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Insulin therapy

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WHICH PATIENTS NEED INSULINCo Insulin should be given to all patients with type 1 diabetesns Insulin Therapy FOR TYPE 2 DIABETES Consider initiating combination insulin injectable therapy when blood glucose is>300350 mg/dL and/or A1C is >1012%. ider initiating combination insulin injectable therapy when blood glucose is>300350 mg/dL and/or A1C is >1012%.

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INSULIN PREPARATIONS

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Human versus analogs The time to peak and the duration of action of human insulin preparations (NPH [Neutral Protamine Hagedorn] and regular insulin do not replicate endogenous basal and postprandial insulin secretion. Thus, insulin analogs (lispro, aspart, glulisine, glargine, detemir, degludec) were developed.

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The very rapid-acting insulin analogs have both faster and shorter duration of action than regular insulin for pre- meal coverage The long-acting analogs have a longer and flatter profile than NPH for basal coverage.

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To produce an insulin preparation with a faster onset and shorter duration of action than regular insulin, modifications were made in the insulin molecule to prevent it from forming hexamers or polymers that slow absorption and delay action.

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As an example, insulin aspart is identical to human regular insulin except for a substitution of aspartic acid for proline at position B28. This substitution results in a reduction in hexamer formation and consequently more rapid absorption faster onset of action, and shorter duration of action

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Insulin glargin is identical to human insulin except for a substitution of glycine for asparagine in position A21 and by the addition of two arginine molecules in the B-chain of the insulin molecule. These modifications result in a change in the pH such that, after subcutaneous administration, glargine precipitates in the tissue forming hexamers, which delays absorption and prolongs duration of action.

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Glargine has no appreciable peak and a duration of action that usually lasts 24 hours. Glargine cannot be mixed with rapid-acting insulins as the kinetics of both the glargine and rapid-acting insulin will be altered.

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Insulin therapy in type 2 diabetes mellitus

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combination oral agent and insulin therapy Basal insulin o NPH insulin has been used commonly at bedtime o Insulin glargine (once daily) o detemir (once or twice daily)

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The long-acting insulins, glargine and detemir, may have some modest clinical advantages over NPH less symptomatic and nocturnal hypoglycemia in type 2 diabetes with the important disadvantage of higher cost.

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Insulin dose If a bedtime dose of NPH, detemir, or glargine insulin is being added to oral hypoglycemic drug therapy, we recommend starting at 10 units or 0.2 units per kg

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Fasting blood glucose (FBG) should be measured every day. An increase of 2 to 4 units in the bedtime insulin dose should be made periodically (approximately every three days) if the mean FBG is above 130 mg/dL during this time.

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If fasting glucose levels are very elevated (>250 mg/dL ) or if a patient is known to be very insulin resistant, initial doses can be higher and titration more aggressive.

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Optimal timing of insulin dose NPH insulin may be most effective if given at bedtime In contrast, a morning rather than a bedtime dose of insulin glargine may provide better glycemic control in patients with type 2 diabetes who are also treated with an oral agent. Ann Intern Med 2003

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If basal insulin has been titrated to an acceptable fasting blood glucose level, but A1C remains above target, consider advancing to combination injectable therapy to cover postprandial glucose excursions. Options include adding a GLP-1 receptor agonist mealtime insulin

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A less studied alternative,transitioning from basal insulin totwice-daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix), could also be considered. Regular human insulin and human NPH-Regular premixed formulations (70/30) are less costly alternatives to rapid- acting insulin analogs and premixed insulin analogs, respectively, but their pharmacodynamic profiles make them suboptimal for the coverage of postprandial glucose excursions

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Insulin therapy in type 1 diabetes mellitus

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CHOICE OF INSULIN REGIMEN Multiple daily injections Continuous subcutaneous insulin infusion

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conventional insulin therapy Before the conclusion of the DCCT in 1993, the most commonly used insulin regimens (ie, "conventional insulin therapy") consisted of twice-daily injections of short-acting (regular) and intermediate-acting insulin.

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This regimen was not physiologic and is no longer recommended unless the patient cannot or will not comply with an intensive insulin regimen.

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Multiple daily insulin inject Basal insulin NPH Insulin glargine Insulin detemir In type 1 diabetes, insulin glargine may have a slight glycemic advantage and detemir less risk of severe hypoglycemia compared with NPH.

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In patients with type 1 diabetes (but not type 2), glycemic control is similar if once-daily glargine is given before breakfast, before dinner, or at bedtime but there is less nocturnal hypoglycemia with breakfast administration.

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bolus insulin regular insulin Rapid-acting insulin

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Advantages of rapid-acting insulin It decreases the postprandial rise in blood glucose concentration. It is more convenient because it can be injected 10 to 15 minutes prior to or up to immediately after meals The action of insulin lispro is not blunted by mixing with NPH insulin just before injection, as is the action of regular insulin N Engl J Med 2005

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Multiple daily insulin inject

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Choosing basal/bolus insulin The choice of basal and bolus insulin for a multiple daily injection regimen depends upon patient preference, lifestyle, and cost concerns

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Insulin dose Most newly diagnosed patients with type 1 diabetes can be started on a total daily dose of 0.2 to 0.4 units of insulin per kg per day. approximately one-half of the total dose should be given as a basal insulin

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the NPH is usually given as approximately two-thirds of the dose in the morning and one-third at bedtime. The remainder of the total daily dose (TDD) is given as short or rapid-acting insulin, divided before meals.