1. www.diabetesclinic.ca 1 INTENSIVE INSULIN THERAPY J. Robin Conway M.D. Diabetes Clinic, Smiths Falls, ON 1-800-717-0145

2. www.diabetesclinic.ca 2 Objectives Optimize diabetes management Assist you in initiating insulin in your office –When to start insulin therapy? –Insulins, doses, delivery options –Patient training

3. www.diabetesclinic.ca 3 Challenges in Initiating Insulin? Patient attitudes 1. Patient attitudes –Fear of needles –Insulin viewed as a threat by patient & physician –Hypoglycemia Physician Attitudes 2. Physician Attitudes –Discomfort with insulin Lack of knowledge and experience –Fear of needles

4. www.diabetesclinic.ca 4 Type 1 Diabetes: Impaired or absent ß cell function: –  insulin secretion Normal insulin action: –  insulin sensitivity The insulin deficiency results in unacceptable blood glucose control

5. www.diabetesclinic.ca 5 Type 2 Diabetes: Double Impairment Impaired ß cell function: –  insulin secretion Impaired insulin action: –  insulin resistance Results in unacceptable blood glucose control

6. www.diabetesclinic.ca 6 Type 1 & 2 Diabetes: Key Concepts Minimizing the complications of diabetes requires: –Early diagnosis and treatment of diabetes –Maintaining HbA 1C level < 7% Achieving HbA 1C < 7% requires control of post-prandial and fasting hyperglycemia

7. www.diabetesclinic.ca 7 CDA Guidelines (for glycemic control) NormalOptimal A 1C level (0.04-0.06) (< 0.07) Preprandial glycemia (mmol/L) 3.5-6.14-7 Postprandial glycemia (mmol/L) 4.4-7.87-11 Haars s et al., CMAJ 2003; 159 (Suppl.): S1-29. Gerstein, H.C. et al. CDA views on the UKPDS and revision of the guidelines affected by the results of this study.

8. www.diabetesclinic.ca 8 Steps to Glycemic Control Establish glycemic objectives –Target fasting and post-prandial glycemia Diet counseling with exercise component Diabetes education for every patient Pharmacological treatment; oral and insulin

9. www.diabetesclinic.ca 9 Patient Counselling Topics A.Review symptoms and treatment of hypoglycemia B.Proper training and correct use of glucose monitor C.Target desired glycemic levels for each patient

10. www.diabetesclinic.ca 10 A. Hypoglycemia Definition: Glycemia < 3.8 mmol Patients may experience hypoglycemia at different glycemic levels

11. www.diabetesclinic.ca 11 Symptoms of Hypoglycemia Mild < 3.3 mmol/L Neurovegetative symptoms –Sweating –Trembling –Palpitations –Anxiety –Tingling –Pallor –Hunger Moderate to Severe < 2.8 mmol/L Symptoms of glucopenia –Confusion –Visual disturbances –Weakness –Speech disorder –Behavioural disorder –Drowsiness –Coma –Convulsions

12. www.diabetesclinic.ca 12 Preventing Hypoglycemia Check BG 4-6 times per day Carry glucose tablets Have Glucagon Kit available

13. www.diabetesclinic.ca 13 Preventing Hypoglycemia Test before driving and ideally 1 hour later (target: over 5.5 mmol/L) Perform two SMBG 30 minutes apart prior to bedtime (confirming rising or falling BG) When drinking alcohol, perform SMBG hourly With exercise, perform SMBG pre- and post- exercise If hypoglycemia episodes persist, raise target glucose levels

14. www.diabetesclinic.ca 14 Hypoglycemia Treatment Guidelines The Rule of 15 If BG is 4 mmol/L or below –Treat with 15 grams of carbohydrates (glucose tabs) –Check BG in 15 minutes, and if not above 4 mmol/L, repeat treatment Glucagon Current emergency kit readily available and knowledgeable person trained to administer

15. www.diabetesclinic.ca 15 Preventing Hyperglycemia and DKA Monitor BG 4-6 times per day Use Correction Boluses when appropriate

16. www.diabetesclinic.ca 16 Hyperglycemia Treatment Guidelines The Key to Preventing DKA 1st BG over 14 mmol/L: Take a correction bolus, check again in 1 hour Call physician immediately or go to ER if nausea and vomiting are present

17. www.diabetesclinic.ca 17 B. Patient Training Training by a multidisciplinary team at DEC is IDEAL for: –Diet counseling –Education on the injection sites –Education on the various injection devices –Evaluation of the patient’s support network Other resources may exist for training, i.e. retail pharmacy

18. www.diabetesclinic.ca 18 C. Blood Glucose Monitoring To adjust the insulin treatment To detect or confirm hypoglycemia or severe hyperglycemia To adjust treatment to the circumstances of daily life using an insulin scale prescribed by the attending physician To improve patient safety and increase motivation to comply with treatment

19. www.diabetesclinic.ca 19 Ideal Testing Frequency Stable type 2 –1-2 readings/day Type 1 or Unstable type 2 – 3-8 readings/day Important to stress the need to vary testing times –AC, PC, h.s. and prn during the night

20. www.diabetesclinic.ca 20 Injection Tools and Options Durable delivery devices –Novolin-Pen ® 3 –Novolin-Pen ® Junior –InDuo ® –Innovo ® –HumaPen ® Insulin pumps Syringes Disposable: multidose, prefilled (3.0 mL) –NovolinSet ® (NPH, Toronto, 30/70 ) –Humulin ® N

21. www.diabetesclinic.ca 21 Advancing Insulin Therapy Through Device Innovation

22. www.diabetesclinic.ca 22 We are trying to duplicate how the pancreas works in releasing insulin for someone who doesn’t have diabetes Goal of Insulin Therapy

23. www.diabetesclinic.ca 23 Non-diabetic Insulin and Glucose Profiles 9.0 6.0 3.0 0 789101112123456789 Insulin Glucose a.m.p.m. BreakfastLunchSupper 75 50 25 0 Basal insulin Basal glucose Insulin (µU/mL) Glucose (mmo/L) Time of Day

24. www.diabetesclinic.ca 24 Insulin Preparations Start 3-4 hrs. Peakless Humulin ® U vial only Lantus (Glargine) vial only Levemir (Detemir) cartridge Prolonged action Start 1.5 hrs Peak 7 hr Novolin ® ge NPH Humulin ® N Intermediate Vial and cartridge Start 30-60 min. Peak 4 hr Novolin ® ge Toronto Humulin ® R Short-acting (regular) Vial and cartridge Start < 15 min. Aspart (NovoRapid ® ) Lispro (Humalog ® ) Rapid-acting Vial and cartridge

25. www.diabetesclinic.ca 25 Insulin PreMixes Regular + intermediate –Novolin ® 10/90, 20/80, 30/70, 40/60, 50/50 –Humulin ® 30/70, 20/80 Analogue Pre-Mix –Humalog ® 25/75 (insulin lispro protamine suspension) –NovoMix 30* (protaminated insulin aspart) * Not available

26. www.diabetesclinic.ca 26 Normal Blood Glucose Levels Blood Glucose (mmols) 10- 8- 6- 4- 2- 0 8am noon 6pm 2am 4am 8am Time

27. www.diabetesclinic.ca 27 Normal Blood Glucose Levels Blood Glucose (mmols) 10- 8- 6- 4- 2- 0 8am noon 6pm 2am 4am 8am Time

28. www.diabetesclinic.ca 28 Two injections/day Blood Glucose (mmols) 8am noon 6pm 2am 4am 8am Time R or H + N in AMR or H + N at Supper 10- 8- 6- 4- 2- 0

29. www.diabetesclinic.ca 29 Three injections/day Blood Glucose (mmols) 8am noon 6pm 2am 4am 8am Time R or H + N in AM R or H at Supper N before bed 10- 8- 6- 4- 2- 0

30. www.diabetesclinic.ca 30 Four injections/day Blood Glucose (mmols) 8am noon 6pm 2am 4am 8am Time R or H at every mealN or U once or twice/day 10- 8- 6- 4- 2- 0

31. www.diabetesclinic.ca 31 Continuous Infusion Blood Glucose (mmols) 8am noon 6pm 2am 4am 8am Time 10- 8- 6- 4- 2- 0

32. www.diabetesclinic.ca 32 Limitations of Regular Human Insulin Slow onset of activity –Should be given 30 to 45 minutes before meal Inconvenient for patients Long duration of activity –Lasts up to 12 hours Potential for late postprandial hypoglycaemia (4-6 hours) –Need for additional snack

33. www.diabetesclinic.ca 33 Adherence to Injection Recommendation (Canada) 4% 42% 32% 22% 0 100 30–45 min 15–30 min0–15 min % of Respondents B e f o r e Meal After "When do you inject your insulin?" 1998 Roper Starch Canada, Premix Insulin Using Respondents.

34. www.diabetesclinic.ca 34 Dissociation of Regular Human Insulin Regular Human Insulin 10 -3 M 10 -5 M10 -8 M peak time 2-4 hr  formulation capillary membrane hexamersdimersmonomers

35. www.diabetesclinic.ca 35 Objectives for the Development of Short- Acting Insulin Analogues Modify time action to address –Postprandial hyperglycemia –Hypoglycemia Improve safety and convenience

36. www.diabetesclinic.ca 36 Whats’ new in type 1 diabetes treatment? Insulin analogues. Physiological insulin replacement Aggressive “intensive” management –4 injections per day –Insulin infusion pumps –Continuous glucose monitoring systems –Integrated technologies for monitoring control

37. www.diabetesclinic.ca 37 Non-diabetic Insulin and Glucose Profiles 9.0 6.0 3.0 0 789101112123456789 Insulin Glucose a.m.p.m. BreakfastLunchSupper 75 50 25 0 Basal insulin Basal glucose Insulin (µU/mL) Glucose (mmo/L) Time of Day

38. www.diabetesclinic.ca 38 NovoRapid ® (insulin aspart) Time-Action Profile 024681012141618202224 Onset: 10-20 minutes Maximum effect: 1-3 hours Duration: 3-5 hours NovoRapid ® Rapid-acting insulin analogue

39. www.diabetesclinic.ca 39 We are trying to duplicate how the pancreas works in releasing insulin for someone who doesn’t have diabetes Goal of Insulin Therapy

40. www.diabetesclinic.ca 40 Insulin Therapy Options MDI therapyMDI therapy –0.5 units/kg = total daily dose –4x/day 40% NPH @ hs and 60% rapid acting analogue ac meals –For patients with significant complications (i.e. renal failure, foot infections, CVD, etc…)

41. www.diabetesclinic.ca 41 In someone without diabetes, the pancreas delivers a small amount of insulin continuously to cover the body’s non-food related insulin needs. Basal Insulin

42. www.diabetesclinic.ca 42 The amount of insulin required to cover the food you eat. Fast-acting or Short-acting (clear) insulin works as a Bolus Insulin Bolus Insulin

43. www.diabetesclinic.ca 43 Why count carbs? More precise way of measuring the impact of a meal on blood sugar Lets you decide how much insulin is needed to “cover” the meal Greater flexibility -eat what you want, when you want to eat it

44. www.diabetesclinic.ca 44 Fine Tuning: Bolus Doses Carbohydrate counting or pre-determined meal portion Individualized insulin to carbohydrate dose or insulin to meal dose Adjust bolus based on post-meal BGs or next pre-meal BG

45. www.diabetesclinic.ca 45 Fine Tuning: Basal Rate Monitor BG pre-meal, post-meal, bedtime, 12am, and 2-4am Test fasting BG with skipped meals Adjust nighttime basal based on 2-4am and pre-breakfast BG Adjust basal by 0.1 u/hr to avoid over-correction

46. www.diabetesclinic.ca 46 Novolin ® ge 30/70 Time-Action Profile Premixed insulin Onset: 0.5 hour Maximum effect: 2-12 hours Duration: 24 hours

47. www.diabetesclinic.ca 47 30/70 - Twice/day

48. www.diabetesclinic.ca 48 30/70 Dose Calculation Weight = 80 kg 80 kg x 0.3 U/kg = 24 U 2/3 in the AM = 16 Units 1/3 at supper = 8 Units

49. www.diabetesclinic.ca 49 Dosage Changes Change insulin dose so that peak of action corresponds to most abnormal value (pre-meal) If all values are abnormal - start with fasting glycemia followed by lunch, supper and bedtime Change the dose by increments of 1-4 U Not more than twice/week Monitor for PATTERNS in hypoglycemia

50. www.diabetesclinic.ca 50 NovoRapid ® Penfill ® Rapid-acting human insulin analogue (insulin aspart) Novolin ® ge Toronto Penfill ® Short-acting insulin (insulin injection, human biosynthetic) Novolin ® ge NPH Penfill ® Intermediate-acting Insulin (insulin injection, human biosynthetic)024681012141618202224 Onset: 10-20 minutes Maximum effect: 1-3 hours Duration: 3-5 hours Onset: 0.5 hour Maximum effect: 1-3 hours Duration: 8 hours Onset: 1.5 hours Maximum effect: 4-12 hours Duration: 24 hours Full Range of Novo Nordisk Insulins

51. www.diabetesclinic.ca 51 Somogyi Effect Hyperglycemia secondary to asymptomatic hypoglycemia (especially at night) If the insulin is increased in evening, the problem worsens Check capillary glycemia around 3 a.m. to eliminate hypoglycemia In this case, reduce the h.s. NPH

52. www.diabetesclinic.ca 52 Follow-Up: The Patient’s Role Every Day Check BG 4-6 times a day, and always before bed Follow hypoglycemia guidelines Follow hyperglycemia guidelines Every 3 months Visit healthcare provider - even if feeling well Review log book and pump settings with physician Get an A1c test Every month  Review DKA prevention  Check BG - 3am (overnight) - 1 and/or 2-hour post-meal BG for all meals on a given day

53. www.diabetesclinic.ca 53 Case Study #1 Patient R.M., DM for 9 years BMI = 34, Meds: metformin 1000 mg BID and glyburide 10 mg BID, Avandia 8 mg OD HbA 1C is 9.5 %, FBS 11.8 What is the next step?

54. www.diabetesclinic.ca 54 Case Study #2 Patient K.G., DM for 15 years BMI = 23 Meds: Metformin 1000 mg BID and Gluconorm 2 mg TID HbA 1C = 8.5%, FBS 7.4 Post MI What is the next step?