Treatment of NIDDM With Insulin Agonists or Substitutes

Abstract

Non-insulin-dependent diabetes mellitus (NIDDM) is a common disorder occurring in 3-6% of adults in most western populations. In the United States, 29% of patients with diabetes take insulin; of these, 76% have NIDDM. Insulin therapy is usually required at some time in NIDDM. Insulin therapy improves the abnormalities of NIDDM (reduced beta-cell function, increased hepatic glucose production, reduced peripheral glucose disposal, lipid abnormalities). Insulin and sulfonylurea agents have comparable effects on mild forms of NIDDM, but for more severe forms, insulin is usually superior. Combination insulin-sulfonylurea treatment may improve the response to sulfonylureas, although long-term well-controlled trials have not been conducted. Short-term insulin treatment may restore response to sulfonylureas. Other promising treatments (human proinsulin, nasal insulin, somatostatin) have not shown any advantage over conventional insulin therapy. Insulin causes hypoglycemia and peripheral hyperinsulinemia. The hazards of hyperinsulinemia, e.g., weight gain and hypoglycemia, have been overstated, and questions about its atherogenic effects remain to be resolved. The effect of glycemic control on macro- and microvascular complications has not been established; however, maintaining fasting blood glucose levels of less than 6.7 mM may protect against progression of retinopathy, neuropathy, and nephropathy and reduce the severity of ischemic stroke. Dosage algorithms generally use intermediate- or long-acting insulin to control basal glycemia, with regular insulin added before meals if needed to control postprandial glycemia. Effective therapy depends on the patient being informed, cooperative, and willing to self-monitor blood glucose. Insulin treatment intermittency increases the risk for immune complications (resistance and allergy). Overall, patients with NIDDM can benefit from insulin therapy.

Dropout and Relapse During Diabetes Care

“…Between 25 and 35% of all patients with diabetes mellitus use insulin (16). Patients who were receiving insulin treatment were more likely to remain in follow-up than those whose treatment consisted of oral hypoglycemic medications or diet alone.…”

Treatment of Non-Insulin-Dependent Diabetes Mellitus and its Complications

“…Approximately 30% of NIDDM patients will eventually require insulin (Galloway 1990;Genuth 1992). Since NIDDM patients are constantly exposed to hyperglycaemia, the ~-cell, despite its dysfunction, continues to counter increased glucose by releasing insulin in an irregular and erratic manner until there is further decline in insulin release.…”

Thiazolidinediones: a new class of antidiabetic drugs

“…Over the last four decades, oral therapies for Type 2 (noninsulin dependent) diabetes mellitus (DM) have focused on sulphonylureas and metformin, with acarbose introduced in 1990 ( Table 1). The benefits of these drugs on glycaemic levels, as monotherapy and in combination, are well documented[1–6], and insulin is available for patients with advanced symptoms or poor control[4, 7–10]. However, current antidiabetic agents can claim only a modest impact against the progressive nature of diabetes and its chronic microvascular and macrovascular complications[11–16].…”