Targeting Glycemic Control

To achieve optimal glycemic control, treatment generally needs to target either 1 or both of the 2 primary processes that contribute to the pathogenesis of diabetes: insulin deficiency and insulin resistance.

Type 1 diabetes is characterized by a total or near-total deficiency in endogenous insulin secretion. This deficiency results from selective destruction of the pancreatic islet beta cells, which is generally caused by an autoimmune disorder. As a result, these patients are ketosis-prone. They absolutely require lifetime insulin treatment and are at high risk for hypoglycemia, which is the major complication of treatment. Precise replacement of insulin secretion is the goal of therapy.

By comparison, people with type 2 diabetes usually demonstrate both resistance to insulin and deficient insulin secretion. Treatment of these patients is complex because of the progressive nature of the disease and the multifaceted physiologic defects. It often takes years for subclinical hyperglycemia to present as symptomatic disease. This is particularly problematic because of the complications, both micro- and macrovascular, that often develop during this asymptomatic stage. The insulin resistance in type 2 diabetes is manifested by overproduction of glucose by the liver, impaired ability to deposit glucose in muscle, and increased breakdown of fat leading to high levels of free fatty acids.

Conventional treatment of patients with type 2 diabetes usually begins with recommendations for lifestyle changes (ie, diet and physical activity) often in parallel with monotherapy with an oral agent. If initial approaches fail, then a multidrug regimen, often including insulin, is prescribed. However, because of increasing recognition of the progressive nature of type 2 diabetes and the high risk for micro- and macrovascular complications, physicians are treating diabetes earlier and more aggressively to achieve glycemic control.

The new oral agents and insulin analogues that have been developed over the past several years are aimed at treating diabetes in a way that mimics the normal physiologic insulin response to a meal in a person without diabetes. They offer physicians and patients more options for achieving optimal glycemic control and allow treatment to be tailored to the individual needs of each patient. The descriptions of the newer oral agents and insulin analogues presented below can help physicians and their patients decide which primary therapy is most suitable.

This write up appeared as part of an article entitled “Diabetes Management in the 21st Century: Multiple Therapeutic Options for Achieving Glycemic Control” CME, Author: John B. Buse, MD, PhD, CDE, FACE.  The entire contents of this CME activity is available at www.medscape.com/viewarticle/418598_3.  You must subscribe to Medscape to view this article.