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Diagnosis and Management of Type 2 Diabetes, Tenth Edition

Oct 4, 2010

Insulin Therapy, Chapter 9 – Part 1

Steve V. Edelman, MD, Professor of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego


Robert R. Henry, MD, Professor of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego


Diagnosis_and_Management_of_Type_2_DiabetesInsulin therapy most commonly is reserved for patients in whom an adequate trial of diet, exercise, and oral antidiabetic agents has failed. However, institution of insulin therapy is commonly delayed inappropriately for months to years in such patients. Both physicians and patients are hesitant to start “the needle” because of fear, ignorance, and time constraints. There is no question that the benefits of improved glycemic control outweigh the initial hassles and risks of insulin therapy. We encour­age early use of insulin soon after it is evident that oral antidiabetic agents are failing.

Many insulin regimens are recommended, although it is not clear from the literature which regimen is best. This chapter will focus on the different insulin regimens commonly used to normalize glucose levels and A IC in patients with type 2 diabetes mellitus.

Based on the natural history of type 2 diabetes, many patients will eventually require therapy with insulin. The period of time before insulin is required tends to be highly variable and is based on numerous factors. The most important explanation is the extent of beta-cell exhaus­tion resulting in relative endogenous insulinopenia. This leads to progressive loss of compensatory hyperinsu­linemia, which is required to achieve and maintain a suf­ficient degree of glycemic control, especially in patients taking oral hypoglycemic agents. In other cases, obesity, pregnancy, or any number of medications, as well as a variety of illnesses, may exacerbate the insulin-resistant state and convert a patient previously well controlled on an oral-agent regimen to one requiring insulin.

In addition to the natural history of type 2 diabetes, there is heterogeneity in its pathophysiology, which may influence when patients require insulin. Some patients diagnosed with type 2 diabetes may actually be closer to insulin-dependent or type I diabetes with severe insulinopenia. Many of these patients have been shown to have islet cell antibody (ICA) positivity or antibodies to glutamic acid decarboxylase (GAD), with a decreased C-peptide response to glucagon stimulation and a propen­sity for primary oral medication failure. Latent autoim­mune diabetes in adults, or LADA, is the term coined by the ADA to label this type of patient. There are also wide geographic and racial differences that may influence the need for insulin therapy. For example, Asian patients with type 2 diabetes tend to be thinner, to be diagnosed with diabetes at an earlier age, to experience failure of oral hypoglycemic agents much sooner, and to be more sensitive to insulin therapy than the classic centrally obese Caucasian patient.

Insulin therapy can improve or correct many of the metabolic abnormalities present in patients with type 2 diabetes mellitus. Exogenous insulin administration significantly reduces glucose levels by suppressing hepatic glucose production, increasing PPG utilization, and improving the abnormal lipoprotein levels commonly seen in patients with insulin resistance. Insulin therapy may also decrease or eliminate the effects of glucose toxicity by reducing hyperglycemia to improve insulin sensitivity and /3-cell secretory function.

© Copyright 2010. Steven V. Edelman, MD, Robert R. Henry, MD, Professional Communications, Inc. All rights reserved.


Next Week: Application of Intensive Insulin Therapy (Chapter 9)

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