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UPDATE ON CHILDHOOD DIABETES MELLITUS

UPDATE ON CHILDHOOD DIABETES MELLITUS. Abdelaziz Elamin MD, PhD, FRCPCH Professor of Child Health Sultan Qaboos University. DEFINITION. The term diabetes mellitus describes a metabolic disorder of multiple etiologies characterized by chronic

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UPDATE ON CHILDHOOD DIABETES MELLITUS

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  1. UPDATE ON CHILDHOOD DIABETES MELLITUS Abdelaziz Elamin MD, PhD, FRCPCH Professor of Child Health Sultan Qaboos University

  2. DEFINITION • The term diabetes mellitus describes a metabolic disorder of multiple etiologies characterized by chronic hyperglycemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects of insulin secretion, insulin action or both.

  3. DIABETES EPIDEMIOLOGY • Diabetes is the most common endocrine problem & is a major health hazard worldwide. • Incidence of diabetes is alarmingly increasing all over the globe. • Incidence of childhood diabetes range between 3-50/100,000 worldwide; in Oman it is estimated as 4/100000 per year.

  4. OLD CLASSIFICATION (1985) • Type 1, Insulin-dependent (IDDM) • Type 2, Non Insulin-dependent (NIDDM) • obese • non-obese • MODY • IGT • Gestational Diabetes

  5. WHO CLASSIFICATION 2000 • Is based on etiology not on type of treatment or age of the patient. • Type 1 Diabetes (idiopathic or autoimmune b-cell destruction) • Type 2 Diabetes (defects in insulin secretion or action) • Other specific types

  6. WHO CLASSIFICATION/2 • Both type 1 & type 2 can be further subdivided into: • Not insulin requiring • Insulin requiring for control • Insulin requiring for survival • Gestational diabetes is a separate entity • Impaired Glucose Tolerance (IGT) indicates blood glucose levels between normal & diabetic cut off points during glucose tolerance test.

  7. Fasting blood glucose level Diabetic Plasma >7.0 mmol Capillary >6.0 mmol IGT Plasma 6.0-6.9 mmol Capillary 5.6-6.0 mmol 2 hours after glucose load (Plasma or capillary BS) IGT 7.8-11.0 Diabetic level > 11.1 (200 mg) DIAGNOSTIC CRITERIA

  8. Types of Diabetes in Children • Type 1 diabetes mellitus accounts for >90% of cases. • Type 2 diabetes is increasingly recognized in children with presentation like in adults. • Permanent neonatal diabetes • Transient neonatal diabetes • Maturity-onset diabetes of the young • Secondary diabetes e.g. in cystic fibrosis or Cushing syndrome.

  9. MODY • Usually affects older children & adolescents • Not rare as previously considered • 5 subclasses are identified, one subclass has specific mode of inheritance (AD) • Not associated with immunologic or genetic markers • Insulin resistance is present

  10. TRANSIENT NEONATAL DIABETES • Observed in both term & preterm babies, but more common in preterm • Caused by immaturity of islet b-cells • Polyuria & dehydration are prominent, but baby looks well & suck vigorously • Highly sensitive to insulin • Disappears in 4-6 weeks

  11. PERMANENT NEONATAL DIABETES • A familial form of diabetes that appear shortly after birth & continue for life • The usual genetic & immunologic markers of Type 1 diabetes are absent • Insulin requiring, but ketosis resistant • Is often associated with other congenital anomalies & syndromes e.g. Wolcott-Rallison syndrome.

  12. TYPE 1 DIABETES: ETIOLOGY • Type 1 diabetes mellitus is an autoimmune disease. • It is triggered by environmental factors in genetically susceptible individuals. • Both humoral & cell-mediated immunity are stimulated.

  13. GENETIC FACTORS • Evidence of genetics is shown in • Ethnic differences • Familial clustering • High concordance rate in twins • Specific genetic markers • Higher incidence with genetic syndromes or chromosomal defects

  14. AUTOIMMUNITY • Circulating antibodies against b-cells and insulin. • Immunofluorescent antibodies & lymphocyte infiltration around pancreatic islet cells. • Evidence of immune system activation. Circulating immune complexes with high IgA & low interferon levels. • Association with other autoimmune diseases.

  15. ENVIRONMENTAL INFLUENCE • Seasonal & geographical variation. • Migrants take on risk of new home. • Evidence for rapid temporal changes. • Suspicion of environmental agents causing disease which is confirmed by case-control experimental animal studies.

  16. ENVIRONMENTAL SUSPECTS • Viruses • Coxaschie B • Mumps • Rubella • Reoviruses • Nutrition & dietary factors • Cow’s milk protein • Contaminated sea food

  17. OTHER MODIFYING FACTORS • The counter-regulatory hormones: • glucagon • cortisol, • catecholamines • thyroxin, • GH & somatostatin • sex hormones • Emotional stress

  18. ETIOLOGIC MODEL • The etiologic model of type 1 diabetes resembles that of Rheumatic fever. • Rheumatic fever was prevented by elimination of the triggering environ. factor (b-streptococci). • Similarly type 1 diabetes may be prevented by controlling the triggering factors in high risk persons.

  19. CLINICAL PRESENTATIONS • Classical symptom triad: • polyuria, polydipsia and weight loss • DKA • Accidental diagnosis • Anorexia nervosa like illness

  20. DIAGNOSIS • In symptomatic children a random plasma glucose >11 mmol (200 mg) is diagnostic. • A modified OGTT (fasting & 2h) may be needed in asymptomatic children with hyperglycemia if the cause is not obvious. • Remember: acute infections in young non-diabetic children can cause hyperglycemia without ketoacidosis.

  21. NATURAL HISTORY • Diagnosis & initiation of insulin • Period of metabolic recovery • Honeymoon phase • State of total insulin dependency

  22. METABOLIC RECOVERY During metabolic recovery the patient may Develop one or more of the following: • Hepatomegaly • Peripheral edema • Loss of hair • Problem with visual acuity These are caused by deposition of glycogen & metabolic re-balance.

  23. HONEYMOON PERIOD • Due to b-cell reserve optimal function & initiation of insulin therapy. • Leads to normal blood glucose level without exogenous insulin. • Observed in 50-60% of newly diagnosed patients & it can last up to one year but it always ends. • Can confuse patients & parents if not educated about it early.

  24. COMPLICATIONS OF DIABETES • Acute: • DKA • Hypoglycemia • Late-onset: • Retinopathy • Neuropathy • Nephropathy • Ischemic heart disease & stroke

  25. TREATMENT GOALS • Prevent death & alleviate symptoms • Achieve biochemical control • Maintain growth & development • Prevent acute complications • Prevent or delay late-onset complications

  26. TREATMENT ELEMENTS • Education • Insulin therapy • Diet and meal planning • Monitoring • HbA1c every 2-months • Home regular BG monitoring • Home urine ketones tests when indicated

  27. EDUCATION • Educate child & care givers about: • Diabetes • Insulin • Life-saving skills • Recognition of Hypo & DKA • Meal plan • Sick-day management

  28. INSULIN • A polypeptide made of 2 b-chains. • Discovered by Bants & Best in 1921. • Animal types (porcine & bovine) were used before the introduction of human-like insulin (DNA-recombinant types). • Recently more potent insulin analogs are produced by changing aminoacid sequence.

  29. FUNCTION OF INSULIN • Insulin being an anabolic hormone stimulates protein & fatty acids synthesis. • Insulin decreases blood sugar • By inhibiting hepatic glycogenolysis and gluconeogenesis. • By stimulating glucose uptake, utilization & storage by the liver, muscles & adipose tissue.

  30. TYPES OF INSULIN • Short acting (neutral, soluble, regular) • Peak 2-3 hours & duration up to 8 hours • Intermediate acting • Isophane (peak 6-8 h & duration 16-24 h) • Biphasic (peak 4-6 h & duration 12-20 h) • Semilente (peak 5-7 h & duration 12-18 h) • Long acting (lente, ultralente & PZI) • Peak 8-14 h & duration 20-36 h

  31. INSULIN CONCENTRATIONS • Insulin is available in different concentrations 40, 80 & 100 Unit/ml. • WHO now recommends U 100 to be the only used insulin to prevent confusion. • Special preparation for infusion pumps is soluble insulin 500 U/ml.

  32. INSULIN REGIMENS • Twice daily: either NPH alone or NPH+SI. • Thrice daily: SI before each meal and NPH only before dinner. • Intensive 4 times/day: SI before meals + NPH or Glargine at bed time. • Continuous s/c infusion using pumps loaded with SI.

  33. INSULIN ANALOGS • Ultra short acting • Insulin Lispro • Insulin Aspart • Long acting without peak action to simulate normal basal insulin • Glargine

  34. NEW INSULIN PREPARATIONS • Inhaled insulin proved to be effective & will be available within 2 years. • Nasal insulin was not successful because of variable nasal absorption. • Oral insulin preparations are under trials.

  35. ADVERSE EFFECTS OF INSULIN • Hypoglycemia • Lipoatrophy • Lipohypertrophy • Obesity • Insulin allergy • Insulin antibodies • Insulin induced edema

  36. PRACTICAL PROBLEMS • Non-availability of insulin in poor countries • injection sites & technique • Insulin storage & transfer • Mixing insulin preparations • Insulin & school hours • Adjusting insulin dose at home • Sick-day management • Recognition & Rx of hypo at home

  37. DIET REGULATION • Regular meal plans with calorie exchange options are encouraged. • 50-60% of required energy to be obtained from complex carbohydrates. • Distribute carbohydrate load evenly during the day preferably 3 meals & 2 snacks with avoidance of simple sugars. • Encouraged low salt, low saturated fats and high fiber diet.

  38. EXERCISE • Decreases insulin requirement in diabetic subjects by increasing both sensitivity of muscle cells to insulin & glucose utilization. • It can precipitate hypoglycemia in the unprepared diabetic patient. • It may worsen pre-existing diabetic retinopathy.

  39. MONITORING • Compliance (check records) • HBG tests • HbA1 every 2 months • Insulin & meal plan • Growth & development • Well being & life style • School & hobbies

  40. ADVANCES IN MONITORING • Smaller & accurate meters for intermittent BG monitoring • Glucowatch continuous monitoring using reverse iontophoresis to measure interstitial fluid glucose every 20 minutes • Glucosensor that measures s/c capillary BG every 5 minutes • Implantable sensor with high & low BG alarm

  41. ADVANCES IN MANAGEMENT • Better understanding of diabetes allows more rational approach to therapy. • Primary prevention could be possible if the triggering factors are identified. • The DCCT studies proves beyond doubt that chronic diabetic complication can be controlled or prevented by strict glycemic control.

  42. TREATMENT MADE EASY • Insulin pens & new delivery products • Handy insulin pumps • fine micro needles • Simple accurate glucometers • Free educational material • computer programs for comprehensive management & monitoring

  43. TELECARE SYSTEMS • IT has improved diabetes care • Internet sites for education & support • Web-based systems for telecare are now available. The patient feeds his HBGM data and get the physician, nurse & dietician advice on the required modification to diet & insulin treatment.

  44. PITFALLS OF MANAGEMENT • Delayed diagnosis of IDDM • The honey-moon period • Detection & treatment of NIDDY • Problems with diagnosis & treatment of DKA & hypoglycemia • Somogi’s effect (dawn phenomenon) may go unrecognized.

  45. FUTURE PROMISES • The cure for IDDM is successful islet cell transplantation, which will be available in the near future. • Primary prevention by a vaccine or drug will be offered to at risk subjects identified by genetic studies. • Gene modulation therapy for susceptible subjects is a promising preventive measure.

  46. Pancreas & Islet Cell Transplantation • Pancreas transplants are usually given to diabetics with end stage renal disease. • Islet cell transplants, the ultimate treatment of type 1 diabetes is under trial in many centers in the US & Europe with encouraging results but graft rejection & recurrence of autoimmunity are serious limitations.

  47. IMMUNE MODULATION • Immunosuppressive therapy for • Newly diagnosed • Prolonged the honey moon • For high risk children • Immune modulating drugs • Nicotinamide • mycophenolate

  48. GENE THERAPY • Blocks the immunologic attack against islet-cells by DNA-plasmids encoding self antigen. • Gene encode cytokine inhibitors. • Modifying gene expressed islet-cell antigens like GAD.

  49. PREDICTION OF DIABETES • Sensitive & specific immunologic markers • GAD Antibodies • GLIMA antibodies • IA-2 antibodies • Sensitive genetic markers • HLA haplotypes • DQ molecular markers

  50. PREVENTION OF DIABETES • Primary prevention • Identification of diabetes gene • Tampering with the immune system • Elimination of environmental factor • Secondary prevention • Immunosuppressive therapy • Tertiary prevention • Tight metabolic control & good monitoring

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