# Understanding Myocardial Recovery in Diabetes and Heart Failure

> **NIH VA I01** · VA SALT LAKE CITY HEALTHCARE SYSTEM · 2021 · —

## Abstract

Diabetes Mellitus (DM) is a global epidemic and its prevalence among US veterans is higher than the civilian
population. Heart failure (HF) is the leading cause of death in diabetics. The coexistence of HF and DM poses
clinical challenges and results in much poorer prognosis. Cardiac metabolism is central in the pathophysiology
of both DM and HF but our understanding of the metabolic adaptations when they coexist is very limited. Co-
existence of HF and DM in humans is a complex chronic condition that is difficult to recapitulate in an animal
model. Hence, HF patients with DM undergoing therapy with left ventricular assist devices (LVAD) present a
unique opportunity, as human cardiac tissue and serum become available, both before and after intervention.
These samples become extremely more informative when we prospectively associate cardiac recovery with
molecular and metabolic changes while on LVAD support. The infusion of non-radioactive 13C tracers in DM
HF patients can further interrogate the dynamic metabolism.
 Our recent studies demonstrated that impairment of glucose oxidation in mice and humans is directly
linked to development of HF. We also found that diabetic HF patients have significantly lower cardiac recovery
rate following LVAD unloading compared to non-diabetics. Interestingly, well-controlled DM patients showed
improvement of cardiac structure and function following LVAD support compared to poorly controlled. We
hypothesize that well-controlled glycemia may enhance myocardial recovery through improved
glucose uptake and oxidation (Aim 1a). We will compare changes of glucose uptake rate between pre- and
post-LVAD implantation for each group. In addition, we will compare the relative flux from pyruvate to lactate,
and from pyruvate to tricarboxylic acid (TCA) cycle between well-controlled and poorly controlled DM patients
using 13C glucose. We will examine whether relative changes in flux of these pathways correlate with relative
changes in cardiac function and structure between the two groups. Since our study of pentose phosphate
(PPP) and one carbon metabolism (OCM) pathways indicated that upregulation of PPP and OCM correlate
with restoration of redox homeostasis (NADP+/NADPH) and recovery, we hypothesize that redox
homeostasis may be restored in diabetic HF patients with well-controlled glycemia through increased
flux of PPP and OCM pathways (Aim 1b). Therefore, the group of well-controlled glycemia is likely to show
significant improvement in relative LVEF and LVEDD change compared to the poorly controlled.
 Studies of HF in humans provided evidence that ß-hydroxybutyrate (ßOHB) utilization may be
upregulated in hypertrophic and failing hearts. However, it is unknown whether this change is adaptive or
maladaptive for myocardial recovery in HF with DM. Our studies showed that monocarboxylate transporter
(MCT) 1 and 4 (involved in ßOHB transport) and ßOHB levels, are significantly higher in cardiac tissues of
diabetic HF patient...

## Key facts

- **NIH application ID:** 10123229
- **Project number:** 1I01CX002291-01
- **Recipient organization:** VA SALT LAKE CITY HEALTHCARE SYSTEM
- **Principal Investigator:** Stavros George Drakos
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-10-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123229

## Citation

> US National Institutes of Health, RePORTER application 10123229, Understanding Myocardial Recovery in Diabetes and Heart Failure (1I01CX002291-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10123229. Licensed CC0.

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