Full-fat Yogurt and Glucose Tolerance
Condition: Pre-Diabetes
MeSH terms: Prediabetic State
Study type: Interventional

Summary: 
      This study determines if substituting full-fat yogurt (i.e., whole, 3.25% fat) for non-fat
      yogurt in the diet can reduce the risk of type 2 diabetes and inflammation in association
      with changes in the composition of the gastrointestinal bacteria prediabetic male and female
      volunteers. The central hypothesis is that dairy fat impacts whole body glucose handling and
      insulin sensitivity as well as inflammation both directly, and indirectly via influencing the
      gut microbiota composition.
    

Detailed description: 
      The overall objective of this study is to determine if substituting full-fat yogurt (i.e.,
      whole, 3.25% fat) for non-fat yogurt in the diet can i) improve whole body glucose handling
      and insulin sensitivity, ii) modulate systemic inflammation, and iii) induce putatively
      beneficial changes in the composition of the colonic microbiota in prediabetic men and women.
      By comparing a diet containing non-fat yogurt with a diet comprising of full-fat yogurt, the
      investigators will address the following specific hypotheses and aims:

      Hypothesis 1: Dietary intake of full-fat yogurt will improve fasting and postprandial markers
      of glucose homeostasis, insulin sensitivity, and pancreatic cell function. Aim 1: Evaluating
      the diet-induced changes in blood glucose and endogenous insulin secretion. This will be
      assessed through a mixed meal tolerance test and oral glucose tolerance test.

      Hypothesis 2: Dietary intake of full-fat yogurt will relatively reduce systemic inflammation.
      Aim 2: Examine diet-induced changes in inflammatory tone. This will be assessed through
      measurements of circulating (plasma) pro- and anti-inflammatory cytokines, cytokine
      production assays from in vitro-stimulated peripheral blood mononuclear cells, and plasma
      stimulated cytokine production in immortalized human cell lines.

      Hypothesis 3: A diet containing full-fat yogurt will alter the colonic bacteria structure
      (e.g. decrease the Firmicutes/Bacteroidetes ratio). Aim 3: Characterize diet-induced
      alterations in colonic bacteria structure (composition and density) via next-generation
      sequencing and real-time Polymerase Chain Reaction Assays (PCR).

      This study recruits 32 pre-diabetic female and male volunteers (50:50) aged 45-75 using a
      double-blinded, randomized crossover design to compare two experimental diets, 1) a low-fat
      diet containing fat-free yogurt (total fat: 28% energy), and 2) a higher fat diet consisting
      of whole 3.25% fat yogurt (total fat: 38% energy). Fat in the whole yogurt accounts entirely
      for the arithmetic difference in fat of 10% energy between the two diets. The study will
      consist of two 21-day experimental diet periods preceded by a 7-day control diet. The total
      length of study will be 8 weeks. The diet during the control diet periods will be an average
      U.S. diet to establish a normalized fatty acid intake among the subjects and to standardize
      the subject's physiologic state before each experimental diet. At the end of the first
      control period ("run-in") and at the end of each of the experimental diets, a mixed meal
      tolerance test and an oral glucose test will be performed to assess diet-induced changes in
      whole-body glucose handling and insulin sensitivity. In addition, blood and stool samples
      will be collected to examine diet-induced alterations in inflammatory tone and
      gastrointestinal microflora.
    

Intervention name(s): Full-fat yogurt; Non-fat yogurt
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Controlled diet that includes three daily servings of whole (3.25% fat) yogurt.; Controlled diet that includes three daily servings of fat-free yogurt.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This study will employ a controlled, randomized, double-blinded crossover trial comparing two diets.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Prediabetes; Glucose Tolerance; Bioactive fatty acids; Insulin sensitivity; Diet; Milk fat; Lipid metabolism; Inflammation markers; Fecal microbiota composition; Dairy