Clinical, Behavioral & Outcomes Research
The major focus of the section on Clinical, Behavioral and Outcomes Research is to elucidate the underlying genetic and environmental determinants of types 1 and 2 Diabetes Mellitus (T1D and T2D) and its complications, and to develop effective new treatment strategies to prevent or delay the development of diabetes and diabetes complications in high-risk individuals. We maintain an active clinical research environment to train future investigators. The scope of ongoing investigations range from small physiologic projects to large NIH-funded multi-center trials.
There are over 240 unique active IRB approved human protocols at the Joslin, of which over 150 involve active patient participation, with others based on medical record review, the study of biospecimens, or those closed to enrollment but under data analysis. The over 150 active studies include a wide range of investigations that can be described as observational (70%) or interventional (30%); single site (60%) or multicenter (40%); and involve participants who are adult (75%), pediatric (10%), or both (15%). Studies are lead by more then 45 Principal Investigators. Investigators in the section collaborate extensively with members of basic research sections at the Joslin and with investigators in the surrounding Harvard-affiliated teaching hospitals and at other academic institutions.
Long term follow-up of patients in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) demonstrates no evidence for substantial long-term decline in cognitive function in a large group of patients with type 1 diabetes, despite relatively high rates of recurrent severe hypoglycemia. NEJM, 2007.
In collaboration with Kahn (Obesity), Cypess has demonstrated the presence of functionally active brown adipose tissue in adult humans that can be quantitated by PET-CT. The amount of brown adipose tissue correlates with body mass index, suggesting a potential role of brown adipose tissue in human metabolism. NEJM, 2009.
During extended 10 year follow-up of the cohort involved in the Diabetes Prevention Program, cumulative incidence of new onset diabetes remained lowest in the lifestyle group and prevention or delay of diabetes with either lifestyle or metformin can persist over a decade. Lancet, 2009.
In collaboration with Shoelson (CMP), Goldfine is leading multi-center trials to target inflammation with salsalate in order to lower glycemia in patients with T2D, to improve insulin sensitivity in patients with impaired glucose tolerance, and to reduce the progression of cardiovascular plaque in patients with coronary artery disease and metabolic syndrome, using novel imaging techniques of multi-detector computed tomographic angiography (MDCTA). (U01DK074556; Veterans Administration Merit Award; and P50 HL083813). Clinical and Translational Science, 2008. Diabetes Care, 2008. Annals of Internal Medicine, 2010
In the multicenter Look AHEAD trial, Horton and collaborators have demonstrated intensive lifestyle intervention can produce weight loss and improvements in fitness, glycemic control, and CVD risk factors in patients with type 2 diabetes that can be sustained over four years. Additionally, maximal graded exercise tests are abnormal in a large proportion of patients who do not have cardiovascular disease symptoms. Long term follow-up will determine the clinical significance of the abnormal exercise tests. Archives of Internal Medicine, 2010. Diabetes Care, 2010.
Continuous glucose monitoring technology has been shown to improve glycemic control in adult patients with type 1 diabetes by Wolpert and collaborators of the Juvenile Diabetes Research Foundation (JDRF) Continuous Glucose Monitoring Study Group. NEJM 2010.
Goldfine and young investigator collaborators at the Children’s Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, demonstrate that exposure to fine particulate matter of air pollution is associated with increased prevalence of type 2 diabetes, even in multivariate models that adjust for age, gender, ethnicity, BMI, physical activity, fast food restaurant density, per capita income, and education. This is now being studied by Horton in greater detail as part of an NIH-funded program-project grant in collaboration with investigators at the Harvard School of Public Health. Diabetes Care, 2010.
Gaglia lead proof of concept trials to develop a noninvasive method to visualize T1D at the level of the target organ in patients with active insulitis, by specifically visualizing islet inflammation, manifest by microvascular changes and monocyte/macrophage recruitment and activation using magnetic resonance imaging of magnetic nanoparticles (MNPs). Novel non-invasive imaging opens techniques could provide important methodology to follow T1D progression and monitoring the ability of immunomodulatory agents to clear insulitis. JCI, 2011.