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First step into insulin therapy

First step into insulin therapy. (How to start insulin in a patient not controlled on OADs). By. Dr.Muhammad Tahir Chaudhry. B.Sc.M.B;B.S(Pb).C.diabetology(USA). The breakthrough: Toronto 1921 – Banting & Best. Normal physiologic patterns of glucose and insulin secretion in our body.

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First step into insulin therapy

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  1. First step into insulin therapy (How to start insulin in a patient not controlled on OADs) By Dr.Muhammad Tahir Chaudhry B.Sc.M.B;B.S(Pb).C.diabetology(USA)

  2. The breakthrough: Toronto 1921 – Banting & Best

  3. Normal physiologic patterns of glucose and insulin secretion in our body

  4. How Is Insulin Normally Secreted?

  5. The rapid early rise of insulin secretion in response to a meal is critical, • because • it ensures the prompt inhibition of endogenous glucose production by the liver • disposal of the mealtime carbohydrate load, thus limiting postprandial glucose excursions.

  6. Basal insulins NPH • Humulin N (Eli Lilly) • Insulatard (Novo) (also available as insulatard Novolet pen) • Dongsulin N (Highnoon) • Insuget N (Getz) =========================================== Analogs Glargine (Lantus) Lantus Solostar Pen (Sanofi Aventis) Detemir (Levimir) by Novo

  7. Basal Insulins The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.

  8. Bolous insulins (Mealtime or prandial) Human Regular • Humulin R (Eli Lilly) • Actrapid (Novo) (Also available as Actrapid novolet pen) • Dongsulin R (Highnoon) • Insuget R (Getz) ========================================== Analogs • Lispro (Humolog) by Eli Lilly • Novorapid by Novo • Aspart • Glulisine (Apidra) by Sanofi Aventis

  9. Bolous insulins (Mealtime or prandial) The time course of action of any insulin may vary in different individuals, or at different times in the same individual. Because of this variation, time periods indicated here should be considered general guidelines only.

  10. Pre mixed 70/30 (70% N,30% R) • Humulin 70/30 (Eli Lilly) • Mixtard 30 (Novo) (Also available as Mixtard 30 Novolet Pen) • Dongsulin 70/30 (Highnoon) • Insuget 70/30 (Getz) =================================== Analogs • Novomix 30 (Novo) • Humolog Mix 25(Lilly) • Humolog Mix 50(Lilly)

  11. Types of Insulin 1. Rapid-acting 2. Short-acting 3. Intermediate-acting 4. Premixed 5. Long-acting 6. Extended long-acting (Analogs) (Regular) (NPH) (70/30) (Lantus)

  12. Indications for Insulin Use in Type 2 Diabetes Pregnancy (preferably prior to pregnancy) Acute illness requiring hospitalization Perioperative/intensive care unit setting Postmyocardial infarction High-dose glucocorticoid therapy Inability to tolerate or contraindication to oral antiglycemic agents Newly diagnosed type 2 diabetes with significantly elevated bloodglucose levels (pts with severe symptoms or DKA) Patient no longer achieving therapeutic goals on combination antiglycemic therapy

  13. Proposed Algorithm of therapy for Type 2 Diabetes Inadequate Non pharmacological therapy • Severe symptoms • Severe hyperglycaemia • Ketosis • pregnancy 2 oral agents 3 oral agents 1oral agent Add Insulin Earlier in the Algorithm

  14. First step intoInsulin therapy

  15. What we have in our pockets? • Basal Insulins (NPH,Lantus) • Bolus Insulins(Human Regular) • Premixed (Human 70/30)

  16. The ADA Recommendations on the Use of Insulin in Type 2 Diabetes

  17. Touch Pad Question Currently, roughly ____ of my patients with type 2 diabetes are taking some form of insulin. 1. >80% 2. 60-80% 3. 40-60% 4. 20-40% 5. 0-20%

  18. Touch Pad Question When it comes to first-line insulin, I tend to prescribe: 1. An intermediate-acting insulin with fast-acting insulin as needed 2. A long-acting or extended long-acting insulin with fast-acting insulin as needed 3.A premixed insulin

  19. Advantages of Insulin Therapy Oldest of the currently available medications, has the most clinical experience Most effective of the diabetes medications in lowering glycemia Can decrease any level of elevated HbA1c No maximum dose of insulin beyond which a therapeutic effect will not occur Beneficial effects on triglyceride and HDL cholesterol levels Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  20. Disadvantages of Insulin Therapy Weight gain ~ 2-4 kg May adversely affect cardiovascular health Hypoglycemia However, rates of severe hypoglycemia in patients with type 2 diabetes are low… Type 1 DM: 61 events per 100 patient-years Type 2 DM: 1-3 events per 100 patient-years Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  21. Balancing Good Glycemic Control with a Low Risk of Hypoglycemia… Glycemic control Hypoglycemia

  22. Rates of Hypoglycemia for Premixed vs. Long-Acting Insulin + OAD Mean number of confirmed hypoglycemic events per patient-year in a 28-week study 6 p=0.0009 5.73 Premixed insulin Insulin glargine + OADs 5 4 Events per patient-year 3 2.62 2 p=0.0449 p=0.0702 1 1.04 0.05 0.00 0.51 0 Symptomatic Nocturnal Severe Adapted from Janka et al. Diabetes Care 2005;28:254-9.

  23. Rates of Hypoglycemia for Premixed vs. Long-Acting Insulin + OAD in Elderly Patients 12 Rate of event per patient-year Premixed (n=63) Glargine + OAD (n=69) p=0.01 10 p=0.008 8 6 p=0.06 4 2 0 All episodes of hypoglycemia All confirmed episodes of hypoglycemia Confirmed symptomatic hypoglycemia Adapted from Janka HU et al. J Am Geriatr Soc 2007;55(2):182-8.

  24. The ADA Treatment Algorithm for the Initiation and Adjustment of Insulin

  25. Initiating and Adjusting Insulin Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c≤7%... Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range:add rapid-acting insulin at dinner If HbA1c7%... If HbA1c≤7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c7%... If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Continue regimen; check HbA1c every 3 months Continue regimen; check HbA1c every 3 months Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

  26. Step One… Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c≤7%... Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range:add rapid-acting insulin at dinner If HbA1c7%... If HbA1c≤7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c7%... If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Continue regimen; check HbA1c every 3 months Continue regimen; check HbA1c every 3 months Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

  27. Step One: Initiating Insulin Start with either… Bedtime intermediate-acting insulin or Bedtime or morning long-acting insulin Insulin regimens should be designed taking lifestyle and meal schedules into account Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  28. Step One: Initiating Insulin, cont’d Check fasting glucose and increase dose until in target range Target range: 3.89-7.22 mmol/l (70-130 mg/dl) Typical dose increase is 2 units every 3 days, but if fasting glucose >10 mmol/l (>180 mg/dl), can increase by large increments (e.g., 4 units every 3 days) Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  29. If hypoglycemia occurs or if fasting glucose < 3.89 mmol/l (70 mg/dl)… Reduce bedtime dose by ≥4 units or 10% if dose >60 units Step One: Initiating Insulin, cont’d Reduction in overnight and fasting glucose levels achieved by adding basal insulin may be sufficient to reduce postprandial elevations in glucose during the day and facilitate the achievement of target A1C concentrations. Nathan DM et al. Diabetes Care 2006;29(8):1963-72. While using basal insulin alone,never stop or reduce ongoing oral therapy

  30. If HbA1c is <7%... Continue regimen and check HbA1c every 3 months If HbA1c is ≥7%... Move to Step Two… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  31. With the addition of basal insulin and titration to target FBG levels, only about 60% of patients with type 2 diabetes are able to achieve A1C goals < 7%.[36] In the remaining patients with A1C levels above goal regardless of adequate fasting glucose levels, postprandial blood glucose levels are likely elevated.

  32. Step Two… Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c≤7%... Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range:add rapid-acting insulin at dinner If HbA1c7%... If HbA1c≤7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c7%... If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Continue regimen; check HbA1c every 3 months Continue regimen; check HbA1c every 3 months Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

  33. Step Two: Intensifying Insulin If fasting blood glucose levels are in target range but HbA1c ≥7%, check blood glucose before lunch, dinner, and bed and add a second injection: If pre-lunch blood glucose is out of range, add rapid-acting insulin at breakfast If pre-dinnerblood glucose is out of range, add NPH insulin at breakfast or rapid-acting insulin at lunch If pre-bed blood glucose is out of range, add rapid-acting insulin at dinner Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  34. Making Adjustments Can usually begin with ~4 units and adjust by 2 units every 3 days until blood glucose is in range When number of insulin Injections increase from 1-2………..Stop or taper of insulin secretagogues (sulfonylureas). Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  35. If HbA1c is <7%... Continue regimen and check HbA1c every 3 months If HbA1c is ≥7%... Move to Step Three… After 2-3 Months… Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  36. Step Three… Bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin (initiate with 10 units or 0.2 units per kg) Check FG and increase dose until in target range. If HbA1c≤7%... Pre-lunch BG out of range: add rapid-acting insulin at breakfast Pre-dinner BG out of range:add NPH insulin at breakfast or rapid-acting insulin at lunch Pre-bed BG out of range:add rapid-acting insulin at dinner If HbA1c7%... If HbA1c≤7%... Hypoglycemia or FG >3.89 mmol/l (70 mg/dl): Reduce bedtime dose by ≥4 units (or 10% if dose >60 units) Target range: 3.89-7.22 mmol/L (70-130 mg/dL) If HbA1c7%... If fasting BG in target range, check BG before lunch, dinner, and bed. Depending on BG results, add second injection (can usually begin with ~4 units and adjust by 2 units every 3 days until BG in range) Continue regimen; check HbA1c every 3 months Continue regimen; check HbA1c every 3 months Recheck pre-meal BG levels and if out of range, may need to add another injection; if HbA1c continues to be out of range, check 2-hr postprandial levels and adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care. 2006;29(8):1963-72.

  37. Step Three: Further Intensifying Insulin Recheck pre-meal blood glucose and if out of range, may need to add a third injection If HbA1c is still ≥ 7% Check 2-hr postprandial levels Adjust preprandial rapid-acting insulin Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  38. Premixed Insulin Not recommended during dose adjustment Can be used before breakfast and/or dinner if the proportion of rapid- and intermediate-acting insulin is similar to the fixed proportions available Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

  39. Key Take-Home Messages Insulin is the oldest, most studied, and most effective antihyperglycemic agent, but can cause weight gain (2-4 kg) and hypoglycemia Insulin analogues with longer, non-peaking profiles may decrease the risk of hypoglycemia compared with NPH insulin Premixed insulin is not recommended during dose adjustment

  40. Key Take-Home Messages, cont’d When initiating insulin, start with bedtime intermediate-acting insulin, or bedtime or morning long-acting insulin After 2-3 months, if FBG levels are in target range but HbA1c ≥7%, check BG before lunch, dinner, and bed,and, depending on the results, add 2nd injection (stop sulfonylureas here) After 2-3 months, if pre-meal BG out of range, may need to add a 3rd injection; if HbA1c is still ≥7% check 2-hr postprandial levels and adjust preprandial rapid-acting insulin.

  41. Regimen # 2

  42. First calculate total daily dose of insulin Body weight in kgs / 2 • e.g; an 80 kg person will require roughly about 40 units / day.

  43. Dose calculation……..contd Split the total calculated dose into 4 (four) equal s/c injections. • ¼ of total dose as regular insulin s/c half-hour ( ½ hr ) before the three main meals with 6 hrs gap in between. • ¼ total calculated dose as NPH insulin s/c at 11:00 p.m. with no food to follow.

  44. Dose calculation: example For example in an 80-kg diabetic requiring 40 units per day, start with: • 08:00 a.m. --- 10 units regular insulin s/c ½ hr before breakfast. • 02:00 p.m. --- 10 units regular insulin s/c ½ hr before lunch. • 08:00 p.m. --- 10 units regular insulin s/c ½ hr before dinner. • 11:00 p.m. --- 10 units NPH/ lantus insulin s/c

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