2008 Clinical Practice Guidelines - Canadian Diabetes Association

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2008 CLINICAL PRACTICE GUIDELINES S46 Insulin Therapy in Type 1 Diabetes Canadian Diabetes Association Clinical Practice Guidelines Expert Committee This chapter was prepared by Alice Cheng MD FRCPC, Amir Hanna MB BCh FRCPC, Tina Kader MD FRCPC CDE and Cindy Richardson MD FRCPC KEY MESSAGES • Basal-prandial insulin regimens (e.g. multiple daily injections or continuous subcutaneous insulin infusion) are the insulin regimens of choice for all adults with type 1 diabetes. • Insulin regimens should be tailored to the individual’s treatment goals, lifestyle, diet, age, general health, motivation, hypoglycemia awareness status and ability for selfmanagement. • All individuals with type 1 diabetes should be counselled about the risk, prevention and treatment of insulininduced hypoglycemia. INTRODUCTION Insulin therapy remains the mainstay of glycemic control in people with type 1 diabetes. Insulin preparations are primarily produced by recombinant DNA technology, and are formulated either as structurally identical to human insulin or as a modification of human insulin (insulin analogues) to alter their pharmacokinetics. Animal insulins are becoming less commercially available. Insulin preparations are classified according to their duration of action, and are further differentiated by their time of onset and peak actions (Table 1). Premixed insulin preparations are available, but are not generally suitable for intensive treatment in patients with type 1 diabetes, who usually need to frequently change the individual components of their insulin regimens. INSULIN DELIVERY SYSTEMS Insulin can be administered by syringe, pen or pump (continuous subcutaneous insulin infusion [CSII]). Insulin pen devices facilitate the use of multiple injections of insulin. CSII therapy is a safe and effective method of intensive insulin therapy for selected patients and may provide some advantages over other methods of intensive therapy, particularly in individuals with higher baseline glycated hemoglobin (A1C) (1-5). INITIATION OF INSULIN THERAPY Patients must receive initial and ongoing education that includes comprehensive information on how to care for and use insulin; prevention, recognition and treatment of hypoglycemia; sick-day management; adjustments for food intake (e.g. carbohydrate counting) and physical activity; and selfmonitoring of blood glucose (SMBG). INSULIN REGIMENS Insulin regimens should be tailored to the individual’s treatment goals, lifestyle, diet, age, general health, motivation, hypoglycemia awareness status and ability for self-management. Social and financial aspects should also be considered. After insulin initiation, some patients go through a “honeymoon period,” during which insulin requirements may decrease.This period is, however, transient (usually weeks to months), and insulin requirements will increase with time. While fixed-dose regimens (conventional therapy) were once the most commonly used regimens and are occasionally still used, they are not preferred. The Diabetes Control and Complications Trial (DCCT) conclusively demonstrated that intensive treatment of type 1 diabetes significantly delays the onset and slows the progression of microvascular and macrovascular complications (6,7).The most successful protocols for type 1 diabetes rely on basal-bolus (basal-prandial) regimens that are used as a component of intensive diabetes therapy. Basal insulin is provided by an intermediate-acting insulin or a long-acting insulin analogue once or twice daily. Prandial (bolus) insulin is provided by a short-acting insulin or a rapid-acting insulin analogue given at each meal. Such protocols attempt to duplicate normal pancreatic insulin secretion. Prandial insulin dose must take into account the carbohydrate content and glycemic index of the carbohydrate consumed, exercise around mealtime and the fact that the carbohydrate to insulin ratio may not be the same for each meal (breakfast, lunch and dinner). Prandial insulins can also be used for correction doses to manage hyperglycemia. Compared with regular insulin, insulin lispro or insulin aspart in combination with adequate basal insulin result in improved postprandial glycemic control and A1C, while minimizing the occurrence of hypoglycemia (8-11). Regular insulin should ideally be administered 30 to 45 minutes prior to a meal. In contrast, insulin aspart and insulin lispro should be administered 0 to 15 minutes before meals. In fact, their rapid onset of action allows for these insulins to be administered up to 15 minutes after a meal. However, preprandial injections achieve better postprandial control and possibly better overall glycemic control (12,13). Insulin aspart has been associated with improved quality of life (14). Insulin
glulisine, another short-acting analogue that has been approved but is not yet commercially available in Canada, has been shown to be equivalent to insulin lispro for glycemic control, with greater A1C reduction when given preprandially as opposed to postprandially (15,16). When used as a basal insulin in patients with good glycemic control, the long-acting analogues insulin glargine and insulin detemir (with regular insulin or rapid-acting insulin analogues for meals), result in lower fasting plasma glucose (FPG) levels and less nocturnal hypoglycemia compared with once- or twice-daily NPH insulin (8,17-23). Given the potential severe consequences of nocturnal hypoglycemia (discussed below), the avoidance of this complication is of critical clinical importance. When compared with 4-times-daily NPH insulin, insulin glargine was associated with lower A1C and less hypoglycemia (21). Among people with type 1 diabetes, insulin glargine has been shown to have a longer duration of action compared with detemir (24). Insulin detemir has a flatter pharmacodynamic profile than NPH insulin (22). Twice-daily insulin detemir as the basal component of a basal-bolus insulin regimen has been shown Table 1.Types of insulin to reduce nocturnal hypoglycemia compared with twicedaily NPH insulin (23,25). There has been a trend towards improved A1C with both insulin glargine and insulin detemir that has reached significance in several studies (25-28). Due to concerns that alterations in the pharmacokinetics may occur, mixing glargine or detemir with other insulins in the same syringe is not recommended by the manufacturers. In patients using CSII, insulin aspart and lispro have been shown to be superior to regular insulin by improving postprandial glycemic control and reducing hypoglycemia (29-32). Although human insulins and insulin analogues are used by virtually all adults with type 1 diabetes, animal insulins are still accessible in Canada (see Related Website, page S49). INHALED INSULIN Inhaled insulin has been approved for use in Canada, but is not yet commercially available. It has been studied as a rapidacting insulin administered before meals in a regimen that uses subcutaneous long-acting insulin either once or twice daily. Studies in adults have demonstrated equivalent glycemic control, reduced FPG levels and increased patient satisfaction Insulin type (trade name) Onset Peak Duration Prandial (bolus) insulins Rapid-acting insulin analogues (clear) • Insulin aspart (NovoRapid) • Insulin lispro (Humalog) • Insulin glulisine (Apidra) Short-acting insulins (clear) • Humulin-R • Novolin ge Toronto Inhaled insulin Basal insulins Intermediate-acting (cloudy) • Humulin-N • Novolin ge NPH Long-acting basal insulin analogues (clear) • Insulin detemir (Levemir) • Insulin glargine (Lantus) Premixed insulins Premixed regular insulin – NPH (cloudy) • Humulin 30/70 • Novolin ge 30/70, 40/60, 50/50 Premixed insulin analogues (cloudy) • Biphasic insulin aspart (NovoMix 30) • Insulin lispro/lispro protamine (Humalog Mix25 and Mix50) 10–15 min 10–15 min 10–15 min 30 min 10–20 min 1–3 h 90 min 1–1.5 h 1–2 h 1–1.5 h Note: Physicians should refer to the most current edition of Compendium of Pharmaceuticals and Specialties (Canadian Pharmacists Association; Ottawa, Ontario, Canada) and product monographs for detailed information. 2–3 h 2 h 5–8 h Not applicable 3–5 h 3.5–4.75 h 3–5 h 6.5 h 6 h Up to 18 h Up to 24 h (glargine 24 h, detemir 16–24 h) A single vial or cartridge contains a fixed ratio of insulin (% of rapid-acting or short-acting insulin to % of intermediate-acting insulin) S47 MANAGEMENT
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2008 Clinical Practice Guidelines - Canadian Diabetes Association

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