Clinical Trial to Assess the Effects of Dairy on Insulin Sensitivity and β-Cell Function

Study Overview
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Brief Summary
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The aim of this trial is to evaluate the effects of dairy product consumption on insulin sensitivity and pancreatic β-cell function in men and women at risk for the development of type 2 diabetes mellitus (T2DM) who habitually consume beverages high in sugar (non-diet sodas and fruit juice cocktails).

Official Title
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A Randomized, Controlled, Crossover Trial to Assess the Effects of Dairy Intake on Insulin Sensitivity and β-Cell Function in Men and Women at Risk for Diabetes Who Are Habitual Consumers of High Sugar Beverages

Conditions
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Diabetes

Intervention / Treatment
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* Other: Low-fat dairy
* Other: Sugar-sweetened beverages


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subject is male or female, 18-74 yrs of age, inclusive subject reports habitual consumption of ≥2 servings/d of high-sugar beverages (e.g., non-diet soda, fruit juice cocktails) subject has waist circumference ≥33.0 inches for women and ≥36.0 inches for men subject is at risk for development of type 2 diabetes mellitus (T2DM), based on 1 or more of the following: fasting glucose 100-125 mg/dL; glycosylated hemoglobin 5.7-6.4%, or ≥20% risk of developing diabetes in the next 7.5 yrs based on the San Antonio Heart Study prediction equation subject has a score of 7-10 on the Vein Access Scale at screening subject is normally active and judged to be in good health on the basis of medical history, physical examination and routine lab tests if female, subject is willing to schedule treatment visits during the follicular phase of the menstrual cycle, defined as days 1-14, where day 1 is 1st day of menses subject has a menstrual cycle duration ranging in length form 24-36 d (if premenopausal) subject is willing to maintain a stable body weight and follow his/her habitual diet and exercise pattern, except for inclusion of study product, throughout the trial subject is willing to maintain his or her habitual intake of coffee, tea, and alcoholic beverages throughout the trial subject agrees to limit intake of non-study related dairy products to ≤1 serving per day during each treatment period subject is ambulatory and willing to refrain from vigorous physical activity and consumption of alcoholic beverages 24 h prior to each test day subject has no plans to change smoking habits during the study period subject is willing to abstain from tobacco use 1 h prior to and during visits on LMTT test days subject has no health conditions that would prevent him/her from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine lab test results Exclusion Criteria: subject has abnormal lab test results of clinical importance, including, but not limited to, TG ≥400 mg/dL, fasting creatinine ≥1.5 mg/dL, alanine aminotransferase or aspartate aminotransferase ≥1.5 times the upper limit of normal at screening subject has a body mass index ≥45.0 kg/m2 subject has fasting blood glucose ≥126 mg/dL at screening or known diabetes mellitus (type 1 or T2DM) subject has a habitual intake of ≥4 servings/d of dairy food and beverages subject has known allergy or sensitivity to study product or any ingredients of study product. Subjects with lactose intolerance will be allowed to use products such as Lactaid dietary supplements subject has a history of coronary heart disease, congestive heart failure, or serious ventricular dysrhythmias (ventricular tachycardia or fibrillation) subject has a change in body weight of >4.5 kg within 4 weeks of screening subject uses medications known to influence carbohydrate metabolism subject has recent use of antibiotics subject has an active infection subject has unstable use of anti-hypertensive medications, thyroid hormone replacement, or lipid-altering drugs within 4 weeks of screening subject has unstable use of lipid-altering foods or dietary supplements within 4 weeks of screening subject uses niacin at doses >200 mg/d within 4 weeks of screening subject has history of extreme dietary habits, e.g., Atkins, high protein subject has a history or presence of clinically important endocrine, cardiac, renal, hepatic, pulmonary, biliary, pancreatic, gastrointestinal, or neurologic disorders that could interfere with interpretation of study results subject has history of dysphagia, swallowing disorders, or intestinal motility disorders subject has history of cancer subject has uncontrolled hypertension at screening (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low-fat dairy<br>3 servings/d of low-fat dairy | Other: Low-fat dairy<br>* 2 servings/d of 2% non-flavored, unsweetened milk + 1 serving/d sweetened low-fat yogurt<br>|
| Placebo Comparator: Sugar-sweetened beverages<br>3 servings/d of sugar-sweetened foods | Other: Sugar-sweetened beverages<br>* 2 servings/d of non-diet soda + 1 serving/d of non-dairy pudding<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Matsuda Insulin Sensitivity Index (MISI) | MISI calculated from glucose and insulin data obtained during a liquid meal tolerance test (LMTT). MISI = 10,000 divided by the square root of the quantity of fasting glucose x fasting insulin x mean post-load glucose from samples collected at 30, 60, 90 and 120 min after the start of the liquid meal x mean post-load insulin from samples collected at 30, 60, 90 and 120 min after the start of the liquid meal | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist circumference | Measured using a non-stretch anthropometric tape | 6 weeks | 
| Blood pressure | Standardized vital signs measurements will include resting blood pressure and pulse measured using an automated blood pressure measurement device. | 6 weeks | 
| Fasting and 2-hr LMTT insulin and glucose concentrations | During the LMTT subjects consume a liquid meal load (two-8 oz servings of Ensure®, Ross Products Division, Abbott Laboratories, Columbus, Ohio), and blood samples will be obtained at t = -10, 30, 60, 90, and 120 min ± 5 min where t = 0 min is the start of meal consumption. Serum insulin and plasma glucose concentrations will be measured in fasting (-10 min) and 2 hr (120 min) samples. | 6 weeks | 
| Homeostasis model assessment of insulin resistance (HOMA-IR) | HOMA-IR = the quantity of fasting glucose in mg/dL x fasting insulin in microunits/mL divided by 405 | 6 weeks | 
| Homeostasis model assessment of beta-cell function (HOMA%B) | HOMA%B = 360 x fasting insulin in microunits/mL divided by fasting glucose in mg/dL minus 63 | 6 weeks | 
| Glucose total area under the curve (AUC) from 0-120 min | Glucose total AUC 0-120 min will be calculated using the trapezoidal rule on glucose concentrations in blood samples collected at -10, 30, 60, 90, and 120 min where 0 min is the start of the liquid meal consumption in the LMTT. | 6 weeks | 
| Insulin total AUC 0-120 min | Insulin total AUC 0-120 min will be calculated using the trapezoidal rule on insulin concentrations in blood samples collected at -10, 30, 60, 90, and 120 min where 0 min is the start of the liquid meal consumption in the LMTT. | 6 weeks | 
| 30 min Δ insulin/Δ glucose | Change in insulin from baseline to 30 min of the LMTT will be divided by the change in glucose from baseline to 30 min of the LMTT | 6 weeks | 
| AUC insulin/AUC glucose | AUC for insulin divided by the AUC for glucose | 6 weeks | 
| Disposition Index | Disposition index = MISI x the quantity of AUC for insulin divided by the AUC for glucose | 6 weeks | 
| Fasting plasma total cholesterol (total-C) |  | 6 weeks | 
| Fasting plasma low-density lipoprotein cholesterol (LDL-C) | Calculated as LDL-C = total-C minus HDL-C minus the quantity of triglycerides (TG) divided by 5 | 6 weeks | 
| Fasting plasma high-density lipoprotein cholesterol (HDL-C) |  | 6 weeks | 
| Fasting plasma total-C/HDL-C | Calculated as total-C concentration divided by HDL-C concentration | 6 weeks | 
| Fasting plasma non-HDL-C | Calculated as non-HDL-C = total-C minus HDL-C | 6 weeks | 
| Fasting plasma TG |  | 6 weeks | 
| Serum 25-hydroxy vitamin D [25(OH)D] |  | 6 weeks | 
| Plasma high-sensitivity C-reactive protein (hs-CRP) |  | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin sensitivity