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Full-fat Yogurt and Glucose Tolerance

Primary Purpose

Pre-Diabetes

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Full-fat yogurt
Non-fat yogurt
Sponsored by
University of Vermont Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Pre-Diabetes focused on measuring Prediabetes, Glucose Tolerance, Bioactive fatty acids, Insulin sensitivity, Diet, Milk fat, Lipid metabolism, Inflammation markers, Fecal microbiota composition, Dairy

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Clinical Research Center, University of Vermont Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Full-fat yogurt

Non-fat yogurt (Control)

Arm Description

Participants will receive a 21-day controlled diet that includes three daily servings of whole (3.25% fat) yogurt (38% of energy from fat, 44% of energy from carbohydrates, and 18% of energy from protein).

Participants will receive a 21-day controlled diet that includes three daily servings of fat-free yogurt (28% of energy from fat, 54% of energy from carbohydrates, and 18% of energy from protein).

Outcomes

Primary Outcome Measures

Changes in insulin sensitivity and β-cell function: MMTT
Evaluated through mixed meal tolerance test (MMTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.
Changes in insulin sensitivity and β-cell function: OGTT
Evaluated through oral glucose tolerance test (OGTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.

Secondary Outcome Measures

Changes in inflammatory markers
Evaluated 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 prior to and post experimental diets. Inflammatory markers that will be measured are: interleukins 1beta, 6, 8, and 10 (IL-1beta, IL-6, IL-8, and IL-10), and tumor necrosis factor alpha (TNFalpha). All measurements will be reported as pg/mL.
Changes to Colonic microbiota structure: density
Evaluated through analysis of colonic bacteria structure (composition and density) of specific colonic microbiota prior to and post experimental diets. Density of colonic bacteria will be measured in log copies/ug feces.
Changes to Colonic microbiota structure: relative abundance
Evaluated through analysis of colonic bacteria structure (composition and density) of specific colonic microbiota prior to and post experimental diets. Relative abundance of Taxa of colonic bacteria will be reported as a percentage (%).

Full Information

First Posted
June 1, 2018
Last Updated
June 29, 2022
Sponsor
University of Vermont Medical Center
Collaborators
National Dairy Council
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1. Study Identification

Unique Protocol Identification Number
NCT03577119
Brief Title
Full-fat Yogurt and Glucose Tolerance
Official Title
Full-fat Yogurt and Glucose Tolerance
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
April 30, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Vermont Medical Center
Collaborators
National Dairy Council

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pre-Diabetes
Keywords
Prediabetes, Glucose Tolerance, Bioactive fatty acids, Insulin sensitivity, Diet, Milk fat, Lipid metabolism, Inflammation markers, Fecal microbiota composition, Dairy

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
This study will employ a controlled, randomized, double-blinded crossover trial comparing two diets.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Full-fat yogurt
Arm Type
Experimental
Arm Description
Participants will receive a 21-day controlled diet that includes three daily servings of whole (3.25% fat) yogurt (38% of energy from fat, 44% of energy from carbohydrates, and 18% of energy from protein).
Arm Title
Non-fat yogurt (Control)
Arm Type
Experimental
Arm Description
Participants will receive a 21-day controlled diet that includes three daily servings of fat-free yogurt (28% of energy from fat, 54% of energy from carbohydrates, and 18% of energy from protein).
Intervention Type
Dietary Supplement
Intervention Name(s)
Full-fat yogurt
Intervention Description
Controlled diet that includes three daily servings of whole (3.25% fat) yogurt.
Intervention Type
Dietary Supplement
Intervention Name(s)
Non-fat yogurt
Intervention Description
Controlled diet that includes three daily servings of fat-free yogurt.
Primary Outcome Measure Information:
Title
Changes in insulin sensitivity and β-cell function: MMTT
Description
Evaluated through mixed meal tolerance test (MMTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.
Time Frame
Baseline, 4 weeks, and 8 weeks
Title
Changes in insulin sensitivity and β-cell function: OGTT
Description
Evaluated through oral glucose tolerance test (OGTT) prior to and post experimental diets. Tests will be quantified using the area under the curve (AUC) of the temporal changes in blood glucose, insulin, C-peptide, and incretins (GLP-1 and GIP) using fasting and serial postprandial blood samples. All measurements will be reported as mol/L.
Time Frame
Baseline, 4 weeks, and 8 weeks
Secondary Outcome Measure Information:
Title
Changes in inflammatory markers
Description
Evaluated 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 prior to and post experimental diets. Inflammatory markers that will be measured are: interleukins 1beta, 6, 8, and 10 (IL-1beta, IL-6, IL-8, and IL-10), and tumor necrosis factor alpha (TNFalpha). All measurements will be reported as pg/mL.
Time Frame
Baseline, 4 weeks, and 8 weeks
Title
Changes to Colonic microbiota structure: density
Description
Evaluated through analysis of colonic bacteria structure (composition and density) of specific colonic microbiota prior to and post experimental diets. Density of colonic bacteria will be measured in log copies/ug feces.
Time Frame
Baseline, 4 weeks, and 8 weeks
Title
Changes to Colonic microbiota structure: relative abundance
Description
Evaluated through analysis of colonic bacteria structure (composition and density) of specific colonic microbiota prior to and post experimental diets. Relative abundance of Taxa of colonic bacteria will be reported as a percentage (%).
Time Frame
Baseline, 4 weeks, and 8 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jana Kraft, PhD
Organizational Affiliation
University of Vermont
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Research Center, University of Vermont Medical Center
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
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