Epidemiology of Type 2 Diabetes Mellitus

Title: Epidemiology of Type 2 Diabetes Mellitus

Principal Investigator: Richard Donahue, PhD, MPH

Funding Agency: NIH/NIDDKD

Period: 07/01/02 - 05/31/07

Abstract: People with type 2 diabetes mellitus (DM) are two to four times more likely to die than nondiabetic people; cardiovascular disease presenting as the most frequent macrovascular complication. Although substantial progress has been made in the treatment of type 2 DM, preventing the disease still presents a formidable public health challenge. Targeted and meaningful prevention will require a further understanding of the etiology and pathophysiology of type 2 DM.

The American Diabetic Association (ADA) recognizes type 2 diabetes mellitus (DM) to be a separate and distinct disease entity from type 1 DM. Recent basic science, clinical and epidemiological studies have provided important clues towards potential important mechanisms leading to type 2 diabetes. These studies have indicated that these mechanisms may be diverse. Among the areas investigated, the most promising include: inflammation, autoimmunity, endothelial function and genetic predisposition. For example, recent clinical and epidemiological data indicate that cytokines, endothelial dysfunction and antigenic stimulation may provide important mechanisms whereby insulin resistance and beta cell failure cause DM. However, type 1 and type 2 may share some commonalities. For example, some 10% to 30% of adults diagnosed with type 2 DM may have an autoimmune process, which leads to beta cell destruction, and need for insulin replacement. This condition has been termed latent autoimmune diabetes of adults (LADA) by Zimmet et al. or type 1.5 DM by Palmer. As noted by Pickup et al, an altered immune system that includes chronic inflammation may underlie the majority of type 2 cases. The overall aim of this proposal is to gain a more complete understanding of the etiology of DM in older adults by investigating the hypothesized mechanisms.

This proposal has been focused to address the following specific aims and hypotheses:

  1. Markers of chronic inflammation: C-reactive protein (CRP), fibrinogen, tumor necrosing factor alpha (TNFa) and its soluble receptor 2 (TNFa sR2), interleukin 6 (IL6), and IL6 soluble receptor (IL6SR) are associated with increased risk of type 2 DM;
  2. Markers of endothelial function : E-selectin, ICAM1, and VCAM1 predict incident type 2 DM; and
  3. Antibodies to islet cell antigen 2 (IA2) and/or glutamic acid decarboxylase (GAD65) increase the risk of developing type 2 DM.

This grant application will take advantage of an existing cohort of older adults who reside in Western New York and utilize frozen (-1900) plasma from our Biologic Specimen Bank to provide baseline samples of the relevant biochemical and genetic factors. We will recall approximately 3,000 people and use a matched case/control design to accomplish these aims.