Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes

Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes CTMS 20-0042

The study team will examine the effect of a ketogenic diet alone and ketogenic diet supplemented with oral ketones on how the body of individuals with type 2 diabetes respond to insulin, regulates insulin secretion, food intake and energetic pathways and influences body fat distribution.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes; Energy Supply; Deficiency; Glucose Metabolism Disorders (Including Diabetes Mellitus)
• Intervention / Treatment: Other: Standard weight maintaining diet; Other: Weight maintaining isocaloric ketogenic diet; Dietary supplement: Beta-hydroxy butyrate

Detailed Description

Subjects will be randomized into three groups (1) standard, weight maintaining diet containing approximately 25-35% protein, 45-55% carbohydrate, 20-30% fat; (2) weight maintaining isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate, 70-80% fat; (3) weight maintaining isocaloric diet containing approximately 15-25% protein, 5-10% carbohydrate, 70-80% fat supplemented with the ketone ester of beta-hydroxy butyrate, 8 grams every 8 hours to further increase the plasma ketone concentration by ~3 mM. Subjects will be further randomized on the basis of:

(i) HbA1c 7.0-8.5% and 8.5-10.5% to ensure similar baseline levels of glucose control and (ii) drug naïve versus drug-treated. At the time of screening, after a 10-12 hour overnight fast, indirect calorimetry will be performed with a ventilated hood system for 60 minutes to measure baseline energy expenditure. An initial weight maintenance energy requirement estimate as 1.5 times resting energy expenditure (obtained by indirect calorimetry) will be started. Diets will consist of a 10-day rotating menu using NutriAdmin for meal planning and Nutrition Maker for analysis of recipes Food will be prepared in the Cafeteria and or the Metabolic Kitchen at the Texas Diabetes Institute and certified by a dietician. Subjects will report to the diet kitchen at 8 AM on Monday through Saturday where they will eat their breakfast and pick up food for their lunch and dinner. On Saturday, participants also will be given food for their Sunday meals. Subjects will maintain a daily dietary log with all food consumed. On each visit subjects will be weighed; dietary log will be reviewed and the caloric content of the diet will be adjusted to maintain the body weight constant. Blood pressure will be measured in the reclining position x 2 separate days. Antidiabetic medications will not be changed during the study unless hypoglycemia (fasting plasma glucose <70 mg/dl or symptoms) occurs. The study duration will be 10 days which should be sufficient to observe the effect of hyperketonemia on glucose/lipid metabolism and energy expenditure. If participant cannot come on the last days of his/her diet treatment, than we will extend this period up to 13 days and participant will be given diet for additional days till completion of the study visits.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Eugenio Cersosimo, MD; Phone Number: 210-358-7200; Email: cersosimo@uthscsa.edu

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • University of Texas Health Science Center at San Antonio
    • San Antonio, Texas, United States, 78207
      • University Health Systems-Texas Diabetes Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age from 18-70 years
2. BMI = 27.5-42 kg.m2
3. HbA1c = 7.0-10.5
4. Weight stable (±4-5lb) in the preceding 3 months
5. Good general health

Exclusion Criteria:

1. Use of medications that affect glucose tolerance other than metformin/sulfonylurea/DPP4 Inhibitor
2. Major organ disease
3. Estimated Glomerular filtration rate (eGFR) <60 ml/min
4. Type 1 diabetes
5. Hematocrit < 34 (if HbA1c is in the 8.5 to 10% range)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard Weight Maintenance; Standard weight maintenance diet will be provided for 10 days for subjects who are not currently treated with a T2DM medication.	Other: Standard weight maintaining diet; Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat
Active Comparator: Isocaloric Diet; Isocaloric diet will be provided for 10 days for subjects who are currently treated with a T2DM medication included in the inclusion criteria	Other: Weight maintaining isocaloric ketogenic diet; Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat
Active Comparator: Isocaloric Diet with Beta-hydroxy butyrate; Isocaloric diet with Beta-hydroxy butyrate will be provided for 10 days for subjects who are not currently treated with a T2DM medication.	Other: Weight maintaining isocaloric ketogenic diet; Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat; Dietary supplement: Beta-hydroxy butyrate; A supplement of ketone ester of beta-hydroxy butyrate; Other Names: BHOB

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fasting plasma glucose (FPG)	A change in FPG will be measured	Baseline to 10 days
Hepatic Glucose production (HGP)	Change of hepatic glucose production will be measured using 3H-glucose infusion	Baseline to 10 days
Whole Body Fat Oxidation	Change in whole body fat oxidation will be measured using indirect calorimetry	Baseline to 10 days
Total Body Fat	Change in whole body fat	Baseline to 10 days
Hepatic Fat Content	Change in hepatic fat content	Baseline to 10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Insulin	Change in plasma insulin will be measured	Baseline to 10 days
C-peptide	Change in C-peptide will be measured	Baseline to 10 days
Free Fatty Acid (FFA)	Change in FFA will be measured	Baseline to 10 days
Glycerol level	Change in Glycerol level will be measured	Baseline to 10 days
Low density lipoproteins (LDL)	Change in LDL	Baseline to 10 days
High density lipoproteins (HDL)	Change in HDL	Baseline to 10 days
Triglycerides	Change in triglyceride levels	Baseline to 10 days
Urine Microalbumin excretion	Change in urine microalbumin excretion	Baseline to 10 days
Glycated hemoglobin test (HbA1c)	Change in HbA1c	Baseline to 10 days
Fructosamine level	Change in fructosamine	Baseline to 10 days

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Ralph DeFronzo, MD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2020
• Primary Completion (Actual): April 25, 2023
• Study Completion (Actual): April 25, 2023

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 10, 2021

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Insulin secretion; Ketogenic diet; Body fat
• Additional Relevant MeSH Terms: Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders
• Other Study ID Numbers: HSC20200230H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Information will be shared as summary results on ClinicalTrials.gov and in a peer-reviewed scientific journal publication
• IPD Sharing Time Frame: After study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No