetes treatment plan takes round-the-clock commitment. To meet the demands of diabetes management, you may need a good support network.

Anxiety and depression are common in people living with diabetes. Talking to a counselor or therapist may help you cope with the lifestyle changes or stressors that come with a type 2 diabetes diagnosis.

Support groups can be good sources of diabetes education, emotional support, and helpful information, such as how to find local resources or where to find carbohydrate counts for a favorite restaurant. If you're interested, your health care provider may be able to recommend a group in your area.

You can visit the American Diabetes Association website to check out local activities and support groups for people living with type 2 diabetes. The American Diabetes Association also offers online information and online forums where you can chat with others who are living with diabetes. You can also call the organization at 800-DIABETES (800-342-2383).

Preparing for your appointment

Keeping your annual wellness visits enables your health care provider to screen for diabetes and to monitor and treat conditions that increase your risk of diabetes — such as high blood pressure, high cholesterol or a high BMI.

If you are seeing your health care provider because of symptoms that may be related to diabetes, you can prepare for your appointment by being ready to answer the following questions:

  • When did your symptoms begin?
  • Does anything improve the symptoms or worsen the symptoms?
  • What medicines do you take regularly, including dietary supplements and herbal remedies?
  • What are your typical daily meals? Do you eat between meals or before bedtime?
  • How much alcohol do you drink?
  • How much daily exercise do you get?
  • Is there a history of diabetes in your family?

If you are diagnosed with diabetes, your health care provider will begin a treatment plan. You may be referred to a doctor who specializes in hormonal disorders (endocrinologist). Your care team may also include the following specialists:

  • Dietitian
  • Certified diabetes educator
  • Foot doctor (podiatrist)
  • Doctor who specializes in eye care (ophthalmologist)

Talk to your health care provider about referrals to other specialists who will be providing care.

Questions for ongoing appointments

Before any appointment with a member of your treatment team, make sure you know whether there are any restrictions, such as fasting before taking a test. Questions that you should regularly review with your doctor or other members of the team include:

  • How often do I need to monitor my blood sugar, and what is my target range?
  • What changes in my diet would help me better manage my blood sugar?
  • What is the right dosage for prescribed medications?
  • When do I take the medications? Do I take them with food?
  • How is management of diabetes affecting treatment for other conditions? How can I better coordinate treatments or care?
  • When do I need to make a follow-up appointment?
  • Under what conditions should I call you or seek emergency care?
  • Are there brochures or online sources you recommend?
  • Are there resources available if I'm having trouble paying for diabetes supplies?

What to expect from your doctor

Your provider is likely to ask you a number of questions at regularly scheduled appointments, including:

  • Do you understand your treatment plan and feel confident you can follow it?
  • How are you coping with diabetes?
  • Have you experienced any low blood sugar?
  • Do you know what to do if your blood sugar is too low or too high?
  • What's a typical day's diet like?
  • Are you exercising? If so, what type of exercise? How often?
  • Do you sit for long periods of time?
  • What challenges are you experiencing in managing your diabetes?

By Mayo Clinic Staff

Metformin: Current knowledge - PMC

1. Scheen AJ, Paquot N. Metformin revisited: A critical review of the benefit-risk balance in at-risk patients with type 2 diabetes. Diabetes Metab. 2013;39:179–90. [PubMed] [Google Scholar]

2. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: An update. Ann Intern Med. 2002;137:25–33. [PubMed] [Google Scholar]

3. Hundal RS, Inzucchi SE. Metformin: New understandings, new uses. Drugs. 2003;63:1879–94. [PubMed] [Google Scholar]

4. Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res. 2008;5:157–67. [PubMed] [Google Scholar]

5. Rafieian-Kopaei M, Baradaran A. Combination of metformin with other antioxidants may increase its renoprotective efficacy. J Ren Inj Prev. 2013;2:35–6. [PMC free article] [PubMed] [Google Scholar]

6. Seo-Mayer PW, Thulin G, Zhang L, Alves DS, Ardito T, Kashgarian M, et al. Preactivation of AMPK by metformin may ameliorate the epithelial cell damage caused by renal ischemia. Am J Physiol Renal Physiol. 2011;301:F1346–57. [PMC free article] [PubMed] [Google Scholar]

7. Sung JY, Choi HC. Metformin-induced AMP-activated protein kinase activation regulates phenylephrine-mediated contraction of rat aorta. Biochem Biophys Res Commun. 2012;421:599–604. [PubMed] [Google Scholar]

8. Rosen P, Wiernsperger NF. Metformin delays the manifestation of diabetes and vascular dysfunction in Goto-Kakizaki rats by reduction of mitochondrial oxidative stress. Diabetes Metab Res Rev. 2006;22:323–30. [PubMed] [Google Scholar]

9. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352:854–65. [PubMed] [Google Scholar]

10. Nasri H. On the occasion of the world diabetes day2013; Diabetes education and prevention; a nephrology point of view. J Ren Inj Prev. 2013;2:31–2. [PMC free article] [PubMed] [Google Scholar]

11. Tertti K, Ekblad U, Vahlberg T, Rönnemaa T. Comparison of metformin and insulin in the treatment of gestational diabetes: A retrospective, case-control study. Rev Diabet Stud. 2008;5:95–101. [PMC free article] [PubMed] [Google Scholar]

12. Balani J, Hyer SL, Rodin DA, Shehata H. Pregnancy outcomes in women with gestational diabetes treated with metformin or insulin: A case-control study. Diabet Med. 2009;26:798–802. [PubMed] [Google Scholar]

13. Cheung NW. The management of gestational diabetes. Vasc Health Risk Manag. 2009;5:153–64. [PMC free article] [PubMed] [Google Scholar]

14. Kidson W. Polycystic ovary syndrome: A new direction in treatment. Med J Aust. 1998;169:537–40. [PubMed] [Google Scholar]

15. National Collaborating Centre for Women's and Children's Health. Fertility: Assessment and treatment for people with fertility problems. London: Royal College of Obstetricians and Gynaecologists. 2004;97:58–9. [Google Scholar]

16. Balen A. Royal college of Obstetricians and Gynaecologists. Metformin therapy for the management of infertility in women with polycystic ovary syndrome. [Last cited on 2009];2008 Dec;:12–3. [Google Scholar]

17. The Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23:462–77. [PubMed] [Google Scholar]

18. Palomba S, Pasquali R, Orio F, Jr, Nestler JE. Clomiphene citrate, metformin or both as first-step approach in treating anovulatory infertility in patients with polycystic ovary syndrome (PCOS): A systematic review of head-to-head randomized controlled studies and meta-analysis. Clin Endocrinol (Oxf) 2009;70:311–21. [PubMed] [Google Scholar]

19. Al-Inany H, Johnson N. Drugs for an ovulatory infertility in polycystic ovary syndrome. BMJ. 2006;332:1461–2. [PMC free article] [PubMed] [Google Scholar]

20. Tang T, Lord JM, Norman RJ, Yasmin E, Balen AH. Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, D-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst Rev. 2009:CD003053. [PubMed] [Google Scholar]

21. Radosh L. Drug treatments for polycystic ovary syndrome. Am Fam Physician. 2009;79:671–6. [PubMed] [Google Scholar]

22. Palomba S, Orio F, Falbo A, Russo T, Tolino A, Zullo F. Clomiphene citrate versus metformin as first-line approach for the treatment of anovulation in infertile patients with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92:3498–503. [PubMed] [Google Scholar]

23. Li D, Yeung SC, Hassan MM, Konopleva M, Abbruzzese JL. Antidiabetic therapies affect risk of pancreatic cancer. Gastroenterology. 2009;137:482–8. [PMC free article] [PubMed] [Google Scholar]

24. Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. BMJ. 2005;330:1304–5. [PMC free article] [PubMed] [Google Scholar]

25. Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: A cohort study among people with type 2 diabetes. Diabetes Care. 2009;32:1620–5. [PMC free article] [PubMed] [Google Scholar]

26. Chong CR, Chabner BA. Mysterious metformin. Oncologist. 2009;14:1178–81. [PubMed] [Google Scholar]

27. Ben Sahra I, Le Marchand Brustel Y, Tanti JF, Bost F. Metformin in cancer therapy: A new perspective for an old antidiabetic drug? Mol Cancer Ther. 2010;9:1092–9. [PubMed] [Google Scholar]

28. Esteghamati A, Eskandari D, Mirmiranpour H, Noshad S, Mousavizadeh M, Hedayati M, et al. Effects of metformin on markers of oxidative stress and antioxidant reserve in patients with newly diagnosed type 2 diabetes: A randomized clinical trial. Clin Nutr. 2013;32:179–85. [PubMed] [Google Scholar]

29. Shirzad H, Shahrani M, Rafieian-Kopaei M. Comparison of morphine and tramadol effects on phagocytic activity of mice peritoneal phagocytes in vivo. Int Immunopharmacol. 2009;9:968–70. [PubMed] [Google Scholar]

30. Shirzad M, Kordyazdi R, Shahinfard N, Nikokar M. Does royal jelly affect tumor cells? J HerbMed Plarmacol. 2013;2:45–8. [Google Scholar]

31. Shirzad H, Kiani M, Shirzad M. Impacts of tomato extract on the mice fibrosarcoma cells. J HerbMed Pharmacol. 2013;2:13–6. [Google Scholar]

32. Shirzad H, Taji F, Rafieian-Kopaei M. Correlation between antioxidant activity of garlic extracts and WEHI-164 fibrosarcoma tumor growth in BALB/c mice. J Med Food. 2011;14:969–74. [PubMed] [Google Scholar]

33. Rafieian-Kopaei M. Medicinal plants and the human needs. J Herb Med Plarmacol. 2012;1:1–2. [Google Scholar]

34. Nasri H, Rafieian-Kopaei M. Metformin improves diabetic kidney disease. J Nephropharmacol. 2012;1:1–2. [PMC free article] [PubMed] [Google Scholar]

35. Nayer A, Ortega LM. Catastrophic antiphospholipid syndrome: A clinical review. J Nephropathol. 2014;3:9–17. [PMC free article] [PubMed] [Google Scholar]

36. Carr A, Samaras K, Thorisdottir A, Kaufmann GR, Chisholm DJ, Cooper DA. Diagnosis, prediction and natural course of HIV-1 protease-inhibitor-associated li- podystrophy, hyperlipidemia, and diabetes mellitus: A cohort study. Lancet. 1999;353:2093–9. [PubMed] [Google Scholar]

37. Shahbazian H. World diabetes day; 2013. J Ren Inj Prev. 2013;2:123–4. [PMC free article] [PubMed] [Google Scholar]

38. Murata H, Hruz PW, Mueckler M. The mechanism of insulin resistance caused by HIV protease inhibitor therapy. J Biol Chem. 2000;275:20251–4. [PubMed] [Google Scholar]

39. Saint-Marc T, Touraine JL. Effects of metformin on insulin resistance and central adiposity in patients receiving effective protease inhibitor therapy. AIDS. 1999;13:1000–2. [PubMed] [Google Scholar]

40. Rafieian-Kopaei M, Nasri H. Ginger and diabetic nephropathy. J Ren Inj Prev. 2012;2:9–10. [PMC free article] [PubMed] [Google Scholar]

41. Baradaran A. Lipoprotein (a), type 2 diabetes and nephropathy; the mystery continues. J Nephropathol. 2012;1:126–9. [PMC free article] [PubMed] [Google Scholar]

42. Nasri H. Renoprotective effects of garlic. J Ren Inj Prev. 2012;2:27–8. [PMC free article] [PubMed] [Google Scholar]

43. Nasri H, Behradmanesh S, Maghsoudi AR, Ahmadi A, Nasri P, Rafieian-Kopaei M. Efficacy of supplementary vitamin D on improvement of glycemic parameters in patients with type 2 diabetes mellitus: A randomized double blind clinical trial. J Ren Inj Prev. 2014;3:31–4. [PMC free article] [PubMed] [Google Scholar]

44. Tavafi M. Complexity of diabetic nephropathy pathogenesis and design of investigations. J Ren Inj Prev. 2013;2:61–5. [PMC free article] [PubMed] [Google Scholar]

45. Behradmanesh S, Nasri P. Serum cholesterol and LDL-C in association with level of diastolic blood pressure in type 2 diabetic patients. J Ren Inj Prev. 2012;1:23–6. [PMC free article] [PubMed] [Google Scholar]

46. Rahimi Z. ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy. J Nephropathol. 2012;1:143–51. [PMC free article] [PubMed] [Google Scholar]

47. Nasri H. Comment on: Serum cholesterol and LDL-C in association with level of diastolic blood pressure in type 2 diabetic patients. J Ren Inj Prev. 2012;1:13–4. [PMC free article] [PubMed] [Google Scholar]

48. Nasri H. Acute kidney injury and beyond. J Ren Inj Prev. 2012;21:1–2. [PMC free article] [PubMed] [Google Scholar]

49. Rouhi H, Ganji F. Effect of N-acetyl cysteine on serum Lipoprotein (a) and proteinuria in type 2 diabetic patients. J Nephropathol. 2013;2:61–6. [PMC free article] [PubMed] [Google Scholar]

50. Tavafi M. Diabetic nephropathy and antioxidants. J Nephropathol. 2013;2:20–7. [PMC free article] [PubMed] [Google Scholar]

51. Behradmanesh S, Derees F, Rafieian-kopaei M. Effect of Salvia officinalis on diabetic patients. J Ren Inj Prev. 2013;2:57–9. [PMC free article] [PubMed] [Google Scholar]

52. Kadkhodaee M, Sedaghat Z. Novel renoprotection methods by local and remote conditioning. J Ren Inj Prev. 2014;3:37–8. [PMC free article] [PubMed] [Google Scholar]

53. Tavafi M. Protection of renal tubules against gentamicin induced nephrotoxicity. J Ren Inj Prev. 2012;2:5–6. [PMC free article] [PubMed] [Google Scholar]

54. Gheissari A. Acute kidney injury and renal angina. J Ren Inj Prev. 2013;2:33–4. [PMC free article] [PubMed] [Google Scholar]

55. Nasri H. Preventive role of erythropoietin against aminoglycoside renal toxicity induced nephropathy; Current knowledge and new concepts. J Ren Inj Prev. 2012;2:29–30. [PMC free article] [PubMed] [Google Scholar]

56. Nematbakhsh M, Ashrafi F, Pezeshki Z, Fatahi Z, Kianpoor F, Sanei MH, et al. A histopathological study of nephrotoxicity, hepatoxicity or testicular toxicity: Which one is the first observation as side effect of Cisplatin-induced toxicity in animal model. J Nephropathol. 2012;1:190–3. [PMC free article] [PubMed] [Google Scholar]

57. Cadenas E, Boveris A, Ragan CI, Stoppani AO. Production of superoxide radicals and hydrogen peroxide by NADH-ubiquinone reductase and ubiquinol-cytochrome c reductase from beef-heart mitochondria. Arch Biochem Biophys. 1977;180:248–57. [PubMed] [Google Scholar]

58. Rafieian-Kopaie M, Baradaran A. Plants antioxidants: From laboratory to clinic. J Nephropathol. 2013;2:152–3. [PMC free article] [PubMed] [Google Scholar]

59. Baradaran A, Mahmoud Rafieian-Kopaei M. Histopathological study of the combination of metformin and garlic juice for the attenuation of gentamicin renal toxicity in rats. J Ren Inj Prev. 2012;2:15–21. [PMC free article] [PubMed] [Google Scholar]

60. Hernandez GT, Nasri H. World Kidney Day 2014: Increasing awareness of chronic kidney disease and aging. J Ren Inj Prev. 2014;3:3–4. [PMC free article] [PubMed] [Google Scholar]

61. Amini FG, Rafieian-Kopaei M, Nematbakhsh M, Baradaran A, Nasri H. Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats. J Res Med Sci. 2012;17:621–5. [PMC free article] [PubMed] [Google Scholar]

62. Rafieian-Kopaei M, Baradaran A. Teucrium polium and kidney. J Ren Inj Prev. 2012;2:3–4. [PMC free article] [PubMed] [Google Scholar]

63. Tolouian R, Hernandez G. Prediction of diabetic nephropathy: The need for a sweet biomarker. J Nephropathol. 2013;2:4–5. [PMC free article] [PubMed] [Google Scholar]

64. Piwkowska A, Rogacka D, Jankowski M, Dominiczak MH, Stepinski JK, Angielski S. Metformin induces suppression of NAD(P)H oxidase activity in podocytes. Biochem Biophys Res Commun. 2010;393:268–73. [PubMed] [Google Scholar]

65. Merriwether DA, Clark AG, Ballinger SW, Schurr TG, Soodyall H, Jenkins T, et al. The structure of human mitochondrial DNA variation. J Mol Evol. 1991;33:543–55. [PubMed] [Google Scholar]

66. Suzuki S, Hinokio Y, Komatu K, Ohtomo M, Onoda M, Hirai S, et al. Oxidative damage to mitochondrial DNA and its relationship to diabetic complications. Diabetes Res Clin Pract. 1999;45:161–8. [PubMed] [Google Scholar]

67. Kim J, Shon E, Kim CS, Kim JS. Renal podocyte injury in a rat model of type 2 diabetes is prevented by metformin. Exp Diabetes Res 2012. 2012:210821. [PMC free article] [PubMed] [Google Scholar]

68. Liu Z, Li J, Zeng Z, Liu M, Wang M. The antidiabetic effects of cysteinyl metformin, a newly synthesized agent, in alloxan- and streptozocin-induced diabetic rats. Chem Biol Interact. 2008;173:68–75. [PubMed] [Google Scholar]

69. Gheshlaghi F. Toxic renal injury at a glance. J Ren Inj Prev. 2012;1:15–6. [PMC free article] [PubMed] [Google Scholar]

70. Gheissari A, Hemmatzadeh S, Merrikhi A, Fadaei Tehrani S, Madihi Y. Chronic kidney disease in children: A report from a tertiary care center over 11 years. J Nephropathol. 2012;1:177–82. [PMC free article] [PubMed] [Google Scholar]

71. Behradmanesh S, Nasri H. Association of serum calcium with level of blood pressure in type 2 diabetic patients. J Nephropathol. 2013;2:254–7. [PMC free article] [PubMed] [Google Scholar]

72. Kari J. Epidemiology of chronic kidney disease in children. J Nephropathol. 2012;1:162–3. [PMC free article] [PubMed] [Google Scholar]

73. Lalau JD. Lactic acidosis induced by metformin: Incidence, management and prevention. Drug Saf. 2010;33:727–40. [PubMed] [Google Scholar]

74. Scheen AJ. Metformin and lactic acidosis. Acta Clin Belg. 2011;66:329–31. [PubMed] [Google Scholar]

75. Howlett HC, Bailey CJ. A risk-benefit assessment of metformin in type 2 diabetes mellitus. Drug Saf. 1999;20:489–503. [PubMed] [Google Scholar]

76. Emslie-Smith AM, Boyle DI, Evans JM, Sullivan F, Morris AD. DARTS/MEMO Collaboration. Con-traindications to metformin therapy in patients with Type 2 diabetes-a population-based study of adherence to prescribing guidelines. Diabet Med. 2001;18:483–8. [PubMed] [Google Scholar]

77. Sulkin TV, Bosman D, Krentz AJ. Contraindications to metformin therapy in patients with NIDDM. Diabetes Care. 1997;20:925–8. [PubMed] [Google Scholar]

78. Holstein A, Nahrwold D, Hinze S, Egberts EH. Contraindications to metformin therapy are largely disregarded. Diabet Med. 1999;16:692–6. [PubMed] [Google Scholar]

79. Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mel-litus. Cochrane Database Syst Rev. 2010 [PubMed] [Google Scholar]

80. Mardani S, Nasri H, Hajian S, Ahmadi A, Kazemi R, Rafieian-Kopaei M. Impact of Momordica charantia extract on kidney function and structure in mice. J Nephropathol. 2014;3:35–40. [PMC free article] [PubMed] [Google Scholar]

81. Roussel R, Travert F, Pasquet B, Wilson PW, Smith SC, Jr, Goto S, et al. Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med. 2010;170:1892–9. [PubMed] [Google Scholar]

82. Isoherranen M, Thummel KE. Drug metabolism and transport during pregnancy: How does drug disposition change during pregnancy and what are the mechanisms that cause such changes? Drug Metab Dispos. 2013;41:256–62. [PMC free article] [PubMed] [Google Scholar]

83. Eyal S, Easterling TR, Carr D, Umans JG, Miodovnik M, Hankins GD, et al. Pharmacokinetics of metformin during pregnancy. Drug Metab Dispos. 2010;38:833–40. [PMC free article] [PubMed] [Google Scholar]

84. Lautatzis ME, Goulis DG, Vrontakis M. Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: A systematic review. Metab Clin Exp. 2013;62:1522–34. [PubMed] [Google Scholar]

85. Ardalan MR, Rafieian-Kopaie M. Antioxidant supplementation in hypertension. J Ren Inj Prev. 2014;3:39–40. [PMC free article] [PubMed] [Google Scholar]

86. The Endocrine Society. Diagnosis and Treatment of Polycystic Ovary Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2013:2013–350. [PMC free article] [PubMed] [Google Scholar]

87. Tamadon MR, Baradaran A, Rafieian-Kopaei M. Antioxidant and kidney protection; differential impacts of single and whole natural antioxidants. J Ren Inj Prev. 2014;3:41–2. [PMC free article] [PubMed] [Google Scholar]

88. Nasri H, Behradmanesh S, Ahmadi A, Rafieian-Kopaei M. Impact of oral vitamin D (cholecalciferol) replacement therapy on blood pressure in type 2 diabetes patients: A randomized, double-blind, placebo controlled clinical trial. J Nephropathol. 2014;3:29–33. [PMC free article] [PubMed] [Google Scholar]

89. Pickering JW, Endre ZH. The definition and detection of acute kidney injury. J Ren Inj Prev. 2014;3:21–5. [PMC free article] [PubMed] [Google Scholar]

90. Blumer I, Hadar E, Hadden DR, Jovanoviè L, Mestman JH, Murad MH, et al. Diabetes and pregnancy: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98:4227–49. [PMC free article] [PubMed] [Google Scholar]

Basic principles of therapy for type 2 diabetes | Dedov

Most patients with diabetes mellitus (DM) 2 types are chronically in a state decompensation of carbohydrate metabolism, which accelerates the pace of development and progress l macro- and microvascular complications leading to to a decrease in the quality of life, premature disability and death of patients. Analysis reasons for this phenomenon showed that when selecting therapy is not always taken into account all known links in the pathogenesis of type 2 diabetes. Concerning the vast majority of patients receive only monotherapy with one or another oral hypoglycemic drug (PSSP). cup sulfonylurea derivatives (PSM). Except In addition, in some cases, the lack of strict control and self-monitoring of the state of carbohydrate metabolism in combined with an increased thirst threshold in long-term support in old age illusion of relative well-being, which hinders the adoption of decisive measures aimed at to optimize treatment. In other cases, even with regular glycemic control, patients. and often doctors, ignore the discovered unsatisfactory indicators of the status of carbohydrate exchange and change therapy only in those cases when glycemia exceeds recommended values by 50% or more. Finally, if there is no effect from ongoing therapy, despite the appointment maximum daily doses of PSSP, insulin therapy is either not prescribed at all, or significantly later than is actually necessary. Instead of additions to ongoing insulin therapy are made attempts to achieve state compensation carbohydrate metabolism by further increasing daily dose of PSSP or a combination of the two various PSM.

In the pathogenesis of atherosclerosis in type 2 diabetes, an important well-known risk factors play a role: arterial hypertension, dyslipidemia, central obesity, insulin resistance, hyperinsulinemia, impaired fibrinolysis, smoking and hyperglycemia [eleven]. Multicenter studies have shown direct correlation between decompensation SD, i.e. hyperglycemia, and progression of atherosclerosis. Therefore, the normalization of carbohydrate metabolism is an important link in the fight against macrovascular complications in this disease [9, ten].

It is known that one of the compensation criteria Type 2 diabetes is a fasting glucose below 6.1 mmol/l and below 8.0 mmol/l after meals. In the same time It is widely believed that older people age compensation criteria may be less stringent given the risk of hypoglycemia poorly recognized by such patients [3]. However, there is no doubt that the decompensation of diabetes mellitus in senile persons age activates catabolic processes, predisposes to the development of acute and accelerates the progression of late complications of diabetes mellitus. Ten-year follow-up of elderly patients, suffering from type 2 diabetes, showed that with decompensation diseases, the incidence of stroke and cardiovascular disease increases dramatically regardless of on the duration of the disease [5]. Wherein mortality from these causes is progressively increasing with an increase in HbA|C from 8.7 to 9.1% [7, 8].

Analysis of literature data and own experience in achieving compensation of the disease in patients with diabetes 2 types allows us to note the following. priority positions when choosing individual criteria for compensation of carbohydrate metabolism, regardless from the age of the patient, are saved the patient's intelligence, the presence of his individual means of self-control and the necessary amount of knowledge, ensuring the adoption of adequate decisions in emergency and everyday situations. In the presence of the aforementioned conditions, and in the absence of with a history of acute cerebrovascular accident and unstable angina strive to achieve sugar compensation diabetes according to the recommendations of the European N1DDM Policy Group (see table). In other cases in the presence of limiting circumstances it is possible to achieve levels of glycemia and glycated hemoglobin corresponding to the state subcompensation. In any case, a prerequisite therapy, as shown above, is compensation of carbohydrate metabolism.

Achievement of carbohydrate state compensation exchange should be carried out in stages. So, at the first stage, all patients should be eliminated decompensation of diabetes mellitus, i.e. ensure fasting glycemia <7.8 mmol/l, and 2 hours after food intake - < 10.0 mmol / l. At the second stage to achieve stable glycemia corresponding to the state of subcompensation of diabetes mellitus, namely, glycemia on the natoshak 6. 1-7.8 mmol / l, and after food - 8.0-9.5 mmol/l. It is at this stage of therapy the issue of individual criteria should be resolved compensation of carbohydrate metabolism in everyone specific patient. Deciding to achieve in a patient, compensation for diabetes means a transition to the third stage of treatment, which is usually accompanied by more intensive therapy.

Currently in the treatment of patients with type 2 diabetes type use diet, exercise, derivatives sulfonylureas, metformin, inhibitors β-glucosidase and insulin therapy. Extension knowledge about the pathogenesis of type 2 diabetes and the impact of those or other hypoglycemic measures for disease has now made it possible to reconsider the role of each of them in achieving compensation diseases.

Subcaloric diet and exercise are key to successful diabetes management diabetes in general and type 2 diabetes in particular. So, even minor physical activity, corresponding to daily walking in the amount of 10,000 steps lead to a significant reduction in insulin resistance (IR) and improved utilization glucose in muscle tissue. subcaloric diet with leads to weight loss over time which reduces the available IR and provides glucose uptake by tissues. Carbohydrate restriction in general and refined, in particular, prevents postprandial hyperglycemia and contributes to the normalization of glycemia during the day. However, in the presence of visceral obesity, usually occurring in patients with type 2 diabetes, diet unable to significantly reduce night production glucose by the liver and thus reduce morning hyperglycemia. In case of impossibility achieve the desired glycemia on an empty stomach against the background of monotherapy with a diet, regardless of the duration disease, consideration should be given to adding to the treatment of certain hypoglycemic drugs. It has now been proven that fasting hyperglycemia is not only important pathogenetic factor in the development of atherosclerosis with type 2 diabetes, but also the main link that violates secretion of insulin due to the provision of glucose toxicity to β-cells. So, in the study UK.PDS (6-year Follow Up) has been shown to over time with any therapy functional the ability of β-cells is depleted, however, the greatest decreased own secretion of insulin during the first 6 years of the disease was observed in group of patients who were on diet monotherapy, unable for the most part cases to ensure normoglycemia on the stomach [6].

The elimination of hyperglycemia in the morning is an extremely important link in the complex of measures, aimed at improving the state of carbohydrate metabolism. Chronic hyperglycemia on the stomach is one of the earliest and most permanent laboratory signs of type 2 diabetes. Proof the presence of such a phenomenon as glucose toxicity, leading over time to a violation functions of β-cells, forced to change the view on hyperglycemia only as a marker of diabetes mellitus. Currently, hyperglycemia in general and on the stomach. in particular, considered as the most important link in the pathogenesis of type 2 diabetes, risk factor for development atherosclerosis and as an independent phenomenon, impeding compensation of this disease. This fact dictates the need achieve and maintain normal or level of glycemia close to it on an empty stomach and during days [1, 4].

In the presence of peripheral IR, significant fluctuations in fasting blood glucose levels. Islets of Langerhans are very sensitive to these changes and normally respond immediately on them by an increase in insulin production and a decrease glucagon production. Studies of basal and stimulated insulin secretion in patients Type 2 diabetes clearly indicates the presence of symptoms relative hormone deficiency. So, in particular, the fact of insufficient basal secretion has been proven insulin at night, despite the presence hyperinsulinemia. At the same time, the magnitude of the insulin secretory defect directly correlates with the degree fasting hyperglycemia. So. in the morning glycemia below threshold basal insulinemia and insulin secretory response to various stimuli practically do not differ from the norm. However, when presence of hyperglycemia on the stomach stimulation of β-cells glucose to a greater extent and arginine to a lesser extent degree immediately reveals significant violations insulin response. From a clinical point of view This phenomenon means that in the presence of hyperglycemia Natoshak insulin secretory response of cells to stimulation with sulfonylurea derivatives during the subsequent period of time, those. in the morning, at least it will turn out insufficient, and the achievement of compensation for the disease will be practically impossible. certain role in maintaining fasting hyperglycemia in type 2 diabetes, it is attributed to a violation of glucagon secretion, which is manifested by the inability of β-cells suppress glucagon secretion and subsequent hyperglucagonemia. In addition, IR of hepatocytes in combined with impaired insulin secretion leads to relative deficiency of this hormone in liver, which plays an important role in metabolism SJK. Studies have clearly shown that when there is the greatest morning hyperglycemia, and, consequently, the least insulinemia, in the blood of patients with type 2 diabetes, maximum FFA concentration. Introduction to such sick insulin leads to maintenance normoglycemia in the morning and a decrease in the level of FFA, because an adequate amount of insulin suppresses lipolysis and hyperproduction of FFA [6].

FFAs, in turn, play a critical role in worsening insulin resistance and maintaining hyperglycemia in patients with type 2 diabetes. In addition to the above the effects of FFA, it should be noted that the latter have a direct suppressive effect binding and internalization of insulin hepatocytes (lipotoxicity). This in turn enhances peripheral hyperinsulinemia, leads to a decrease in glycogen synthesis and activation gluconeogenesis in the liver.

Thus, it is clear that the consequences of events occurring in the liver at night, expressed hyperglycemia on an empty stomach, to a large extent degrees hinder the achievement of compensation carbohydrate metabolism at least in the future daytime.

It was discussed above why diet and PSM with relative hypoinsulinemia, unable to adequately reduce the increase production of glucose by the liver at night. proceeding of this, the drug of first choice in the absence of contraindication is metformin, prescribed before bedtime. In recent years, it has become known that under the influence of metformin not only increases the affinity of insulin receptors and their conformation changes, but they are also stimulated receptor and post-receptor pathways for the transmission of insulin signal. At the same time, there is an increase effects of insulin responsible for translocation own glucose transporters plasma membrane, resulting in an increase uptake of glucose by the liver, muscle and fat cells. Enhancement of translocation GLUT-1 and GLUT-4, i.e. decrease in existing insulin resistance, closely correlated with admission glucose into cells [2, 14].

The use of metformin contributes to a significant decrease in fasting glycemia due to increase under its influence of sensitivity liver cells to insulin, inhibition in the liver processes of gluconeogenesis and glycogenolysis, and as well as an increase in glycogen synthesis. As a result studies have shown that metformin reduces hepatic glucose production (GWP) by an average of 30%, which leads to a decrease in the level fasting blood glucose. So, it was shown that with a decrease in GWP by 17.6%, fasting glycemia reduced by about 40%. The main mechanism which leads to a decrease in GWP, is the suppression of hepatic gluconeogenesis. Metformin reduces the production of glucose from alanine, pyruvate, lactate, glutamine, and glycerol. it occurs primarily as a result of inhibition intake of the listed substrates of gluconeogenesis into hepatocytes and inhibition of its key enzymes - pyruvate carboxylase, fructose-1,6-biphosphatase and glucose-6-phosphatase. Assign metformin is advisable at bedtime, starting with 500 mg. In case of insufficient reduction in glycemia need to gradually increase the dose drug up to 850-1000 mg. In the absence of the desired effect or if the patient has contraindications to the use of metformin should be considered the question of prescribing before bedtime (at 10 p. m.) a prolonged or combination insulin dose of 0.1 units / kg. To rule out nocturnal hypoglycemia, as well as to address the issue of the rate of increase doses of long-acting insulin sleep requires glycemic control at 3 am. If a glycemia at this time of day is above 10 mmol / l, the dose of insulin at bedtime is immediately increased by 4 units, and if within 6-10 mmol / l, then for 2 units. Daily monitoring required glycemia on the stomach, and every 2-3 days - at 3 am. In this case, it is advisable to reduce the dose of metformin up to 500-850 mg. Normalization of fasting glycemia and decreased production of FFA during insulin therapy eliminates existing glucose and lipotoxicity, which improves insulin secretory ability β-cells and allows you to further refuse from insulin. Combination therapy with metformin and insulin given at bedtime reduces risk of weight gain and reduces the need in exogenous insulin.

In patients with predominant insulin resistance and obesity, metformin should be considered as a drug of first choice and for normalization daytime glycemia. In addition to the above above the effects of the action of this drug, such as a decrease in IR and increased GWP. metformin delays intestinal absorption glucose. When using therapeutic doses of metformin is more likely to occur delayed absorption of carbohydrates, tk. total volume administered labeled glucose is not reduced. Undoubtedly, This effect of metformin plays an important role role in achieving carbohydrate compensation exchange, because "smoothes" the peaks of postprandial hyperglycemia.

Studies have shown that metformin significantly increases the utilization of glucose in the intestine, enhancing anaerobic glycolysis there as in a state of saturation, and on an empty stomach. Most likely, due to increased glucose utilization in the intestine, which exceeds the activity this process in muscles at rest. the greatest Metformin is active in the mucosa lining of the small intestine.

Thus, the action of metformin in the intestine makes a significant contribution to the prevention postprandial rise in glycemia. Yes, clinical observations show that during therapy metformin blood sugar after a meal decreases by an average of 20 - 45%.

The usual daily dose of metformin is 500-1700 mg, and daily - up to 3000 mg. Maximum Saturation with the drug is usually achieved when taking a dose of 3 g. In this regard, the appointment higher doses are considered inappropriate, tk. does not further enhance the antihyperglycemic effect.

If there are contraindications to metformin or an increased risk development of lactic acidosis, in the daytime it is advisable the use of β-glucosidase inhibitors with each write by reception. The drugs of this group inhibit the fermentation of polysaccharides, which slows down the process of absorption of glucose into the blood reduces postprandial hyperglycemia. Given the mechanism of action of β-glucosidase inhibitors, it is clear that they cannot have a significant effect on fasting glycemia.

Unable to achieve the desired level glycemia 2 hours after a meal during treatment metformin indicates a significant violation of insulin secretion by β-cells, its relative scarcity and the need to add PSM to stimulate endogenous secretion hormone.

In the initial stages of the disease, when choosing the type PSM preference should be given to those drugs, who have the lowest risk of developing hypoglycemic conditions (glimepiride, long-acting glipizide, micronized j forms of glibenclamide, gliclazide, gliquidone). At lack of compensation for carbohydrate metabolism after 2 h after eating, it is necessary to prescribe the maximum daily dose of the received PSM, and while maintaining hyperglycemia - replace it with glimepiride, glipizide or glibenclamide, which have the highest affinity for the receptors of ATP-dependent potassium channels of β-cells.

Recently proven successful both new sulfonylurea derivatives and and new forms of known drugs of this hypoglycemic group, namely glimepiride (Amaryl), GITS form of glipizide (Glucotrol XL), micronized forms of glibenclamide (maninil 1.75 and 3.5).

Due to the binding of glimepiride to a protein with molecular weight of 65 Kd on the receptor of ATP-dependent potassium channels of β-cells (all other known PSMs bind to the 140 Kd protein). this drug has a number of pharmacokinetic and pharmacodynamic features that have a positive effect on its performance. Thus, glimepiride interacts with the receptor β-cells 2.5 times faster than glibenclamide, and dissociates with it at 9times faster. This achieves very fast onset of action and low risk of hypoglycemia when you miss, write and exercise. Single use of the drug, providing its required concentration during the day, reduces the chance of missing medication. Wide range of doses of tablet forms glimepiride facilitates the selection of the necessary daily dosage and its intake by patients.

GITS form of glipizide - Glucotrol XL, also has a number of positive properties that distinguish it from traditional. So. special shape tablets provide a gradual intake of the drug into the blood and its constant concentration during days with a single dose. Advantages The pharmacokinetics of glipizide are rapidly the onset of action of the drug after administration. Education in the process of inactivation of glipizide 4 metabolites, do not have a hypoglycemic effect, minimizes the risk of developing hypoglycemic reactions during physical exertion, skipping food and in the elderly [12, 13].

If daytime hyperglycemia persists before breakfast, a prolonged or combined insulin at a dose of 0.1 units / kg with gradual increase in the latter until reaching desired glycemic values. With absence obvious signs of insulin deficiency (progressive weight loss, decrease in basal and stimulated C-peptide, ketoacidosis) appropriate prescribe combination therapy PSM and insulin, the benefits of which are obvious. So, PSM provide the secretion of endogenous insulin directly into the portal vein, synthesis glycogen and decreased gluconeogenesis in the liver, and also reduce postprandial hyperglycemia. Insulin given before breakfast and working during the daytime, reduces the relative deficiency and provides the necessary basal hormone levels, which is manifested by normalization glycemia between meals. Purpose insulin at bedtime suppresses nocturnal production glucose and FFA by the liver and normalizes fasting glycemia. Daily requirement for exogenous insulin in combination therapy (insulin + PSM/metformin) reduced by insulin by 25-50% compared with monotherapy.

Subject to preservation of own secretion insulin should be avoided short action to normalize glycemia after eating first. To a certain degree the role of short-acting insulin can play the very act of eating. The supply of food and digestion is activated by the most important non-glucose stimulators of insulin secretion (acetylcholine, cholecystokinin, glucagon-like peptide-1, gastric inhibitory polypeptide, etc.), which together with PSM is able to provide sufficient the level of hormone secretion required for the utilization of glucose taken with food.

If there are confirmed signs of deficiency insulin or if there is an absolute indication to his prescription for long-acting insulin short-acting insulin added before the main meals, and all PSSPs are canceled.

Prevention of the development of type 2 diabetes Medical On Group Lyubertsy

Diabetes mellitus type 2 (DM2) - an endocrine disease characterized by chronic hyperglycemia (increased blood glucose levels), which is based on predominantly insufficient insulin secretion with impaired insulin action (insulin resistance) or insulin resistance with impaired insulin secretion, or both factor a.

The diagnosis of diabetes mellitus is made at : an increase in the level of glucose in the blood plasma of more than 7.0 mmol / l on an empty stomach and more than 11.1 mmol / l 2 hours after an oral glucose tolerance test or a random determination during the day, as well as an increase in the level of glycated hemoglobin more than 6.5%. Diagnosis requires a double glycated hemoglobin level or a single glycated hemoglobin test + a single glucose test.

There are concepts such as :

  • Impaired fasting glycemia (IGN) is a disorder of carbohydrate metabolism characterized by an increase in fasting plasma glucose (FPG) from 6. 1 to 7.0 mmol/l.

  • Impaired Glucose Tolerance (IGT) - Plasma glucose values ​​after an oral glucose tolerance test (OGTT) range from 7.8 to 11.0 mmol/L.

  • Pre-diabetes is a disorder of carbohydrate metabolism that leads to a high risk of developing diabetes mellitus (DM) when plasma glucose values ​​are insufficient for diagnosing diabetes.

To date, DM2 is one of the most common non-communicable diseases in the world - the number of patients in 2015 exceeded 300 million people. DM2 is manifested by various symptoms of damage to organs and tissues, leading to a significant decrease in the quality of life, disability of patients, and an increased risk of premature death. The main causes of death in T2DM are various lesions of the circulatory system and oncological diseases. DM is a high risk factor for the development of cardiovascular diseases, and changes in carbohydrate metabolism already at the stage of impaired glucose tolerance are an independent risk factor for cardiovascular lesions.

Prevention of type 2 diabetes:

  1. Non-pharmacological prevention methods:
    • Successful lifestyle changes are effective in reducing the progression of IGT in T2DM.
    • Intense lifestyle change: 7% weight loss, low-calorie, low-fat diet and moderate exercise - 150 minutes per week.
  • Medications for the prevention of type 2 diabetes:
  • Metformin (Glucophage). A decrease in the transition of prediabetes to T2DM was noted on average in 25-40% of cases, however, when compared with non-pharmacological methods in young patients with obesity, the effectiveness of metformin increased and was comparable to that in the group of intensive lifestyle changes.

    The main action of metformin is aimed at reducing glucose production by the liver by increasing the sensitivity of liver cells to insulin, suppressing gluconeogenesis from its precursors such as lactate, pyruvate, glycerol, which normalizes fasting glucose levels.

    In addition, the mechanism of action of metformin is aimed at overcoming tissue resistance to the action of insulin, mainly in the liver and muscle tissue, which increases glucose utilization by tissues and indirectly improves insulin secretion by pancreatic β-cells (reduction of compensatory hyperinsulinemia). Metformin reduces hyperglycemia without causing hypoglycemia. The drug does not stimulate insulin secretion and does not have a hypoglycemic effect in healthy individuals.

    Metformin has a beneficial effect on lipid metabolism: it reduces the content of total cholesterol, low-density lipoprotein and triglerides. While taking the drug, body weight either remains stable or moderately decreases. In pre-diabetes, it is advisable to take metformin 2 times a day in order to improve insulin secretion by pancreatic β-cells (decrease in compensatory hyperinsulinemia).

    Before prescribing the drug, you should make sure that there are no contraindications to the appointment of metformin.

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