DIABETES Paediatrics and Adolesence

1. DIABETES Paediatrics and Adolesence Dr Aisling Myers Clinical Lecturer

2. Classification • Type 1 (Autoimmune, Idiopathic) • Type 2 • Others • Genetic defects of β-cell function (e.g. MODY) • Pancreatic diseases (e.g. cystic fibrosis) • Endocrinopathies (e.g. Cushing Syndrome) • Iatrogenic (e.g. Glucocorticoids) • Infections (e.g. Congenital Rubella) • Other syndromes (e.g Prader Willi Syndrome) • Gestational

3. Diabetes – Type 1 • Most common metabolic disease in the young • Third most common chronic disorder in childhood after asthma and cerebral palsy • Life threatening, life long • Incidence rising, presenting at younger age • Chronic hyperglycaemia • Defect in insulin secretion / action

4. Normoglycaemia

5. Uncontrolled Diabetes Mellitus

6. Insulin deficiency

7. Pathogenesis • Deficiency of insulin secretion • Prone to ketoacidosis • T-cell mediated pancreatic islet β-cell destruction • β-cell destruction – occurs at variable rate • Process begins months/years before presentation with clinical symptoms. ? Viral trigger • Clinically symptomatic when ~ 90% of β-cells destroyed • HLA genes – 8-10 fold risk if HLA-DR3 or HLA-DR4

8. Serological Markers • Serological markers present in 85-90% at presentation • Autoimmune pathologic process • Islet cell Autoantibodies (ICA) • Insulin Autoantibodies (IAA) • Glutamic Acid Decarboxylase (GAD)

9. Epidemiology • Over 50% diagnosed before 15 yrs • T1DM – accounts for >90% of childhood and adolescent diabetes • Type 2 – becoming more common • Incidence variable - Highest in Finland. • 12 – 15% will have affected first degree relative • 3 times more likely to develop diabetes if father also affected vs mother • Screening unethical unless part of trial – no effective methods of prevention

10. Diagnosis 1 • Symptoms……plus • Hyperglycaemia (random blood sugar >11mmol/litre) Or • Fasting blood sugar >7.0 mmol/litre Or • 2hr post prandial sugar >11 mmol/litre Or • OGTT

11. Diagnosis 2 • Presentation • Polyuria, polydipsia, weight loss • Glycosuria, Ketonuria • Diabetic Ketoacidosis (DKA) – urgent • Non-ketotic hyperosmolar state • Recent onset enuresis in previously trained child • Vaginal candidiasis (prepubertal) • Vomiting • Chronic weight loss, failure to thrive • Recurrent skin infections

12. Management • Urgent (same day) referral to multidisciplinary paediatric diabetes care team • Admission or home based care • Admit: • DKA • <2 yrs old • Social / Emotional issues • Family living long distance from hospital • Peripheral hospital

13. DKA • Clinical history • Polyuria, polydipsia, wgt loss, abdo pain, weakness, vomiting, confusion, stupor, coma. • Clinical signs • Dehydration, smell of ketones, lethargy, drowsiness, Kussmaul breathing • Biochemical signs • Ketones (blood/urine), hyperglycaemia (>11), acidosis (pH < 7.3), other electrolyte abnormalities

14. DKA • Airway Breathing Circulation (ABC) • Admit ICU • IV access x 2 • Oxygen • Fluid resuscitation / IV Insulin / Potassium • Electrolyte monitoring (hrly, 2hrly, 4hrly) – K+ • Close monitoring • Sepsis/Infection • Neurological deterioration • Cerebral oedema

15. Subcutaneous insulin when clinically well and tolerating food / fluids Injection sites Abdomen Thighs Buttocks Insulin

16. Insulin Preparations

17. Insulin Regimens • 1, 2 or 3 injections per day: rapid or short acting insulin premixed or self mixed with intermediate acting insulin • MDI regimen: rapid or short acting insulin before meals with intermediate or long acting insulin • Insulin pump therapy (CSII) – most physiological. Requires commitment , competence and good family support

18. Phases of Diabetes • Preclinical diabetes • Months or years prior to presentation • Antibodies (Islet cell, Insulin, Glutamic Acid Decarboxylase) - positive • Presentation • Partial remission (“Honeymoon” Phase) • 80% of cases transient decrease in insulin requirements • Duration – weeks to months • Important to inform parents that this phase is transient • Chronic • Lifelong insulin therapy

19. Education • Insulin • Monitoring glycaemic control (HbA1C) • Diet • Exercise • Smoking / Alcohol / Substance misuse • Intercurrent illness (sick days) • Hypoglycaemic episodes • Avoidance, detection, management

20. Multidisciplinary Team • Consultant and diabetic team • Diabetic Nurse Specialists • Dietician • Psychology • Social Worker • Ophthalmology • Chiropody • GP

21. Follow-Up • Aim for frequent blood sugar monitoring (usually 4 BM’s daily – fingerprick) • Aim for pre-prandial sugar: 4 – 8 mmol/L • Aim for post-prandial sugar: < 10mmol/L • Adjust insulin doses accordingly • Liaise with diabetic team (phone / clinic) • Monitor sugars more often during intercurrent illness

22. Clinic Visits • Monitor growth (height, weight, BMI) • Pubertal development • HbA1C (< 7.5%) • Check injection sites • Review foot care • Annual screen • Retinopathy • Nephropathy (Microalbuminuria, Blood Pressure) • Associated conditions • Thyroid disease • Coeliac Disease

23. Ongoing Care • Constant re-education • Encourage family involvement • Psychology (NB in teenage years) • Tailor insulin therapy and delivery methods to each patient / family • Screen for complications • Transition to adult care – smooth

24. Surgical Procedures • In centres with facilities for care of children/young people with diabetes • Agree protocol for safe management. • Ensure first on list. • Inform anaesthetic team • Check regular blood sugars • Check electrolytes (K) • Check for glycosuria, ketonuria

25. Complications • Short Term / Ongoing • Hypoglycaemia • DKA • Sick days • Lipohypertrophy (48%) • Psychological • Long Term • Retinopathy • Nephropathy • Neuropathy • Macrovascular Disease

26. Hypoglycaemia • Carry T1DM identification (bracelet) • Rapid access to CHO and blood sugar monitor • Educate carers re glucagon administration and advice to seek medical assistance if failing to respond (seizures can occur if untreated) • Patients – increase awareness and respond appropriately • Avoid over corrections at meals especially at night – overnight or fasting hypo • Avoid very low HbA1C

27. DKA • Untreated – stupor, coma, death • Follow proposed guidelines for institution • Initial management in HDU • Transfer to paeds ICU if not responding • Outrule co-existing sepsis • Monitor closely for signs of deterioration • Impaired consciousness • Suspected cerebral oedema

28. Sick Days • Sick Day Rules • Extra blood sugars • Check for ketones • Hrly / 2 hrly snacks • If persistent vomiting or if not tolerating – bring to hospital • Regular phone contact with nurse specialist/team • NEVER OMIT INSULIN

29. Psychological / Social Issues • Emotional / Behavioural • Family Conflict • Anxiety / Depression • Eating Disorders • Cognitive Disorders • Behavioural / Conduct Disorders • Non – compliance

30. Complications

31. Visual impairment Blindness Poor glycaemic control Laser treatment if sight threatening Ophthalmology check annually from 12 years or if diagnosed >5yrs Long Term - Retinopathy

32. Renal failure Hypertension Early morning urine for microalbuminuria Albumin:Creatinine ratio Monitor BP at clinic visits Screen annually from 12 yrs or if diagnosed > 5yrs Long Term - Nephropathy

33. Stroke Ischaemic Heart Disease Peripheral Vascular Disease Long Term - Macrovascular

34. Associated Conditions/Complications • Impaired growth and development • Late pubertal development • Obesity (excessive exogenous insulin assoc with high energy intake) • Autoimmune conditions • Hypothyroidism • Hyperthyroidism • Coeliac Disease • Addison’s Disease

35. Other types of Diabetes

36. Type 2 Diabetes • Rising prevalence – associated with increasing obesity

37. Type 2 Diabetes • Insulin resistance • Acanthosis nigricans • High insulin or c-peptide levels • Dyslipidemia • Polycystic ovarian syndrome • More common in ethnic minority groups • Japan – more common than T1DM

38. Type 2 Diabetes • Commonly presents in mid-puberty • Confused with MODY (monogenic maturity onset diabetes of the young) • Screen if obese, positive family history or signs of insulin resistance • Lifestyle changes – diet, exercise • Pharmacotherapy – not licensed in children • Early intervention – best prevention

39. Neonatal Diabetes • Very rare (1 in 400,000 births) • Insulin requiring hyperglycaemia in first 3-6 mths of life • May be associated with IUGR (intra uterine growth retardation) • 50% cases transient • Permanent – associated with pancreatic aplasia, genetic mutations • Predisposition to impaired glucose tolerance and Type 2 diabetes in later life

40. Cystic Fibrosis (CFRD) • Insulin deficiency • Insulin resistance • Infections • Medications (steroids, bronchodilators) • Occurs late in disease (adolescence, early adulthood) • Cirrhosis contributes to insulin resistance • Onset of CFRD – poor prognostic indicator • Poor control – promotes catabolism • Screening – OGTT as part of annual screen >10yrs • Insulin doses usually smaller than in classic T1DM

41. MODY • Maturity Onset Diabetes of the Young • Single gene disorder causing β cell dysfunction • Autosomal dominant family history • Endogenous insulin secretion • Not prone to ketoacidosis • No signs of insulin resistance • Usually require less insulin than classic T1DM • Mutations found in >80% of patients (5)

42. Other causes • Drug-induced diabetes • Neurosurgery (Dexamethasone) • Oncology (chemotherapy) • Stress Hyperglycaemia • Reported in up to 5% attendances to A&E • Acute illness, trauma, post seizure, fever • Recheck blood sugar series when well

43. Islet Cell Transplantation • Islet cells replaced with harvested donor cells • Typically receive cells from up to 3 donors • Experimental therapy • Shortage of donor material • Still require insulin therapy • Anti-rejection drugs – severe side effects

44. The Future

45. Key Points • Lifelong disease • Never omit insulin • Healthy lifestyle for all the family • Good glycaemic control • Screen for complications • Prevention better than cure!

46. Thank You