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Scientific Review

Dawn E. DeWitt, MD, MSc; Irl B. Hirsch, MD

JAMA. 2003;289:2254-2264.

Context  Newer insulin therapies, including the concept of physiologic basal-prandial insulin and the availability of insulin analogues, are changing clinical diabetes care. The key to effective insulin therapy is an understanding of principles that, when implemented, can result in improved diabetes control.

Objective  To systematically review the literature regarding insulin use in patients with type 1 and type 2 diabetes mellitus (DM).

Data Sources  A MEDLINE search was performed to identify all English-language articles of randomized controlled trials involving insulin use in adults with type 1 or type 2 DM from January 1, 1980, to January 8, 2003. Bibliographies and experts were used to identify additional studies.

Study Selection and Data Extraction  Studies were included (199 for type 1 DM and 144 for type 2 DM, and 38 from other sources) if they involved human insulins or insulin analogues, were at least 4 weeks long with at least 10 patients in each group, and glycemic control and hypoglycemia were reported. Studies of insulin-oral combination were similarly selected.

Data Synthesis  Twenty-eight studies for type 1 DM, 18 for type 2 DM, and 48 for insulin-oral combination met the selection criteria. In patients with type 1 DM, physiologic replacement, with bedtime basal insulin and a mealtime rapid-acting insulin analogue, results in fewer episodes of hypoglycemia than conventional regimens. Rapid-acting insulin analogues are preferred over regular insulin in patients with type 1 DM since they improve HbA_1C and reduce episodes of hypoglycemia. In patients with type 2 DM, adding bedtime neutral protamine Hagedorn (isophane) insulin to oral therapy significantly improves glycemic control, especially when started early in the course of disease. Bedtime use of insulin glargine results in fewer episodes of nighttime hypoglycemia than neutral protamine Hagedorn regimens. For patients with more severe insulin deficiency, a physiologic insulin regimen should allow lower glycemic targets in the majority of patients. Adverse events associated with insulin therapy include hypoglycemia, weight gain, and worsening diabetic retinopathy if hemoglobin A_1C levels decrease rapidly.

Conclusions  Many options for insulin therapy are now available. Physiologic insulin therapy with insulin analogues is now relatively simple to use and is associated with fewer episodes of hypoglycemia.

Author Affiliations: Division of General Internal Medicine, Department of Medicine, University of Washington (Dr DeWitt); and Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, and Diabetes Care Center, University of Washington Medical Center (Dr Hirsch), Seattle.

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