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Leveraging electronic medical records to perform large-scale diabetes pharmacogenomics among ancestrally diverse patient populations

Award Number: R01DK113003
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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ABSTRACT Diabetes mellitus is a modern day scourge, affecting an ever increasing proportion of individuals worldwide, including 26 million Americans currently. Moreover, type-2 diabetes (T2D) disproportionately affects historically disadvantaged U.S. minority groups, as evidenced by the much higher rates of disease and more severe complications among African American individuals. Although there are multiple therapeutic classes of oral medication available for treating T2D, metformin is currently recommended as the first-line therapy. Metformin lowers blood glucose levels by reducing hepatic gluconeogenesis, improving skeletal muscle insulin sensitivity, and limiting intestinal glucose uptake. It has also been shown to be an effective therapy for preventing incident diabetes. Despite being one of the most frequently prescribed drugs worldwide, very little is known about the biologic mechanism(s) through which metformin mediates its effect. This knowledge would be of value therapeutically to better understand and predict treatment response. By extension, even less is known about the activity of metformin among African American individuals, as few studies have included substantial numbers of non-European population groups. This application will help rectify existing knowledge gaps by studying a large and diverse patient population with T2D. Specifically, we will utilize electronic medical record (EMR) data for large-scale diabetes pharmacogenomics. These data have the advantage of being able to account for medication use and drug exposure over time; to provide substantial numbers of individuals for combined and population group specific analyses; and to assess clinical end-points both retrospectively and prospectively. In this application, we propose the following study aims: 1) To assess whether there are differences in metformin treatment response by self-reported race-ethnicity and genetic ancestry; 2) To use novel, gene-based association approaches to identify both shared and population group specific genetic variants influencing metformin's effect on blood glycemia (i.e., HbA1c levels); and 3) To replicate our findings in a separate group of patients and to include additional exploratory analyses to assess whether the identified genetic variants influence diabetes-related microvascular events, macrovascular events, and adverse drug reactions. The knowledge gained through this study will directly address the goals of Health People 2020 – “achieve health equity, eliminate disparities, and improve the health of all groups.”


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	HENRY FORD HEALTH SYSTEM	1 FORD PL	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	1/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $605,577 )
2021	2021	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	3/19/2021	NON-COMPETING CONTINUATION	$605,577
														Subtotal = $605,577

Issue Date FY: 2020 ( Subtotal = $635,940 )
2020	2020	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	2/20/2020	NON-COMPETING CONTINUATION	$635,940
														Subtotal = $635,940

Issue Date FY: 2019 ( Subtotal = $640,328 )
2019	2019	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	3/18/2019	NON-COMPETING CONTINUATION	$640,328
														Subtotal = $640,328

Issue Date FY: 2018 ( Subtotal = $643,378 )
2018	2018	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	4/30/2018	NON-COMPETING CONTINUATION	$64,338
2018	2018	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/22/2018	NON-COMPETING CONTINUATION	$579,040
														Subtotal = $643,378

Issue Date FY: 2017 ( Subtotal = $642,048 )
2017	2017	HENRY FORD HEALTH SYSTEM	1 FORD PLACE	DETROIT	MI	48202	WAYNE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/20/2017	NEW	$642,048
														Subtotal = $642,048

Grand Total All Awards = $3,167,271

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Leveraging electronic medical records to perform large-scale diabetes pharmacogenomics among ancestrally diverse patient populations

Award Number: R01DK113003

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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