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

NCT ID: NCT03772067

Last Updated: 2018-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-28

Study Completion Date

2019-10-20

Brief Summary

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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)

Detailed Description

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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,

Conditions

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Type2 Diabetes Healthy Obesity, Metabolically

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Parallel assignment
Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

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MBdiet

This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will contain 38 g protein mostly from milk and dairy products.

Group Type EXPERIMENTAL

Continuous glucose monitoring CGM

Intervention Type DEVICE

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

Clock Genes m RNA expression

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Body Weight

Intervention Type OTHER

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

Blood levels of HbA1c

Intervention Type DIAGNOSTIC_TEST

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

OBdiet

This arm consist on 3 month on Bdiet with high energy and protein breakfast (660 +/-20 kcal), medium sized lunch (580+/-20 kcal) and dinner reduced in energy (300+/-20 kcal), with distribution of calories: breakfast 44%, lunch 37% and dinner 19%. The breakfast will 38 g protein without milk or dairy products mostly from other proteins, i.e. eggs, tuna, soy, oatmeal. Milk product will be avoided in this diet also in other meals along the day.

Group Type ACTIVE_COMPARATOR

Continuous glucose monitoring CGM

Intervention Type DEVICE

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

Clock Genes m RNA expression

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Body Weight

Intervention Type OTHER

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

Blood levels of HbA1c

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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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

Intervention Type DEVICE

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type DIAGNOSTIC_TEST

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

Intervention Type OTHER

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

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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CGM CG PPG Insulin GLP-1 DPP4 CCK PYY Weight HbA1c

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Zohar Landau

UNKNOWN

Sponsor Role collaborator

Shani Tsameret

UNKNOWN

Sponsor Role collaborator

Tel Aviv University

OTHER

Sponsor Role lead

Responsible Party

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Daniela Jakubowicz

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Diabetes Unit E. Wolfson Hospital

Holon, Tel Aviv, Israel

Site Status

Daniela Jakubowicz

Holon, Wolfson Medical Center, Israel

Site Status

Countries

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Israel

Central Contacts

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DANIELA JAKUBOWICZ, MD

Role: CONTACT

Phone: +972508105552

Email: [email protected]

Julio Wainstein, MD

Role: CONTACT

Phone: +972506296940

Email: [email protected]

Other Identifiers

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0226-17-WOMC

Identifier Type: -

Identifier Source: org_study_id