# Ketones, Muscle Metabolism, and SGLT2 Inhibitors

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $36,235

## Abstract

Abstract
The growing epidemic of Type 2 Diabetes (T2DM), with approximately 36 million patients in the United States
alone, requires the active engagement of scientists from a variety of disciplines. Pharmaceuticals are being
developed for the management of glucose metabolism, regulation of insulin sensitivity, and various other
pathophysiological factors of T2DM. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been recently
developed to help manage blood sugar and have proven effective for various components of metabolic
syndrome. In SGLT2i trials, cardiovascular outcomes emphasized a marked reduction of heart failure and
decreases in adverse cardiac events in diabetics with prior heart disease. It is speculated, from studies
showing elevated fasting ketone concentration in diabetics taking SGLT2i compared to controls, that a
preference for a compensatory ketone metabolism is both kickstarted by SGLT2i’s and enhances
cardiovascular metabolic performance. The goal of the research in this proposal is to develop quantitative
magnetic resonance imaging (MRI) and spectroscopy (MRS) capabilities for the evaluation of various cardiac
functional parameters and in-vivo measurement of phosphorus metabolites and intramyocellular lipids in
human skeletal muscle and myocardium. These studies will be implemented through a protocol created using
phantom test models and validated in human subjects. Aim 1. To use cardiac MRI and 1H-MRS to measure
differences in intramyocellular lipids content and pericardial lipid volume for the comparison of cardiovascular
performance between normal glucose tolerant subjects and subjects with T2DM. In Aim 2, we shall use
phosphorus-31 MRS (31P-MRS) and hydrogen-1 (1H-MRS) to measure metabolite concentrations in skeletal
muscle of normal glucose tolerant and T2DM subjects. In Aim 3, we shall develop 31P-MRS to measure
metabolite concentrations in myocardium and to evaluate, in conjunction with 1H-MRS, cardiac metabolite
concentrations in normal glucose tolerant subjects and subjects with T2DM.

## Key facts

- **NIH application ID:** 10632818
- **Project number:** 3R01DK107680-06A1S1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** RALPH A DEFRONZO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $36,235
- **Award type:** 3
- **Project period:** 2016-07-15 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10632818

## Citation

> US National Institutes of Health, RePORTER application 10632818, Ketones, Muscle Metabolism, and SGLT2 Inhibitors (3R01DK107680-06A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10632818. Licensed CC0.

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