Energy Supply; Deficiency, Glucose Metabolism Disorders (Including Diabetes Mellitus), Type 2 Diabetes
Conditions
Keywords
Ketogenic diet, Body fat, Insulin secretion
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.
Interventions
OTHERStandard weight maintaining diet
Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat
OTHERWeight maintaining isocaloric ketogenic diet
Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat
DIETARY_SUPPLEMENTBeta-hydroxy butyrate
A supplement of ketone ester of beta-hydroxy butyrate
Sponsors
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Subjects will be randomized into 3 groups. Each group will be assigned to one of 4 arms.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fasting plasma glucose (FPG) | Baseline to 10 days | A change in FPG will be measured |
| Hepatic Glucose production (HGP) | Baseline to 10 days | Change of hepatic glucose production will be measured using 3H-glucose infusion |
| Whole Body Fat Oxidation | Baseline to 10 days | Change in whole body fat oxidation will be measured using indirect calorimetry |
| Total Body Fat | Baseline to 10 days | Change in whole body fat |
| Hepatic Fat Content | Baseline to 10 days | Change in hepatic fat content |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| High density lipoproteins (HDL) | Baseline to 10 days | Change in HDL |
| Triglycerides | Baseline to 10 days | Change in triglyceride levels |
| Plasma Insulin | Baseline to 10 days | Change in plasma insulin will be measured |
| Glycated hemoglobin test (HbA1c) | Baseline to 10 days | Change in HbA1c |
| Fructosamine level | Baseline to 10 days | Change in fructosamine |
| Urine Microalbumin excretion | Baseline to 10 days | Change in urine microalbumin excretion |
| C-peptide | Baseline to 10 days | Change in C-peptide will be measured |
| Free Fatty Acid (FFA) | Baseline to 10 days | Change in FFA will be measured |
| Glycerol level | Baseline to 10 days | Change in Glycerol level will be measured |
| Low density lipoproteins (LDL) | Baseline to 10 days | Change in LDL |
Countries
United States
Outcome results
None listed