Effect of Ketogenic Diet on Glucose Metabolism and Energy Expenditure in Type 2 Diabetes
Condition: Glucose Metabolism Disorders (Including Diabetes Mellitus); Energy Supply; Deficiency; Type 2 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metabolic Diseases; Glucose Metabolism Disorders
Study type: Interventional

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.
    

Intervention name(s): Standard weight maintaining diet; Weight maintaining isocaloric ketogenic diet; Beta-hydroxy butyrate
Intervention type(s): Other; Other; Dietary Supplement
Intervention description(s): Diet containing diet approximately 25-35% protein, 45-55% carbohydrate, 20- 30% fat; Isocaloric ketogenic diet containing approximately 15-25% protein, 5-10% carbohydrate,70- 80% fat; A supplement of ketone ester of beta-hydroxy butyrate
Other intervention name(s): BHOB
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.
Masking: None (Open Label)
Primary purpose: Other
Keywords: Ketogenic diet; Body fat; Insulin secretion