Treatment of Type 1 diabetes

1. Dr. Amir Babiker MBBS, FRCPCH (UK), CCT (UK) Consultant Paediatric Endocrinologist, KKUH and Assistant Professor, King Saud University Treatment of Type 1 diabetes

2. A metabolic disorder of multiple aetiologies characterized by: Chronic hyperglycemia Disturbances of CHO, fat and protein metabolism Defects of insulin secretion, insulin action or both. DM

3. Diagnostic Criteria Diabetes mellitus is characterized by recurrent or persistent hyperglycaemia, and is diagnosed by demonstrating any one of the following:[ • OR Symptoms of hyperglycaemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl) • A positive result, in the absence of unequivocal hyperglycemia, should be confirmed by a repeat of any of the above methods on a different day.

4. T1DM (IDDM, Juvenile DM): Autoimmune, idiopathic T2DM (NIDDM, Adult onset):Obesity, Acanthosis nigricans, FH. Gestational DM Other: Monogenic, congenital, neonatal, 2ry..etc Types of DM

7. Map of published incidence rates (per 100 000) of type 1 diabetes in children. Source: Solte´sz et al. (2).Childhood type 1 diabetesPediatric Diabetes 2007: 8 (Suppl. 6): 6–14

11. Prevent death & alleviate symptoms Achieve biochemical control Maintain growth & development Prevent acute complications Prevent or delay late-onset complications Management Goals

12. Insulin: Regular and NPH (1/3 and 2/3) Analogues (Mixed, ultra short, Detemir & Glargine) Insulin pumps (CSII): Open and closed loops. Support: Education: CHO counting, I:CHO, Self care & injections, hypos management, Sick day rules Psychological Annual review: Examination, Invx: Blood and urine, Eye Life style: Diet (CHO = 50 - 60%, Fats: < 30%, Proteins 10 – 20%) Sensible exercise Management Components

13. Honeymoon phase or partial remission: weeks to 2 years, due to B cell hyperplasia. Early morning hyperglycaemia: with NPH & Regular (Somogyi & Dawn phenomena) Sick day rules: Check Blood sugar every 2-4 hrs Check ketones Drink plenty of fluids Need extra insulin to clear ketones Never omit insulin Hypoglycaemia may be a problem especially in young children Concepts

14. Children with T1DM who have: Hyperglycaemia (BG >11 mmol/l) pH < 7.3 Bicarbonate < 15 mmol/l With ketonaemia and/ or ketonuria. and who has: Acidotic respiration, dehydration, drowsiness and/or abdominal pain/vomiting DKA

15. They can die from : Cerebral oedema: This is unpredictable, occurs more frequently in younger children and newly diagnosed diabetes and has a mortality of around 25%. Hypokalaemia: This is preventable with careful monitoring and management Aspiration pneumonia: NGT. DKA

16. Target blood glucose: 4 – 8 mmol/l. Treat all blood glucose below 4 mmol/l to avoid hypo unawareness. Symptoms: Sympathetic: pallor, tachycardia, sweating, tremors Neuroglycopoenic: irritability, headache, nausea, seizure, stupor, coma Hypoglycaemia

17. Causes: Missed or delayed meal Exercise Alcohol Overdose of insulin Impaired food absorption (CD) Addison’s disease Treatment: Oral CHO: glucose tabs, gel and fluids I/M glucagon 10% Dx 2 ml/kg bolus Hypoglycaemia

18. Physiological insulin replacement Assessment of glycaemic control (SMBG) Hospital tests (HbA1c, …etc) Insulin dosage adjustment Healthy diet Diabetes education Modern Management“Optimized” or “Intensive” therapy.

19. Intensive Therapy for Diabetes:Reduction in Incidence of Complications T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus. *Not statistically significant due to small number of events. †Showed statistical significance in subsequent epidemiologic analysis. DCCT Research Group. N Engl J Med. 1993;329:977-986; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117; UKPDS 33: Lancet. 1998;352: 837-853; Stratton IM, et al. Brit Med J. 2000;321:405-412.

20. Multiple-component insulin regimen Careful balance of food intake, activity, and insulin dosage Daily self-monitoring of blood glucose (SMBG) Patient adjustments of food intake and insulin dosage and use of insulin supplements according to predetermined plan Defined target blood glucose levels (individualized) Frequent contact between patient and staff Patient education and motivation Psychological support Assessment (HbA1c and annual review) Elements of Intensive therapy

21. Representative target blood glucose levels suitable foryoung otherwise healthy patient

22. Insulin Since the discovery of insulin less than 100 years ago, diabetes treatment and technology have come a long way in helping people with diabetes manage their disease.

25. Types of InsulinJAMA 2003;289:2254-64 - Clin Pharmacology Online, 2009

26. Comparison of Human Insulin and AnaloguesJAMA 2003;289:2254-64. Clin Pharmacology Online, 2009

30. Relationship with the patients/families: Communication: Education – Motivation –Support Dose or treatment changes Basic concepts: Insulin analogues - basal bolus regimen CHO Counting I:CHO ratio IS (CF) Principles of Management

31. Once daily insulin (NPH or basal)- partial remission Twice daily Three times a day 4 times a day Continuous subcutaneous insulin infusion (CSII) Closing the loop (Artificial pancreas) Insulin regimens

32. Twice daily regimens

33. 3 times/day regimen

34. 4 times/day regimen

36. This is the most intensive regime with three pre-prandial doses of short /rapid acting insulin and a bedtime dose of intermediate or long acting insulin. While this regime offers no improvement in metabolic control compared to any other insulin regime, this may be the most suitable regimen for people who do not have a stable daily routine as the time and dose of insulin can be varied according to when the meal is taken and its carbohydrate content. Generally 30 - 50% of the total daily insulin requirements should be given as intermediate or long acting insulin at bedtime with the remaining insulin being given as short / rapid acting before breakfast, lunch and evening meal depending on the needs of the individual. Basal bolus regimen

37. Dose adjustmentPremixed/Biphasic insulin (2/day)

38. Dose adjustment - MDI

39. Insulin may need adjusting for exercise, meal composition, patterns in blood sugar levels, during illness and weight loss or gain episodes. Do not adjust dose on a “single” raised blood glucose. Adjust according to the chart above and monitor for at least 48 hours to judge the effect before further adjustment Blood glucose target range should be set Individually for each patient. Dose adjustment is individualized and needs to be monitored closely. Patients should be educated to adjust their own insulin Document change of insulin dose in the nursing notes. If problems persist in controlling the blood glucose level seek advice from the Diabetologist. General Advice on Insulin Dose Adjustment

40. Insulin Pumps (CSII)

43. Current technologies Insulin analogues Fast acting: lispro, aspart, glulisuline long acting (basal): glargine, detemir, Degludec Insulin pump therapy (CSII) Continuous Glucose Monitoring systems (CGMS) Insulin dose delivery & adjustment strategies Patient education/empowerment tools SMBG + basal/bolus therapy CHO counting techniques (DAFNE: Dose Adjustment for Normal Eating) Insulin sensitivity Type 1 diabetes – children/adolescents

44. • Limitations of current treatment approaches • Future therapy options: Immune manipulation/modulation Optimizing Sc insulin delivery Optimizing Sc insulin action New approaches to the management ofType 1 diabetes

45. 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 Challenges

47. Thank You