Insulins in type 2 diabetes mellitus
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- 1.Insulins in Type 2 DiabetesMellitus Dr. Sharat S. Kolke MD, DNB
2. WhenWhyHow? 3. Serum Insulin levelEndogenous insulin Time (hrs)Dynamic nature of normal endogenous insulin secretion.Main components are basal insulin and postprandialinsulin. 4. cell function at diagnosis and later 5. Insulin over the ages.1922 Insulin discovered by Banting and Best1923 Insulin commercially available1930s to 1940s PZI, NPH and lente insulin1960s to 1970s Purified animal insulin1980s Human insulin by r DNA technology2000 Insulin analogues 6. Onset ofPeak (h)Duration of Action (h)Action (h)Human insulin 0.5-1 2-4 6-10 Regular NPH 1-3 5-710-20 Lente1-3 4-810-20 Ultralente 2-4 Unpredictable16-20 AnalogsLispro 5 min-15 min 14-5(Humalog)Aspart 5 min-15 min 14-5(Novolog)Glargine 1-2 Flat~24(Lantus) 7. Serum Insulin level Endogenous insulinTime (hrs)Dynamic nature of normal endogenous insulin secretion.Main components are basal insulin and postprandialinsulin. 8. Split self mixedInsulin treatment Regimens Split pre mixedBasal bolus 9. Split self mixedEffective for helping patients achieve glycemic controlProblems with mixing techniqueInaccurate dosing ratiosReducing the effectiveness of the short-acting insulin. 10. Self pre-mixedThe benefits of premixed insulin formulations(such as a human insulin 30/70 mixed suspension)1. reduced errors2. and improved dosing accuracy3. the convenience of using a single vial. 11. Applying the Basal/Bolus Insulin Concept Basal insulin Nearly constant day-long insulin level Suppress hepatic glucose production between mealsand overnight Cover 50% of daily needs Bolus insulin (mealtime) Immediate rise and sharp peak at 1 hour Limit postmeal hyperglycemia Cover 10% to 20% of total daily insulin requirement at eachmealIdeally, each component should come from a different insulin,with a specific profile 12. Barriers Reassurances with Insulin TherapyInsulin resistance Improves insulin sensitivity by reducingglucotoxicityCardiovascular No evidence of atherosclerotic effects (CV) risk May reduce CV riskWeight gainModestHypoglycemia Rarely causes severe events 13. Practical guidelines Combination regimensAverage patient Early combination of insulin secretagogue and insulin sensitizer Most simple and cost-effective Start low-dose, once-daily sulfonylurea with increasing doses of Metformin Full-dose sulfonylurea in combination with maximally tolerated MetforminFor marked insulin resistance Combination of Metformin + GlitazoneIf target HbA1c 120 mg/dLIncrease by 4 units if FBG >140 mg/dLIncrease by 6 units if FBG >180 mg/dL 15. Practical guidelines Advancing to Basal Bolus insulinIndicated when FBG acceptable butHbA1c >7% and/orSBGM before dinner >160-180 mg/dLInsulin options To glargine, add mealtime lispro or aspart To bedtime NPH, add morning NPH and mealtime lispro oraspartOral agent options Continue sulfonylurea for endogenous secretion? Continue metformin for weight control? Continue glitazone for glycemic stability? 16. Are Analogues better? 17. What are the different analoguesavailable? Insulin Lispro (Humalog) Insulin Aspart (Novorapid R) Insulin Glargine (Lantus) Insulin Detemir (Levemir)How do they differ from conventional insulin?The main difference is usually in the timeaction profile. This means the new insulineither works faster and for shorter periods or have a more prolonged course of action for twenty four hours. 18. What are the potential benefits? Timing of injections can be injected immediatelybefore meals Risk of hypoglycaemia may be less particularlynocturnal hypoglycaemia Compliance may be improved with use of once dailylong acting analogues The need for snacks between meals may be reducedwith short acting analogues Some advantages in terms of weight gain 19. Are analogues more effective thanconventional insulin?The advantage in terms of improvedglycaemic control is not that great.It is possible to achieve equally goodcontrol using conventional insulin.Are they safe to use during Pregnancy?These drugs have not as yet been licensed for use in pregnancy 20. In conclusion.. Strict glycemic control is the only to prevent chronic complications. Strict glycemic control without hypoglycemia. Insulin regimens that closely mimic physiologic insulin secretory patterns must be used. The older conventional insulin products do not have time-action profiles that closely mimic normal secretory patterns. Analogues offer the physician the ability to closely approximate endogenous insulin secretory patterns.