Diabetes Mellitus. Mohamed Ahmed Fouad Lecturer of Pediatrics Jazan Faculty of Medicine

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1 Diabetes Mellitus Mohamed Ahmed Fouad Lecturer of Pediatrics Jazan Faculty of Medicine

2 Define DM in children Differentiate types of DM Discus Etiology and Risk Factor Reason clinical presentations Set up plan for management Objectives

3 Definition : Diabetes mellitus is a metabolic disorder characterized by relative or absolute insufficiency of insulin, and resultant disturbances of carbohydrate metabolism.

4 Classification Type 1: *IDDM : there is absolute deficiency of insulin (partial or complete ) Type 2 : *NIDDM : here the insulin is normal but the problem in the response to insulin. *Serum concentration of insulin may be normal or moderately depressed.

5 Maturity onset Diabetes of Young ((MODY)) : *In this type there is strong family history of type 2DM in a pattern suggestive AD inheritance. *In this type there no association with HLA, autoimmunity and islet cell Abs *Insulin resistance does not occur in these patients; instead the primary abnormality is an insufficient insulin secretory response to glycemic stimulation. Treatment depends on the type and can include the use of sulfonylureas. 2ry DM associated with other diseases : 1-pancreatic diseases 2- endocrinal disease : Cushing 3- genetic diseases : prader willi syndrome, Down 4-insulin receptor abnormalities Neonatal diabetes

6 Etiology

7 Etiology of IDDM It is multifactorial 1-Genetic predisposition A higher incidence of IDDM is associated with HLA- DR3,DR4,B8&B15. 2-Autoimmune response Autoimmune response : production of Abs either : A-Antibcell Abs (islet cell Abs) b-antiinsulin Abs. 3-enviromental factors *Early exposure to cow milk feeding may be factor in triggering DM, so DM is low in breast feed infants *Viruses : mumps, measles, coxackie-b2,4&5 initiate IDDM in genetically predisposed individuals *These infection act by 2 mechanisms : 1- Autoimmunity 2-change the antigenicity of the cell

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9 Epidimiology of the IDDM *Sex : both are equally affected *Age of presentation : 5-7 years & at puberty *Season : autumn &winter *There is definite increased incidence of diabetes in chidren with congenital rubella *Prevelance of IDDM in Saudi Arabian children and adolescents is 109 per 100,000.. (Al-Herbish AS.,etal; Saudi Med J Sep;29(9):1285-8(

10 Normal Insulin Metabolism Insulin after a meal: *Stimulates storage of glucose as glycogen *Inhibits gluconeogenesis *Enhances fat deposition in adipose tissue *Increases protein synthesis

11 Fasting state: *Counter-regulatory hormones (especially glucagon) stimulate glycogen glucose When glucose unavailable during fasting state *Lipolysis (fat breakdown) *Proteolysis (amino acid breakdown)

12 Pathogenesis of DM ALTERED CHO METABOLISM Insulin Glucose Utilization + Glycogenolysis Hyperglycemia Glucosuria (osmotic diuresis) Polyuria* (and electrolyte imbalance) Polydipsia* * Hallmark symptoms of diabetes

13 ALTERED PROTEIN METABOLISM Insulin Protein Catabolism Gluconeogenesis (amino acids glucose) Hyperglycemia Weight Loss and Fatigue ALTERED FAT METABOLISM Insulin Lipolysis Free fatty acids + ketones Acidosis + Weight Loss

14 Symptoms of Diabetes *As blood glucose levels become elevated (hyperglycemia), Glucose is excreted in the urine and excessive urination (polyuria) occurs because of osmotic diuresis. *Increased fluid loss leads to dehydration and excessive thirst (polydipsia). *Since cells are starved of glucose, the patient experiences increased hunger (polyphagia). *Paradoxically, the diabetic patient often loses weight, since the cells are unable to take up glucose. These are the classic signs and symptoms of DM. *2ry nocturnal enuresis *ketoacidosis in 30% *Hypoglycemia : in case of insulin overdose

15 Complications of Diabetes Major organs/systems showing changes Cardiovascular system Long term complications myocardial infarct; atherosclerosis; hypertension; microangiopathy; cerebral vascular infarcts; cerebral hemorrhage Pancreas islet cell loss; insulitis (Type 1); amyloid (Type 2) Kidneys Eyes Nervous system Peripherals nephrosclerosis; glomerulosclerosis; arteriosclerosis; pyelonephritis retinopathy; cataracts; glaucoma autonomic neuropathy; peripheral neuropathy peripheral vascular atherosclerosis; infections; gangrene

16 Associated Autoimmune Disorders Thyroid (Hashimoto s, Graves ): 5-10% Celiac Disease: 6% Addison s disease: <1%

17 A for a newly diagnosed patient : Diagnostic Criteria *Symptoms of diabetes and a casual plasma glucose 200 mg/dl, OR *Fasting plasma glucose 126 mg/dl on more than one occasion, OR *2-hour plasma glucose 200 mg/dl during an oral glucose tolerance test. *a HgbA1c 6.5%.

18 *urine glucosuria +- ketone bodies. *serum insulin determination & C-peptide radio immune assay : to differentiate between type 1 and type 2. *Islet cell antibodies (ICA) : in 80-90percent of newly diagnosed type 1 DM. *Anti-insulin antibodies: in percent of newly diagnosed IDDM

19 B-for follow up : -daily blood glucose monitoring. -long term follow up /3 months by HBA1C. Measurements of glycohemoglobin or hemoglobin A1c (HgbA1c) reflect the average blood glucose concentration over the preceding 3 months and provide a means for assessing long-term glycemic control. HgbA1c should be measured four times a year, and the results should be used for counseling of patients.

20 The American Diabetes Association has set HgbA1c targets based on age with children less than 6 years having an HgbA1c target of 7.5% to 8.5%, ages 6 to 13 years HgbA1c target of less than 8%, and ages 13 to 18 years HgbA1c target of less than 7.5%. Measurements of HgbA1c are inaccurate inpatients with hemoglobinopathies. Glycosylated albumin or fructosamine can be used in these cases. 4-Every year the following are done : a-blood urea & serum creatinine. b-cholesterol,lipoprotein, HDL,LDL. e-fundus examination after 5 years of onset of micro albumin in urine.

21 lines of ttt : 1-Diet. 2-Excersise. 3-Insulin. 4-Psycological. 5-Health education. 6-Home glucose monitoring.

22 Diet It is recommended that carbohydrates contribute 50% to 65% of the total calories, protein 12% to 20%, and fat <30%. Saturated fat should contribute <10% of the total caloric intake High fiber content is recommended.

23 Types of insulin

24 Insulin Dose For a patient with new-onset DM1, typical starting total daily doses are approximately 0.5 to 0.7 U/kg/24 hours for pre-pubertal patients and approximately 0.7 to 1 U/kg/24 hours for adolescents, using any number of the available insulin combinations.

25 Insulin regimen

26 2 Injections/day using regular/nph Postprandial glucose levels for breakfast/dinner covered by short acting insulin, lunch and overnight sugars covered by NPH Advantage: 2 Injections/day. Disadvantage: *NPH given at supper does not last until breakfast, leading to high AM BS. *NPH in AM does not cover lunch BS well. *Inflexible- need to eat meals at consistent times with snacks to avoid hypoglycemia *MORE hypoglycemia with this regimen when control is tight

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28 How to use this regamin

29 *The totally daily caloric intake canbe divided as fellow : 3 meals +3 mid meal snacks 1-20% in the breakfast 10 % mid-morning snack 2-20 % in lunch 10 % mid afternoon snack 3-30% in dinner 10% evening snack *Meals and snacks should be kept constant time each day. *Diet with high fiber contenets are useful in control of blood glucose in DM.

30 4 Injections/day using Lispro/Glargine One dose basal insulin during day and overnight, with rapid/short acting insulin covering meals. Advantage: *More flexible: timing and amount of meals *Allows patient to be in control, instead of insulin controlling lifestyle *Allows for frequent corrections/adjustments through the day *When used correctly will provide the best A1c with less hypoglycemia! Disadvantage: Its 4 injections

31 Intensive therapy reduced risk by: 76% for retinopathy 54% for nephropathy 69% for neuropathy 41% for macrovascular disease

32 How to use this regimen 50% is given usually at bed time as long-acting insulin, while the remainder is given as fast-acting insulin, divided according to the need for corrections of high glucose levels and for meals.

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34 Psychosocial Support Every newly diagnosed family should meet with a psychologist Guilt Anger Fear Denial Depression

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36 Type 1 versus type 2 diabetes No set of criteria or diagnostic test can consistently distinguish between T1DM and T2DM. Therefore, differentiating between the two types is based upon a combination of the clinical presentation and history, often supported by laboratory studies. Clinical characteristics: Body habitus Patients with T2DM are usually obese. In contrast, children with T1DM are usually not obese and often have a recent history of weight loss. Age About 45 percent of children with T1DM present before 10 years of age. By contrast, almost all cases of T2DM present after 10 years of age

37 Insulin resistance Patients with T2DM frequently have acanthosis nigricans (a sign of insulin resistance),these findings are less likely in children with T1DM. Family history Up to 10 percent of patients with T1DM have an affected close relative, whereas 75 to 90 percent of those with T2DM have an affected close relative