Clinical trial NCT01939782: Metabolic Clock Genes During Fasting and After Food Intake in Type 2 Diabetics
Official title: Metabolic Clock Gene Expression in Peripheral Blood Cells During Fasting and After Food Intake in the Breakfast in Type 2 Diabetic Patients
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 2 Diabetes
Keywords: Metabolic CLock Genes (MCG)
Type 2 Diabetes (T2D)
Lead sponsor: Tel Aviv University
Sponsor class: OTHER
First posted: 2013-09-11
Enrollment: 30
Sex: ALL
Minimum age (years): 26
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: DIAGNOSTIC

Brief summary: This study is undertaken to explore whether compared to extension of overnight fast until lunch versus the breakfast consumption influence the oscillation of the metabolic clock gene expression in peripheral blood cells (PBC), at noon and after isocaloric lunch in type 2 diabetic patients.

Detailed description: Most of our metabolic function is controlled by metabolic clock genes that regulate glucose, lipid metabolism and several other circadian metabolic pathways involved in insulin resistance obesity and type 2 diabetes. The main group of clock genes resides in the SCN nuclei and is synchronized by light/dark signals. However similar clock oscillators called peripheral clocks are found in almost all tissues, including in the liver, heart, kidney, intestine, skeletal muscles, and adipocytes and in peripheral blood cells (PBC). The peripheral clocks, and specially those metabolic clock genes, seem to be controlled mainly by food cues.

The time of food intake synchronize simultaneously and in parallel way almost all the peripheral metabolic clock genes including those expressed and in peripheral blood cells (PBC) i.e. leucocytes, monocytes; allowing to explore the oscillation of the metabolic clock gene expression of the whole body by assessing its expression in the PBC. Impaired oscillation of the metabolic clock gene mRNA expression was found in diabetic animal models and in patients with type 2 diabetes and were inversely correlated with HbA1c.

In support of these finding we reported that high calorie breakfast with reduced dinner improved insulin sensitivity and weight loss rate among obese subjects, while in type 2 diabetic patients the high calorie breakfast was associated with improvement of HbA1c.

Moreover, recently was shown that very short time (only 120 min) after food intake in the breakfast, was sufficient to reset the expression of the circadian clock genes.

This study is undertaken to explore whether compared to extension of overnight fast until lunch versus the breakfast consumption influence the oscillation of the metabolic clock gene expression in peripheral blood cells (PBC), at noon and after isocaloric lunch in type 2 diabetic patients.

Eligibility criteria: Inclusion Criteria:

INCLUSION CRITERIA FOR PATIENTS WITH TYPE 2 DIABETES

1. Type 2 diabetic patients
2. HbA1C \> 6.5%
3. Duration of diabetes: 0.5 to 30 years
4. Subjects ≥ 26 and ≤ 65 years of age
5. BMI: \> 26 kg/m2
6. All oral antidiabetic treatments and will be allowed, not insulin treatment
7. Normal liver and kidney function
8. Normal thyroid function
9. Stable physical activity pattern during the three months immediately preceding study
10. No metabolic disease other than diabetes
11. Usually wakes up between 06:00 and 07:00 and goes to sleep between 22:00 and 24:00.
12. Normal TSH and FT4 levels
13. No shift work within 5 years of the study
14. Did not cross time zones within 1 month of the study
15. Acceptable health beside diabetes based on interview, medical history, physical examination, and laboratory tests
16. Read and understood the informed consent form and signed it voluntarily

INCLUSION CRITERIA FOR HEALTHY NON-DIABETIC PATIENTS

1. Healthy non diabetic, and not known as diabetic
2. Fating glucose \<100 mg/dl
3. HbA1C \<5.7 %
4. Not taking any antidiabetic drugs
5. Subjects ≥ 26 and ≤ 65 years of age
6. BMI: \<26 kg/m2
7. Normal liver and kidney function
8. Normal TSH and FT4 levels
9. Usually wakes up between 06:00 and 07:00 and goes to sleep between 22:00 and 24:00.
10. No shift work within 5 years of the study
11. Did not cross time zones within 1 month of the study
12. Acceptable health based on interview, medical history, physical examination, and laboratory tests
13. Read and understood the informed consent form and signed it voluntarily

Exclusion Criteria:

EXCLUSION CRITERIA FOR ALL 2 GROUPS (HEALTHY AND DIABETICS)

1. Clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, malignant disease
2. Type 1 diabetes
3. Treatment with Insulin
4. Serum creatinin level \> 1.5 mg/dl
5. Pregnancy or lactation
6. Illicit drug abuse or alcoholism
7. Subjects taking anoretic drugs during the month immediately prior to study
8. Subjects on steroid treatment
9. Subjects known by the principal investigator to be unable to cooperate for any reason.
10. Abnormal liver function tests defined as an increase by a factor of at least 2 above the upper normal limit of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
11. Night or rotating shift work
12. Jet lag during the 2 week period immediately prior to study onset

Primary outcomes:
measure: Metabolic Clock Gene Expression in Peripheral Blood Cells(PBC),
timeFrame: Blood samples for the clock genes will be taken at 8:30, 12:00 (before lunch) and at 15:30 (3 1/2h after lunch)
Secondary outcomes:
measure: Serum glucose insulin and intact GLP-1 levels
timeFrame: Blood samples for glucose insulin and intact GLP-1 levels will be taken after overnight fast at 8:30 and then at 9:00, 10:30 , 12:00, 12:30, 14:00 and 15:30
measure: Serum Triglycerides and Free Fatty Acids
timeFrame: Blood samples for Triglycerides and Free Fatty Acids will be taken after overnight fast at 8:30 and then at 9:00, 10:30 , 12:00, 12:30, 14:00 and 15:30
measure: DPP4 plasma activity
timeFrame: Blood samples for DPP4 plasma activity will be taken after overnight fast at 8:30, before lunch at 12:00 and at 15:30
measure: Serum Cortisol
timeFrame: Blood samples for Cortisol will be taken after overnight fast at 8:30 and then at 9:00, 10:30, 12:00, 12:30, 14:00 and 15:30
Other outcomes:
Locations:
city: Holon
country: Israel
facility: Daniela Jakubowicz MD
state: N/A = Not Applicable
Study officials:
affiliation: Diabetes Unit E. Wolfson Medical Center. Tel Aviv University
name: Daniela Jakubowicz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jakubowicz D, Wainstein J, Landau Z, Raz I, Ahren B, Chapnik N, Ganz T, Menaged M, Barnea M, Bar-Dayan Y, Froy O. Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial. Diabetes Care. 2017 Nov;40(11):1573-1579. doi: 10.2337/dc16-2753. Epub 2017 Aug 22.