For Scientists Research Information Alumni Connection

Edward S. Horton, M.D.

Research Summary

1. The Diabetes Prevention Program and Diabetes prevention Program Outcomes Study (DPP/DPPOS)

The DPP/DPPOS Research Group , which consists of 27 centers in the United States, continues to implement the long-term follow-up of the 3 major study groups (Intensive Lifestyle Modification, Metformin Treatment and Controls) for the development of diabetes mellitus and its long term complications. We are now beginning to plan for the end-of-study procedures which will take place over the next 3 –and final- years of the DPPOS 11-year study. The current version of the protocol (DPPOS version 3.0) and manual of operations incorporate several new procedures (and accompanying revised informed consents) that had been included in the proposal for the current 5-year period of DPPOS. Those procedures, including end-of-study fundus photography, which will serve as an important component of the primary outcome, and two batteries of tests that will measure functionality and cognition, respectively, are now underway. In addition to the new procedures above that were implemented, a proposal to measure coronary artery calcification (CAC) was prepared by the Research Group and was subsequently funded by NHLBI and will be initiated in the near future.

The implementation of the protocol has continued with a high rate of retention (>95%), annual visits (88%), and data completion at visits (99% for most measures). All study participants continue to be offered regularly scheduled support sessions for lifestyle intervention (HELP program), while the original intensive lifestyle intervention group continues with the somewhat more intensive BOOST program. These programs are designed by a central lifestyle work group and are implemented locally. The original metformin treatment group continues to receive metformin as a study-supplied drug and approximately 50% of the original cohort continues to take at least 80% of assigned medication based on pill counts. An additional and substantial fraction of the original metformin group continues to take metformin at lower doses.

2. The Action for Health in Diabetes (LookAHEAD) Study

The Look AHEAD study, now in its 10th year, has continued to proceed very smoothly. It is a multicenter, randomized clinical trial examining the long-term effects (up to 13.5 years) of an intensive lifestyle intervention program on cardiovascular morbidity and mortality in overweight or obese persons with Type 2 Diabetes.  

Weight loss for participants assigned to the Lifestyle Intervention (ILS) arm of the trial has been excellent.  On average participants lost 8.6% at year 1; 4.7% at year 4; and 4.1% at year 7.  The intervention has been effective in all age, gender, and race/ethnicity groups.  Across all clinics, 68% of participants had a > 5% weight loss at year 1 and 46% had a > 5% weight loss at year 7.  Fitness increased by 13.5% at year 1 and 2.4% at year 4, relative to baseline.  All centers have maintained the regular contact schedule with Lifestyle participants and conducted study wide campaigns.  The classes for the Diabetes Support and Education (DSE) participants, which serves as the control group for the study, are considered optional and are used primarily for retention purposes.  In the first year, 4 classes were offered, with 1 class on diabetes required.  In all subsequent years, 3 optional classes have been provided. 

The primary outcome measures in Look AHEAD are related to CVD mortality and morbidity and are collected by phone interview at 6-month intervals and as part of the annual clinic visit.  Outcomes interviews (with deaths excluded) have been completed by more than 94% of participants each year. Currently < 5% of the total sample is considered “inactive” because they have missed their two most recent outcomes assessments (excluding those who are deceased).  The study has now begun completing 8 year visits for our participants. Several new measures have been added to the 8 year visits (with an ARRA funding supplement). These will include self-report measures of falls and collection and storage of urine samples.  To date, there have been 73 peer-reviewed presentations and 48 peer-reviewed manuscripts. The year 1 results were published in Diabetes Care in 2007 and the year 4 data were published in Archives of Internal Medicine in 2010.

3. Study of Diabetes, Cardiac Disease and Air Pollution Vulnerability.

The purpose of this study is to determine if air pollution affects the cardiovascular system in people with type 2 diabetes mellitus, with special emphasis on the role of traffic-related particle pollution. Eligible subjects with type 2 diabetes are studied on 5 different occasions, each two weeks apart, to determine cardiac rhythm and function, endothelial-dependent and -independent vasodilatation using high resolution brachial artery ultrasound, central aortic hemodynamics using Pulse Wave Analysis and affects on plasma biomarkers of endothelial function, inflammation, coagulation and oxidative stress. Results of these measures are correlated with exposure to a wide variety of air pollutants, measured both centrally at the Harvard School of Public Health and its satellite locations as well as by home monitoring methods.  A Total of 70 subjects have participated in the study, which is now completed and in the data analysis and publication stage.

Biography

Dr. Horton is Professor of Medicine at Harvard Medical School and a Senior Investigator at Joslin. Dr. Horton received his medical degree from Harvard Medical School and completed residency training at Dartmouth and Duke University. He has had a long and distinguished career in diabetes, and is the recipient of numerous awards and honors, including serving as President of the American Diabetes Association and President of the American Society of Clinical Nutrition. Before coming to Joslin in 1993, Dr. Horton was Chairman of the Department of Medicine at the University of Vermont.

His major interests include obesity and insulin resistance as they relate to diabetes mellitus and cardiovascular disease; the regulation of energy balance and metabolic fuel homeostasis; the regulation of glucose transport and metabolism in skeletal muscle and adipose tissue; and the effects of exercise and physical training on insulin sensitivity. He is also Principal Investigator or Co-Investigator for several large NIH-funded studies including the Diabetes Prevention Program, the LookAHEAD Study and a Study of Diabetes, Cardiac Disease and Air Pollution Vulnerability. He has over 300 publications to his credit.