Clinical trial NCT05421390: Effect of Dairy Products on Insulin Resistance
Official title: Effect of Dairy Products on Insulin Resistance in Overweight and Obese Individuals with Prediabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Sensitivity
Glucose Intolerance
PreDiabetes
Lead sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
Sponsor class: OTHER
Collaborators: name: Dairy Farmers of Canada
First posted: 2022-06-16
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of the study is to determine the effect of dairy consumption on insulin sensitivity in overweight and obese adults with prediabetes. Men and women (30-65 y) will be recruited from the greater Montreal area. Upon screening, those with prediabetes will complete a 2-wk run-in period in which participants will consume 1 serving/d of reduced-fat dairy. Adherent participants will be randomized by sex into 1 of 3 groups: ≤1 serving/d of dairy (limited dairy) or 2-3 servings/d of reduced-fat or regular-fat dairy for 12 weeks. Participants will be instructed on how to incorporate foods into their diet in a manner that prevents changes in their body weight. The hyperinsulinemic-euglycemic clamp will be used before and after the intervention to document potential changes in insulin sensitivity as the primary outcome. In addition, glycemic variables, body composition, and cardiometabolic risk factors will be assessed as secondary outcomes. Serum lipidomic and global gene expression responses to the intervention in subcutaneous adipose tissue will be measured as exploratory variables. Adherence to intervention will be assessed at each visit by food diaries, a record of consumed dairy products, and serum proportion of 15:0, 17:0, and t16:1n7 fatty acids as objective biomarkers of dairy fat intake.

Detailed description: The randomized controlled trial will be preceded by a 2-week run-in period in which participants will consume 1 serving/day of reduced-fat dairy. Following the run-in period, adherent participants will be randomly assigned to one of the three treatment groups (n=20 per group) in a 1:1:1 allocation ratio. Stratified permuted block randomization will be used to ensure adequate balance among groups using a computer-generated list of random numbers. Due to the nature of the test products, participants cannot be blinded to the diet intervention. However, outcome assessors will be blinded to treatment allocation.

During the screening visit, and after obtaining informed consent, eight, height, waist circumference, blood pressure, and pulse will be measured. Standard blood and urine tests, an OGTT, chest X-ray, electrocardiogram, and a physical exam will be performed. In addition, volunteers will be interviewed regarding demographic information, medical and family history, dietary habits, and physical activity using questionnaires.

At the run-in visit, participants will retrieve their dairy products and a dietitian will instruct them on how to incorporate incorporating 1 serving of reduced-fat dairy products each day into their habitual diet. Participants will be asked to record their food intake for 3 consecutive days (including one weekend day). They will also receive an accelerometer and instructions for use on the same 3-days they record their food intake. Participants will maintain a daily record of consumed dairy products during the run-in periods and throughout the study.

At the baseline and 12-week intervention visits, participants will undergo a hyperinsulinemic-euglycemic clamp to assess systemic insulin sensitivity. In addition, body composition will be measured by dual-energy X-ray absorptiometry and resting energy expenditure by indirect calorimetry. A biopsy of subcutaneous adipose tissue from the thigh will be taken at fasting.

During the 12-week intervention, participants in the limited dairy group will be instructed to limit their intake of dairy products to ≤1 serving/d of dairy. Participants in the 2-3 dairy servings of reduced or regular fat dairy groups will be provided with the study products. Serving sizes will be 250 mL milk, 175 g yogurt, and 50 g cheese. The dietitian will instruct participants individually on how to incorporate the dairy products into their habitual diets by reducing the intake of other foods of equivalent caloric content and complementary nutrient density, to maintain stable body weight. No additional dietary changes will be recommended.

At the monthly follow-up visits, weight, blood pressure, and pulse will be measured. In addition, participants will complete questionnaires about their health and physical activity. At each visit, they will be asked to track their food intake for 3 consecutive days (including one weekend day) using a mobile application on their smartphone or, if not possible, in written food diaries. Additionally, a blood sample will be collected to measure fatty acid biomarkers of dairy intake. On the second monthly visit, they will also receive an accelerometer and instructions for use on the same 3-days they record their food intake for the 12-week visit.

At the final follow-up visit, participants' weight, blood pressure, and pulse will be measured, and they will complete questionnaires regarding their health and activity. They will undergo an oral glucose tolerance test, as well as blood and urine tests, as described for the first visit.

Eligibility criteria: Inclusion Criteria:

* Aged between 30 and 65 years,
* Able to provide informed consent,
* Stable weight and dietary habits over a period of 3 months,
* Body mass index of 25-40 kg/m2,
* Waist circumference ≥94 cm for men, ≥80 cm for women,
* One or more indicators of prediabetes:

  1. 5.7-6.4% HbA1c
  2. fasting 5.6-6.9 mmol/L glucose, or
  3. 7.8-11.0 mmol/L glucose at 2-h OGTT

Exclusion Criteria:

* Current smokers,
* Pregnant or planning to become pregnant in the next 6 months,
* Breastfeeding,
* Participation in a weight loss program in the past 3 months,
* Dairy allergy or lactose intolerance,
* Any diagnosed eating disorders,
* Substance abuse (drugs or alcohol \>3 drinks/day),
* Diagnosed medical conditions such as cardiovascular disease, anemia, kidney disease, liver disease and any cancer, other than skin, within 5 years.
* Diabetes diagnosis,
* Abnormal electrocardiogram or chest X-Ray,
* Treatment with diuretics, certain β-blockers, bronchodilators, daily nonsteroidal anti-inflammatory drugs, anticoagulants or antiplatelet agents (except prophylactic aspirin 81 mg/d), antianginals, antiarrhythmics, oral steroids, or other medications known to affect glucose metabolism,
* Refusal to temporarily stop taking supplements (vitamin D, calcium, multivitamins, herbal remedies),
* Serum creatinine \> 120 µmol/L,
* Hemoglobin \< 120 g/L,
* Liver function tests ≥ 2× upper limit,
* Positive viral serology,
* Inaccessible veins.

Primary outcomes:
measure: Change in whole-body insulin sensitivity
timeFrame: Difference between baseline and 12-weeks intervention visit
Secondary outcomes:
measure: Change in glucose tolerance
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in Matsuda index
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in Insulinogenic index
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in oral disposition index
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in Homeostatic Model Assessment for Insulin Resistance
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in glycated hemoglobin
timeFrame: Difference between screening and 13-week follow-up visit
measure: Change in total lean body mass
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total fat mass
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in visceral fat mass
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in systolic blood pressure
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in diastolic blood pressure
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total cholesterol
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total triglycerides
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total LDL-cholesterol
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total HDL-cholesterol
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total non-HDL-cholesterol
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in C-reactive protein
timeFrame: Difference between baseline and 12-weeks intervention visit
Other outcomes:
measure: Change in resting energy expenditure
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in metabolic flexibility
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total energy expenditure
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in metabolic equivalent of task
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in total energy intake
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in dairy fat intake biomarkers
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in serum lipidomic signatures
timeFrame: Difference between baseline and 12-weeks intervention visit
measure: Change in subcutaneous adipose tissue gene expression signature
timeFrame: Difference between baseline and 12-weeks intervention visit
Locations:
city: Montréal
country: Canada
facility: RI-MUHC
state: Quebec
Study officials:
affiliation: RI-MUHC
name: Sergio A Burgos, PhD
role: PRINCIPAL_INVESTIGATOR
References: