Clinical trial NCT02709915: Effect of Meal Frequency and Timing on Insulin Dose and Clock Gene in Type 2 Diabetic Patients
Official title: Effect of Meal Frequency and Timing on Glycemic Control, Daily Insulin Dose Requirements and Clock Gene Expression in Uncontrolled Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Tel Aviv University
Sponsor class: OTHER
First posted: 2016-03-16
Enrollment: 28
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Insulin Dose
timeFrame: Baseline, 2 week and at 12 weeks
Secondary outcomes:
measure: HbA1c
timeFrame: Baseline, 2 weeks and at 12 weeks
measure: Overall Glycemia
timeFrame: Baseline, 2 week and at 12 weeks
measure: Clock Gene mRNA expression
timeFrame: Baseline, 2 week and at 12 weeks
Other outcomes:
measure: Body Weight
timeFrame: Baseline, 2 week and at 12 weeks
Locations:
city: Holon
country: Israel
facility: Daniela Jakubowicz
state: Wolfson Medical Center
Study officials:
affiliation: Wolfson Medical Center
name: Julio Wainstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jakubowicz D, Landau Z, Tsameret S, Wainstein J, Raz I, Ahren B, Chapnik N, Barnea M, Ganz T, Menaged M, Mor N, Bar-Dayan Y, Froy O. Reduction in Glycated Hemoglobin and Daily Insulin Dose Alongside Circadian Clock Upregulation in Patients With Type 2 Diabetes Consuming a Three-Meal Diet: A Randomized Clinical Trial. Diabetes Care. 2019 Dec;42(12):2171-2180. doi: 10.2337/dc19-1142. Epub 2019 Sep 23.