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

NCT ID: NCT04791787

Last Updated: 2024-06-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-25
• Study Completion Date: 2023-04-25

Brief Summary

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.

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.

Conditions

Glucose Metabolism Disorders (Including Diabetes Mellitus); Energy Supply; Deficiency; Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Standard Weight Maintenance

Standard weight maintenance diet will be provided for 10 days for subjects who are not currently treated with a T2DM medication.

Group Type: ACTIVE_COMPARATOR

Standard weight maintaining diet

Intervention Type: OTHER

Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat

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

Group Type: ACTIVE_COMPARATOR

Weight maintaining isocaloric ketogenic diet

Intervention Type: OTHER

Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat

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.

Group Type: ACTIVE_COMPARATOR

Weight maintaining isocaloric ketogenic diet

Intervention Type: OTHER

Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat

Beta-hydroxy butyrate

Intervention Type: DIETARY_SUPPLEMENT

A supplement of ketone ester of beta-hydroxy butyrate

Interventions

Standard weight maintaining diet

Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat

Intervention Type: OTHER

Weight maintaining isocaloric ketogenic diet

Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat

Intervention Type: OTHER

Beta-hydroxy butyrate

A supplement of ketone ester of beta-hydroxy butyrate

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

BHOB

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

The University of Texas Health Science Center at San Antonio

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ralph DeFronzo, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Health at San Antonio

Locations

University Health Systems-Texas Diabetes Institute

San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Countries

United States

Other Identifiers

HSC20200230H

Identifier Type: -

Identifier Source: org_study_id