Dr. Horton is a Senior Investigator in the Section on Clinical, Behavioral & Outcomes Research. He is a Professor of Medicine at Harvard Medical School, where he also received his medical degree. He completed residency training at Dartmouth Medical School and Duke University. Dr. Horton is the recipient of numerous awards and honors, including serving as President of the American Diabetes Association and President of the American Society for Clinical Nutrition. In June 2004, he received the Distinguished Physician Award from the Endocrine Society and in September 2006, the Novartis Award in Diabetes for Long-Standing Achievement. He has presented the results of his research at numerous national and international meetings and been published in many prestigious journals. Before coming to Joslin in 1993, Dr. Horton was Chairman of the Department of Medicine at the University of Vermont.

People with diabetes have a two-to-four times greater risk of developing cardiovascular disease (CVD) than those without diabetes. Dr. Horton is studying ways to prevent this problem.

Dr. Horton is the Principal Investigator of several studies focusing on prevention of CVD events in patients with diabetes. These include: (1) the Look AHEAD Study, which examines whether intensive lifestyle modifications will decrease CVD events and other complications in people with established type 2 diabetes, as compared with a program of support and education; (2) research on blood-vessel inflammation and cardiovascular system dysfunction in populations with diabetes and pre-diabetes to determine the risk of developing CVD; and (3) investigations of interventions expected to reduce CVD risk.

Several of these studies found that cardiovascular function improved with the use of the statin atorvastatin, the angiotensin-converting enzyme (ACE) inhibitor quinapril, as well as lifestyle modifications such as weight loss and increased physical activity. An ongoing study focuses on the effects of pioglitazone on improving endothelial (blood-vessel lining) function and preserving pancreatic beta-cell function in people with impaired glucose tolerance or type 2 diabetes.

Dr. Horton is also the Principal Investigator of the Diabetes Prevention Program, a national study designed to compare the effectiveness of various treatments for impaired glucose tolerance (a risk factor for type 2 diabetes). The initial phase of the trial demonstrated that treatment with metformin reduced patients’ progression to diabetes by 31 percent. Treatment by intensive lifestyle modifications—emphasizing weight loss and increased physical activity—reduced progression by 58 percent. These results were the same across all racial and ethnic groups and for both men and women. Obese patients did better on metformin than did leaner patients, and younger patients did better than older ones. Intensive lifestyle change was effective across all age groups and in both leaner and more obese patients. The next phase of the study focuses on the effects of the interventions on the development of CVD and other long-term complications.

Dr. Horton is also studying the effects of new medications for the treatment of type 2 diabetes and the effects of different diets (high carbohydrate, high saturated fat or high monosaturated fat) on endothelial dysfunction and arterial stiffness. In addition, he is using the pulse wave analysis technique to study arterial stiffness as an indicator of atherosclerosis risk in patients with diabetes and pre-diabetes.

He and his colleagues hope to develop protocols that will be useful in measuring and monitoring CVD risk in patients with diabetes. Another goal is to better understand how the interaction of diet, weight loss and increased physical activity can reduce the risk of myocardial infarction, stroke and peripheral vascular disease, and thus decrease both morbidity and mortality in this population.

Selected References
Economides PA, Khaodhiar L, Casselli A, Caballero AE, Keenan H, Bursell SE, King GL, Johnstone MT, Horton ES, Veves A.  The effect of vitamin E on endothelial function of micro-and macrocirculation and left ventricular function in type 1 and type 2 diabetic patients.  Diabetes 54:204-211, 2005.

Ratner R, Goldberg R, Haffner S, Marcovina S, Orchard T, Fowler S, Temprosa M; Diabetes Prevention Program Research Group. Impact of intensive lifestyle and metformin therapy on cardiovascular disease risk factors in the Diabetes Prevention Program. Diabetes Care 28:888-894, 2005.

O’Neill MS, Veves A, Zanobetti A, Sarnat JA, Gold DR, Economides PA, Horton ES, Schwartz J. Diabetes enhances vulnerability to particulate air pollution-associated impairment in vascular reactivity and endothelial function.  Circulation 111:2913-2920, 2005.

Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S; Diabetes Prevention Program Research Group.  The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 142:611-619, 2005.

Kitabchi AE, Temprosa M, Knowler WC, Kahn SE, Fowler SE, Haffner SM, Andres R., Saudek C, Edelstein SL, Arakaki R, Murphy MB, Shamoon H; Diabetes Prevention Program Research Group.  Role of insulin secretion and sensitivity in the evolution of type 2 diabetes in the Diabetes Prevention Program: effects of lifestyle intervention and metformin. Diabetes 54:2404-2414, 2005.

Buras J, Reenstra WR, Orlow D, Horton ES, Veves A.  Troglitazone-induced changes in adiponectin do not affect endothelial function in diabetes.  Obes Res 13: 1167-1174, 2005.