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Metabolic Clock Genes During Fasting and After Food Intake in Type 2 Diabetics (MCG-T2D)

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ClinicalTrials.gov Identifier: NCT01939782
Recruitment Status : Unknown
Verified April 2015 by Daniela Jakubowicz, Tel Aviv University.
Recruitment status was:  Recruiting
First Posted : September 11, 2013
Last Update Posted : April 22, 2015
Sponsor:
Information provided by (Responsible Party):
Daniela Jakubowicz, Tel Aviv University

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.

Condition or disease Intervention/treatment Phase
Type 2 Diabetes Other: No Breakfast (NoB) Other: Yes Breakfast (YesB) Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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 Start Date : February 2015
Estimated Primary Completion Date : September 2015
Estimated Study Completion Date : November 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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).
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).
Other Name: NoB

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).
Other Name: YesB

Active Comparator: 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).
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).
Other Name: NoB

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).
Other Name: YesB




Primary Outcome Measures :
  1. Metabolic Clock Gene Expression in Peripheral Blood Cells(PBC), [ Time Frame: 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) ]
    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)


Secondary Outcome Measures :
  1. Serum glucose insulin and intact GLP-1 levels [ Time Frame: 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 ]

    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.


  2. Serum Triglycerides and Free Fatty Acids [ Time Frame: 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 ]
    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

  3. DPP4 plasma activity [ Time Frame: Blood samples for DPP4 plasma activity will be taken after overnight fast at 8:30, before lunch at 12:00 and at 15:30 ]
    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)

  4. Serum Cortisol [ Time Frame: 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 ]
    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



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Ages Eligible for Study:   26 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01939782


Contacts
Contact: Daniela Jakubowicz, MD 972508105552 daniela.jak@gmail.com
Contact: Oren Froy, PhD 972546237664 oren.froy@mail.huji.ac.il

Locations
Israel
Daniela Jakubowicz MD Recruiting
Holon, N/A = Not Applicable, Israel, 58100
Contact: Daniela Jakubowicz, MD    972508105552    daniela.jak@gmail.com   
Contact: Julio Wainstein, MD    972506296940    vainstein@wolfson.health.gov.il   
Sponsors and Collaborators
Tel Aviv University
Investigators
Principal Investigator: Daniela Jakubowicz, MD Diabetes Unit E. Wolfson Medical Center. Tel Aviv University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daniela Jakubowicz, Prof. Daniela Jakubowicz MD, Tel Aviv University
ClinicalTrials.gov Identifier: NCT01939782     History of Changes
Other Study ID Numbers: 0102-13-WOMC
First Posted: September 11, 2013    Key Record Dates
Last Update Posted: April 22, 2015
Last Verified: April 2015

Keywords provided by Daniela Jakubowicz, Tel Aviv University:
Metabolic CLock Genes (MCG)
Type 2 Diabetes (T2D)

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents