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Obesity complicating type 1 diabetes in young people: Physiology and Impact of GLP-1 analogue anti-obesity treatment on cardiometabolic risk factors

Award Number: R01DK134398
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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PROJECT SUMMARY/ABSTRACT This proposal aims to characterize the impact of GLP-1 analogue obesity treatment on mechanisms of modifiable cardiometabolic risk factors in young people with type 1 diabetes (T1D) complicated by obesity through assessment of adipose, glucose, and lipid physiology. Obesity and overweight impact 40% of adolescents and young adults with T1D, a population in whom T1D alone already drastically increases future cardiovascular disease risk. Our preliminary data indicate that regardless of BMI category, most adolescents with T1D have a visceral to subcutaneous adipose tissue ratio as high as youth with obesity and prediabetes. This visceral fat ratio in youth with T1D is proportional to the degree of hepatic insulin resistance. The study will comprehensively assess drivers of cardiometabolic risk factors in young people with T1D and obesity while examining the impact of GLP-1 analogue obesity treatment on visceral adipose tissue (the ratio of visceral to visceral+subcutaneous adipose tissue), insulin resistance, and postprandial lipemia. To achieve these aims, we will utilize 1) an abdominal MRI to quantify abdominal adipose distribution, 2) the stepped euglycemic hyperinsulinemic clamp with stable isotope tracers to assess insulin resistance and gluconeogenesis, 3) a DEXA scan to measure body composition, and 4) a high-fat mixed meal tolerance test to quantify postprandial changes in atherogenic lipoproteins. After completing these assessments, 54 young adults with T1D and obesity who meet the criteria for anti-obesity pharmacotherapy will be randomized to 1- year of treatment with oral semaglutide or placebo. The metabolic assessments will be repeated at 1-year of the treatment. A comparator group of 15 young adults with T1D and lean body mass index will undergo the metabolic studies at one-time point. Carrying out the proposed research program is critical to advance the understanding of the strategies to reduce cardiometabolic risk and impact the pathophysiologic mechanisms promoting cardiometabolic risk in young patients with T1D and obesity. This is consistent with the NIDDK's mission to improve the health and quality of life of individuals with diabetes. Results will reveal the intricacies of cardiometabolic disease risk and potential treatment in young people with T1D complicated by obesity.


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: 2024 ( Subtotal = $698,781 )
2024	2024	YALE UNIV	150 MUNSON ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	6/27/2024	NON-COMPETING CONTINUATION	$698,781
2024	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	11/14/2023	NEW	$0
														Subtotal = $698,781

Issue Date FY: 2023 ( Subtotal = $723,984 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	SOUTH CENTRAL CT	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/3/2023	NEW	$723,984
														Subtotal = $723,984

Grand Total All Awards = $1,422,765

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Obesity complicating type 1 diabetes in young people: Physiology and Impact of GLP-1 analogue anti-obesity treatment on cardiometabolic risk factors

Award Number: R01DK134398

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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