1 Lecture No 3. The treatment of patients with diabetes mellitusPrepared of prof. L.Bobyreva
2 During last decades the wide research of new methods of treatment of diabetes mellitus is very active. But in spite of definite successes of these investigations the traditional methods have priority. They are diet, insulin injection, peroral sugar-reducing drugs.
3 Dietotherapy Dietotherapy is the major and traditional method of treatment of patients with diabetes mellitus. It is used during more than two centuries. At present it is the base of treatment of any form of disease. It is major and permanent component of therapy for patients with diabetes mellitus independently of type, severity, and duration of the disease. Diet must be kept daily during the whole life. It can be modified subject to age, development of accompanied diseases, and definite diabetic complications.
4 At present the major principles of dietotherapy are:Physiological balanced ratio of major ingredients of food: carbohydrates average 50-60%, fats average 25-30%, and proteins average 15-20%. Calculation of energy value of daily food ration taking into account sex, age, energy consumption depending on labor activity of definite patient and his/her body weight, which the patient must have in norm (ideal body weight). Leaving out of easily digestible refined carbohydrates from patient’s nutrition, their severe restriction, and restriction of products, which have large amount of carbohydrates (sucrose and glucose) with equal distribution of carbohydrates between meals.
5 The major principles of dietotherapy (continuation)Stable regimen of nutrition with subdivided meals (5-6 times a day) in the presence of definite izo-high-calorie distribution of food value of ratio in accordance with work regimen and the character of sugar-reducing therapy. Using high-vitamin and lipotropic products.
6 Labor activity of individual is divided into 5 groups depending on the difficulty of work :Group 1: very easy work: mental work (administrators, managers, accountants, scientists, doctors of non-surgical specialization, lawyers, artists and others). Group 2: easy work: easy physical work, mental work combined with easy physical exertion (services sector, nurses, hospital attendants, agronomists, seamstresses and others).
7 Group 3: the work of moderate level: (surgeons, operatives, textile-workers, adjusters, metalworkers, the workers of communal-general service and food industry and others). Group 4: heavy work: builders: metallurgists, the workers of oil industry and gas industry, machine-operators and others). Group 5: very heavy work: diggers, bricklayers, miners, loaders, concrete workers, unskilled workers and others).
8 Project number of kcal per 1 kg of ideal theoretical weightThe group of work activity The character of work activity Number kcal 1 kg of ideal body weight 1 Very easy 20 2 Easy 25 3 Moderate 30 4 Heavy 40 5 Very heavy 45-60
9 Ideal mass of the body, kgThe ideal theoretical body weight is determined according to Brock formula: Daily requirement in calories = Ideal body weight × Project number of calories Height, cm Ideal mass of the body, kg Height – 100 Height – 105 Height – 110 186 and higher Height – 115
10 The using the tables of equivalent of products containing carbohydrates by grain-producing units simplifies the planning of menu. GRAIN-PRODUCING UNIT (GPU) - is the equivalent of replacement of products containing carbohydrates by contents grams of carbohydrates in them, calories. Average daily requirement of adult is grain-producing units.
11 The regimen of food intake for person with diabetes mellitus consists of three major food intakes (breakfast, dinner, and supper) and three additional meals (the second breakfast, afternoon snack, and late supper). The major food intake includes in 25% of daily number of calories (dinner: 30%), additional meals includes 10% or 1-2 grain-producing units.
12 Insulin-therapy At present insulin is the single effective method of treatment of patients with IDDM and patients with NIDDM with the first and secondary sulfamide resistance. Its using is necessary for 30% of the patients. By the pity in Poltava region this number amounts 14.8% only.
13 Indications for insulin-therapy prescription are:IDDM regardless of age; Ketoacidosis and diabetic coma in patients with any type of diabetes mellitus; NIDDM if dietotherapy and sugar-reducing medications are unsuccessful or there is significant and progressive weight loss of any genesis; NIDDM in patients with prolonged inflammatory processes of any location, blood disorders with leukopenia and thrombocytopenia, anemia, with severe form of liver disorders, gastrointestinal tract and kidneys with functional insufficiency, severe form of polyneuropathy, marked pain syndrome, trophic ulcer, in the period of pregnancy, delivery, and lactation.
14 It is necessary to note the indications to insulintherapy in patients with NIDDM can have temporary character (insulin prescription during the period of surgical operation etc.). According to origin insulin can be beef (cow), pig, and human insulin. Animal insulin is produced from pancreas of cattle and pig. At present beef insulin are almost not used, it is connected with the difficulty of its purification. Human insulin is divided into semi-synthetic and biosynthetic (genetically engineered). Nowadays there are not any official data about the prevalence of human insulin as compared with pig multi-component insulin, and human biosynthetic insulin as compared with semi-synthetic one.
15 According to effect duration insulin is divided into:insulin having ultra-short effect (analogues of insulin) – Новорапид (Novorapid); insulin having short effect – Монодар (Monodar), Хумодар Р (Humodar R); insulin having moderate duration effect – Монодар Б (Monodar B), Монодар-Лонг (Monodar-Long), Хумодар Б (Humodar B); insulin having prolonged effect – Монодар Ультралонг (Monodar Ultralong), Лантус (Lantus); combined preparations – Монодар К15 (Monodar K15), Монодар К30 (Monodar K30), Монодар К50 (Monodar K50), Хумодар К15 (Humodar K15), Хумодар К25 (Humodar K25), Хумодар К50 (Humodar K50).
16 Effect development’s schemes of all insulin groupsPreparation of ultra-short effect’s duration Preparation of short effect’s duration Preparation of medium effect’s duration Preparation of long effect’s duration Onset of effect min, Peak – 1 hour, duration – 3 hours. Onset of effect - 30 min, Peak – 2 hour, duration – 6-7 hours. Onset of effect – 1 hour, Peak – 4-6 hours, duration – hours. Onset of effect – 1/5-2 hours, Peak – hours, duration – till 24 hours. Onset of effect – 6-8 hours, Peak – hours, duration – till hours. Hours
17 Effect development’s schemes of all insulin groups (continuaton)Combined preparations 15% - short effect insulin, 85% - prolonged effect insulin. 25% - short effect insulin, 75% - prolonged effect insulin. 50% - short effect insulin, 50% - prolonged effect insulin. Hypodermic injection Hours Sugar-reducing activity of insulin
18 Schemes of insulintherapySugar-reducing activity of insulin Hypodermic injection Hours Schemes of insulintherapy
19 Dependence of daily requirement of insulin, MO/kgDependence of daily requirement of insulin in patients with diabetes mellitus from their functional condition Functional condition Dependence of daily requirement of insulin, MO/kg The phase of chronic remission ("honey-moon") 0,3 The condition of stable compensation 0,4-0,5 Fist revealed diabetes mellitus without ketosis 0,5-0,6 Pregnancy 0,6 Marked decompensation 0,7-0,8 Ketosis, ketoacidosis, infections, and stress 0,9-1 Pubertal period, the third trimester of pregnancy 1 Precoma До 1,5 Diabetic coma До 2
20 The age of child, years old Insulin, MO/kg Dependence of daily requirement of insulin in children with diabetes mellitus depending on the age The age of child, years old Insulin, MO/kg Fist revealed diabetes mellitus uncomplicated by ketosis To 1 year 0,1-0,125 1-3 years 0,15-0,17 More then 3 years 0,2-0,5 Diabetes mellitus complicated by ketosis or ketoacidosis Ketosis, ketoacidosis 1,25-1,5 Precoma, coma 2 Notes: for infants the first injection is not more than MO/kg (intravenous) and 0.5 MO/kg (subcutaneous); for children at the age of 1 to 3 years old the first injection is not more than MO/kg (intravenous and subcutaneous).
21 It is estimated that after using of 1 grain-producing unit (GPU) the level of glycemia rises in 1.6‑2.2 mmol/l. The level of decreasing of glycemia after injection of 1 un of insulin is the same - 1.6‑2.2 mmol/l. Therefore the dose of insulin is estimated by the following: 1 unit of insulin per 1 GPU. But it is necessary to take into account the requirement of insulin per 1 GPU changes during the day. In the morning it includes MO, afternoon it is 1 MO, and in the evening it is MO. For final selecting of insulin dose it is necessary to take into account the results of glycemia before each injection. It is necessary to note that oriental distribution of insulin dose before breakfast and dinner is 2/3 of daily dose; before the supper and sleeping it is 1/3 of daily dose. The correction of insulin dose must be carried out daily on the base of data of self-control of glycemia during 24 hours.
22 The distribution of daily volume of carbohydrates (GPU) and daily insulin dose (MO) depends on the food intake Food intake Carbohydrates, % GPU Insulin, % MO Total Breakfast 20 Tiffin (the second breakfast) 10 Dinner 30 60% (Afternoon) snack Supper The second supper 40%
23 Complications of insulintherapyHypoglycemia It develops in 30% of patients receiving insulin. In % of cases it is the cause of death. Clinical manifestations appear in decreasing glycemia level below than mmol/l (30-50mg%). Sometimes due to quick decreasing the glucose level in the blood this level is mmol/l to 7-8 mmol/l and etc. As a rule it is related with overdosage of insulin (sort-term effect more often). Chronic overdosage of insulin (Somodgy's phenomenon) This state is characterized by sudden increasing glucose level in the blood after hypoglycaemic reaction, which follows after insulin injection. This phenomenon is sometimes called posthypoglycaemic hyperglycemia. The daily dose must be increased by 10-20%.
24 Complications of insulintherapyThe phenomenon of "daybreak" It is characterized by rising glycemia early in the morning at 4.00 to 6.00 o'clock a.m. It is related with daily rhythm of contrinsulin hormones (adrenalin, cortisol, and somatotropin especially and others. It is necessary to check the level of glycemia early in the morning at the expense of prolonged. Insulin resistance It is therapeutic resistance concerning exogenous insulin. It appears after exogenous insulin injection. Its rate is 1% to 50%: light – daily insulin dosage is MO; moderate – MO; and severe – more than 200 units MO. The diet keeping must be strict. The patient's therapy must be converted into intensive insulintherapy, as a rule by insulin of short-term effect.
25 Complications of insulintherapyInsulin lipodystrophy It is manifested by atrophy (atrophic form) or hypertrophy (hypertrophic form) of subcutaneous base in the sites of insulin injection. The treatment consists of the keeping of technique rules of insulin injecting, physioprocedure . Allergic insulin reaction Local and general. Hyposensitization by mild doses of insulin, selection of insulin.
26 Peroral sugar-reducing medications combining with diet is the main method of treatment the majority of patients with NIDDM The major directions of modern pathogenic therapy of diabetes mellitus (the second type) The main mechanism of effect Chemical name of medications group International name Commercial name 1. Stimulation of insulin secretion 1. Derivatives of sulfanilurea: Generation I Acetohexamide Cartubamide Tolasamide Tolbutamide Chlorpropamide Dimelor Bucarban Tolinase Butamid Ediabinese Generation II Glibenclamide Glibornuride Glicvidon Gliclazideb Glipizide Maninil Glinor Glurenorm Diabeton Minidiab
27 The major directions of modern pathogenic therapy of diabetes mellitus (the second type)The main mechanism of effect Chemical name of medications group International name Commercial name 1. Stimulation of insulin secretion 1. Derivatives of sulfanilurea: Generation III Glimepiride Amaril 2. Derivative of benzoic acid Repaglipide Novonorm 3. Derivative of insulitropic acid Nateglinide Starlix 2. Decreasing insulin-resistance 1. Thiazolidi-nedions Roziglytazon Pyoglytazon Avandia Actos 2. Biguanides Metphormine Buphormine Dianormed Adebit
28 The major directions of modern pathogenic therapy of diabetes mellitus (the second type)The main mechanism of effect Chemical name of medications group International name Commercial name 3. Inhibition of gluconeogenesis 1. Biguanides Metphormine Buphormine Dianormed Adebit 2. Thiazolidine-dions Roziglytazon Pyoglytazon Acarboza Avandia Actos Glycobay 4. Inhibition of glucose absorption into the blood 1. Inhibitors of alfa-glycosidase Miglytol Vocliboz 2. Huaric acid Guar gum Guarem
29 Transplantation methods of treatmentIn 1998 American scientists James Thompson and John Backer succeeded in separate the human embryonic stem cells (ESC). The results of experimental work published in "Science" journal in 1999 have been recognized as the third the most important event in biological science of the XX century after discovering of double DNA helix and decoding of human genome. Unique propety of ESC, pluripotency (the ability to give the beginning to 350 different types of cells), was an incitement to rapid research directed to the study of ESC and opened wide prospects their practical using in biology and medicine, first of all in transplantology.
30 Billions of cells of growing organism (human or animal) originate from one cell (zygote), which is formed due to fusion of male and female gametal cells. This cell includes the information about the organism and the scheme of its consistent unfolding. This is the way of human organism development, which consists of 1014 cells. As the result of embryogenesis, the fertilized ovum is divided and gives rise to the cells, which have not any other functions except the transmission of genetic material into the following cell generations. This is ESC, their genome is in "zero point", i.e. the mechanisms determining the specialization are not included and any cells can develop from them. STEM CELLS
31 Thus the first major property of ESC is pluripotencyThus the first major property of ESC is pluripotency. The inclusion of various genes occurs during human embryo development under the action of so-called embryonic inductors. After that the families of different stem cells are formed and the segmentation of embryo occurs, i.e. the areas of the prospective organs are marked structurally. Multiplying, progenies of these stem cells follow to the definite specialization way. This process is called "commitment". As the result of mitosis of stem cell one of the daughter cell serves its properties, the other one is specialized. In the organism of adult there are stem cells of tissues. Due to the division of these cells the tissue structure is renewed. Using human stem cells in medical practice: ESC of human are the important source for allotransplantation. They permit to take the pure cell populations of one type. After transplantation they can replace own cells of recipient damaged or affected by the disease.
32 The transplantation of fetal tissues: clinical transplantology dealing with organs transplantation has definite difficulties connected with the problems of medical ethics, excessive labour intensiveness and high payment of operations, complications for receiving necessary material, great risk of immune graft-versus-host reaction, and complications due to immunosuppression therapy. The majorities of these problems are disappeared during cell transplantation therapy using. The most acceptable material for these purposes as the donor material is the fetal cells and tissues. The vital native and conserved fetal cells and tissues, their homogenates, extracts and biological active compounds released from them are inserted to the patients. According to histogenesis these are different types (skin, nervous tissue, marrow, pancreas, liver and others) and placental tissues.
34 Decreasing of insulin requirement in patients with I type diabetes mellitus
35 Dynamics of sugar-reducing medications doses in patients with II type diabetes mellitus
36 Indices of pacients with diabetus mellitus quality of life (from questionnaire)Control group Experimental group Before treatment 3 monthes after treatment 1 year after treatment State of health 1.7 2.2 1.9 1.4 4.4 4.1 Activity 1.6 2.4 1.5 4.2 4.0 Mood 2.5 2.3 4.5 3.7 I type Indices Control group Experimental group Before treatment 3 monthes after treatment 1 year after treatment State of health 2.0 2.4 2.2 1.9 4.0 3.8 Activity 2.5 2.3 3.9 Mood 2.1 2.6 4.2 II type Favourable state of health– higher 4 points; Unfavorable state of health– lower 4 points; Norm – 5.0 –5.5 points.
37 Dynamics of sugar-reducing medications doses in patients with II type diabetes mellitus (secondary insulin-dependent)
38 3 monthes after treatmentIndices of pacients with II type diabetes mellitus (secondary insulin-dependent) quality of life (from questionnaire) Indices Control group Experimental group Before treatment 3 monthes after treatment 1 year after treatment State of health 1.8 2.2 2.1 1.7 4.3 4.0 Activity 2.0 2.5 2.3 4.1 3.8 Mood 2.7 2.4 Favourable state of health– higher 4 points; Unfavorable state of health– lower 4 points; Norm – 5.0 –5.5 points.
39 Speculative scheme of induction of recipient’s insular apparatus reparation by transplantPlacenta+ embryonal pancreas ESC pluripotential cell RSĆ primary ectoderm primary mesoderm primary entoderm ´´ embrionic ectoderm RSC extraembrionic entoderm mesoderm ´´´ Entoderm of intestinal tube Vitelline entoderm Embrional epithely of pancreas of liver of stomach of bowels Epithely of vitelline sac of allantois Mature of vitelline sac Tissue derivative zygote morula blastula Embrional germs