? Type 2 diabetes is a growing health problem. Major precursors to diabetes include obesity and genetic susceptibility. The at-risk for diabetes phenotype (""""""""prediabetes"""""""") has been characterized by clinical research studies but needs better characterization in health care systems that serve as the major locus for prevention and treatment. This is a mid-career investigator award in patient-oriented research (K24) proposal. The candidate, James B. Meigs MD MPH, has devoted his patient-oriented research career to study of the etiology and prevention of type 2 diabetes. This award will support the following broad Specific Aims: ? 1. Elucidate the roles of obesity and genetic risk in the pathogenesis of type 2 diabetes by tests of hypotheses that a) adipokine dysregulation is the link whereby obesity causes type 2 diabetes; b) arrayed and specific candidate single nucleotide polymorphisms (SNPs) are associated with type 2 diabetes and related quantitative traits; ? 2. Translate epidemiological knowledge of the prediabetes phenotype into clinical application for population health benefit by tests of hypotheses that a) prediabetes defined by surrogate markers available in the electronic health record (EHR) has a phenotype whose metabolic profile is similar to that of prediabetes defined rigorously in clinical and epidemiologic studies; b) people with """"""""EHR prediabetes"""""""" have health care utilization and clinical outcomes intermediate between those without EHR prediabetes and those with clinical diabetes, suggesting value in identifying such people for intervention to reduce risk; ? 3. Build on the candidate's successful research and mentoring program by ensuring mid-career protected time for a) patient-oriented research program development within the superb environment of Harvard, Massachusetts General Hospital and an extensive network of research collaborations; b) expanded capacity to provide a greater depth of mentoring to a larger number of patient-oriented research junior investigators. ? Patient-oriented research is critical to the translation of scientific knowledge into population health benefit. Type 2 diabetes is a rapidly growing clinical and public health problem. This mid-career award application seeks directly to address the need for patient-oriented research and mentoring focused on the causes and consequences of type 2 diabetes. Expanded knowledge of precursors of type 2 diabetes is critical to identify novel approaches for prevention and control of the widening diabetes epidemic. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24DK080140-02
Application #
7496115
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2007-09-20
Project End
2012-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
2
Fiscal Year
2008
Total Cost
$190,031
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Liu, Dajiang J (see original citation for additional authors) (2017) Exome-wide association study of plasma lipids in >300,000 individuals. Nat Genet 49:1758-1766
Jason, Flannick (see original citation for additional authors) (2017) Sequence data and association statistics from 12,940 type 2 diabetes cases and controls. Sci Data 4:170179
Hruby, Adela; Ma, Jiantao; Rogers, Gail et al. (2017) Associations of Dairy Intake with Incident Prediabetes or Diabetes in Middle-Aged Adults Vary by Both Dairy Type and Glycemic Status. J Nutr 147:1764-1775
Berkowitz, Seth A; Berkowitz, Theodore S Z; Meigs, James B et al. (2017) Trends in food insecurity for adults with cardiometabolic disease in the United States: 2005-2012. PLoS One 12:e0179172
Wheeler, Eleanor; Leong, Aaron; Liu, Ching-Ti et al. (2017) Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis. PLoS Med 14:e1002383
Manning, Alisa (see original citation for additional authors) (2017) A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes 66:2019-2032
Berkowitz, Seth A; Basu, Sanjay; Meigs, James B et al. (2017) Food Insecurity and Health Care Expenditures in the United States, 2011-2013. Health Serv Res :
Merino, Jordi; Udler, Miriam S; Leong, Aaron et al. (2017) A Decade of Genetic and Metabolomic Contributions to Type 2 Diabetes Risk Prediction. Curr Diab Rep 17:135
de Vries, Paul S; Sabater-Lleal, Maria; Chasman, Daniel I et al. (2017) Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study. PLoS One 12:e0167742

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