Outpatient Insulin Therapy in Type 1 and Type 2 Diabetes Mellitus

Abstract

Context Newer insulin therapies, including the concept of physiologic basalprandial 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.

A hemochromatosis-causing mutation C282Y is a risk factor for proliferative diabetic retinopathy in Caucasians with type 2 diabetes

“…This finding suggests the existence of other factors, such as differences in the ability of insulin secretion, differences in the frequency of episodes of hypoglycemia, or adverse events associated with insulin therapy (hypoglycemia, worsening diabetic retinopathy if HbA 1c decreases rapidly) (DeWitt andHirsch 2003, Dahl-Jorgensen et al 1985).…”

7. Approaches to Glycemic Treatment

“…Since the DCCT, a number of rapidacting and long-acting insulin analogs have been developed. These analogs are associated with less hypoglycemia in type 1 diabetes, while matching the A1C lowering of human insulins (1,12).…”

“…There are excellent reviews to guide the initiation and management of insulin therapy to achieve desired glycemic goals (1,2,3). Although most studies of MDI versus pump therapy have been small and of short duration, a systematic review and meta-analysis concluded that there were no systematic differences in A1C or severe hypoglycemia rates in children and adults between the two forms of intensive insulin therapy (4).…”

Case Files of the Harvard Medical Toxicology Fellowship at Children’s Hospital Boston: An Insulin Overdose

“…Currently available recombinant insulin products are designed to have dramatically different pharmacokinetic profiles to facilitate multiple strategies for outpatient glucose management [2,3].…”