Type 2 Diabetes
Conditions
Keywords
Metabolic CLock Genes (MCG), Type 2 Diabetes (T2D)
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.
Interventions
OTHERNo 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).
OTHERYes 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).
Sponsors
Tel Aviv University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
26 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Metabolic Clock Gene Expression in Peripheral Blood Cells(PBC), | 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
| Measure | Time frame | Description |
|---|---|---|
| Serum glucose insulin and intact GLP-1 levels | 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. |
| Serum Triglycerides and Free Fatty Acids | 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 |
| DPP4 plasma activity | 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) |
| Serum Cortisol | 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 |
Countries
Israel
Contacts
Primary ContactDaniela Jakubowicz, MD
Backup ContactOren Froy, PhD
Outcome results
None listed