Purpose

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.

Conditions

Eligibility

Eligible Ages
Between 18 Years and 70 Years
Eligible Genders
All
Accepts Healthy Volunteers
Yes

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 Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Subjects will be randomized into 3 groups. Each group will be assigned to one of 4 arms.
Primary Purpose
Other
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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
  • Dietary Supplement: Beta-hydroxy butyrate
    A supplement of ketone ester of beta-hydroxy butyrate
    Other names:
    • BHOB
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

Recruiting Locations

University Health Systems-Texas Diabetes Institute
San Antonio, Texas 78207
Contact:
Aurora Merovci, MD, MPH
210-567-5790
merovci@uthscsa.edu

University of Texas Health Science Center at San Antonio
San Antonio, Texas 78229
Contact:
Ralph DeFronzo, MD
210-567-6691
defronzo@uthscsa.edu

More Details

Status
Recruiting
Sponsor
The University of Texas Health Science Center at San Antonio

Study Contact

Ralph DeFronzo, MD
210-567-6691
defronzo@uthscsa.edu

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.