Full-fat Yogurt and Glucose Tolerance

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* Men and women and not expecting major lifestyle changes while on study
* Age 45-75
* Overweight and obesity (BMI 20-45 kg/m2)
* Stable body weight for the last 6 months (no more than a +/- 5% change)
* Diagnosis of prediabetes, defined as either impaired fasting glucose (fasting glucose: 100-125 mg/dL), impaired glucose tolerance (blood glucose levels of between: 140-199 mg/dL 2-hr post 75-g oral glucose tolerance test), and/or a hemoglobin A1C (HbA1C) level ranging from 5.7% to 7.0% (if HbA1C above 6.4%, monotherapy of Metformin)
* Women: Post-Menopausal: no menses previous 12 mos.; Follicular Stimulating Hormone (FSH) \> 20 mIU/mL
* Consuming at least 25% of calories from fat (screening will be based an online fat screener:

http://nutritionquest.com/wellness/free-assessment-tools-for-individuals/fat-intake-screener/

* Normal cognition
* Read and understand English
* Have a telephone
* Willing to follow the study coordinator's/manager's and dietitian's instructions

Exclusion Criteria:

* Fasting blood glucose ≥126 mg/dL, HbA1C ≥7.0% without monotheraoy of Metformin
* Subject with any chronic disease, inflammatory disease (e.g., asthma, rheumatoid arthritis, Crohn's disease or inflammatory bowel disease) and previous diagnosis of HIV or hepatitis C
* Pregnant or breastfeeding women or women on hormone replacement therapy (for previous 3 months)
* Intolerance to dairy foods (i.e., lactose intolerance or protein allergy), food allergies, or significant food preferences, dietary restrictions (vegetarian, vegan lifestyle), or food aversions that would interfere with diet adherence
* History of a diagnosed eating disorder
* Known/diagnosed gastrointestinal problems (e.g., inflammatory bowel disease, irritable bowel syndrome, etc.)
* Antibiotics use during the past 6 months
* Habitual use of tobacco or controlled substances, and dietary supplements during the study and 1 month prior to the study
* On medically prescribed diets or following a diet (e.g., to lose weight) or use of obesity or weight-loss treatments such as dietary interventions or pharmacotherapy
* Chronic anti-inflammatory medications, or frequent use (\>25% of the time) of over-the-counter medication including laxatives and antacids (subjects with occasional use of allergy or cold medicine, NSAIDS, acetaminophen, or aspirin will be recruited, but these drugs will not be permitted during the study, except for acute administration up to 3 days prior to the outcome variables).
* Waist circumference \>40 inches in men and \>35 inches in women
* Current diagnosis of uncontrolled hypertension (systolic BP: \>160mmHg, diastolic BP: \>95mmHg), (may receive treatment for hypertension as long as 1) on a stable regime for the previous 6 wk, and 2) no anticipated change while on the study)
* Untreated hyperlipidemia \[may receive treatment for hyperlipidemia (statins) as long as 1) on a stable regime for the previous 6 wk, and 2) no anticipated change while on the study)
* Participation on regular basis in competitive sports or habitual aerobic exercise training, which we will arbitrarily define a consisting of \> 3 bouts/wk of aerobic exercise (unable to speak comfortably) for more than 20 min
* Lifestyle or schedule incompatible with the study protocol
* Psychiatric or behavioral conditions that in the view of the principal investigator may present a safety hazard to the participant or interfere with study participation or the ability to follow the intervention protocol