Role of resveratrol supplementation in regulation of glucose hemostasis, inflammation and oxidative stress in patients with diabetes mellitus type 2: A randomized, placebo-controlled trial.

OBJECTIVE: The objective was to determine the effects of resveratrol supplementation on glucose homeostasis, oxidative stress, inflammation and microRNAs expression in patients with diabetes mellitus type 2 on oral hypoglycemic drugs. METHOD: This was a randomized, double blinded placebo-controlled parallel group trial. The diabetic patients (n = 110) were randomly assigned either to resveratrol (n = 55) and placebo (55) groups after informed consent and given once daily resveratrol 200 mg and cellulose capsules respectively for 24 weeks. Fasting glucose, insulin, HbA1c, lipid profile, TNF- α, IL-6, hs-CRP, MDA & circulatory microRNAs were measured at start and end of 24- week intervention. RESULTS: Out of 110 patients recruited, 94 patients completed the study comprising of 45 in resveratrol and 46 in placebo group. The resveratrol supplementation after 24 weeks was resulted in significant reduction [mean difference (95%CI)] of plasma glucose[- 0.50(-0.94 to -0.06)], insulin[- 1.31(-2.24 to -0.38)], homeostatic model assessment of insulin resistance[- 0.83(-1.37 to -0.29)], malondialdehyde[- 0.36(-0.61 to -0.11)], high sensitive-C-reactive protein[- 0.35(-0.70 to -0.01)], tumor necrosis factor-alpha[- 1.25(-1.90 to -0.61)] and interleukin-6[- 1.99(-3.29 to -0.69)]. More than two-fold down regulation in miRNA-34a, miRNA-375, miRNA-21, miRNA-192 and up regulation in miRNA-126 and miRNA-132 expression was noted in patients receiving resveratrol as compared to placebo. No side effects were reported during the trial. CONCLUSION: Resveratrol supplementation contributes in improvement of glycemic control by reducing insulin resistance. It has significant beneficial impact on chronic inflammation, oxidative stress and associated microRNA expression in diabetic patients. Thus, supplementation of resveratrol along with oral hypoglycemic agents may be useful in the reduction of diabetic associated complications.

Does mild hepatitis on liver biopsy warrant immediate combination anti viral therapy in chronic hepatitis C patients?

BACKGROUND: Not all patients with histologically mild chronic Hepatitis C progress to cirrhosis. Many patients being treated on the basis of raised ALT and positive PCR alone may not be actually requiring it. METHODS: All adult patients suffering from chronic Hepatitis C, qualifying for combination interferon ribavirin therapy, under went liver biopsies. Tissue samples were sent to Armed Forces Institute of Pathology (AFIP) Rawalpindi for histopathology. Reporting was done according to modified Ishaq score. RESULTS: Total number of patients was 147. Out of these, 75 (51%) were female and 72 (49%) were male. Mean age of females and males were 35.1 +/- 8.12 and 36.31 +/- 8.56 year respectively. Out of these, 19 (12.9%) were stage zero, 61 (41.5%) at stage 1, and 31 (21.1%) at stage 2 of modified fibrotic Ishaq score. In all, 111 (75.5%) of the patients were < or = 2 of modified Ishaq fibrotic score in either sex or 80 (54.4%) < or = 1 of modified Ishaq fibrotic stage. The necroinflammatory score has been divided into minimal (0-3), mild (4-8), moderate (9-13), and severe (14-18). About the same number of our patients (74%) had minimal to mild inflammation. CONCLUSION: Since the majority of the patients have fibrotic score less than 3, so it will be cost effective to individualise their treatment on liver histpathology. Patients with low fibrotic score and minimal to mild inflammation may not be treated, but only monitored with serial ALT and liver biopsy every 4-5 years. Treatment may be started if there is increase in fibrosis on surveillance biopsy. However, there is a need to conduct prospective studies in similar group of patients to evaluate the natural course of disease in untreated patients.