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

Type 2 Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04791787
• Other study ID #: HSC20200230H
• Status: Completed
• Phase: N/A
• Start date: November 25, 2020
• Est. completion date: April 25, 2023

Study information

• Verified date: June 2024
• Source: The University of Texas Health Science Center at San Antonio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: April 25, 2023
• Est. primary completion date: April 25, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Energy Supply; Deficiency
• Glucose Metabolism Disorders
• Glucose Metabolism Disorders (Including Diabetes Mellitus)
• Metabolic Diseases
• Type 2 Diabetes

Intervention

Other:
• Standard weight maintaining diet
Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat
• 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

Locations

Country	Name	City	State
United States	University Health Systems-Texas Diabetes Institute	San Antonio	Texas
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center at San Antonio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting plasma glucose (FPG)	A change in FPG will be measured	Baseline to 10 days
Primary	Hepatic Glucose production (HGP)	Change of hepatic glucose production will be measured using 3H-glucose infusion	Baseline to 10 days
Primary	Whole Body Fat Oxidation	Change in whole body fat oxidation will be measured using indirect calorimetry	Baseline to 10 days
Primary	Total Body Fat	Change in whole body fat	Baseline to 10 days
Primary	Hepatic Fat Content	Change in hepatic fat content	Baseline to 10 days
Secondary	Plasma Insulin	Change in plasma insulin will be measured	Baseline to 10 days
Secondary	C-peptide	Change in C-peptide will be measured	Baseline to 10 days
Secondary	Free Fatty Acid (FFA)	Change in FFA will be measured	Baseline to 10 days
Secondary	Glycerol level	Change in Glycerol level will be measured	Baseline to 10 days
Secondary	Low density lipoproteins (LDL)	Change in LDL	Baseline to 10 days
Secondary	High density lipoproteins (HDL)	Change in HDL	Baseline to 10 days
Secondary	Triglycerides	Change in triglyceride levels	Baseline to 10 days
Secondary	Urine Microalbumin excretion	Change in urine microalbumin excretion	Baseline to 10 days
Secondary	Glycated hemoglobin test (HbA1c)	Change in HbA1c	Baseline to 10 days
Secondary	Fructosamine level	Change in fructosamine	Baseline to 10 days