Treatment of Diabetes Mellitus Dr. Vereshchahina Natalija

The treatment of patients with DM is very important and may be difficult because of problems in achieving of normal glucose control. There is good evidence that hyperglycemia conveys risks for all of the common long-term complications of DM, which are the major cases of excess morbidity and mortality in diabetics.

Criteria of DM compensation

 Research studies have found that lifestyle changes can prevent or delay the onset of type 2 diabetes among high- risk adults.  These studies included people with IGT and other high-risk characteristics for developing diabetes.  Lifestyle interventions included diet and moderate-intensity physical activity (such as walking for 2 1/2 hours each week).  In the Diabetes Prevention Program, a large prevention study of people at high risk for diabetes, the development of diabetes was reduced 58% over 3 years. Prevention or delay of diabetes: Life style modification

 Studies have shown that medications have been successful in preventing diabetes in some population groups.  In the Diabetes Prevention Program, people treated with the drug metformin reduced their risk of developing diabetes by 31% over 3 years.  Treatment with metformin was most effective among younger, heavier people (those years of age who were 50 to 80 pounds overweight) and less effective among older people and people who were not as overweight.  Similarly, in the STOP-NIDDM Trial, treatment of people with IGT with the drug acarbose reduced the risk of developing diabetes by 25% over 3 years.  Other medication studies are ongoing. In addition to preventing progression from IGT to diabetes, both lifestyle changes and medication have also been shown to increase the probability of reverting from IGT to normal glucose tolerance. Prevention or delay of diabetes: Medications

Management of Diabetes Mellitus

The major components of the treatment of diabetes are: Management of DM Diet and Exercise A Oral hypoglycaemic therapy B Insulin Therapy C

 Diet is a basic part of management in every case. Treatment cannot be effective unless adequate attention is given to ensuring appropriate nutrition.  Dietary treatment should aim at: ◦ ensuring weight control ◦ providing nutritional requirements ◦ allowing good glycaemic control with blood glucose levels as close to normal as possible ◦ correcting any associated blood lipid abnormalities A. Diet

The following principles are recommended as dietary guidelines for people with diabetes:  Dietary fat should provide 25-35% of total intake of calories but saturated fat intake should not exceed 10% of total energy. Cholesterol consumption should be restricted and limited to 300 mg or less daily.  Protein intake can range between 10-15% total energy (0.8-1 g/kg of desirable body weight). Requirements increase for children and during pregnancy. Protein should be derived from both animal and vegetable sources.  Carbohydrates provide 50-60% of total caloric content of the diet. Carbohydrates should be complex and high in fibre.  Excessive salt intake is to be avoided. It should be particularly restricted in people with hypertension and those with nephropathy. A. Diet (cont.)

 Physical activity promotes weight reduction and improves insulin sensitivity, thus lowering blood glucose levels.  Together with dietary treatment, a programme of regular physical activity and exercise should be considered for each person. Such a programme must be tailored to the individual’s health status and fitness.  People should, however, be educated about the potential risk of hypoglycaemia and how to avoid it. Exercise

There are currently four classes of oral anti- diabetic agents: i. Biguanides ii. Insulin Secretagogues – Sulphonylureas iii. Insulin Secretagogues – Non-sulphonylureas iv. α-glucosidase inhibitors v. Thiazolidinediones (TZDs) B. Oral Anti-Diabetic Agents

 If glycaemic control is not achieved (HbA1c > 6.5% and/or; FPG > 7.0 mmol/L or; RPG >11.0mmol/L) with lifestyle modification within 1 – 3 months, ORAL ANTI-DIABETIC AGENT should be initiated.  In the presence of marked hyperglycaemia in newly diagnosed symptomatic type 2 diabetes (HbA1c > 8%, FPG > 11.1 mmol/L, or RPG > 14 mmol/L), oral anti-diabetic agents can be considered at the outset together with lifestyle modification. B.1 Oral Agent Monotherapy

Oral hypoglycemic agents. Inadequate control of hyperglycemia by the diet and exercises interventions suggests the need for a good glucose-lowering agent. Oral hypoglycemic agents are useful only in the chronic management of patients with type 2 DM. The most commonly used are: - the sulfanilureas, - biguanides, - alpha-glucosidase inhibitors, - non-sulfanylureas insulin stimulators (glinides), - thiosolidinediones (glitazones).

As first line therapy: Obese type 2 patients, consider use of metformin, acarbose or TZD. Non-obese type 2 patients, consider the use of metformin or insulin secretagogues Metformin is the drug of choice in overweight/obese patients. TZDs and acarbose are acceptable alternatives in those who are intolerant to metformin. If monotherapy fails, a combination of TZDs, acarbose and metformin is recommended. If targets are still not achieved, insulin secretagogues may be added B.1 Oral Agent Monotherapy (cont.)

Sulfanilureas include: first generation: Tolbutamide, Chlorpropamide, Tolazemide, Acetohexamide (now are not used in treatment of the diabetics); second generation: Glibenclamide (Maninil (3,5 mg, 5 mg), Daonil (5 mg)), Gliquidon(Glurenorm (0,03), Minidiab (5 mg)), Gliclazide (Diamicron (0,08)), Glipizide; third generation: Glimepiride (Amaryl (1 mg, 2 mg).

Contrandications to sulfanilureas usage type 1 DM; blood diseases; acute infections, heart, cerebral diseases; trauma; pregnant diabetics or lactation; III – IV stages of angiopathy (but Glurenorm can be used in patients chronic renal failure, because of gastrointestinal tract excretion); coma and precoma.

Action of biguanides inhibition of gastrointestinal glucose absorption; decreasing of glyconeogenesis, lipogenesis; enhancing glucose transport into muscle cells; increasing the quantity of insulin’s receptors; stimulation of anaerobic and partly aerobic glycolis; anorrhexogenic effects.

Indications to biguanides usage Obese patients with type 2 DM, with middle severity of the disease without ketosis. They can be used with the combination of sulfanilureas when sulfonylureas alone have proved inadequate to treat DM.

Contraindications to biguanides usage type 1 DM; heart and lung disease with their insufficiency (chronic heart and lung failure); status with hypoxemia; acute and chronic liver and kidney diseases with decreased function; pregnant diabetics, lactation; old age; alcoholism; coma and precoma.

Action of non-sulfanylureas insulin stimulator. Stimulation of insulin production at meal times; very rapid absorbtion from the intestine and metabolizing in the liver; (plasma half-life is less than 1 hour).

Indications for insulin therapy 1. All patients with type 1 DM. 2. Some patients with type 2 DM: uncontrolled diabetes by diet or oral hypoglycemic agents; ketoacidosis, coma; acute and chronic liver and kidneys disease with decreased function; pregnancy and lactation; II – IV stages of angiopathy; infection diseases; acute heart and cerebral diseases; surgery.

Insulin preparations of short action Insulinaction beginningmaximumduration Monodar Indar 30 min1 - 3 h5 - 8 h Humodar R (полусинт.) Indar Humodar RR (рекомб) Indar Humodar R100 Indar Humodar R100R Indar Farmasulin HN Farmak Actrapid (МС, НМ) Novo-Nordisk

Insulin preparations of intermediate action Insulinaction beginningmaximumduration Monodar B Indar 1 – 1,5 h6 - 8 h12 – 18 h Humodar B Indar Farmasulin Н NР Farmak Protaphan (МС, НМ) Novo-Nordisk Insuman basal Aventis Humulin NPH Lilly Monotard НМ Novo-Nordisk

Insulin preparations of long action Insulinaction beginningmaximumduration Farmasulin НL Farmak 3 – 4 h h24 – 30 h Ultralente Humulin Lilly Ultratard НМ МC Suinsulin Ultralong Indar Glargine (Lantus) Aventis - (human analog, recombinant) 24 h Detemir Levemir

Some peculiarities of insulin therapy: insulin acts faster when is administrated i/v; subcutaneous and intramuscular absorption of insulin is decreased in the dehydrated or hypotensive patients; it is necessary to change the insulin injection site (because the absorption is more rapid from the new sites); the most rapid absorption from the abdomen; exercise accelerates insulin absorption (before planned exercise program patient has to decrease insulin dose or take more caloric diet).

Side effects (complications) of insulin therapy. 1. Hypoglycemia. - This complication represents insulin excess and it can occur at any time (frequently at night (common symptom: early-morning headache)). - Precipitating factors: irregular ingesting of food; extreme activity; alcohol ingestion; drug interaction; liver or renal disease; hypopituitarism; adrenal insufficiency.

Side effects (complications) of insulin therapy. - Treatment (preventing coma): to eat candy or to drink sweet orange juice (when the symptoms develop); to receive intravenous glucose; 1 mg of glucagon administrated subcutaneously; gradual reduction of insulin dose in future.

Clinical presentation. Hypoglycemia

Treatment Insulin–treated patients are advised If the symptoms of hypoglycemia develop, the patients have to drink a glass of fruit juice or water with 3 tbsp. of table sugar added or to eat candy, and to teach their family members to give such treatment if they suddenly exhibit confusion or inappropriate behavior:

1.glucagon 0,5 – 1 unit (0,5 – 1 ml) s/c, i/m or i/v. If the patient does not respond to 1 unit of glucagon within 25 minutes, further injections are unlikely to be effective, and are not recommended; 2.an i/v injection of 20 or 100 ml of 40 % glucose, followed by a continuous infusion of 5 % glucose (10 % glucose may be needed) until it clearly can be stopped safely; 3.glucocorticoids and adrenaline are helpful as well.