The aim of this study is to examine whether the chronic administration during 12 weeks of polyphenols contained in Red Grape Cells (RGC) powder has an effect on mRNA expression of SIRT1 and Clock Genes, on circulating levels of HbA1c, lipids, blood pressure and on postprandial response of glucose, lipids, insulin, C-peptide and GLP-1 in patients with type 2 diabetes .

There is a growing body of evidence demonstrating that polyphenols and specially the most investigated Resveratrol contained in the Red Grape Cells (RGC) exert beneficial effects on several markers of metabolic syndrome i.e. antioxidant, anti-inflammatory, anti-atherosclerotic, vasodilator and antihypertensive activity.

Many of this beneficial metabolic effects of polyphenols, occurs via activation of sirtuin-1 or silent information regulator-1 gene (SIRT1). This gene is expressed in adipose tissue, muscle, endothelium, peripheral blood cells, etc where it plays a pivotal role in the regulation of Circadian Clock Genes (CCG) involved in glucose lipid metabolism, endothelial function, etc .

By activation of SIRT1 and CCG the polyphenols, may influence the circadian secretion of adiponectin, insulin, asymmetric dimethylarginine (ADMA) and other hormones that influence insulin sensitivity, muscular glucose uptake, NO synthesis, nocturnal hepatic glucose production, lipolisis and endothelial function It was shown in several studies in animals and in clinical studies in subjects with metabolic syndrome that SIRT1 expression and its regulation of the CCG, improves insulin sensitivity in skeletal muscle, preventing weight gain; improves pancreatic beta-cell function enhancing insulin secretion and glucose tolerance. It was associated with increased lipolisis in white adipose tissue, decreased glycolysis, increased fatty acid oxidation in skeletal muscle and with increase Nitric Oxide in the endothelium.

Given that polyphenols directly on the clock genes or by enhancing SIRT1 expression appears to counter some of the effects of a high-fat diet, obesity and metabolic syndrome, by protecting against insulin resistance, hyperglycemia, and dyslipidemia and endothelial dysfunction.

It rise the possibility that the polyphenols contained in Red Grape Cells (RGC) by activation SIRT1 may also exert beneficial effects in subjects affected by type 2 diabetes

Inclusion Criteria:

1. Type 2 diabetes patients

2. HbA1C > 7 %

3. Duration of diabetes: 0.5 to 20 years

4. Subjects ≥ 30 and ≤70 years of age

5. BMI: 22 to 35 kg/m2

6. Fasting Triglyceride serum level ≥ 150 mg/dl

7. All oral antidiabetic treatments will be allowed, with the exception of thiazolidinediones (glitazones).i.e. pioglitazone (Actos) or rosiglitazone (Avandia). Insulin and no GLP-1 analogs will not be allowed.

8. Normal liver and kidney function

9. Normal thyroid function

10. Acceptable health beside diabetes based on interview, medical history, physical examination, and laboratory tests

11. Willingness to avoid the use of over-the-counter medications, herbs, or supplements throughout the entire study.

12. Willingness to avoid ingestion of any foods containing peanuts, bilberries, blueberries, cranberries, strawberries, raspberries, grapes, grape juice, cocoa powder, dark chocolate, and red wine throughout the entire study

13. Stable physical activity pattern during the three months immediately preceding study

14. Usually wakes up between 06:00 and 07:00 and goes to sleep between 22:00 and 24:00.

15. No shift work within 5 years of the study

16. Did not cross time zones within 1 month of the study

17. Read and understood the informed consent form and signed it voluntarily

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Exclusion Criteria:

1. Type 1 diabetes

2. Clinically significant pulmonary, cardiac, renal, hepatic, neurologic, psychiatric, infectious, malignant disease

3. 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)

4. Pregnancy or lactation

5. Illicit drug abuse or alcoholism

6. Treatment with thiazolidinediones (glitazones).i.e. pioglitazone (Actos) or rosiglitazone (Avandia).

7. Insulin and or GLP-1 analogs will not be allowed.

8. Anti hyperlipidemic treatment with fibrates. Statins will be allowed

9. Subjects taking anoretic drugs during the month immediately prior to study

10. Subjects on steroid treatment

11. Those with major illnesses, liver, heart, kidney, lung, infectious, neurological, psychiatric, immunological or neoplastic diseases,

12. Those with eating disorders

13. Known hypersensitivity to grapes, soy and/or casein

14. Subjects after bariatric surgery, will be excluded

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