Diabetes Mellitus in the Era of Proteomics

Diabetes mellitus is a disease that has been known to exist for thousands of years and that afflicts 6% of the population. Because of its prevalence, chronicity, and propensity to cause end-organ damage, diabetes and its complications engenders about 100 billion dollars in health care costs each year in the United States. Most individuals with diabetes have type 2 diabetes mellitus (T2DM). 1 These patients may have elevated, normal, or slightly decreased insulin levels. They have variable degrees of insulin resistance, in association with an inability of the beta cell to compensate for this resistance, and are not ketosisprone under basal conditions. The age of onset of this disease is usually after age 40 but it often also occurs at age 20 or 30, or even at a younger age. Most, but not all, individuals with this form of diabetes are obese. Many also have hypertension, hyperlipidemia, heart disease, and peripheral vascular disease, exhibiting the so-called dysmetabolic syndrome. Furthermore, with the aging of our population and as a consequence of sedentary life styles, the incidence of T2DM will continue to increase. Alarmingly, T2DM is also afflicting younger individuals more frequently than ever before, and this progression into the youthful segment of the population is independent of a specific type of diabetes termed maturity onset diabetes of the young or MODY. Thus, MODY is distinct from T2DM and represents, instead, an interesting group of monogenic forms of diabetes in which specific genetic alterations have been clearly delineated (1). Another major form of diabetes mellitus is type 1 diabetes mellitus (T1DM). These patients frequently have very low or undetectable insulin levels, are dependent on exogenous insulin for survival, and are ketosis-prone. The onset of the disease usually occurs before age 20, but may occur at any age. This review will focus on the molecular alterations in T2DM and on several findings in cell lines and in animal models of diabetes that are based on proteomics-driven technology.