Effect of Meal Frequency and Timing on Insulin Dose and Clock Gene in Type 2 Diabetic Patients

Not Applicable

Completed

• Conditions: Type 2 Diabetes
• Interventions: Other: Breakfast Diet (Bdiet); Other: 6Meal Diet (6Mdiet

• Registration Number: NCT02709915
• Lead Sponsor: Tel Aviv University

Brief Summary

This study is undertaken to explore in patients with uncontrolled T2D treated with insulin, whether a diet with large breakfast and lunch with small dinner (Bdiet) will enhance CG expression and will be more effective for weight loss and for achieving glycemic control and reduction of total daily insulin dose (first end point), compared to an isocaloric diet with 6 small meals distributed evenly along the day

Detailed Description

Obese patients with type 2 diabetes (T2D) and insulin resistance (IR), often require sequential increments of total daily insulin dose (TDID). This causes weight gain, worsens IR, leading to further increase of TDID and persistent hyperglycemia. In these patients, weight loss (WL) and reduction of IR are mandatory in order to achieve glucose control with less TDID. Impaired clock gene (CG) expression is linked to obesity and IR in T2D and it was shown in animals and T2D patients treated with oral anti-hyperglycemic drugs, that WL diet with restricted meal timing to specific hours, restored CG expression and was more effective for WL and for reduction of hyperglycemia compared to isocaloric WL diet, (commonly recommended for T2D), consisting of small meals randomly distributed along the day.

The investigators hypothesized that in patients with uncontrolled T2D treated with insulin, a diet with large breakfast and lunch with small dinner (Bdiet) will enhance CG expression and will be more effective for WL and for achieving glycemic control and reduction of TDID, compared to an isocaloric diet with 6 small meals distributed evenly along the day (6Mdiet).

This will be a randomized parallel, open label clinical study. Thirty overweight and obese insulin-treated T2D patients with HbA1c\>7.5% will be assigned to 12 weeks of 2 isocaloric diets: either Bdiet or 6Mdiet. HbA1c and CG mRNA expression in white blood cells and overall daily glycemia measured during 14 days, will be assessed before diet, after 14 days and at the end of the diet intervention. The TDID (first end point ) will be adjusted by physician, according to the results of self-monitoring of blood glucose on 3 consecutive days at baseline and before each of the visits.

Study Timeline

• Study First Submitted: 2016-03-07
• Study First Submitted QC: 2016-03-15
• Study First Posted: 2016-03-16
• Study Start: 2016-11
• Primary Completion: 2017-10
• Study Completion: 2019-02
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-24
• Last Update Posted: 2019-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 28

Inclusion Criteria

• T2D patients with stable insulin treatment for at least 3 month preceding the study.
• HgA1c >7.5 %.
• Age > 30 years.
• BMI: 27-34 kg/m2.
• Treatment with antidiabetic drugs (i.e. metformin, DPP4 inhibitors, glinides) and GLP-1 analogs.
• Anti-hypertensive treatment will be allowed.
• Lipid-lowering medication.

Exclusion Criteria

• Type 1 diabetes.
• Major illnesses (liver, heart, kidney, infectious, neurological, psychiatric, immunological, active malignancy).
• Presently dieting.
• Change in weight of > 4.5 kg within 3 month prior to study onset.
• Night or rotating shift workers.
• Those who crossed more than 2 time zones during 2-week period prior to study onset.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Breakfast Diet (Bdiet)	Breakfast Diet (Bdiet)	The Bdiet will consist in 3 meals with distribution of calories: breakfast 50%, lunch 33% and dinner 17%.
Breakfast Diet (Bdiet)	6Meal Diet (6Mdiet	The Bdiet will consist in 3 meals with distribution of calories: breakfast 50%, lunch 33% and dinner 17%.
6 small meals diet (6Mdiet)	6Meal Diet (6Mdiet	The 6Mdiet will consist on 6 meals (breakfast, lunch and dinner and 3 snacks) with distribution of calories: breakfast 15%, lunch 25%, dinner 30% and 10% each of the three snacks.
6 small meals diet (6Mdiet)	Breakfast Diet (Bdiet)	The 6Mdiet will consist on 6 meals (breakfast, lunch and dinner and 3 snacks) with distribution of calories: breakfast 15%, lunch 25%, dinner 30% and 10% each of the three snacks.

Primary Outcome Measures

Name	Time	Method
Insulin Dose	Baseline, 2 week and at 12 weeks	The effects of two diets (Bdiet and 6Mdiet) will be compared on their efficacy on total insulin dose reduction measured at baseline, after 2 weeks and at the end (12 weeks) of both diet interventions

Secondary Outcome Measures

Name	Time	Method
HbA1c	Baseline, 2 weeks and at 12 weeks	The effect of the two diets (Bdiet and 6Mdiet) will be compared on the efficacy on the reduction of HbA1c measured at baseline, after 2 weeks and at the end (12 weeks) of both diet interventions
Overall Glycemia	Baseline, 2 week and at 12 weeks	The effect of the two diets on all-day glycemia will be assessed with continuous blood monitoring system at baseline, after 2 weeks and after 12 weeks of the two diet intervention
Clock Gene mRNA expression	Baseline, 2 week and at 12 weeks	The measurement of mRNA expression of clock gene in circulating white blood cells will be assessed at baseline, after 2 weeks and after 12 weeks of the two diet intervention

Trial Locations

Locations (1)

Daniela Jakubowicz; 🇮🇱 Holon, Wolfson Medical Center, Israel