# EFFICACY AND SAFETY OF A KETOGENIC DIET IN TYPE 1 DIABETES

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2024 · $641,303

## Abstract

PROJECT SUMMARY
 Type 1 diabetes (T1D) is caused by autoimmune destruction of β-cells that causes dependence on
exogenous insulin. Despite remarkable advances in diabetes device technology, less than 25% of adults with
T1D achieve the recommended HbA1c target of <7.0%. Moreover, subcutaneous delivery of insulin eliminates
the normal portal-to-peripheral insulin gradient and causes “iatrogenic hyperinsulinemia” and whole-body
insulin resistance, which increases the risk of cardiovascular complications. Novel therapies that improve
glycemic control and reduce insulin requirements are needed to improve outcomes in people with T1D.
 A very-low-carbohydrate ketogenic diet (≤50 g carbohydrate/day) could reduce glycemic variability, total
daily insulin requirement, and HbA1c in people with T1D. Indeed, several case series and observational
studies of using a ketogenic diet (KD) in people with T1D have observed such benefits. However, we are not
aware of any randomized controlled trials (RCTs) that evaluated the efficacy of KD for >7 days in people with
T1D. In addition, there are serious concerns regarding the safety and tolerability of a KD in patients with T1D,
including the potential for an increased risk of hypoglycemia, diabetic ketoacidosis, dyslipidemia, insulin
resistance, decreased bone mineral density, and impaired quality of life. The purpose of this proposal is to
conduct a two-site (Washington University School of Medicine in St. Louis, MO and Sansum Diabetes
Research Institute in Santa Barbara, CA) 26-week RCT to evaluate the clinical efficacy, metabolic function,
safety, socio-behavioral impact, acceptability and potential for dissemination of an isocaloric KD compared with
an American Diabetes Association-recommended control diet in 80 adults with T1D.
 The following specific aims will be addressed: 1) determine the clinical efficacy and cardiometabolic
effects of KD therapy in patients with T1D, including glycemic control [percent time-in-range 70-180 mg/dL
(primary outcome), percent time in 70-140 mg/dL, mean glucose, glucose variability, and HbA1c], insulin
sensitivity (determined by the hyperinsulinemic-euglycemic clamp procedure) (primary outcome), daily insulin
requirement, 24-hour serial plasma glucose, FFA, triglyceride, insulin, glucagon, and ketone body
concentrations; plasma lipid profile, hepatic de novo lipogenesis and cholesterol synthesis, body composition
(fat-free mass, fat mass, appendicular lean mass, intra-abdominal adipose tissue, and intrahepatic triglyceride
content), and selected plasma markers of inflammation; 2) assess the safety of KD therapy with respect to
hypoglycemia, hyperketonemia, renal function and bone health; and 3) assess socio-behavioral factors and
implementation outcomes, including sociodemographic factors (social determinants, unmet social needs),
behavioral factors (eating behaviors, food cravings, diabetes distress and quality-of-life); and implementation
outcomes (acceptability, feasibility, p...

## Key facts

- **NIH application ID:** 10776246
- **Project number:** 1R01DK137837-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Samuel Klein
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $641,303
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10776246

## Citation

> US National Institutes of Health, RePORTER application 10776246, EFFICACY AND SAFETY OF A KETOGENIC DIET IN TYPE 1 DIABETES (1R01DK137837-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10776246. Licensed CC0.

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