Treatment of children and adolescents with diabetes

1. A practical reference manual Treatment of children and adolescents with diabetes Dr. Birthe S Olsen, Consultant PaediatricianDr. Henrik Mortensen, Chief Physician, Senior Paediatric Endocrinologist Department of Paediatrics, Glostrup University Hospital, Copenhagen, Denmark

2. Childhood diabetes • 90% Type 1 diabetes • Absolute or relative insulin deficiency • Auto-immune process • Pancreatic beta-cell destruction Definition

3. Aetiology • Genetic susceptibility: • HLADR3, HLADR4: risk increased • HLADR2 : risk reduced • Environmental factors: • viral factors • nutritional factors Definition

4. Epidemiology • Most common endocrine disease in childhood • Highest incidence in Finland and Sardinia • Highest incidence in males • Highest incidence at 10–12 years and 5–7 years • Increasing incidence in very young children (0–4 years) • Seasonality • More common in families where father has diabetes Definition

5. Pre-diabetes phase • Gradual destruction of beta-cells • Development of auto-antibodies: • ICA • IAA • GADA Definition

6. Prevention • Primary intervention: • aim: reducing the prevalence of a given condition in susceptible individuals • Example: cow's milk exclusion in infancy • Secondary intervention: • aim: early detection of a given disease and stopping or slowing further progression • Example: ENDIT study • Tertiary intervention: • aim: preventing complications associated with a disease • Example: improvement in glycaemic control, screening for complications Definition

7. Management – primary goals • To ensure that insulin is available for all children • To ensure that the child gradually takes over the responsibility for the disease (self-care) • To ensure optimum glycaemic control • To ensure freedom from diabetic complications • To ensure normal growth and development The newly diagnosed child

8. Early diagnosis • Symptoms and signs: • polydipsia • polyuria • night-time incontinence • loss of weight • irritability • abdominal pain • visual disturbances • frequent infections The newly diagnosed child

9. Early diagnosis • Diagnosis: • fasting blood-glucose concentration > 7.7 mmol/l • random blood-glucose concentration > 11 mmol/l • glucosuria • ketonuria • ketoacidosis • Differential diagnosis: • inflamed appendix • pneumonia • urinary tract infection The newly diagnosed child

10. The multi-disciplinary team • The cornerstone in childhood diabetes management: • a paediatric endocrinologist • a specialised nurse • a specialised dietician • a chiropodist • a specialised social worker • a childhood psychologist • close collaboration with other relevant departments The team

11. The multi-disciplinary team • The team should… • have common attitudes and philosophy • meet regularly for discussion and education • develop written material dealing with daily-life and emergency issues • encourage research into childhood diabetes • attend in-service training The team

12. Diabetes education 1 • Initial ‘survival’ education: • the causes of diabetes • insulin management • injection technique • blood glucose measurements • acceptable blood glucose values • advice about hypo- and hyperglycaemic episodes • dietary advice Diabetes education

13. aetiology and pathology injection devices and methods blood-glucose monitoring diet insulin adjustments hypoglycaemia insulin-treatment hyperglycaemia sick-day management sport alcohol drug abuse travelling gynaecological issues complications Diabetes education 2 Over the next months and years a more comprehensive education programme, adjusted to the age and maturity of the child: Diabetes education

14. Diabetes education 3 • The knowledge and skills of the child should be regularly assessed • Re-education should be performed accordingly Diabetes education

15. Treatment • At diagnosis • Remission phase • Long-term Initial treatment

16. Non-ketotic child • Insulin: • subcutaneous • multiple dose rapid-acting insulin before meals, or • combination of rapid- and intermediate-acting insulin twice daily • insulin requirements may exceed 1.5–2 IU/kg/24 hours • Potassium: • < 12 years 750 mg KCl for 3–4 days • > 12 years 1500 mg KCl for 3–4 days Initial treatment

17. Non-ketoacidotic child • hospital stay as short as possible • in paediatric setting • frequent visits to out-patient clinic • 24-hour hot-line service • home and institution visits • Always managed at hospital in case of: • ketoacidosis • severe dehydration • very young age • infection • psychosocial problems • language and cultural difficulties Initial treatment

18. The remission phase • Duration from weeks to months • Shorter in young children • Blood glucose values between 4–8 mmol/l • Decreasing insulin requirements < 0.5 IU/kg/24 hours • One daily insulin injection is often sufficient • Insulin injections should not be abandoned Partial remission phase

19. Long-term management • Twice daily or multiple insulin injections • Regular blood glucose measurements • At least 4 visits to out-patient clinic every year • Instant HbA1c measurements at every visit • Height and weight measurements at every visit • Physical examination with pubertal staging every year • Regular screening for diabetes related complications Partial remission phase

20. Insulin • All children with Type 1 diabetes must have insulin • Consequences of long-term insulin omission: • growth retardation • delayed puberty • poor metabolic control • microvascular complications • short life expectancy • poor quality of life Insulin

21. Insulin types and duration of action Onset of action (h or min) 30 min. 1–2 h 0.5–1 h 0.5–1 h 0.5–1 h 0.5–1 h 0.5–1 h 10–20 min. Peak action (h) 1–3 4–12 2–8 5–10 5–9 1–3 1–3 1–3 Maximal duration (h) 6–8 18–24 18–24 18–24 18–24 18–24 18–24 3–5 Insulin preparation • Short-acting • Intermediate-acting • Premixed insulin 10/90 • Premixed insulin 20/80 • Premixed insulin 30/70 • Premixed insulin 40/60 • Premixed insulin 50/50 • Rapid-acting insulin analogue Insulin

22. Short-acting insulin • Clear solution • Indications for use: • daily management of diabetes, alone or in combination with intermediate-acting insulin • hyperglycaemia • sick-day management • intravenous therapy Insulin

23. Intermediate-acting insulin • Cloudy solution (should be thoroughly mixed before use) • Indications for use: • daily management of diabetes, alone or in combination with short-acting insulin Insulin

24. Pre-mixed insulin • Cloudy solution (should be thoroughly mixed before use) • Indications for use: • daily management of diabetes, alone or in combination with short-acting insulin Insulin

25. Rapid-acting insulin (Insulin Aspart) • Clinicalbenefits • improved metabolic control compared with human soluble insulin • fewer hypoglycaemic episodes • no post-prandial hypoglycaemia • rapid onset of action • short duration of action • better quality of life and improved convenience Insulin

26. Rapid-acting insulin (Insulin Aspart) • Patient targeting: • newly diagnosed children and adolescents with diabetes • children and adolescents currently on basal/bolus regimens • children and adolecents with poorly controlled diabetes on twice daily therapies Insulin

27. Storage of insulin • Stable at room temperature for weeks • Should not be exposed to temperatures > 25ºC or under freezing point • Unused vials and cartridges should be stored in the refrigerator • Should never be exposed to sunlight • Should never be frozen Insulin

28. Injection sites • Short acting insulin: • injected subcutaneously into the abdomen at a 45° angle • Intermediate-acting and pre-mixed insulins: • injected subcutaneously in the front of the thighs or into the buttocks at a 45° angle Insulin

29. Insulin absorption • Factors influencing insulin absorption: • injection site • injection depth • insulin type • insulin dose • physical exercise • skin temperature Insulin

30. Insulin requirements • Remission period • < 0.5 IU/kg/24 hours • Pre-pubertal period • 0.6–1.0 IU/kg/24 hours • Pubertal period • 1.0–2.0 IU/kg/24 hours Insulin

31. Insulin regimens • Insulin regimens should be: • adjusted to age, maturity and motivation • as simple as possible • Children for multiple injection therapy should: • be selected carefully • understand the relationship between insulin, food and physical exercise • be motivated and have family support • be willing to measure blood glucose several times each day • be willing to inject insulin at school Insulin

32. Insulin regimens • Most widely used insulin regimens: • twice-daily injections, mixture short and intermediate, before breakfast and the evening meal • three daily injections, mixture short and intermediate before breakfast, short-acting before the evening meal and intermediate-acting before bed • short-acting insulin before main meals, intermediate before bed Insulin

33. Insulin distribution • Twice daily injection regimen: • 2/3 of daily dose before breakfast, • 1/3 before supper • both 2/3 intermediate-acting and 1/3 short-acting insulin • Three-times daily injection regimen: • 40–50% before breakfast (2/3 intermediate- and 1/3 short-acting) • 10–15% short-acting before supper • 40% intermediate-acting before bed. • Multiple injection regimen: • 30–40 % (intermediate) before bed • the rest (short-acting) before main meals Insulin

34. Insulin adjustments Twice-daily injection regimen: • Blood glucose high: Dose of insulin to increase • Before breakfast or overnight Evening intermediate-acting • Before lunch Morning short-acting • Before dinner Morning intermediate-acting • Before bed Evening short-acting • Blood glucose low: Dose of insulin to decrease • Before breakfast or overnight Evening intermediate- acting • Before lunch Morning short-acting • Before dinner Morning intermediate-acting • Before bed Evening short-acting Insulin

35. Insulin adjustments Three-times daily injection regimen: • Blood glucose high: Dose of insulin to increase • Before breakfast or overnight Evening intermediate- acting • Before lunch Morning short-acting • Before dinner Morning intermediate-acting • Before bed Evening short-acting • Blood glucose low: Dose of insulin to decrease • Before breakfast or overnight Evening intermediate- acting • Before lunch Morning short-acting • Before dinner Morning intermediate-acting • Before bed Evening short-acting Insulin

36. Insulin adjustments Basal-bolus (multiple injection) regimen: • Blood glucose high: Dose of insulin to increase • Before breakfast or overnight Evening intermediate-acting • Before lunch Morning short-acting • Before dinner Lunch time short-acting • Before bed Evening short-acting • Blood glucose low: Dose of insulin to decrease • Before breakfast or overnight Evening intermediate-acting • Before lunch Morning short-acting • Before dinner Lunch time short-acting • Before bed Evening short-acting Insulin

37. Diet • Nutritional advice should take intoconsideration: • individual requirements • local customs • family dietary habits • General recommendations: • eat a broad variety of food • eat plenty of bread, cereals, vegetables and fruit • eat only small amounts of sugar • in young children fat intake should not be restricted • older children and adolescents should eat a low fat diet • choose food with small amounts of salt • encourage breast-feeding at least until six months of age Diet

38. Diet: principles • Number of meals: • 3 main meals • 3 snacks • adapted to age, physical activity and insulin regimen • Energy intake: • 1000 calories (4180 Kj) + 100 calories/year of age • 50–55% of energy from carbohydrates • 30% of energy from fat • 15–20% of energy from protein Diet

39. Carbohydrates • Glycaemic index (GI): • carbohydrate ranking system • based on post-prandial blood glucose response • low GI = slow, sustained blood glucose response (e.g. rice, pasta) • high GI = rapid and high blood-glucose response (e.g. white bread, candy/sweets, cornflakes, honey, sugar) Diet

40. Carbohydrates • Carbohydrate exchange system: • based on the carbohydrate content and not the weight of the food • makes it easy to exchange carbohydrate containing food elements (e.g. 15 g carbohydrates in candy for 15 g carbohydrates in fruit) • one exchange usually contains 10–15 g carbohydrate Diet

41. Effects of exercise • Increases insulin sensitivity • Improves the physical state • Reduces the risk of cardiac diseases • Reduces the risk of hypertension • Does not improve metabolic control • Increases the risk of hypoglycaemia Exercise

42. Food adjustments Exercise

43. Guidelines • Measure blood glucose before, during and after physical exercise • Increased risk of hypoglycaemia 12–40 hours after strenuous physical exercise • Reduce short-acting insulin accordingly • Blood glucose before bedtime should be > 10–12 mmol/l Exercise

44. Definition and causes • Blood glucose < 3 mmol/l • Mild (Grade 1): recognised and treated orally by the patient • Moderate (Grade 2): treated orally, with help from someone else • Severe (Grade 3): unconscious or having fits – nothing by mouth • Causes: • strenuous exercise • missed meals • injection errors Hypoglycaemia

45. Neurogenic: sweating hunger tremor pallor restlessness Neuroglycopenic: weakness headache change in behaviour tiredness visual and speech disturbances vertigo lethargy confusion fits and unconsciousness Symptoms Hypoglycaemia

46. Mild hypoglycaemia (Grade 1): 10–20 g glucose tablets, juice or sweet drinks 1–2 slices of bread Moderate hypoglycaemia (Grade 2): 10–20 g glucose tablets 1–2 slices of bread Severe hypoglycaemia(Grade 3): Outside hospital: children < 10 years: 0.5 mg glucagon i.m. children > 10 years: 1.0 mg glucagon i.m. In hospital: bolus glucose (20%) 1 ml/kg over 3 min followed by glucose (10%), 0.2 ml/kg/min Treatment Hypoglycaemia

47. Definition and aetiology • Severity degree: • Mild ketoacidosis bicarbonate > 16 and< 22 mmol/l • Moderate ketoacidosis bicarbonate > 10 and< 16 mmol/l • Severe ketoacidosisbicarbonate < 10 mmol/l • Characterised by: • absolute insulin deficiency • increased level of counter regulatory hormones • Aetiology: • newly diagnosed • infections • insulin omission Diabetic ketoacidosis

48. Symptoms and signs • Dehydration • Vomiting • Loss of weight • Kussmaul respirations • Acetone smell • Impaired sensorium • Shock Diabetic ketoacidosis

49. Diagnosis • Clinical appearance • Hyperglycaemia • Ketonuria • Ketonaemia • Plasma bicarbonate < 22 mmol/l Diabetic ketoacidosis

50. Treatment: fluid • Due to the risk for overhydration: • fluid volume in the first 24 hours should not exceed 4 l/m2 • rehydration over 24–36 hours • Initiate treatment with isotonic 0.9 % saline: • 1st hour: 20 ml/kg body weight (previous) • 2nd hour: 10 ml/kg body weight • 3rd hour onwards: 5 ml/kg body weight • When blood glucose levels are below 12 mmol/l: • 5–10 % glucose solution Diabetic ketoacidosis