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

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

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).

Study Overview

• Status: Completed
• Conditions: Diabetes
• Intervention / Treatment: Other: Low-fat dairy; Other: Sugar-sweetened beverages

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Illinois
    • Addison, Illinois, United States, 60101
      • Provident Clinical Research (now Biofortis)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean circulating glucose level	Mean circulating glucose level will be measured over 24 h in the continuous glucose monitoring (CGM) subset of subjects	6 weeks
Mean daytime glucose values	Mean daytime glucose values (6 am to 8 pm) measured in the CGM subset of subjects	6 weeks
Mean evening/nighttime glucose values	Mean evening/nighttime glucose values (8 pm to 6 am) measured in the CGM subset of subjects	6 weeks
Mean peak postprandial glucose	Mean peak postprandial glucose values during CGM after the lunch and dinner meals	6 weeks

Collaborators and Investigators

• Sponsor: Provident Clinical Research
• Collaborators: BioFortis; Dairy Research Institute
• Investigators: Study Director: Kevin C Maki, PhD, Biofortis Clinical Research, Inc.

Publications and helpful links

General Publications

• Maki KC, Nieman KM, Schild AL, Kaden VN, Lawless AL, Kelley KM, Rains TM. Sugar-sweetened product consumption alters glucose homeostasis compared with dairy product consumption in men and women at risk of type 2 diabetes mellitus. J Nutr. 2015 Mar;145(3):459-66. doi: 10.3945/jn.114.204503. Epub 2015 Jan 7.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: September 3, 2013
• First Submitted That Met QC Criteria: September 3, 2013
• First Posted (Estimated): September 6, 2013

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Insulin sensitivity
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Hyperinsulinism; Hypersensitivity; Insulin Resistance
• Other Study ID Numbers: PRV-1222