Paradigm Shifts in the Management of Type 2 Diabetes

Corporate-sponsored Symposium
Supported by a joint unrestricted educational grant from Aventis, inc (a member of the sanofi aventis group) and Pfizer, Inc
Saturday, June 11, 2005
5:30-8:00 AM

Faculty:
Julio Rosenstock, MD
Vivian Fonseca, MD
William T Cefalu, MD

Reported by Joelle Escoffery, PhD

The goal of this symposium was to redefine the role of insulin in the treatment and prevention of type 2 diabetes and cardiovascular disease. Current treatment paradigms are stepwise in nature, beginning with therapeutic lifestyle change, followed by oral therapies, and finally initiating insulin as a “last resort” treatment. This treatment approach of multiple therapies is necessitated by the progressive beta-cell decline that characterizes type 2 diabetes. However, recent research has suggested that earlier use of insulin may provide sustained optimal glucose control, as well as a period of “beta-cell rest” that can result in improved insulin secretion over time. A variety of studies have demonstrated that when newly diagnosed type 2 patients were treated with intensive physiology insulin therapy for a period of 2 week, they were able to maintain normoglycemia for a period of 6 months to a year. Further, patients who maintained glycemic control over a period of a year following only 2 weeks of intensive insulin therapy showed significantly improved beta-cell function and first-phase insulin response. These data suggest that early use of insulin therapy may be an effective therapeutic strategy for preserving beta-cell function.

Insulin and insulin sensitizers may also be important for the reduction of cardiovascular risk. Although several epidemiological reports have indicated a connection between insulin use and cardiovascular events, existing data do not support a causal relationship. Rather, patients using insulin are likely to be older, to have a longer diabetes duration, and to be suboptimally treated with insulin (eg, given insulin in a way that does not mimic normal physiology). The United Kingdom Prospective Diabetes Study (UKPDS) showed no increase in cardiovascular events among insulin-treated patients. Further, recent studies have shown beneficial effects of insulin on cardiovascular risk. The beneficial effects insulin include effects mediated by glycemic improvements, as well as direct effects of insulin on atherosclerotic processes, including suppression of C-reactive protein and other inflammatory cytokines. Thiazoladienediones (TZDs) also have anti-inflammatory effects and may have a beneficial effect on cardiovascular risk.

Although early use of insulin may delay progression of type 2 diabetes and reduce atherosclerotic processes, there are many barriers to its use. Patients may be unwilling to take multiple daily injections, and healthcare providers may lack the resources to support patients taking insulin. Advances in insulin delivery, including dermal, intranasal, oral, spray, and inhaled insulins, may increase patient willingness.