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Inflammation in human obesity and type 2 diabetes

Award Number: R01DK108056
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2018
PERIOD OF PERFORMANCE END DATE: 03/31/2021

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Inflammation in human obesity and type 2 diabetes - ¿ DESCRIPTION (provided by applicant): Inflammation is generally required for the development of insulin resistance in obese animals, consistent with demonstrations that inflammation predisposes obese people to be metabolically unhealthy. In contrast, obese people with negligible inflammation are often metabolically healthy. The role of inflammation as an accelerator of obesity-associated metabolic decline indicates that an inflammatory signature can predict the transition from obese/metabolically healthy to obese/insulin resistant/type 2 diabetes (T2D). Our proposed work will comprehensively define inflammatory signature(s) during T2D etiology and pathogenesis to fill critical gaps in 1. Identifying people most likely to transition to T2D in response to obesity; 2. Pinpointing treatments to new targets thus improve the currently modest efficacy of anti-inflammatory drugs in T2D; and 3. Using targeted therapies to uncouple obesity from inflammatory-mediated complications such as T2D and cardiovascular disease. We have used a multivariate mathematical approach to identify a previously unappreciated inflammatory signature that differentiates obese/non-T2D, obese/pre-T2D and obese/T2D subjects. This signature includes multiple T cell cytokines, many of which are preferentially produced by the Th17 or Th1 T cell subsets. Our identification of a human T cell inflammatory signature coupled with the proposed extention of the analyses to additional putative sources of "diabetogenic" inflammation provide unique opportunities to address important outstanding questions in the relationship between inflammation and T2D pathogenesis. We will test the hypothesis that a T cell signature that distinguishes T2D from non-T2D subjects is a predictive biomarker for T2D pathogenesis through a longitudinal multiple-PI project involving experts in human immunometabolism, cytokine network modeling and clinical research in obesity. The possibility that a cytokine signature validated by the proposed work will identify people who require more intensive monitoring, intervention or new anti-inflammatory drugs to delay or prevent obesity-associated T2D has tremendous potential to change clinical practice, emphasizing both the impact and the urgency of the project.


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: 2021 ( Subtotal = -$6,501 )
2021	2019	UNIVERSITY OF KENTUCKY RESEARCH FOUNDATION, THE	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	9/8/2021	NON-COMPETING CONTINUATION	-$6,501
														Subtotal = -$6,501

Issue Date FY: 2019 ( Subtotal = $555,701 )
2019	2019	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	4	3/20/2019	NON-COMPETING CONTINUATION	$555,701
														Subtotal = $555,701

Issue Date FY: 2018 ( Subtotal = $609,772 )
2018	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	3	7/30/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$468,472
2018	2018	UNIVERSITY OF KENTUCKY	500 S LIMESTONE 109 KINKEAD HALL	LEXINGTON	KY	40526	FAYETTE	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	5/9/2018	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$609,772
2018	2017	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	7/30/2018	NON-COMPETING CONTINUATION	-$468,472
														Subtotal = $609,772

Issue Date FY: 2017 ( Subtotal = $712,576 )
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	3/21/2017	NON-COMPETING CONTINUATION	$641,318
2017	2017	TRUSTEES OF BOSTON UNIVERSITY	85 E NEWTON ST M-921	BOSTON	MA	02118	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/16/2017	NON-COMPETING CONTINUATION	$71,258
														Subtotal = $712,576

Issue Date FY: 2016 ( Subtotal = $740,375 )
2016	2016	BOSTON UNIVERSITY	25 BUICK ST	BOSTON	MA	02215	SUFFOLK	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	3/4/2016	NEW	$740,375
														Subtotal = $740,375

Grand Total All Awards = $2,611,923

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Inflammation in human obesity and type 2 diabetes

Award Number: R01DK108056

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2018

PERIOD OF PERFORMANCE END DATE: 03/31/2021

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