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Obesity risk in African American women is determined by a diet-by-phenotype interaction

Award Number: R01DK115483
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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Summary African-American (AA) women are disproportionately burdened by obesity. Our published data have led to the provocative hypothesis that this disparity has physiologic underpinnings. Specifically, AA women are characterized by a high acute insulin secretory response to a glucose challenge, as well as reduced hepatic insulin extraction, which together lead to postprandial circulating insulin concentrations that can be several fold higher than those observed in Caucasian (European-American, EA) women. The lipogenic actions of insulin could favor partitioning of energy to adipose tissue at the expense of ATP (energy) production. In fact, AA women have lower energy requirements than EA women, and are more energetically efficient. High insulin secretion, however, is only one factor that determines insulin action; another major factor is insulin sensitivity. Our data have shown that over time, weight (fat) gain in obesity-prone AA women is higher in those who are more insulin sensitive, whereas “obesity-resistant” (constitutionally lean) AA women have relatively lower insulin sensitivity. Our data also suggest that the lipogenic actions of insulin in AA women are exacerbated by a high-glycemic diet, which promotes insulin secretion. Finally, our data have shown that over time weight (fat) gain in AA women is predicted by the combination of insulin sensitivity and dietary glycemic load. Taken together, these observations suggest that many AA women are predisposed to obesity by their endocrine make-up, and that this predisposition is exacerbated by a high-glycemic diet. A natural corollary of this hypothesis is that for implementation of intentional weight loss, a low- (vs high-) glycemic diet will promote greater loss of body fat, and will enable successful weight loss maintenance by increasing energy expenditure. This corollary is supported by our preliminary data that indicate a 50% greater loss of fat with low- vs high-glycemic diet under controlled conditions in AA women. The project proposed herein will test these hypotheses through a randomized clinical weight loss trial of high- vs low-glycemic diets in obese AA women. The study has both an efficacy phase (controlled feeding during weight loss) to probe physiologic mechanisms (energy expenditure, metabolic efficiency), and an effectiveness phase (6-month free-living follow-up) to test the hypothesis that the low-glycemic diet will be more effective at promoting weight loss maintenance due in part to improved adherence and quality of life, and ease of implementing the diet. This study is innovative in that it proposes to test a specific physiologic mechanism that may underlie propensity to obesity; it includes both efficacy and effectiveness outcomes; it involves both quantitative and qualitative methodology; and it tackles optimization of both weight loss and weight loss maintenance. This study is intended to provide the evidence base necessary to improve the clinical care approach to weight loss.


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: 2022 ( Subtotal = $631,918 )
2022	2022	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	5	4/4/2022	NON-COMPETING CONTINUATION	$631,918
														Subtotal = $631,918

Issue Date FY: 2021 ( Subtotal = $639,953 )
2021	2021	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	4/23/2021	NON-COMPETING CONTINUATION	$639,953
														Subtotal = $639,953

Issue Date FY: 2020 ( Subtotal = $648,373 )
2020	2020	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	4/6/2020	NON-COMPETING CONTINUATION	$648,373
														Subtotal = $648,373

Issue Date FY: 2019 ( Subtotal = $655,991 )
2019	2019	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	4/12/2019	NON-COMPETING CONTINUATION	$655,991
														Subtotal = $655,991

Issue Date FY: 2018 ( Subtotal = $665,347 )
2018	2018	UNIVERSITY OF ALABAMA AT BIRMINGHAM	701 S 20TH ST	BIRMINGHAM	AL	35294	JEFFERSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/24/2018	NEW	$665,347
														Subtotal = $665,347

Grand Total All Awards = $3,241,582

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Obesity risk in African American women is determined by a diet-by-phenotype interaction

Award Number: R01DK115483

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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