1. DIABETES MELLITUS IN CHILDREN: CLINICAL FEATURES, DIAGNOSTICS AND TREATMENT As. Prof. Sakharova Inna. Ye., MD,PhD

2. Diabetes mellitus (DM)  a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both (WHO, 1999)

3. Destruction of  -cells of islet of Langerhans cause an absolute deficiency of insulin, leading to type I diabetes mellitus (insulin- dependent diabetes mellitus, DM type 1).

5. 10% of all DM cases Insulin deficiency Juvenile onset HLA DR 3+4 associations: o53% of people with type I diabetes have one DR3 and one DR4, with one of these coming from each parent. oOnly 3% of people without diabetes have this DR3/DR4 combination. 4 genes thought to be important 30 - 50% concordance in identical twins Positive family history with 10% Associated with other autoimmune diseases

7. Clinical classification of DM type 1. SeverityGlycemic control Complications - Mild - Moderate - Severe - Ideal - Optimal - Suboptimal - High risk for the life - Acute - Chronic

8. DM severity criteria Mild form -Absence of ketoacidosis in anamnesis -Absence of micro- and macroangiopathies -Treatment consists of diet, physical exercises, phytotherapy (it’s enough for ideal glycemic control maintaining)

9. DM severity criteria Moderate form -In anamnesis – ketoacidosis (I-II stages) -Presence of diabetic retinopathy I st., diabetic nephropathy I-III st. or diabetic arthropathy I st. -For achievement of ideal glycemic control is necessary to use insulin, or oral drug therapy or combination of both

10. DM severity criteria Severe form -Non stable course of the disease (frequent ketoacidosis cases or coma in anamnesis) -Presence of different chronic complications -Patients need permanent insulin injections

11. Clinical criteria of glycemic control IdealOptimalSuboptimalHigh risk for the life Symp- toms of DM are absent Symptoms are absent, but sometimes can be mild hypogly- cemia Polyuria, polydipsia, poor weight gain. Can be episodes of severe hypogly- cemia Poor vision, painful seizures, growth and sexual development retardation, angiopathies, skin infections, episodes of severe hypogly-cemia

12. Laboratory criteria of glycemic control Glucose, (mmol/L) IdealOptimalSubopti mal High risk for the life Fasting glycemia 3,6-6,14,0-7,0> 8,0> 9,0 After food glycemia 4,4-7,05,0-11,011,0-14,0> 14,0 Night glycemia 3,6-6,0Not < 3,6 9,0 < 3,0 or > 11,0 Hb Alc, % < 6,05< 7,67,6-9,0> 9,0

13. The main evident signs of the DM type 1: hyperglycemia - glucose uptake by cells decreased - glucose utilisation by cells decreased glycosuria polyuria - excessive urine production - blood glucose levels exceed the rate of glomerular filtration by the kidneys - glucose appears in the urine and acts as an osmotic diuretic

14. polydipsia - due to dehydration polyphagia - excessive eating - hypothalamic control of appetite has insulin sensitive transport systems weight loss fatigue and weakness

15. Diagnostic criteria: A random blood glucose level greater than 11,1 mmol/l (i.e.>200 mg/dl), which is verified on a repeat test, is sufficient to make the diagnosis of DM or Fasting blood glucose > 6,1 mmol/l (>110 mg/ dl) (fasting is no food for > 8 hours), which is verified on a repeat test, is sufficient to make the diagnosis of DM

16. Oral glucose tolerance test (OGTT) Obtain a fasting blood sugar level, then administer per os glucose load (1.75 g/kg for children [max 75 g]). Check blood glucose concentration again after 2 hours.

17. Oral glucose tolerance test (OGTT) DiagnosisTime of checking Glucose level (mmol/L) Whole bloodPlasma Diabetes mellitus Fasting  6,1  7,0 In 2 hours  11,1 Impaired Glucose Tolerance (IGT) Fasting  6,1  7,0 In 2 hours  7,8  11,1 Impaired Fasting Glycaemia (IFG): Fasting  5,6  6,1  6,1  7,0 In 2 hours  7,8

18. Laboratory studies: Blood glucose (glycemic profile). Blood glucose tests using capillary blood samples, reagent sticks, and blood glucose meters are the usual methods for monitoring day-to-day diabetes control; Urinalysis for glucose (glucosuric profile); Serum electrolytes  Protein in urine, microalbuminuria - urinary albumin excretion rate (normal level  20  g min)

19. Urinary albumin:creatinine ratio (normal level  2,5mg/mmol for men and <3,5 for women) Ketone bodies in urine and blood (With hyperglycemia and heavy glycosuria, ketonuria is a marker of insulin deficiency and potential DKA) White blood cell count and blood and urine cultures to rule out infection  Glucosylated hemoglobin (Hb Alc ) N 6-9 % for diabetic patient

20. Fructosamine level in blood Islet cell antibodies; Fasting lipid profile (cholesterol, triglycerides, HDL/LDL calculation) Level of C-peptide and insuline in blood

21. Instrumental studies: ECG US examination of abdominal cavity Fundoscopy Densitometry Rheovasography of legs

22. Optimal therapy for diabetes mellitus must include  Insulin  A regimen for physical fitness  Psychological support  Nutritional management

23. Daily insulin doses for children: AgeInsulin dose (Units/kg) Infants (< 1 year)0,1 - 0,125 Toddlers (1-3 years)0,15 – 0,17 3-9 years0,2 – 0,5 9-12 years0,5 – 0,8 > 12 years1,0 and more

24. Insulin has 3 basic formulations: short-acting, regular insulin (aktrapid) medium- or intermediate-acting (protaphan, isophane, lente) and long-acting (ultralente)

26. The main rules of insulinotherapy im children: In ketoacidosis should be used only regular insulin Optimal frequency of injections is 4-5 times per day (if 4 times – 9 a.m.(regular), 13 p.m.(regular), 18 p.m. (regular), 22 p.m (medium-acting); if 5 times – 6 a.m.(regular), 9 a.m.(regular), 14 p.m. (regular), 19 p.m. (regular), 23 p.m (regular); Can be used insulin pompes

27. The catheter at the end of the insulin pump is inserted through a needle into the abdominal fat of a person with diabetes.

30. Designer Ellaluna Taylor has come up with her Flex insulin pump system that targets active diabetes sufferers, as this system functions as a “unique prosthetic skin” that can be worn under clothing, functioning as a discreet glucose management solution. It comes with a PDA-like glucose eReader that will talk to the device, where the latter runs on soft battery technology while its MEMS Nano Pump is used for increased dosage accuracy and reliability.

31. Treatment of diabetic coma (DKA III stage) An initial intravenous bolus of regular insulin at 0.1 U/kg body weight, followed by a continuous infusion of regular insulin at a dose of 0.1 U/kg/hour is the standard therapy (before 50 U of insulin should be diluted in 50 ml of normal saline – than 1 ml will have 1 U of insulin)

32. When glucose decreased to 14 mmol/L (250 mg/dL) – insulin can be injected subcutaneously (dose 1 U/kg/day). If the patient is hemodynamically stable, isotonic saline can be given at a rate of 15-20 mL/kg/hour for the first several hours. Once the serum glucose level is below 200-250 mg/dL, the fluids should be changed to one-half normal saline with dextrose (D5 1/2NS) given at a rate sufficient to replace the free water loss induced by the osmotic diuresis.