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Abdelaziz Elamin MD, PhD, FRCPCH Professor of Child Health Sultan Qaboos University
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.
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.
OLD CLASSIFICATION (1985)
Type 1, Insulin-dependent (IDDM) Type 2, Non Insulin-dependent (NIDDM) – obese – non-obese – MODY IGT Gestational Diabetes
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
.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.
0 mmol Capillary >6.0 mmol 2 hours after glucose load (Plasma or capillary BS) IGT 7.6-6.8-11.1 (200 mg) .9 mmol Capillary 5.0 IGT Plasma 6.0 mmol Diabetic level > 11.0-6.DIAGNOSTIC CRITERIA Fasting blood glucose level Diabetic Plasma >7.
.Types of Diabetes in Children Type 1 diabetes mellitus accounts for >90% of cases.g. in cystic fibrosis or Cushing syndrome. Permanent neonatal diabetes Transient neonatal diabetes Maturity-onset diabetes of the young Secondary diabetes e. Type 2 diabetes is increasingly recognized in children with presentation like in adults.
one subclass has specific mode of inheritance (AD) Not associated with immunologic or genetic markers Insulin resistance is present .MODY Usually affects older children & adolescents Not rare as previously considered 5 subclasses are identified.
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 .TRANSIENT NEONATAL DIABETES Observed in both term & preterm babies.
. Wolcott-Rallison syndrome. but ketosis resistant Is often associated with other congenital anomalies & syndromes e.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.g.
.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.
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 .
Circulating immune complexes with high IgA & low interferon levels.AUTOIMMUNITY Circulating antibodies against b-cells and insulin. Evidence of immune system activation. . Immunofluorescent antibodies & lymphocyte infiltration around pancreatic islet cells. Association with other autoimmune diseases.
Evidence for rapid temporal changes.ENVIRONMENTAL INFLUENCE Seasonal & geographical variation. Migrants take on risk of new home. Suspicion of environmental agents causing disease which is confirmed by case-control experimental animal studies. .
ENVIRONMENTAL SUSPECTS Viruses Coxaschie B Mumps Rubella Reoviruses Nutrition & dietary factors Cow’s milk protein Contaminated sea food .
OTHER MODIFYING FACTORS The counter-regulatory hormones: glucagon cortisol. catecholamines thyroxin. GH & somatostatin sex hormones Emotional stress .
. factor (b-streptococci). Rheumatic fever was prevented by elimination of the triggering environ. Similarly type 1 diabetes may be prevented by controlling the triggering factors in high risk persons.ETIOLOGIC MODEL The etiologic model of type 1 diabetes resembles that of Rheumatic fever.
CLINICAL PRESENTATIONS Classical symptom triad: polyuria. polydipsia and weight loss DKA Accidental diagnosis Anorexia nervosa like illness .
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. .DIAGNOSIS In symptomatic children a random plasma glucose >11 mmol (200 mg) is diagnostic.
NATURAL HISTORY Diagnosis & initiation of insulin Period of metabolic recovery Honeymoon phase State of total insulin dependency .
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. .
Leads to normal blood glucose level without exogenous insulin. Can confuse patients & parents if not educated about it early. .HONEYMOON PERIOD Due to b-cell reserve optimal function & initiation of insulin therapy. Observed in 50-60% of newly diagnosed patients & it can last up to one year but it always ends.
COMPLICATIONS OF DIABETES Acute: DKA Hypoglycemia Late-onset: Retinopathy Neuropathy Nephropathy Ischemic heart disease & stroke .
TREATMENT GOALS Prevent death & alleviate symptoms Achieve biochemical control Maintain growth & development Prevent acute complications Prevent or delay late-onset complications .
TREATMENT ELEMENTS Education Insulin therapy Diet and meal planning Monitoring HbA1c every 2-months Home regular BG monitoring Home urine ketones tests when indicated .
EDUCATION Educate child & care givers about: Diabetes Insulin Life-saving skills Recognition of Hypo & DKA Meal plan Sick-day management .
Discovered by Bants & Best in 1921. Animal types (porcine & bovine) were used before the introduction of humanlike insulin (DNA-recombinant types). .INSULIN A polypeptide made of 2 b-chains. Recently more potent insulin analogs are produced by changing aminoacid sequence.
. muscles & adipose tissue. 2. By inhibiting hepatic glycogenolysis and gluconeogenesis. utilization & storage by the liver. Insulin decreases blood sugar 1. By stimulating glucose uptake.FUNCTION OF INSULIN Insulin being an anabolic hormone stimulates protein & fatty acids synthesis.
ultralente & PZI) Peak 8-14 h & duration 20-36 h . 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.TYPES OF INSULIN Short acting (neutral.
WHO now recommends U 100 to be the only used insulin to prevent confusion. 80 & 100 Unit/ml.INSULIN CONCENTRATIONS Insulin is available in different concentrations 40. . Special preparation for infusion pumps is soluble insulin 500 U/ml.
Thrice daily: SI before each meal and NPH only before dinner. Continuous s/c infusion using pumps loaded with SI. .INSULIN REGIMENS Twice daily: either NPH alone or NPH+SI. Intensive 4 times/day: SI before meals + NPH or Glargine at bed time.
INSULIN ANALOGS Ultra short acting Insulin Lispro Insulin Aspart Long acting without peak action to simulate normal basal insulin Glargine .
. Oral insulin preparations are under trials.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.
ADVERSE EFFECTS OF INSULIN Hypoglycemia Lipoatrophy Lipohypertrophy Obesity Insulin allergy Insulin antibodies Insulin induced edema .
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 .
. Encouraged low salt. low saturated fats and high fiber diet.DIET REGULATION Regular meal plans with calorie exchange options are encouraged. Distribute carbohydrate load evenly during the day preferably 3 meals & 2 snacks with avoidance of simple sugars. 50-60% of required energy to be obtained from complex carbohydrates.
It can precipitate hypoglycemia in the unprepared diabetic patient. .EXERCISE Decreases insulin requirement in diabetic subjects by increasing both sensitivity of muscle cells to insulin & glucose utilization. It may worsen pre-existing diabetic retinopathy.
MONITORING Compliance (check records) HBG tests HbA1 every 2 months Insulin & meal plan Growth & development Well being & life style School & hobbies .
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 .
The DCCT studies proves beyond doubt that chronic diabetic complication can be controlled or prevented by strict glycemic control.ADVANCES IN MANAGEMENT Better understanding of diabetes allows more rational approach to therapy. Primary prevention could be possible if the triggering factors are identified. .
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 .
nurse & dietician advice on the required modification to diet & insulin treatment. The patient feeds his HBGM data and get the physician. .TELECARE SYSTEMS IT has improved diabetes care Internet sites for education & support Web-based systems for telecare are now available.
.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.
. 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.FUTURE PROMISES The cure for IDDM is successful islet cell transplantation. Gene modulation therapy for susceptible subjects is a promising preventive measure.
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.Pancreas & Islet Cell Transplantation Pancreas transplants are usually given to diabetics with end stage renal disease. .
IMMUNE MODULATION Immunosuppressive therapy for Newly diagnosed Prolonged the honey moon For high risk children Immune modulating drugs Nicotinamide mycophenolate .
. Gene encode cytokine inhibitors.GENE THERAPY Blocks the immunologic attack against islet-cells by DNAplasmids encoding self antigen. Modifying gene expressed isletcell antigens like GAD.
PREDICTION OF DIABETES Sensitive & specific immunologic markers GAD Antibodies GLIMA antibodies IA-2 antibodies Sensitive genetic markers • HLA haplotypes • DQ molecular markers .
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 .
Dreams are the seedlings of realities .