Thursday, January 1, 2026 1/1/2026

Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes

Award Number: R01DK137997
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: 09/01/2024
PERIOD OF PERFORMANCE END DATE: 07/31/2027

Group Awards By:

View Award Description

Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes - PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) is a major cause of death in individuals with type 1 diabetes (T1DM), but the underlying mechanisms are not well understood. Despite efforts to control blood glucose levels, patients with T1DM who meet glycemic targets (i.e., HbA1c ≤ 6.9%) are still at a 3-fold increased risk of CVD death. By contrast, studies of a different type of diabetes called glucokinase maturity onset diabetes of the young (GCK- MODY) have found that these individuals do not have an increased risk of CVD, despite having a similar level of long-term high blood glucose. Our previous research suggested that one important difference in CVD risk is that people with T1DM have insulin resistance and those with GCK-MODY do not. Our data suggested that the presence of iatrogenic hyperinsulinemia in T1DM—not hyperglycemia—was the principal factor contributing to the decreased insulin sensitivity. This iatrogenic hyperinsulinemia occurs because patients with T1DM must deliver insulin into the peripheral circulation rather than more physiologically into the hepatic portal circulation. Because this delivery route bypasses first-pass hepatic clearance, people with T1DM have 2½-fold higher peripheral insulin levels than people who have normal insulin secretion. These studies imply that reducing iatrogenic hyperinsulinemia can improve insulin sensitivity and possibly other aspects of cardiometabolic risk. Insulin adjunctive therapies may facilitate the needed reduction in hyperinsulinemia. We will conduct paired experiments to investigate the effects of modifying iatrogenic hyperinsulinemia on three markers of cardiometabolic risk: nitric oxide bioavailability (Aim 1), insulin sensitivity (Aim 2), and thrombotic potential (Aim 3). We will compare the effect of lowering iatrogenic hyperinsulinemia in T1DM to the effect of raising insulinemia by the same amount in individuals at low risk for cardiometabolic disease: those with GCK- MODY and those without diabetes (control). We will compare the three cardiometabolic risk markers in T1DM patients (n=13), GCK-MODY patients (n=7), and those without diabetes (n=7) under conditions of high insulin levels (Hi-Ins, 20-25 μU/mL as seen in T1DM) and normal insulin levels (Eu-Ins, 5-10 μU/mL, as seen in CGK-MODY and control). To allow T1DM participants to acutely lower peripheral insulinemia to normal levels without consequent hyperglycemia, we will use a sodium-glucose cotransporter-2 inhibitor (SGLT2i) as a research tool. Overall, our goal is to determine how much reducing iatrogenic hyperinsulinemia using insulin adjunctive therapy can improve CVD outcomes, and to understand the underlying mechanisms behind this effect. This small, mechanistic pilot study will provide needed data to inform the development of larger trials of insulin adjunctive insulin therapy in T1DM.


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: 2026 ( Subtotal = $0 )
2026	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/2/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $339,060 )
2025	2025	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	8/20/2025	NON-COMPETING CONTINUATION	$339,060
														Subtotal = $339,060

Issue Date FY: 2024 ( Subtotal = $340,747 )
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	8/22/2024	NEW	$340,747
2024	2024	VANDERBILT UNIVERSITY MEDICAL CENTER	1161 21ST AVE S STE D3300 MCN	NASHVILLE	TN	37232	DAVIDSON	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	8/27/2024	NEW	$0
														Subtotal = $340,747

Grand Total All Awards = $679,807

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Cardiometabolic Benefit of Reducing Iatrogenic Hyperinsulinemia Using Insulin Adjunctive Therapy in Type 1 Diabetes

Award Number: R01DK137997

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: 09/01/2024

PERIOD OF PERFORMANCE END DATE: 07/31/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer