Metabolic Clock Genes During Fasting and After Food Intake in Type 2 Diabetics

Type 2 Diabetes Clinical Trial

— MCG-T2D  

Official title:

Metabolic Clock Gene Expression in Peripheral Blood Cells During Fasting and After Food Intake in the Breakfast in Type 2 Diabetic Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01939782
• Other study ID #: 0102-13-WOMC
• Status: Recruiting
• Phase: N/A
• First received: September 2, 2013
• Last updated: April 20, 2015
• Start date: February 2015
• Est. completion date: November 2015

Study information

• Verified date: April 2015
• Source: Tel Aviv University
• Contact: Daniela Jakubowicz, MD
• Phone: 972508105552
• Email: daniela.jak[@]gmail.com
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: November 2015
• Est. primary completion date: September 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 26 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Other:
• No Breakfast (NoB)
In both occasions the blood samples for glucose and insulin, cortisol triglycerides and intact GLP-1 will be taken after overnight fast at 8:30 and thenat 8:30, 9:00, 10:30, 12:00, 12:30, 14:00 and 15:30. The samples for clock genes and for DPP4 plasma activity will be taken at 8:30, 12:00 (before lunch) and at 15:30 (3 1/2 h after lunch).
• Yes Breakfast (YesB)
In both occasions the blood samples for glucose and insulin, cortisol, triglycerides and intact GLP-1 will be taken after overnight fast at 8:30 and then at 8:30, 9:00, 10:30, 12:00, 12:30, 14:00 and 15:30. The samples for clock genes and for DPP4 plasma activity will be taken at 8:30, 12:00 (before lunch) and at 15:30 (3 1/2 h after lunch).

Locations

Country	Name	City	State
Israel	Daniela Jakubowicz MD	Holon	N/A = Not Applicable

Sponsors (1)

Lead Sponsor	Collaborator
Tel Aviv University

Country where clinical trial is conducted

Israel, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Metabolic Clock Gene Expression in Peripheral Blood Cells(PBC),	In all subjects the the blood samples for metabolic clock gene expression in PBC will be evaluated in PBC in two different occasions Fasting No Breakfast (NoB): fasting until lunch at 12:00 Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 In both occasions the blood samples for the clock genes will be taken at 8:30, 12:00 (before lunch) and at 15:30 (3 1/2 h after lunch)	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)	No
Secondary	Serum glucose insulin and intact GLP-1 levels	In all subjects the the blood samples for serum glucose insulin and intact GLP-1 levels will be evaluated, in two different occasions: No Breakfast (NoB): fasting until lunch at 12:00 Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 In both occasions the blood samples for glucose and insulin will be taken after overnight fast at 8:00 and then every hour until 15:30.	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	No
Secondary	Serum Triglycerides and Free Fatty Acids	In all subjects the the blood samples for serum Triglycerides and Free Fatty Acids plasma levels will be evaluated, in two different occasions No Breakfast (NoB): fasting until lunch at 12:00 Yes Breakfast (YesB): eating breakfast at Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00	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	No
Secondary	DPP4 plasma activity	In all subjects the the blood samples for DPP4 plasma activity will be evaluated in PBC in two different occasions No Breakfast (NoB): fasting until lunch at 12:00 Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 In both occasions the blood samples for DPP4 plasma activity will be taken at 8:30, 12:00 (before lunch) and at 15:30 (3 1/2 h after lunch)	Blood samples for DPP4 plasma activity will be taken after overnight fast at 8:30, before lunch at 12:00 and at 15:30	No
Secondary	Serum Cortisol	In all subjects the the blood samples for serum Cortisol will be evaluated, in two different occasions No Breakfast (NoB): fasting until lunch at 12:00 Yes Breakfast (YesB): eating breakfast at Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 Yes Breakfast (YesB): eating breakfast at Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00	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	No