# Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis

> **NIH NIH R01** · BETH ISRAEL DEACONESS MEDICAL CENTER · 2021 · $412,205

## Abstract

Abstract
Diabetic Ketoacidosis (DKA) is a potentially life-threatening disorder that may also expose patients to overt or
sub-clinical morbidity. Even with optimal preventative strategies, a sub-set of patients will inevitably continue to
develop DKA. Thiamine is an essential co-factor for several key enzymes of metabolism including pyruvate
dehydrogenase (gatekeeper for Krebs Cycle). Insulin biosynthesis is impaired in thiamine deficiency rats and
this is likely due to the decreased glucose oxidation. In addition, our preliminary data reveals that patients with
moderate to severe DKA have high rates of thiamine deficiency which is associated with higher levels of
acidosis. Moreover, we have found that thiamine will increase oxygen consumption in vitro for patients with
DKA therefore suggesting a potential functional need regardless of plasma levels. Thiamine deficiency is well
known to result in lactic acidosis secondary to impaired aerobic metabolism and is a causal component of
neurological and memory disorders, specifically the Wernicke-Korsakoff Syndrome. Moreover, glucose loading
has been described as a precipitant of thiamine deficiency and we have demonstrated that metabolic stress
can deplete thiamine levels over time. Thus, we hypothesize that the provision of intravenous thiamine to
patients with DKA will serve as adjunctive measure to more rapidly reverse acidosis and will improve cellular
oxygen consumption potentially with protective effects on beta islet cells of the pancreas. To test this
hypothesis, we will perform a prospective, randomized trial providing thiamine (versus placebo) for DKA. Our
primary endpoint will be more rapid reversal of acidosis in the thiamine group as compared to the placebo arm.
Our secondary outcomes will include determination of whether thiamine will improve cellular oxygen
consumption, reduce lactic acidosis, and shorten hospital length of stay. We also include the exploratory aim of
determining whether thiamine will preserve beta cell function as estimated through C-peptide measurements.
The long-term goal of this line of research is to evaluate thiamine as an adjunctive therapy for DKA. Thiamine
is safe, inexpensive, and easily administered – thus, if our hypothesis is proven true and future research
proves efficacy, adoption of this adjunctive therapy is feasible and significant.

## Key facts

- **NIH application ID:** 10180947
- **Project number:** 5R01DK112886-04
- **Recipient organization:** BETH ISRAEL DEACONESS MEDICAL CENTER
- **Principal Investigator:** Michael William Donnino
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,205
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10180947

## Citation

> US National Institutes of Health, RePORTER application 10180947, Thiamine as Adjunctive Therapy for Diabetic Ketoacidosis (5R01DK112886-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10180947. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*