Friday, April 19, 2024 4/19/2024

PRESERVATION OF BETA CELL FUNCTION IN PREDIABETES: IGT AND IFG

Award Number: R01DK024092
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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ABSTRACT/PROJECT SUMMARY Type 2 diabetes mellitus (T2DM) affects ~29.1 million individuals in the US and is associated with significant morbidity and mortality from both microvascular and macrovascular complications. The microvascular, and to a lesser extent macrovascular, complications primarily are related to hyperglycemia. Therefore, it is logical to initiate therapy early in the natural history of T2DM, at the “prediabetic” stage, with interventions that reverse specific pathophysiologic defects present in IGT and IFG. In both IGT and IFG, the progression to T2DM is characterized by progressive beta cell failure. Although both IGT and IFG represent high risk states for future T2DM, we have shown that they are characterized by distinct pathophysiologic defects. Individuals with IFG have impaired 1st phase insulin secretion and hepatic insulin resistance and both of these defects strongly are correlated with the increase in fasting plasma glucose concentration. In contrast, IGT subjects have decreased 2nd phase insulin secretion and severe muscle insulin resistance. Therefore, one would expect patients with IGT and IFG to respond differently to different pharmacologic interventions. Thus, dapagliflozin, an SGLT2 inhibitor that induces glucosuria, reduces the FPG, and reverses glucotoxicity might be expected to be effective in IFG, while pioglitazone, a thiazolidinedione that activates PPAR¿, reverses lipotoxicity, augments 2nd phase insulin secretion and improves muscle insulin sensitivity, would be expected to be most effective in IGT. Saxagliptin, a DPP4 inhibitor, that augments both 1st and 2nd phase insulin secretion, would be expected to work well in both IGT and IFG. We will test this hypothesis by treating individuals with isolated IGT and isolated IFG with the following interventions: (1) metformin; (2) dapagliflozin; (3) pioglitazone; (4) saxagliptin; (5) placebo for 30 months. After 30 months, all medications will be discontinued for 6 months to examine whether the beneficial effects on beta cell function (insulin secretion/insulin resistance [disposition] index) persist. At baseline, 30, and 36 months subjects will receive: (i) euglycemic insulin clamp, (ii) 2-step hyperglycemic clamp with GLP-1 infusion, (iii) OGTT with measurement of GLP-1 and GIP. This will provide state-of-the-art quantitation of beta cell function and insulin resistance and define the effect of the various pharmacologic interventions on these key pathophysiologic parameters.


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 = $659,788 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	38	7/28/2023	COMPETING CONTINUATION	$674,244
2023	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	37	10/12/2022	NON-COMPETING CONTINUATION	-$14,456
														Subtotal = $659,788

Issue Date FY: 2021 ( Subtotal = $663,044 )
2021	2021	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	37	4/28/2021	NON-COMPETING CONTINUATION	$663,044
														Subtotal = $663,044

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	7/27/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2019 ( Subtotal = $663,044 )
2019	2019	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	36	8/20/2019	NON-COMPETING CONTINUATION	$663,044
														Subtotal = $663,044

Issue Date FY: 2018 ( Subtotal = $663,044 )
2018	2018	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	35	8/10/2018	NON-COMPETING CONTINUATION	$663,044
2018	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	34	12/7/2017	COMPETING CONTINUATION	$73,000
2018	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	33	12/7/2017	EXTENSION WITH OR WITHOUT FUNDS	-$73,000
														Subtotal = $663,044

Issue Date FY: 2017 ( Subtotal = $652,096 )
2017	2017	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	002	34	7/13/2017	COMPETING CONTINUATION	$652,096
2017	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	33	11/18/2016	EXTENSION WITH OR WITHOUT FUNDS	$74,026
2017	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	32	11/18/2016	NON-COMPETING CONTINUATION	-$74,026
														Subtotal = $652,096

Issue Date FY: 2016 ( Subtotal = $522,333 )
2016	2016	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	33	6/10/2016	EXTENSION WITH OR WITHOUT FUNDS	$522,333
														Subtotal = $522,333

Issue Date FY: 2015 ( Subtotal = $519,120 )
2015	2015	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	32	6/19/2015	NON-COMPETING CONTINUATION	$519,120
														Subtotal = $519,120

Issue Date FY: 2014 ( Subtotal = $522,333 )
2014	2014	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	31	6/25/2014	NON-COMPETING CONTINUATION	$522,333
														Subtotal = $522,333

Issue Date FY: 2013 ( Subtotal = $504,051 )
2013	2013	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	30	6/20/2013	NON-COMPETING CONTINUATION	$504,051
														Subtotal = $504,051

Issue Date FY: 2012 ( Subtotal = $532,778 )
2012	2012	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	29	9/17/2012	COMPETING CONTINUATION	$532,778
														Subtotal = $532,778

Issue Date FY: 2010 ( Subtotal = $578,485 )
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Trans-NIH Recovery Act Research Support	000	27	12/30/2009	SUPPLEMENT FOR EXPANSION	$99,000
2010	2010	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	28	8/9/2010	NON-COMPETING CONTINUATION	$479,485
														Subtotal = $578,485

Issue Date FY: 2009 ( Subtotal = $484,329 )
2009	2009	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78229	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	27	6/29/2009	NON-COMPETING CONTINUATION	$484,329
														Subtotal = $484,329

Issue Date FY: 2008 ( Subtotal = $481,457 )
2008	2008	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	26	7/3/2008	NON-COMPETING CONTINUATION	$481,457
														Subtotal = $481,457

Issue Date FY: 2007 ( Subtotal = $494,213 )
2007	2007	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	25	6/21/2007	NON-COMPETING CONTINUATION	$494,213
														Subtotal = $494,213

Issue Date FY: 2006 ( Subtotal = $505,956 )
2006	2006	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	24	8/21/2006	COMPETING CONTINUATION	$505,956
														Subtotal = $505,956

Issue Date FY: 2004 ( Subtotal = $574,035 )
2004	2004	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	23	3/26/2004	NON-COMPETING CONTINUATION	$574,035
														Subtotal = $574,035

Issue Date FY: 2003 ( Subtotal = $561,280 )
2003	2003	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	22		NON-COMPETING CONTINUATION	$561,280
														Subtotal = $561,280

Issue Date FY: 2002 ( Subtotal = $549,359 )
2002	2002	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	21	4/10/2002	NON-COMPETING CONTINUATION	$549,359
														Subtotal = $549,359

Issue Date FY: 2001 ( Subtotal = $544,474 )
2001	2001	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	20	4/30/2001	COMPETING CONTINUATION	$544,474
														Subtotal = $544,474

Issue Date FY: 1999 ( Subtotal = $495,948 )
1999	1999	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	19	5/3/1999	SUPPLEMENT FOR EXPANSION	$72,500
1999	1999	UNIVERSITY OF TEXAS HEALTH SCIENCE CTR AT SAN ANTONIO	7703 FLOYD CURL DRIVE	SAN ANTONIO	TX	78284	BEXAR	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	19	4/30/1999	NON-COMPETING CONTINUATION	$423,448
														Subtotal = $495,948

Issue Date FY: 1998 ( Subtotal = $467,580 ) (Continued on the next page)
Grand Total All Awards = $11,638,747

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PRESERVATION OF BETA CELL FUNCTION IN PREDIABETES: IGT AND IFG

Award Number: R01DK024092

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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