Research

Diabetes, Obesity, and Metabolic Syndrome Research

The American population is experiencing an explosion in Type II diabetes, largely in response to the epidemic of obesity. This national trend of increasing prevalence of obesity and diabetes is especially magnified in Arkansas, which has consistently been ranked as among the most “unhealthy states” in the country. The cost of caring for diabetes and obesity is enormous due to the numerous complications, including heart disease, renal disease, blindness, amputations, etc. Obesity and diabetes are particularly prevalent in minority populations which have traditionally not enjoyed good access to medical care. Finally, the increasing prevalence of obesity in children has now lead to the frequent diagnosis of impaired glucose tolerance and type II diabetes in this population, an entity that was essentially non-existent 20 years ago.

The Diabetes and Obesity program at UAMS involves approximately 15 scientists from the Division of Endocrinology, along with numerous other collaborating investigators from other departments. Much of the research activity from these scientists is centered around mechanisms involved in the early stages of development of type 2 diabetes and obesity, including as insulin resistance, impaired insulin secretion, obesity, and the constellation of findings known as metabolic syndrome*. Together, the total funding for members of the diabetes and obesity group of the Division of Endocrinology total over four million dollars, essentially all of which is from peer reviewed grants from the NIH or the VA.

For example, in studies funded by the NIH and the VA, Dr. Steven Elbein is searching for the early events in diabetes pathogenesis by mapping common genetic variants in families and individuals with type 2 diabetes. Complementary studies are focused on the characterization of insulin secretion in nondiabetic individuals at high risk for diabetes, and on defining the inherited variants in both Caucasian and African American individuals that explain the failure of the pancreatic beta cell to compensate for early declines in insulin sensitivity. Dr. Hua Wang, in collaboration with Dr. Elbein, is focusing on the role of common coding and functional variants that may predispose to diabetes by altering gene expression. Studies conducted by Dr. Philip Kern, also funded by the NIH and VA, examine the effects of adipose tissue and obesity on the development of insulin resistance. The expression by adipose tissue of inflammatory substances and their effects on muscle gene expression and insulin resistance are examined in studies supported by the VA and the NIH, and involve collaborations with Dr. Charlotte Peterson (Geriatrics) and Dr. Robert McGehee (Pediatrics). Dr. Neda Rasouli, in collaboration with Drs. Kern and Elbein, conducts studies targeting the “pre-diabetic” subject with impaired glucose tolerance. These studies examine the mechanism of action of common diabetes medication, such as thiazoledinediones and metformin, and seek to better understand insulin resistance and the partitioning of fat between adipose tissue and muscle. Dr. Debra Simmons conducts investigator initiated studies into nutrition and lipid metabolism. In addition, Dr. Simmons is a Site Director for the ACCORD study, which is an NIH funded study aimed at testing the effects of intensive control of blood sugars, blood pressure and lipid metabolism on heart attacks and strokes in patients with type 2 diabetes.  Dr. Simmons is also a Site Director for the AIM-HIGH study, which is an NIH funded study aimed at testing the effects of control of triglycerides and HDL cholesterol in addition to LDL cholesterol on recurrent heart attacks and strokes in patients with the metabolic syndrome. Dr. Fred Faas is actively involved in investigator-initiated research into lipid metabolism and lipid uptake into tissues, and conducts clinical trials related to new drugs related to lipid metabolism, diabetes, and hypertension. Most of the clinical studies described above are carried out at the VA and utilize the UAMS/VA based General Clinical Research Center*.

Additional studies within the Division of Endocrinology involve basic research into lipid metabolism and diabetes. NIH and VA-funded studies by Drs. Gouri Ranganathan and Philip Kern examine the regulation of lipoprotein lipase, a key protein that controls fat cell lipid accumulation and which controls blood triglyceride levels. These studies help in understanding the molecular mechanism of lipoprotein lipase regulation in diabetes. In addition, Dr. Randall Owens performs basic research, funded by the American Diabetes Association, into the protein synthesis and secretion of important inflammatory proteins made by fat tissue.

Together, these studies involve a broad spectrum of research in diabetes and obesity, beginning with basic research into the cell biology of lipid metabolism, stretching into early translational research which attempts to better understand the mechanisms of early disease development, and finally stretching into clinical trials that attempt to take new knowledge from the bench and apply it to patient care and clinical practice.