Starting Insulin by M Daoud
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This document discusses two case studies of patients with type 2 diabetes mellitus. For the first case, a 50-year old female patient with HbA1c of 8.5-9% on oral medications, the summary recommends starting basal insulin such as glargine or detemir 15-20 units at bedtime. For the second case, a 68-year old obese male patient with HbA1c of 10.5% on maximum oral medications, the summary recommends starting a total daily dose of insulin of 0.3-0.5 units/kg, starting with premixed insulin such as Mixtard 18/10 units. Both cases emphasize individualizing treatment targets and adjusting insulin doses based on self-
![•Age: Older adults
- Reduced life expectancy
- Higher CVD burden
- Reduced GFR
- At risk for adverse events from polypharmacy
- More likely to be compromised from hypoglycemia
Less ambitious targets
HbA1c <7.5–8.0% if tighter
targets not easily achieved
Focus on drug safety
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]](https://image.slidesharecdn.com/startinginsulinmdaoud-150222120105-conversion-gate01/85/Starting-Insulin-by-M-Daoud-61-320.jpg)
Starting Insulin by M Daoud
- 1. Diabetes Mellitus Insulin Therapy Dr. Mohammad Daoud Consultant Endocrinologist KAMC/ NGHA - Jeddah –Saudi Arabia
- 2. Objectives Introduction Insulin :Choices and Profiles Guidelines Adding / Switching to Insulin
- 3. CASE:1 50 - Year-old female ; 8 years history of DM type 2 Meds: Metformin 1gm BD and Gliclazide MR 120 mg , Pioglitazone 30 mg ,and Sitagliptin 100 mg Her diet and physical activity is excellent Her glucose reading at home ; unsatisfactory Last HbA1c 8.5- 9% Best next step in management ?
- 4. CASE:2 61 - Year-old obese male patient DM Type 2 for about 15 years On maximum doses of MFN and SU His FBS 180- 220 mg/dl (10-12 mmol/l) Random readings 200-280 mg/dl (11-15.5 mmol/l) HbA1c of 10.5 % - 11% despite being compliant to treatment and diet You are asked to help him getting better control?
- 5. Insulin glargine 2000 Treatment Milestones in Diabetes Biguanides 1960 Insulin therapy 1922 Sulphonylurea therapy 1950s Insulin pump Late 1970s NPH=neutral protamine Hagedorn; DCCT=Diabetes Control and Complications Trial; UKPDS=United Kingdom Prospective Diabetes Study. Data from Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Boston, Mass: Blackwell Science; 2003. US FDA Center for Drug Evaluation and Research. Available at: http://www.fda.gov/cder/da/ddpa696.htm. Accessed 18 March 2003. Lantus Consumer Information. Available at: http://www.fda.gov/cder/consumerinfo/druginfo/lantus.htm. Accessed 18 March 2003. NPH insulin 1946 Lente insulin therapy 1952 HbA1c testing 1975 DCCT 1993 Rapid-acting insulin analogues 1996 UKPDS 1998 Blood glucose self-monitoring
- 6. GlycemicControl Recommendations EMPOWER the Patient Should be able to Use data Adjust Therapy. (E) ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S21–S22
- 7. ADA-2015
- 8. Correlation of A1C with estimated Average Glucose A1C (%) Mean plasma glucose mg/dl 6 ̴ 120 7 ̴ 150 8 ̴ 180 9 ̴ 210 10 ̴ 240 11 ̴ 270 12 ̴ 300 ADA. V. Diabetes Care. Diabetes Care 2014;37(suppl 1):S23; Table 8
- 12. Basal Insulin: Pharmacokinetics Suppress hepatic glucose production Maintain near normo-glycemia in the fasting state
- 17. Nutritional Insulin: Meal related=Prandial Control postprandial hyperglycemia
- 19. RAARAA RAA RAA=
- 20. RAA RAA RAA RAA=
- 21. Mixed Insulin Humilin 70/30 or Mixtard 70% NPH , 30 % RI Lispro-Mix 25/75 , 50/50 Lispro /Lispro protamine Novo-Mix -30/70: Aspart /Aspart protamine Mix from two separate vials Ex: RI and NPH
- 22. Mixed Insulin - ADA Guidelines Not recommended for Type 1 DM patients Type 2 DM patient: If well controlled …continue Don’t mix Glargine / Detemir with other insulin : Different PH NPH + RI mixing …Use immediately RAI (ex: Lispro / Aspart / Glulisine) + NPH …. use within 15 minutes
- 23. Our Goal To Mimic Normal Physiology
- 24. CASE:1 50 - Year-old female ; 8 years history of DM type 2 Meds: Metformin 1gm BD and Gliclazide MR 120 mg , Pioglitazone 30 mg ,and Sitagliptin 100 mg Excellent diet and physical activity Body weight 70 kg, BMI 28 His SMBG at home ; Unsatisfactory
- 25. How will you asses her glycemic control ? HbA1c Glucose monitoring (SMBG)
- 26. How will you asses his glycemic control ? HbA1c Latest HbA1c 8.5 %- 9 %
- 27. What kind of monitoring will you do ? Fasting , Pre-meals and @ Bed time Vs Fasting , Post-meals and @ Bed time
- 29. Case #1 With higher HbA1C : Pre-meal glucose readings contribute more to the HbA1C With HbA1C closer to target ( ex: <8-8.5%) Post-meal glucose readings contributes more to the HbA1C value
- 30. Breakfast Lunch Dinner Bedtime Before After Before After Before After Day1 11.7 9.0 7.2 7.8 Day2 10.4 8.5 6.9 Day3 9.5 9.6 7.8 Day4 9.7 8.9 6.5 Day5 10.8 8.5 9.5 SMBG Record
- 31. Case #1 Summary She is on maximum doses of oral agents… still she has : Suboptimal glycemic control ; A1c >7% High BG levels, particularly in the morning (fasting)
- 32. ADA-2015
- 33. InsulinRegimens Basal Basal + MDI Pre-mixed What insulin regimen would you prescribe?
- 34. Breakfast Lunch Dinner Bedtime Before After Before After Before After Day1 11.7 9.0 7.2 7.8 Day2 10.4 8.5 6.9 Day3 9.5 9.6 7.8 Day4 9.7 8.9 6.5 Day5 10.8 8.5 9.5 SMBG Record Fasting / Pre-Prandial 80-130 mg /dl ~ 4.5 - 7.5 mmol/L Post--Prandial 140-180 mg /dl ~ 8 - 10 mmol/L
- 35. Case #1 Basal insulin Easy choice : single injection (at bedtime) “Breaks the Ice”
- 37. ADA 2015
- 38. Case #1 Glargine or Detemir 15-20 units added at Bedtime (weight 70 kg) Or Start a dose of 10 units Titrate every 2-3 days Pre-meal /FPG is at target : 80-130 mg/dl (about 4.5 - 7.5 mmol/L )
- 39. Case #1 3 months later : Now at 28 units of Glargine or Detemir at Bedtime.... HbA1c 6.8% Breakfast Lunch Dinner Bedtime Before After Before After Before After Day1 5.7 8.0 8.2 6.8 Day2 6.4 9.0 6.8 Day3 7.0 7.6 6.8 Day4 5.9 7.8 7.5 Day5 6.0 9.0 8.5
- 40. Case #1 Oral agents on board now ? Metformin Keep unless CI ISS /SU keep on board or decrease DPP4 - Keep / less amount of insulin needed Glitazones : Decrease Watch for fluid retention/stop if needed
- 41. Case #1 4 years later : Now at 40 units of Glargine or Detemir at Bedtime.... HbA1c 8.2% Breakfast Lunch Dinner Bedti me Before After Before After Before After Day1 7.5 9.0 12.5 8.2 9.8 Day2 6.9 11.9 9.0 10.5 11.8 Day3 6.8 7.6 10.2 Day4 5.9 13.0 7.8 9.9 9.5 Day5 7.5 9.0 12 8.5 Are you surprised ?
- 42. ADA=American Diabetes Association; HbA1c=hemoglobin A1c Adapted from UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352: 854–865. UKPDS: Glycemic Control Worsens Over TimeMedianHbA1c(%) 0 2 4 0 6 7 8 9 6 8 10 Time from Randomization (y) Upper limit of normal range (6.2%) ADA goal (7.0%) Conventional (n=200) Insulin (n=199) Chlorpropamide (n=129)Glibenclamide (n=148) Metformin (n=181) Diabetes Mellitus Type 2 is a Progressive Disease
- 43. SA- GLA-11-11-04 43 When basal insulin is not enough • Step 1: Think first of titrating the basal insulin dose till reaching FBG target (Often under-dosage) • Step 2: Shift to Basal Plus or Basal-bolus (MDI) regimen : • Number of daily injections up to 4 (1+3) • Inconvenience • Risk of hypoglycemia & Weight gain Add prandial insulin dose (s) as per guidelines
- 44. Case #1 4 years later : Now at 40 units of Glargine or Detemir at Bedtime.... HbA1c 8.2% Breakfast Lunch Dinner Bedtime Before After Before After Before After Day1 7.5 9.0 12.5 8.2 9.8 Day2 6.9 11.9 9.0 10.5 11.8 Day3 6.8 7.6 10.2 Day4 5.9 13.0 7.8 9.9 9.5 Day5 7.5 9.0 12 8.5 Post--Prandial 140-180 mg /dl ~ 8 - 10 mmol/L
- 45. Case #1 Main issue now is post- prandial hyperglycemia Add on : to main meal or all meals RI / RAI Ex : Aspart /Glulisine/ Lispro Insulin 4 u/ meal Adjust according to SMBG
- 46. Basal + ADA 2015
- 48. Case #1 Titrate every 2-3 days Post-meal target 140-180 mg /dl (about 8- 10 mmol/L )
- 49. Case #1 3-4 months later : Now at 40 units of Glargine or Detemir and Aspart 14- 12 -12- at Bedtime.... HbA1c 6.5% Breakfast Lunch Dinner Bedtime Before After Before After Before After Day1 7.5 9.0 9.5 8.0 7.8 Day2 6.9 8.9 7.0 9.5 8.8 Day3 6.8 7.6 8.0 Day4 5.9 8.0 7.8 7.9 9.5 Day5 7.5 9.0 7.8 8.2 Well done
- 50. Case #1 Now on Basal 40 units Meal related 38 units Almost... 50% / 50%
- 51. Case #1 You may chose to use Basal + i.e Basal insulin + meal related insulin added to main meal or the meal with highest post-prandial glucose If not adequate …other meals can be covered also
- 52. Case #1 You may chose to use Premixed Insulin BID Or Premixed analogues : Ex: NovoMix-30/70 or Humalog-Mix 25 in 2-3 doses
- 54. CASE: 2 68-year-old obese male patient DM Type 2 for about 15 years On SU and MFN maximum doses His FPS 180- 220 mg/dl (> 10-12 mmol/l) Random readings 200-280 mg/dl (> 11-15.5 mmol/l) HbA1c of 10.5% despite compliance to Rx and TLC You are asked to help him getting better control?
- 55. CASE:2 He has impaired vision Polyuria , Polydypsia (Weight 70 kg, Height 170 cm) Serum Creatinine 1.15 mg/dl (105 nmol/L) e-GFR ~ 50 ml/min
- 56. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210
- 57. Case #2 Summary Case review Uncontrolled / Symptomatic hyperglycemia High BG levels all over the screen ; fasting and post-meals He is on maximum doses of oral agents Co-morbidities : Renal impairment +…
- 58. ADA/EASD and AACE position statement 2012: individualized HbA1c targets Inzucchi et al. Diabetologia 2012;55:1577–96 6.0 – 6.5% < 8.0%< 7.0%HbA1c target
- 59. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210 What is the proper glycemic targets for this patient ? Is it … Fasting / Pre-Prandial 80-130 mg /dl ~ 4.5 - 7.5 mmol/L Post--Prandial 140-180 mg /dl ~ 8 - 10 mmol/L
- 60. CASE:2 Before BF 2hr PBF Post Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210 Safer targets can be justified for this patient Like… Fasting / Pre-Prandial 100-150 mg /dl Post--Prandial 150-200 mg /dl
- 61. •Age: Older adults - Reduced life expectancy - Higher CVD burden - Reduced GFR - At risk for adverse events from polypharmacy - More likely to be compromised from hypoglycemia Less ambitious targets HbA1c <7.5–8.0% if tighter targets not easily achieved Focus on drug safety Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
- 63. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210 Start TDD of 0.3- 0.5 unit /kg Wt. 70 kg 0.4 unit /kg (you can start with lower limit and adjust) About 28 units total
- 64. CASE:2 TDD of 0.3- 0.5 up to 0.8 unit /kg Wt 70 kg 0.4 unit /kg Start at 28 units total Then SMBG …and adjust Basal/ Bolus Glargine 16 u HS RAI 4-4-4 u TID Premixed Mixtard 18/10 Aspart Mix (30/70) 18/10 OR 12-8-8
- 65. CASE:2 Started Premixed Mixtard 18/10 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210
- 66. CASE:2 Premixed Mixtard 18/10 Dose adjusted gradually to 24 /14 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 145 150 188 125 Day 2 150 148 185 145 Day 3 152 140 190 150
- 67. CASE:2 4 weeks later On Premixed Mixtard 32 /16 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 122 89 138 75 Day 2 110 80 145 85 Day 3 116 100 120 70
- 68. CASE:2 2 months later Premixed Mixtard 32 /16 HbA1c 10.5 % to 8.6% Frequent hypoglycemia ?!! Before BF 2hr PBF Pre Dinner 2hr PP Day 1 122 89 138 75 Day 2 110 60 195 55 Day 3 260 100 120 70
- 70. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 195 230 280 245 Day 2 180 200 205 230 Day 3 220 250 220 210 Basal/ Bolus 0.5 u/kg 18 units Detemir / Glargine Aspart 6 units tid
- 71. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 144 200 120 195 Day 2 160 190 95 200 Day 3 175 200 110 210 1 week later Increased Glargine …18 to 22 u Increased Aspart …10 / 6 / 10
- 72. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 135 170 100 180 Day 2 150 160 110 190 Day 3 140 136 95 170 4 week later Increased Glargine …22 to 26 units Increased Aspart …10 / 6 / 12
- 73. CASE:2 Before BF 2hr PBF Pre Dinner 2hr PP Day 1 135 150 100 150 Day 2 120 140 110 140 Day 3 110 136 95 160 3-4 Months later Glargine …30units Aspart …12 / 8 / 14 HbA1c 10.5% to 7.6%
- 74. CASE:2 Glargine …30units Aspart …14 / 8 / 12 Basal 30 units Prandial 34 units Almost 50/50 0.5 to 0.9 u /kg
- 75. CASE: 2 Oral agents on board now ? Metformin Keep unless CI ISS /SU Stop DPP4 - Keep / less amount of insulin needed Glitazones : Decrease Watch for fluid retention/stop if needed
- 76. To Conclude…
- 78. Summary(continue) Basal Insulin alone …Break the Ice 0.1-0.3 u /kg or fixed 10 u and adjust Early on , Don’t switch ….Add (esp. insulin secretagogues; SU /Glinides) Metformin: Keep unless CI ( Lower insulin doses and less weight gain) TZDs …decrease or stop (Less risk of fluid retention /heart failure)
- 79. Summary(continue) Basal –Bolus Insulin TDD = 0.3-0.5 u /kg Basal Insulin 40-50 % Meal related :50-60 % Insulin secretagogues (SU /Glinides): No need Keep Metformin / maybe TZDs
- 80. Summary(continue) Premixed / Bi-Phasic TDD = 0.3-0.5 u /kg 2/3 am and 1/3 pm OR 2-3 doses (premixed analogues) 10% adjustment role Drawbacks: Hypo /Weight gain/ Larger doses Insulin secretagogues (SU /Glinides): No need Keep Metformin / maybe TZDs
- 81. Summary Start Low …and Go Slow … monitor and adjust Based on a “Trend” Avoid hypoglycemia Patient teaching …Core part of the team