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Treatment of diabetes mellitus Department of Internal Medicine №2 as.-prof. Martynyuk L.P. Plan of lecture • • • • The main principles of DM therapy Methods of treatment DM The main principles of diet Oral hypoglycemic agents. – – – – – – Sulfanilureas biguanides Alpha-glucosidase inhibitors Non-sulfanylureas insulin stimulators Thiozolidindiones Combined preparates • Insulin therapy • Future directions in improving glycemic control • Exercise program • Education of the patients The main principles of DM therapy • • • • Maintenance of metabolic status at normal level or as close to normal as possible (especially blood glucose and lipid concentration). Achievement of DM compensation. Achievement and maintenance of normal or reasonable body weight. Maintenance (preservation) of working capacity. Prophylaxis of acute and chronic complications. Criteria of DM compensation Indexes Level of compensation good sufficient insufficient Fasting glycaemia 4,4 - 6,7 (mmol/l) 2 hours after 4,4 – 8,0 meals Glucosurea (%) 0 Hb Alc (%) < 6,5 Cholesterol < 5,0 (mmol/l) Triglycerides < 1,7 (mmol/l) HDL (mmol/l) > 1,1 Body mass males < 25 index (kg/m2) females < 24 Blood pressure < 135/85 < 7,8 > 7,8 < 10,0 > 10,0 0,5 6,5 – 8 > 0,5 >8 5,0 – 6,5 > 6,5 1,7 – 2,2 > 2,2 0,9 – 1,1 < 27 < 26 < 160/95 < 0,9 > 27 > 26 > 160/95 Methods of treatment DM • • • • • • Diet. Oral hypoglycemic agents or insulin (indications for each vary with the type of DM and severity of the disease). Exercise program. Phytotherapy (plant’s therapy). Nontraditional methods of treatment. Education The main principles of diet The main principles of diet. Normal-calorie diet in patients with type I DM (35-50 kcal/kg of ideal weight (weight = height – 100)) and low-calorie diet in obese persons (mostly in patients with type II DM (20 – 25 kcal/kg of ideal weight)). We try to decrease weight in obese patients on 1-2 kg/month by such diet. • The main principles of diet. Regimen has to be consist of 4 – 5 – 6 small feedings a day. (The most frequent regimen consists of 4 feedings a day, in which: - breakfast comprises 30 % of total calories, - dinner – 40 %, - lunch – 10 %, - supper – 20 %. Sometimes patients need second breakfast (when they have a tendency to develop hypoglycemia). In such case it comprises15 % of the total calories and we decrease the quantity of calories of the first breakfast and dinner). • Exclusion of high-calorie carbohydrates (sugar, biscuits, white bread, alcohol). The main principles of diet. • Increasing the quantity of high fiber-containing foods (fruits (exclusion: banana, grapes), vegetables, cereal grains, whole grain flours, bran. Patients need 40 g fibers per day • Limiting of meat fat, butter, margarine in diet, decrease red and brown meats, increase poultry and fish, encourage skim milk-based cheeses. Should be used skim or low-fat milk, not more than 2 – 3 eggs weekly. • Alcohol should be avoided as much as possible because it constitutes a source of additional calories, it may worsen hyperglycemia, and it may potentiate the hypoglycemic effects of insulin and oral hypoglycemic agents. 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 II DM. • The most commonly used are: - the sulfanilureas, - biguanides, - alpha-glucosidase inhibitors, - non-sulfanylureas insulin stimulators, - repaglinides. Commonly used sulphonylureas 2 nd generation drugs (mg) Glibenclamid (Maninil, Euglucan, Daonil, Glinil, Gilamat, Gliben, Glucoven) Glibornurid (Glutrid) Gliquidon (Glurenorm, Beglicor) 1; 1-2 1,75; 3,5; 5 25 25-75 30 30120 Gliclazid (Diamicron, 80 Diabeton, Predian, Glizid) 30 Diabeton MR Glipizid (Minidiab, 5 Glucontrol, Antidiab) 3 rd generation drugs (mg) Glimepirid (Amaryl) 1-4 1224 8-12 8-12 80320 30120 20 8-12 24 4 24 8-12 Without hepatoand nephrotoxic effects, metabolism through the intestinum Normalizes microcirculation, blood aggregation Commonly used biguanides Name of drug Metformin (Dianormet, Siofor, Metfogamma, Metfordar) Glucophage Forte Buformin (Adebit) Buformin Retard Dose in 1 tabl. 0,25; 0,5 0,5; 0,85 0,05 0,17 Daily dose 0,5-1,5 0,5-2,0 0,1-0,2 0,170,34 Duration of action (hours) 8-10 12-14 8-10 12-14 Alpha-glucosidase inhibitors Name of drug Duration of Dose in Daily action 1 tabl. dose (hours) 0,05; 0,1 0,15-0,6 2,7-9,6 Acarbosa (Glucobay, Glucor, Prandase, Precose) Miglitol 0,025; 0,05; 0,1 Guar (Guarem) 0,05-0,3 2-4 Gum 5,0 (gra- 15-30 nules) - Non-sulfanylureas insulin stimulators Duration Dose in Daily Name of drug of action 1 tabl. dose (hours) Repaglinid 0,001; 0,004- 3 - 4 (Novonorm, Roglid) 0,002; 0,009 (meglitinide analogs) 0,003; 0,004 Nateglinid (Starlix) 0,06; 0,18- 1,5 - 3 (D-Phenilalanine-derivative) 0,12; 0,54 0,18 Commonly used thiozolidinediones Dose Name of drug in 1 tabl. Rosiglitazone 0,002; (Avandia, 0,004; Rosinorm) 0,008 Pioglitazone (Actos, 0,015; Pionorm) 0,03; 0,045 Daily dose Duration of action (hours) 0,0040,008 0,0150,03 Up to 24 hours From the history of insulin Indications for insulin therapy 1. All patients with type I DM. 2. Some patients with type II 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 ultrashort action (human analog, recombinant) Insulin action beginning maximum duration 2-10 min 40 - 50 min 3-5h NovoRapid Novo-Nordisk Humalog Lilly Epaidra Insulin preparations of short action Insulin Monodar Indar Humodar R (полусинт.) Indar Humodar RR(рекомб) Indar Humodar R100 Indar Humodar R100R Indar Farmasulin HN Farmak Actrapid (МС, НМ) Novo-Nordisk action beginning maximum duration 30 min 1-3h 5-8h Insulin preparations of intermediate action Insulin action beginning Monodar B Indar Humodar B Indar Farmasulin Н NР Farmak 1 – 1,5 h Protaphan (МС, НМ) Novo-Nordisk Insuman basal Aventis Humulin NPH Lilly Monotard НМ Novo-Nordisk maximum duration 6-8h 12 – 18 h Insulin preparations of long action Insulin action beginning Farmasulin НL Farmak Ultralente Humulin Lilly Ultratard НМ 3–4h МC Suinsulin Ultralong maximum duration 10 -12 h 24 – 30 h Indar Glargine (Lantus)Aventis Detemir Levemir 24 h (human analog, recombinant) Insulin preparations combined Insumani comb 25/75 Mixtard 30 НМ Monodar К15 Aventis 30 min 1,5-2 h 12-18 h NovoNordisc Indar 30 min 2-8 h 24 h 30-40 min 30-40 min 30 min 30-45 min 30-45 min 30 min 1,5-3 h 12-18 h 1-3 h 12-16 h 1-3 h 1,5-3 h 6-10 h 12-18 h 1,5-3 h 12-18 h 1-3 h 6-10 h Monodar К30 Indar Monodar К50 Indar Humodar К Indar 15 Humodar К25 Indar Humodar К50 Indar Secretion of insulin in health people 3 Breakfast Concentration of insulin 2, Meal secretion 3 Lunch Dinner 1,5 1 0,5 7.00 12.00 0 Basal secretion 19.00 24.00 7.00 Exercise program • Exercise is an excellent adjunct to diet therapy, but it is very ineffective when used as the sole weight-reducing modality. • Exercises must be clearly planned and depend on patient’s abilities and the physical condition, exclusion of the competition’s elements. Exercise program • Exercises may be valuable adjunct to the management of the DM by: • lowering blood glucose concentration; • decreasing insulin requirements; • potentiation the beneficial effects of diet and other therapy. • To prevent hypoglycemia, patients should carefully monitor glucose level and taking of insulin. Mostly they need to reduce the insulin dosage by 20 – 25 % on the day that strenuous exercises is planned. Plant’s therapy (phytotherapy) • • • hypoglycemic action; treatment of chronic diabetics complications; influence on the immune reactivity. Patient’s education • • • • the nature of DM and importance of metabolic control; the principles and importance of good nutrition and reasonable exercise program; the principles of adequate foot, dental and skin care; treatment of DM during the periods of illness; Patient’s education • • • techniques of insulin administration and measurement of urine and blood glucose level (if taking insulin); recognition of hypoglycemia, its causes and methods of prevention; the importance of general and specific measures to minimize in the best possible way diabetic complications and maintain of good overall health. Self - control References • The Merck Manual of Diagnosis and Therapy (seventeenth Edition)/ Robert Berkow, Andrew J. Fletcher and others. – published by Merck Research Laboratories, 1992. – P. 169 - 177. • Manual of Endocrinology and Metabolism (Second Edition)/ Norman Lavin. – Little, Brown and Company.Boston-New York-Toronto-London, 1994. - P. 563 - 566. • Endocrinology (A Logical Approach for Clinicians (Second Edition)). William Jubiz.-New York: WC GrawHill Book, 1985. - P. 261 – 262, 270 – 273.