INSULIN THERAPY IN TYPE 1 DIABETES 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada INSULIN THERAPY IN TYPE 1 DIABETES

INSULIN The Diabetes Control and Complication Trial (DCCT) demonstrated conclusively that intensive treatment of type 1 diabetes significantly lowers microvascular complications. Insulin therapy remains the mainstay of treatment for type 1 diabetes. Insulin is primarily produced by recombinant DNA technology and is formulated either as chemically identical to human insulin or as a modification of human insulin (insulin analogues) designed to improve pharmacokinetics.

INSULIN TYPES Insulin Type Names Rapid-acting analogue (clear) Humalog® (insulin lispro); NovoRapid® (insulin aspart) Fast-acting (clear) Humulin®-R; Novolin®ge Toronto Intermediate-acting (cloudy) Humulin®-N; Humulin®-L; Novolin®ge NPH Long-acting (cloudy) Humulin®-U Extended long-acting analogue (clear) Lantus® (insulin glargine) Premixed (cloudy) Many; fixed ratio combination of rapid- or fast-acting with intermediate-acting

INSULIN DELIVERY Insulin can be administered by syringe, pen or pump (continuous subcutaneous insulin infusion or CSII). Insulin pens facilitate insulin use, both for convenience and for individuals with vision problems or dexterity problems with insulin syringes. CSII therapy is a safe and effective way to deliver intensive diabetes management for selected patients, and may provide some advantages over other methods of intensive management.

INSULIN REGIMENS Insulin regimens should be adapted to an individual’s treatment goals, lifestyle, diet, age, general health, motivation, capacity for hypoglycemic awareness and self-management, and social and financial circumstances. The most successful protocols for type 1 diabetes rely on basal-bolus regimens with NPH, lente, ultralente or insulin glargine once or twice daily as the basal insulin, and regular, lispro, or aspart before each meal. Such protocols attempt to imitate normal pancreatic secretion, which consists of basal secretion and a bolus component.

INSULIN THERAPY IN TYPE 1 DM - RECOMMENDATIONS To achieve glycemic targets in people with type 1 diabetes, multiple daily insulin injections (3 or 4 per day) or the use of CSII as part of an intensive diabetes management regimen should be considered [Grade A, Level 1A]. Insulin aspart or insulin lispro, in combination with adequate basal insulin, is preferred to regular insulin to achieve postprandial glycemic targets and improve A1C while minimizing the occurrence of hypoglycemia [Grade B, Level 2].

INSULIN THERAPY IN TYPE 1 DM - RECOMMENDATIONS Insulin lispro or insulin aspart should be used when CSII is used in patients with type 1 diabetes [Grade B, Level 2]. Buffered regular insulin is equally effective in experienced insulin pump users [Grade B, Level 2]. (Buffered regular insulin is available only by special request through the manufacturer or Health Canada.) Insulin glargine should be considered for use as the basal insulin in well-controlled patients who have problems controlling their FPG levels or to reduce overnight hypoglycemia [Grade B, Level 2].

HYPOGLYCEMIA Drug-induced hypoglycemia is a major obstacle for individuals (especially those with type 1 diabetes) trying to achieve glycemic targets. Hypoglycemia can be severe and result in confusion, coma or seizure. Patients at high risk for severe hypoglycemia should be informed of their risk, and counselled along with their significant others on preventing and treating hypoglycemia.

HYPOGLYCEMIA The risk factors for severe hypoglycemia include: a prior episode of severe hypoglycemia a current low A1C (<6%) hypoglycemia unawareness long duration of diabetes autonomic neuropathy adolescents and preschoolers

INSULIN THERAPY IN TYPE 1 DM - RECOMMENDATIONS Risk factors for severe hypoglycemia should be identified in people with type 1 diabetes so that appropriate strategies can be used to minimize hypoglycemia [Grade D, Consensus]. The following strategies should be implemented to reduce the risk of hypoglycemia and to increase physiologic counterregulatory responses to hypoglycemia in individuals with hypoglycemia unawareness: increased frequency of SMBG, including episodic assessment during sleeping hours; less stringent glycemic targets; and multiple insulin injections [Grade D, Level 4].

INSULIN THERAPY IN TYPE 1 DM - RECOMMENDATIONS All individuals currently using insulin or starting intensive insulin therapy should be counselled about the risk and prevention of insulin- induced hypoglycemia [Grade D, Consensus]. In an attempt to reduce the development of hypoglycemia unawareness in people with type 1 diabetes, the frequency of mild hypoglycemic episodes should be minimized (< 3 episodes per week), particularly in those at high risk [Grade D, Level 4].

INSULIN THERAPY IN TYPE 1 DM - RECOMMENDATIONS To reduce the risk of asymptomatic nocturnal hypoglycemia, individuals should periodically monitor overnight BG levels at a time that corresponds with the peak action time of their overnight insulin and consume a bedtime snack with at least 15 g of carbohydrate and 15 g of protein if their bedtime BG level is < 7.0 mmol/L [Grade B, Level 2].