Clinical trial NCT04791787: 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
Overall status: COMPLETED
Phase: NA
Conditions: Glucose Metabolism Disorders (Including Diabetes Mellitus)
Energy Supply; Deficiency
Type 2 Diabetes
Keywords: Ketogenic diet
Body fat
Insulin secretion
Lead sponsor: The University of Texas Health Science Center at San Antonio
Sponsor class: OTHER
First posted: 2021-03-10
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects will be randomized into 3 groups. Each group will be assigned to one of 4 arms.
Primary purpose: OTHER

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.

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)

Primary outcomes:
measure: Fasting plasma glucose (FPG)
timeFrame: Baseline to 10 days
measure: Hepatic Glucose production (HGP)
timeFrame: Baseline to 10 days
measure: Whole Body Fat Oxidation
timeFrame: Baseline to 10 days
measure: Total Body Fat
timeFrame: Baseline to 10 days
measure: Hepatic Fat Content
timeFrame: Baseline to 10 days
Secondary outcomes:
measure: Plasma Insulin
timeFrame: Baseline to 10 days
measure: C-peptide
timeFrame: Baseline to 10 days
measure: Free Fatty Acid (FFA)
timeFrame: Baseline to 10 days
measure: Glycerol level
timeFrame: Baseline to 10 days
measure: Low density lipoproteins (LDL)
timeFrame: Baseline to 10 days
measure: High density lipoproteins (HDL)
timeFrame: Baseline to 10 days
measure: Triglycerides
timeFrame: Baseline to 10 days
measure: Urine Microalbumin excretion
timeFrame: Baseline to 10 days
measure: Glycated hemoglobin test (HbA1c)
timeFrame: Baseline to 10 days
measure: Fructosamine level
timeFrame: Baseline to 10 days
Other outcomes:
Locations:
city: San Antonio
country: United States
facility: University Health Systems-Texas Diabetes Institute
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
Study officials:
affiliation: University of Texas Health at San Antonio
name: Ralph DeFronzo, MD
role: PRINCIPAL_INVESTIGATOR
References: