Effect of Milk Consumption on Glycemia and Gut Microbiome in T2D (Milk-GM)

Effect of Milk Consumption on Glycemic Control and Gut Microbiome in Type 2 Diabetes

The overall glycemic excursions display circadian variations which are controlled by the circadian clock genes (CCG) and are strongly influenced by meal timing.

Indeed, in T2D, a diet aligned with the CCG, with high-energy and protein breakfast, and reduced in CH dinner (Bdiet) resulted in effective reduction of body weight, HbA1c, and of overall glycemia versus reverse schedule or six meals, with energy and carbohydrates (CH) evenly distributed throughout the day.

in addition to meal timing of Bdiet, the source of protein i.e., Milk and dairy products, by favorable changes in the Guts Microbiome (GM) composition may also play a role in the reduction of overall glycemia of T2D.

The investigators hypothesize that Bdiet schedule with high content of milk and other dairy proteins (YesMdiet), will reduce overall glycemia in T2D, compared to isocaloric and iso-protein Bdiet with another source (nondairy) proteins (NoMdiet).

Study Design: The effect of the two Bdiet interventions on GM will be assessed in T2D participants in a cross-over design, at baseline and after YesMdiet and after NoMdiet, in random order. We expect more favorable changes in glycemic control and in GM composition in YesMdiet versus NoMdiet.

Study Overview

• Status: Not yet recruiting
• Conditions: Type2Diabetes
• Intervention / Treatment: Other: YesMdiet; Other: NoMdiet

Detailed Description

Background: Reduction of the overall glycemic excursion is the main target in the treatment of T2D to reduce HbA1c and cardiovascular risk. The overall glycemic excursions display circadian variations controlled by the circadian clock genes (CG) and are strongly influenced by meal timing.

Indeed, the investigators have recently shown in T2D, that a diet aligned with the CCG, with high-energy and protein breakfast, and reduced in CH dinner (Bdiet) resulted in effective reduction of body weight, HbA1c, and substantial reduction of overall (diurnal and nocturnal) glycemia as compared to the reverse schedule or a diet with six meals, with energy and carbohydrates (CH) evenly distributed throughout the day.

However, in addition to meal timing, the source of protein in Bdiet and the changes of Gut Microbiome (GM) composition, may also play a role in the reduction of overall glycemia. It has been recently shown that consumption of milk and dairy products is associated beneficial effect on overall glycemia. Further, milk and dairy may exert a beneficial effect on overall glycemia by favorable changes in GM composition.

Working hypothesis: Therefore, in this study, we hypothesize that a Bdiet schedule with high content of milk and other dairy proteins (YesMdiet), compared to isocaloric and iso-protein Bdiet with another source (nondairy) proteins (NoMdiet) and may lead to favorable changes in the Gut Microbiota (GM) [Primary end-point] in association with the improvement of overall glycemia in T2D participant under continuous glucose monitoring (CGM) surveillance.

Study Design: The effect of the two Bdiet interventions on GM will be assessed in n=16 participants in a cross-over design, at baseline and after 14 days of Bdiet consuming Milk and dairy products (YesMdiet) or isocaloric Bdiet without milk or dairy products (NoMdiet), in random order in T2D individual undergoing CGM surveillance.

Expected results: We expect more favorable changes in glycemic control and in GM composition in YesMdiet versus NoMdiet.

Scientific Significance: This trial will reveal whether the benefits of Bdiet on glycemic control is further enhanced by milk and dairy consumption, in association with favorable changes in Gut Microbiome

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julio Wainstein, MD; Phone Number: 972-506296940; Email: julio_w@walla.com
• Study Contact Backup: Name: Orit Twito, MD; Phone Number: 972-542270104; Email: orit.twito@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients diagnosed with T2D < 20 years
• HbA1c ≥ 6.5 %.
• BMI - 28-45 kg/m2
• Men and women 30 -75 years of age inclusive
• Normal liver, kidney, and thyroid functions, and eGFR > 45 mL/min/1.73 m2.
• Type 2 diabetes controlled with diet, lifestyle alone, or with antidiabetics other than insulin (i.e. biguanides, sulfonylureas, glinides, SGLT2 inhibitors, DPP4 inhibitors, GLP-1 analogs), with stable doses for at least 3 months before entering the study.
• Stable weight (less than 5% change in body weight in last 3 months before the study - determined by self-reporting or documentation in clinical records).
• Concomitant medication i.e. antihypertensive, anti-lipidemic, anti-thrombotic drugs will be allowed also on a stable dose for at least 3 months before the beginning of the trial.
• Patients that usually wake up between 06:00 and 08:00 and go to sleep between 22:00 and 24:00.
• Should not have shift work within 6 months of the study and should not have crossed time zones within 2 weeks of the study.
• No change in medication or nutrition supplements or physical activity will be made during the study.

Exclusion Criteria:

• Type 1 diabetes or secondary forms of diabetes.
• Patients with latent autoimmune diabetes in adults (LADA).
• Treatment with insulin.
• Serum creatinine level >2mg/dl. Renal dysfunction: eGFR < 45 mL/min/1.73 m2).
• Hepatic dysfunction: liver disease or transaminase levels > 2.5-fold above normal.
• Major illness with life expectancy < 5 years.
• Malignant neoplasm requiring chemotherapy, surgery, radiation, or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer).
• Those taking psychotropic, anorectic medication, steroid treatment, or illicit drug abuse or alcoholism within one year prior to study onset. Pregnancy or lactation.
• Known hypersensitivity to milk components or lactose intolerance.
• Night or rotating shift workers or those who crossed more than 2 time zones during the 2- week period prior to study onset.
• Not able to give informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: YesMdiet; After one week baseline, the participants will be assigned to YesMdiet, consuming milk and dairy products for 14 days	Other: YesMdiet; In the YesMdiet, participants will consume Milk and Dairy products; Other Names: Yes Milk diet
Active Comparator: NoMdiet; After one week baseline, the participants will be assigned to NoMdiet, consuming another source of protein and without milk or dairy products for 14 days	Other: NoMdiet; In the YesMdiet, participants will not consume Milk and Dairy products, only other sources of protein; Other Names: No Milk diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiome	Gut Microbiome composition will be assessed using 16s rRNA sequencing method after 14 days of YesMdiet	14 day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut Microbiome	Gut Microbiome composition will be assessed using 16s rRNA sequencing method after 14 days of NoMdiet	14 days
Overall Glycemia	Overall Glycemia will be assessed using continuous glucose monitoring CGM during 14 days of either YesMdiet or NoBdiet	14 days

Collaborators and Investigators

• Sponsor: Tel Aviv University
• Investigators: Principal Investigator: Daniela Jakubowicz, MD, Wolfson Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): April 28, 2022
• Primary Completion (Anticipated): October 28, 2022
• Study Completion (Anticipated): December 28, 2022

Study Registration Dates

• First Submitted: March 13, 2022
• First Submitted That Met QC Criteria: March 22, 2022
• First Posted (Actual): March 24, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 22, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 0041-22-WOMC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No