The diabetes population and related costs are expected to double in the next quarter century, as more than 79 million Americans are at risk of developing diabetes. In trials, lifestyle changes aimed at weight loss were successful at reducing risk of type 2 diabetes (t2DM), the most common type of diabetes. However, long-term weight maintenance in the clinical setting has proved elusive. Importantly, even after successful weight loss, substantial residual risk (~40-50%) remains and may be attributable to other modifiable factors. Several medications used to treat established t2DM have also been studied for t2DM prevention and many have been shown to delay incident diabetes;however, the role of pharmacotherapy for diabetes prevention is not clear. Therefore, there is a continued and pressing need for identification of modifiable risk factors and interventions that are safe, inexpensive and acceptable to prevent t2DM and decrease diabetes-related disease burden. Based on a large body of recently published studies, vitamin D has emerged as a potential determinant of type 2 diabetes (t2DM) risk. In longitudinal observational studies, higher vitamin D status was associated with up to 83% reduction in the risk of t2DM. However, the evidence to support vitamin D supplementation for prevention of t2DM remains inconclusive. The favorable association between vitamin D status and t2DM risk in observational studies may be confounded by a variety of factors. Directly extending our prior work, the goal of the research described in this grant application is to address the issue of causality by evaluating whether vitamin D is an effective intervention for prevention of t2DM among high-risk individuals. We propose to conduct the vitamin D and type 2 diabetes (D2d) study, a multicenter, randomized, double-masked, placebo- controlled, parallel-group primary prevention clinical trial to evaluate the safety of vitamin D supplementation and its effect on the time to onset of diabetes in participants with pre-diabetes. The need for a trial such as the D2d study has been recognized in recent editorials and reviews, including the 2011 Institute of Medicine report on dietary reference intakes for vitamin D, which identified diabetes as one of the most promising non-skeletal outcomes with an urgent need for rigorously conducted trials to confirm the promising results seen in observational and mechanistic studies. The proposed trial, therefore, addresses an important and timely question and has the potential for significant impact in the clinically important area of t2DM prevention with direct public health implications. The potential impact of the study is heightened by the assembly of a team of highly qualified investigators with complementary expertise and experience in conducting nutrition-based multicenter trials, many of whom have worked together previously.

Public Health Relevance

The proposed trial addresses an important question and has the potential for significant impact in the clinically important area of type 2 diabetes mellitus (t2DM) prevention. If the trial confirms a favorable benefit/harm ratio of vitamin D supplementation, vitamin D would likely be integrated into contemporary strategies to prevention of t2DM in the more than 79 million Americans at risk of developing diabetes and ameliorate the high personal and societal burden of the disease. Relevance of the proposed project to the mission of the NIH (NIDDK and the Office of Dietary Supplements [ODS]): The research addresses important health issues of relevance to both NIDDK and ODS. Nutrition and type 2 diabetes are two obvious areas of interest to NIDDK while vitamin D is a nutrient of significant interest to ODS. Consistent with its strategic planning for 2010-14, the ODS is leading a vitamin D Initiative, which is an evolving partnership with NIH and other federal agencies to fund research that address gaps in knowledge, such as those stated by the 2011 Institute of Medicine report on dietary reference intakes for vitamin D. The Institute of Medicine report specifically identified the link between vitamin D and diabetes as one of the most promising non-skeletal outcomes that require further research with rigorously done trials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project--Cooperative Agreements (U01)
Project #
1U01DK098245-01
Application #
8481985
Study Section
Special Emphasis Panel (ZDK1-GRB-1 (J2))
Program Officer
Malozowski, Saul N
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$9,854,116
Indirect Cost
$1,098,826
Name
Tufts University
Department
Type
DUNS #
079532263
City
Boston
State
MA
Country
United States
Zip Code
02111
LeBlanc, Erin S; Pratley, Richard E; Dawson-Hughes, Bess et al. (2018) Baseline Characteristics of the Vitamin D and Type 2 Diabetes (D2d) Study: A Contemporary Prediabetes Cohort That Will Inform Diabetes Prevention Efforts. Diabetes Care 41:1590-1599
Lovegreen, Olivia; Riggs, Danielle; Staten, Myrlene A et al. (2018) Financial management of large, multi-center trials in a challenging funding milieu. Trials 19:267
Lewis, Michael R; Macauley, Robert C; Sheehan, Patricia R et al. (2017) Management of Hemoglobin Variants Detected Incidentally in HbA1c Testing: A Common Problem Currently Lacking a Standard Approach. Diabetes Care 40:e8-e9
Devchand, Roshni; Sheehan, Patricia; Gallivan, Joanne M et al. (2017) Assessment of a National Diabetes Education Program diabetes prevention toolkit: The D2d experience. J Am Assoc Nurse Pract 29:514-520
Lewis, Michael R; Sheehan, Patricia R; Staten, Myrlene A et al. (2017) Response to Comment on Lewis et al. Management of Hemoglobin Variants Detected Incidentally in HbA1c Testing: A Common Problem Currently Lacking a Standard Approach. Diabetes Care 2017;40:e8-e9. Diabetes Care 40:e150-e151
Angellotti, Edith; Pittas, Anastassios G (2017) The Role of Vitamin D in the Prevention of Type 2 Diabetes: To D or Not to D? Endocrinology 158:2013-2021
Ceglia, Lisa; Nelson, Jason; Ware, James et al. (2017) Association between body weight and composition and plasma 25-hydroxyvitamin D level in the Diabetes Prevention Program. Eur J Nutr 56:161-170
Shahraz, Saeid; Pittas, Anastassios G; Saadati, Mojdeh et al. (2017) Change in Testing, Awareness of Hemoglobin A1c Result, and Glycemic Control in US Adults, 2007-2014. JAMA 318:1825-1827
Kancherla, Vijaya; Elliott Jr, John L; Patel, Birju B et al. (2017) Long-term Metformin Therapy and Monitoring for Vitamin B12 Deficiency Among Older Veterans. J Am Geriatr Soc 65:1061-1066
Alzaman, Naweed S; Dawson-Hughes, Bess; Nelson, Jason et al. (2016) Vitamin D status of black and white Americans and changes in vitamin D metabolites after varied doses of vitamin D supplementation. Am J Clin Nutr 104:205-14

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