Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes
Primary Purpose
Glucose Metabolism Disorders (Including Diabetes Mellitus), Energy Supply; Deficiency, Type 2 Diabetes
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Standard weight maintaining diet
Weight maintaining isocaloric ketogenic diet
Beta-hydroxy butyrate
Sponsored by
About this trial
This is an interventional other trial for Glucose Metabolism Disorders (Including Diabetes Mellitus) focused on measuring Ketogenic diet, Body fat, Insulin secretion
Eligibility Criteria
Inclusion Criteria:
- Age from 18-70 years
- BMI = 27.5-42 kg.m2
- HbA1c = 7.0-10.5
- Weight stable (±4-5lb) in the preceding 3 months
- Good general health
Exclusion Criteria:
- Use of medications that affect glucose tolerance other than metformin/sulfonylurea/DPP4 Inhibitor
- Major organ disease
- Estimated Glomerular filtration rate (eGFR) <60 ml/min
- Type 1 diabetes
- Hematocrit < 34 (if HbA1c is in the 8.5 to 10% range)
Sites / Locations
- University Health Systems-Texas Diabetes Institute
- University of Texas Health Science Center at San Antonio
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Active Comparator
Arm Label
Standard Weight Maintenance
Isocaloric Diet
Isocaloric Diet with Beta-hydroxy butyrate
Arm Description
Standard weight maintenance diet will be provided for 10 days for subjects who are not currently treated with a T2DM medication.
Isocaloric diet will be provided for 10 days for subjects who are currently treated with a T2DM medication included in the inclusion criteria
Isocaloric diet with Beta-hydroxy butyrate will be provided for 10 days for subjects who are not currently treated with a T2DM medication.
Outcomes
Primary Outcome Measures
Fasting plasma glucose (FPG)
A change in FPG will be measured
Hepatic Glucose production (HGP)
Change of hepatic glucose production will be measured using 3H-glucose infusion
Whole Body Fat Oxidation
Change in whole body fat oxidation will be measured using indirect calorimetry
Total Body Fat
Change in whole body fat
Hepatic Fat Content
Change in hepatic fat content
Secondary Outcome Measures
Plasma Insulin
Change in plasma insulin will be measured
C-peptide
Change in C-peptide will be measured
Free Fatty Acid (FFA)
Change in FFA will be measured
Glycerol level
Change in Glycerol level will be measured
Low density lipoproteins (LDL)
Change in LDL
High density lipoproteins (HDL)
Change in HDL
Triglycerides
Change in triglyceride levels
Urine Microalbumin excretion
Change in urine microalbumin excretion
Glycated hemoglobin test (HbA1c)
Change in HbA1c
Fructosamine level
Change in fructosamine
Full Information
NCT ID
NCT04791787
First Posted
March 5, 2021
Last Updated
October 2, 2023
Sponsor
The University of Texas Health Science Center at San Antonio
1. Study Identification
Unique Protocol Identification Number
NCT04791787
Brief Title
Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes
Official Title
Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes CTMS 20-0042
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Completed
Study Start Date
November 25, 2020 (Actual)
Primary Completion Date
April 25, 2023 (Actual)
Study Completion Date
April 25, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The University of Texas Health Science Center at San Antonio
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glucose Metabolism Disorders (Including Diabetes Mellitus), Energy Supply; Deficiency, Type 2 Diabetes
Keywords
Ketogenic diet, Body fat, Insulin secretion
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Subjects will be randomized into 3 groups. Each group will be assigned to one of 4 arms.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Standard Weight Maintenance
Arm Type
Active Comparator
Arm Description
Standard weight maintenance diet will be provided for 10 days for subjects who are not currently treated with a T2DM medication.
Arm Title
Isocaloric Diet
Arm Type
Active Comparator
Arm Description
Isocaloric diet will be provided for 10 days for subjects who are currently treated with a T2DM medication included in the inclusion criteria
Arm Title
Isocaloric Diet with Beta-hydroxy butyrate
Arm Type
Active Comparator
Arm Description
Isocaloric diet with Beta-hydroxy butyrate will be provided for 10 days for subjects who are not currently treated with a T2DM medication.
Intervention Type
Other
Intervention Name(s)
Standard weight maintaining diet
Intervention Description
Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat
Intervention Type
Other
Intervention Name(s)
Weight maintaining isocaloric ketogenic diet
Intervention Description
Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat
Intervention Type
Dietary Supplement
Intervention Name(s)
Beta-hydroxy butyrate
Other Intervention Name(s)
BHOB
Intervention Description
A supplement of ketone ester of beta-hydroxy butyrate
Primary Outcome Measure Information:
Title
Fasting plasma glucose (FPG)
Description
A change in FPG will be measured
Time Frame
Baseline to 10 days
Title
Hepatic Glucose production (HGP)
Description
Change of hepatic glucose production will be measured using 3H-glucose infusion
Time Frame
Baseline to 10 days
Title
Whole Body Fat Oxidation
Description
Change in whole body fat oxidation will be measured using indirect calorimetry
Time Frame
Baseline to 10 days
Title
Total Body Fat
Description
Change in whole body fat
Time Frame
Baseline to 10 days
Title
Hepatic Fat Content
Description
Change in hepatic fat content
Time Frame
Baseline to 10 days
Secondary Outcome Measure Information:
Title
Plasma Insulin
Description
Change in plasma insulin will be measured
Time Frame
Baseline to 10 days
Title
C-peptide
Description
Change in C-peptide will be measured
Time Frame
Baseline to 10 days
Title
Free Fatty Acid (FFA)
Description
Change in FFA will be measured
Time Frame
Baseline to 10 days
Title
Glycerol level
Description
Change in Glycerol level will be measured
Time Frame
Baseline to 10 days
Title
Low density lipoproteins (LDL)
Description
Change in LDL
Time Frame
Baseline to 10 days
Title
High density lipoproteins (HDL)
Description
Change in HDL
Time Frame
Baseline to 10 days
Title
Triglycerides
Description
Change in triglyceride levels
Time Frame
Baseline to 10 days
Title
Urine Microalbumin excretion
Description
Change in urine microalbumin excretion
Time Frame
Baseline to 10 days
Title
Glycated hemoglobin test (HbA1c)
Description
Change in HbA1c
Time Frame
Baseline to 10 days
Title
Fructosamine level
Description
Change in fructosamine
Time Frame
Baseline to 10 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age from 18-70 years
BMI = 27.5-42 kg.m2
HbA1c = 7.0-10.5
Weight stable (±4-5lb) in the preceding 3 months
Good general health
Exclusion Criteria:
Use of medications that affect glucose tolerance other than metformin/sulfonylurea/DPP4 Inhibitor
Major organ disease
Estimated Glomerular filtration rate (eGFR) <60 ml/min
Type 1 diabetes
Hematocrit < 34 (if HbA1c is in the 8.5 to 10% range)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ralph DeFronzo, MD
Organizational Affiliation
University of Texas Health at San Antonio
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Systems-Texas Diabetes Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Facility Name
University of Texas Health Science Center at San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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
Learn more about this trial
Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes
We'll reach out to this number within 24 hrs