Influence of Dairy Protein Breakfast on Glycemia, Weight Loss and Clock Genes in T2D

Type2 Diabetes Clinical Trial

— Mdiet  

Official title:

Influence of Dairy Protein Breakfast on Overall Daily Glycemia, Weight Loss HbA1c and Clock Genes mRNA Expression, in Type 2 Diabetes

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03772067
• Other study ID #: 0226-17-WOMC
• Status: Not yet recruiting
• Phase: N/A
• Start date: December 28, 2018
• Est. completion date: October 20, 2019

Study information

• Verified date: December 2018
• Source: Tel Aviv University
• Contact: DANIELA JAKUBOWICZ, MD
• Phone: +972508105552
• Email: daniela.jak[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study in T2D patients is undertaken to evaluate the effect of previously studied 3Meals Diet, high energy breakfast (Bdiet) with milk and dairy proteins (MBdiet) versus isocaloric diet with same meal distribution but with other sources of protein (OBdiet) overall postprandial glycemia (PPG), weight loss (WL), HbA1c, CG expression and on PPG, insulin, C-peptide, GLP-1, gut peptide YY (PYY), cholecystokinin (CCK), ghrelin, dipeptidyl peptidase-4 plasma activity (DPP-4) and appetite responses after high protein breakfast. challenge including milk and dairy products (MBdiet) and after breakfast challenge with same protein content but different source of protein (OBdiet)

Description:

Increased circadian glucose excursions and overall postprandial glycemia (PPG) are linked to HbA1c and cardiovascular risk in T2D.

Most of the metabolic pathways involved in PPG i.e. secretion of insulin and glucagon-like peptide-1 (GLP-1), are controlled by circadian clock genes (CG). However, the CG regulation is bidirectional, indeed high protein breakfast (B), by increasing insulin and GLP-1 upregulate CG expression leading to reduced overall PPG, HbA1c and weight loss (WL) in T2D. Furthermore in recent study the investigators have shown that in type 2 diabetic patient treated with insulin a diet with 3 Meal Diet consisting in high energy and protein breakfast, medium sized lunch and low energy dinner, with selective time restriction from carbohydrate consumption after 15:00, designed as Bdiet; was more effective approach for reduction of overall PPG, HbA1c and for upregulation of Clock Genes (CG) mRNA expression compared to isocaloric 6 Meal Diet, with calories and macronutrient evenly distributed along the day in three main meals and 3 snack in between.

As the beneficial effects of high energy and protein breakfast in 3Meal diet on the reduction of body weight, overall glycemia and up regulation CG expression, have been demonstrated, in recent studies, we hypothesized that some sources of protein in the breakfast may exert be more beneficial than other source of protein on body weight, PPG, HbA1c and on CG expression Milk consumption is linked to lower risk for obesity and T2D. In acute studies, the addition of milk to carbohydrates in B, displayed greater lowering effect of glucose response after breakfast, lunch and dinner compared with other protein sources.

However the effect of a diet 3Mdiet with high energy and dairy protein breakfast (MBdiet), on overall PPG, weight loss HbA1c, the effect on effect on circadian clock genes and AMPK mRNA expression and on the postprandial glucose, insulin, C-peptide, GLP-1, PYY, CCK, ghrelin, DPP4 plasma activity and appetite has never been explored and never were compared to isocaloric 3Mdiet with other then dairy protein source of protein (OBdiet) in long term study in T2D individuals .

The investigators hypothesize that a diet with high energy and protein breakfast consisting on milk and dairy proteins (MBdiet), by enhancing clock gene expression will lead to more efficient weight loss reduction of overall PPG, and glucose control (HbA1c), compared to a diet with other (non dairy) proteins in the breakfast (OBdiet). The investigators also hypothesize that the dairy breakfast effects in MBdiet may be mediated, at least in part, by integration of events that promote greater postprandial glucose insulin, C-peptide, GLP-1, PYY, and CCK, and greater suppression of ghrelin appetite and DPP4 plasma activity,

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: October 20, 2019
• Est. primary completion date: June 20, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients diagnosed with T2D < 20 years;

• HgA1c = 7.0 %.

• BMI - 28-40 kg/m2

• Men and women 30 -75 years of age inclusive.

• Normal liver, kidney and thyroid functions, negative urinary microalbumin test (urMA) and estimated glomerular filtration rate (eGFR) > 45 mL/min/1.73 m2.

• Type 2 diabetes controlled with diet and lifestyle alone or with antidiabetic treatment other than insulin (i.e. buguanides, 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 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 month of the study and should not have crossed time zones within 2 weeks of 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: (estimated glomerular filtration rate 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 with 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. No change in medication or nutrition supplements or physical activity will be made during the study. Not able to give informed consent

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Healthy Obesity, Metabolically
• Obesity, Metabolically Benign
• Type2 Diabetes
• Weight Loss

Intervention

Device:
• Continuous glucose monitoring CGM
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the overall glucose levels measured with CGM installed in the arm during 14 days at baseline before diet intervention and after 14 days of the beginning of diet intervention

Diagnostic Test:
• Clock Genes m RNA expression
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the blood levels of Clock Genes measured at baseline and after 14 days of diet intervention
• Postprandial Glucose
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma Glucose measured at meal test after 14 days of diet intervention
• Postprandial Insulin
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma Insulin measured at meal test after 14 days of diet intervention
• Plasma GLP-1
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma GLP-1 measured at meal test after 14 days of diet intervention
• DPP4 plasma activity
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial DPP4 plasma activity measured at meal test after 14 days of diet intervention
• Ghrelin
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma Ghrelin measured at meal test after 14 days of diet intervention
• Plasma CCK
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma CCK measured at meal test after 14 days of diet intervention
• Plasma PYY
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the postprandial plasma PYY measured at meal test after 14 days of diet intervention

Other:
• Body Weight
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing the body weight at baseline and every weeks of diet intervention

Diagnostic Test:
• Blood levels of HbA1c
The effect of the two diets (MBdiet and OBdiet) will be compared on the efficacy on changing blood HbA1c measured at baseline and after 90 days of diet intervention diet intervention

Locations

Country	Name	City	State
Israel	Daniela Jakubowicz	Holon	Wolfson Medical Center
Israel	Diabetes Unit E. Wolfson Hospital	Holon	Tel Aviv

Sponsors (3)

Lead Sponsor	Collaborator
Tel Aviv University	Shani Tsameret, Zohar Landau

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clock genes mRNA expression	The effect of the two diets (MBdiet and OBdiet) will be compared on their efficacy on changing the clock genes expression	two weeks
Secondary	Continuous Glucose Monitoring (CGM)	The effect of the two diets (MBdiet and OBdiet) will be compared on their efficacy on changing overall glycemia assessed by Continuous Glucose Monitoring (CGM)	two weeks
Secondary	HbA1c	The effect of the two diets (MBdiet and OBdiet) will be compared on their efficacy on changing HbA1c	3 months
Secondary	Body Weight	The effect of the two diets (MBdiet and OBdiet) will be compared on their efficacy on changing body weight	3 months