mellitus Dr Laurence Lacroix 26.03.2014 1
DEFINITION: Group of diseases characterized by a disorder of glucose homeostasis with high levels of blood glucose resulting from defects in : o insulin production o insulin action o both mechanisms 2
ETYMOLOGY: o 1500 BC: Egyptian manuscript mentioning "too great emptying of the urine o 230 BC: Diabetes comes from the ancient Greek "diabainen" (= to pass through) Démétrios d'apnée o Mellitus means sweet like honey in latin 3
TYPES of DIABETES MELLITUS: o Type 1 DM (insulin-dependent diabetes mellitus (IDDM) or juvenile diabetes) results from the body's failure to produce insulin (requires exogenous insulin). o Type 2 DM (non insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes) results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes combined with an absolute insulin deficiency. 4
TYPES of DIABETES MELLITUS : o Gestational diabetes occurs when pregnant women without a previous diagnosis of diabetes develop a high blood glucose level. It may precede development of type 2 DM. o Other forms: congenital diabetes (due to genetic defects), pancreatic insufficiency related diabetes, glucocorticoid-induced diabetes and several forms of monogenic diabetes (MODY) 5
Let s focus on type I diabetes! 6
glucagon insuline somatostatine Pancreatic 7 polypeptide
PATHOPHYSIOLOGY Type I diabetes o Autoimmune destruction of insulinproducing islet β-cells in the pancreas 8
ETIOLOGY Impaired immunoregulation Low maternal vit D levels? Genetic susceptibility Autoimmune islet cells destruction Insulin deficiency Clinical type 1 diabetes Viral triggers? Vaccinations? Food? Cow milk proteins Cereals Root vegetables 9
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10% 11
5% 12
GENETIC FACTORS Type I diabetes o Increased risk if any member of the family is affected: o mother: 1 4% o father: 4 8% o both parents: 20% o brother or sister: 6% o monozygotic twin: 30 70% o Association with HLA DR3-DQ2 and DR4-DQ8 o Association with over 40 genetic loci 13
EPIDEMIOLOGY: o o Type I diabetes T1D accounts for 5 10% of the total cases of diabetes worldwide 3% annual increase in incidence rate Newly reported cases of Type 1 Diabetes in children 0-14 years per 100 000 children/year (2011) Adapted from the International Diabetes Federation Atlas 14
EPIDEMIOLOGY-AFRICA: o few data in African countries Type 1 diabetes mellitus in the African population: epidemiology and management challenges Acta Biomed 2008; 79: 255-259 15
SEASONAL VARIATIONS: Sloka S. et al. Pediatric Diabetes 2008; 9: 81-86 16
PHYSIOLOGY: 17
PATHOPHYSIOLOGY: Type I diabetes 18
PATHOPHYSIOLOGY: Type I diabetes 19
COMPLICATIONS: Type I diabetes o Microvascular disease o Nephropathy o Retinopathy o Neuropathy o Macrovascular disease (atherosclerosis) o Coronary artery disease o Peripheral vascular disease o Stroke importance of tight glycemic control! 20
ASSOCIATED AUTOIMMUNE DISORDERS: o Autoimmune thyroid dysfunction (20% in patients with T1DM) o TSH screening every 1-2 years o TSH screening at any time if clinical suspicion o Celiac disease (4.5% prevalence) o Tissue transglutaminase antibodies o Endomysial antibodies 21
SYMPTOMS: (1-2 weeks-few months before presentation): classic symptoms o Polyuria (nycturia!) /polydipsia o Polyphagia o Weight loss early symptoms o Fatigue o Vague abdominal pain o Recurrent infections recurrent UTIs, candida infections resistant to treatment 22
KETOACIDOSIS CLINICAL SIGNS: Previously described symptoms + Moderate to severe dehydration o Dry mucous membranes o Reduction in urine output o Decreased peripheral perfusion o delayed capillary refill time > 3 sec o cool and mottled extremities o Irritability o Reflex tachycardia +/- hypotension o Decreased skin turgor 23
KETOACIDOSIS CLINICAL SIGNS: Previously described symptoms +: o Labored breathing with polypnea(kussmaul) o Fruity smelling breath 24
KETOACIDOSIS CLINICAL SIGNS: Previously described symptoms +: o Labored breathing with polypnea(kussmaul) o Fruity smelling breath 25
SYMPTOMS OF KETOACIDOSIS: Previously described symptoms +: o Digestive symptoms o Nausea o Vomiting o Abdominal pain (acute abdomen! ) o Mental status alteration cerebral edema in 0.5%-1% of pediatric DKA cases 26
21-24% mortality 27
DIFFERENTIAL DIAGNOSIS: o Polyuria/polydypsia: o Other forms of diabetes o Diabetes insipidus o DKA: other causes of confusion with severe acidosis o Intoxications o Shock (sepsis) 28
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COMPLEMENTARY EXAMINATION: o Blood: blood glucose level confirms the diagnosis o Serum fasting glucose 7.0 mmol/l (126 mg/dl) OR o A serum glucose 11.1 mmol/l (200 mg/dl) 2 hours after eating 1.75 g/kg (max. 75g) of glucose (oral glucose tolerance test) o Prepare an extra tube of blood for: o A1c Hemoglobin o Autoantibodies o Other viral serologies 30
COMPLEMENTARY EXAMINATION: o Urine: Urinary dipstick testing: o High levels of glucose o Ketones 31
CASE DEFINITION: o Serum fasting glucose 7.0 mmol/l (126 mg/dl) OR o Postprandial serum glucose 11.1 mmol/l (200 mg/dl) 2 hours after ingesting 1.75 g/kg (max. 75g) of glucose (oral glucose tolerance test) OR o A1c Hemoglobin 6.5% AND hyperglycemia AND No other cause of hyperglycemia 32
TREATMENT GOALS: Type I diabetes o Restore euglycemia o Facilitate o metabolism o storage of consumed food 33
TREATMENT: Insulin o 0.5 and 1.0 units/kg/day for children with longstanding diabetes o prepubertal chidren o during puberty 50% longacting insulin 50% rapid or short-acting insulin Total daily dose of insulin 34
The «basal-bolus» or «multiple dailyinjection» regimen: Physiologic insulin secretion of a healthy pancreas. Source: Current Paediatrics, Vol 16, Thompson R, Christie D, Hindmarsh PC, The role for insulin analogs in diabetes care, pp 117-122 o rapid-acting insulin : given with meals and snacks o long-acting insulin : steady amount of insulin with little to no peak between mealtimes 35
DKA TREATMENT: o Fluid and electrolyte therapy o o cautious rehydration over the next 48 hours Monitor K + and give IV K + supplements (intracellular shift of potassium with insulin and reduction of acidosis) o Insulin o Treatment of cerebral edema o Mannitol o Hypertonic saline (3%) 36
TREATMENT: injection pump 37
TREATMENT: Diet o Essential component of a good glycemic control o Medical nutrition therapy 38
TREATMENT: Exercise positively affects the overall: o Physical o Mental o Social health In youth with T1DM Should be encouraged with careful glucose monitoring 39
FAMILY EDUCATION: Type I diabetes Caregivers should be able to: o Check and record blood glucose concentrations using a home blood glucometer o Deliver insulin (syringe or pump) o Detect and treat hypoglycemia o Ideally, multidisciplinary team: pediatric endocrinologist, nurse educator, dietetician, social worker, child life specialist, mental health professional. 40
CONCLUSION: Type 1 diabetes Mellitus can present: o With classic symptoms (polyuria, polydipsia, polyphagia, and weight loss) o With diabetic ketoacidosis (vomiting, abdominal pain, and lethargy in addition to the classic symptoms) o As an incidental finding discovered on urine or blood testing performed for other reasons. o Prompt recognition is important in order to avoid lifethreatening complications o Lifelong careful treatment is important in order to avoid complications 41
SUGGESTED READING: Type I diabetes o Type 1 diabetes mellitus. Gregory JM, Moore DJ, Simmons JH. Pediatr Rev. 2013 May;34(5):203-15 o Epidemiology of Type 1 Diabetes. Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Endocrinol Metab Clin North Am. Sep 2010; 39(3): 481 497. o Insulin Therapy in Children and Adolescents with Type 1 Diabetes. Malik FS, Taplin CE. Paediatr Drugs. 2014 Jan 24. DOI 10.1007/s40272-014-0064-6 42
QUESTIONS 43