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

NCT ID: NCT01939782

Last Updated: 2015-04-22

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2015-11-30

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Type 2 diabetic patients (T2D)

In type 2 diabetic patients (T2D), the investigators will evaluate the metabolic clock gene expression in PBC and serum glucose, insulin, triglycerides, free fatty acids (FFA), cortisol intact GLP-1, triglycerides ,cortisol, plasma free fatty acids (FFA l and DPP4 plasma activity in two different occasions:

1. No Breakfast (NoB): fasting until lunch at 12:00

2. Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 In both occasions the blood samples for glucose and insulin, cortisol 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).

Group Type: EXPERIMENTAL

No Breakfast (NoB)

Intervention Type: OTHER

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)

Intervention Type: OTHER

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).

Healthy No Diabetics

In healthy No Diabetics,: the investigators will evaluate the metabolic clock gene expression in PBC and serum glucose, insulin, triglycerides, free fatty acids (FFA), cortisol intact GLP-1, triglycerides ,cortisol, plasma free fatty acids (FFA l and DPP4 plasma activity in two different occasions:

1. No Breakfast (NoB): fasting until lunch at 12:00

2. Yes Breakfast (YesB): eating breakfast at 8:30 and lunch at 12:00 In both occasions the blood samples for glucose and insulin, cortisol 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).

Group Type: ACTIVE_COMPARATOR

No Breakfast (NoB)

Intervention Type: OTHER

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)

Intervention Type: OTHER

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).

Interventions

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).

Intervention Type: OTHER

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).

Intervention Type: OTHER

Other Intervention Names

NoB; YesB

Eligibility Criteria

Inclusion Criteria

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

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

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

• Minimum Eligible Age: 26 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tel Aviv University

OTHER

Sponsor Role: lead

Responsible Party

Daniela Jakubowicz

Prof. Daniela Jakubowicz MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniela Jakubowicz, MD

Role: PRINCIPAL_INVESTIGATOR

Diabetes Unit E. Wolfson Medical Center. Tel Aviv University

Locations

Daniela Jakubowicz MD

Holon, N/A = Not Applicable, Israel

Site Status: RECRUITING

Countries

Israel

Central Contacts

Daniela Jakubowicz, MD

Role: CONTACT

daniela.jak@gmail.com

972508105552

Oren Froy, PhD

Role: CONTACT

oren.froy@mail.huji.ac.il

972546237664

Facility Contacts

Daniela Jakubowicz, MD

Role: primary

daniela.jak@gmail.com

972508105552

Julio Wainstein, MD

Role: backup

vainstein@wolfson.health.gov.il

972506296940

References

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.

Reference Type: DERIVED

PMID: 28830875 (View on PubMed)

Other Identifiers

0102-13-WOMC

Identifier Type: -

Identifier Source: org_study_id