Medium-term Effects of a Polyphenol-rich Beverage Based on Red Grape Pomace Extract on Non-alcoholic Fatty Liver Disease, Cardiometabolic Risk Profile and Gut Microbiota in Subjects with Type 2 Diabetes

Overview

Nonalcoholic fatty liver disease (NAFLD) is a liver disease characterized by an abnormal accumulation of fat not due to alcohol or drug consumption that can evolve into steatohepatitis (NASH), fibrosis and cirrhosis. Its prevalence is high, affecting approximately 20-30% of the general adult population and is also growing in pediatric age. Obesity, insulin resistance and type 2 diabetes (T2DM) are common and well-known risk factors for NAFLD, which is approximately 2-3 times more prevalent among obese and diabetic individuals. Despite the high and increasing prevalence of NAFLD in the population, its pathophysiology is not fully understood and there is currently no pharmacological treatment available. Recent evidence suggests that dietary polyphenols may have specific beneficial effects on hepatic steatosis and associated sequelae by polyphenol metabolites and their phase II derivatives. Therefore, the aim of our study is to evaluate whether medium-term consumption of a beverage rich in polyphenols extracted from red grape pomace is able to exert beneficial effects on hepatic steatosis, cardiometabolic risk profile and microbiota composition of patients with type 2 diabetes.

Detailed description

A randomized, crossover, placebo-controlled study will be conducted. Twenty patients with type 2 diabetes mellitus (T2DM) recruited from the Diabetes Unit of the University Hospital of Naples "Federico II" who meet the inclusion criteria will be studied. After a 2-week run-in period during which they will stabilize their habitual diet, participants will be randomly assigned to receive either 150 ml/day of a polyphenol-rich red grape pomace beverage (RG) or 150 ml/day of a control beverage (Placebo) for a 6-week period each. The two treatments will be separated by a 2-week wash-out period.

At the end of the run-in, wash-out, and both treatment periods, participants will undergo fasting blood samples to evaluate key metabolic parameters. After each treatment period (RG or placebo), a standardized meal (960 kcal, 18% protein, 30% fat, 52% carbohydrates) will be administered along with 150 ml of either the polyphenol-rich beverage or the control beverage, for postprandial metabolic evaluations.

At the end of both treatments, hepatic fat content, fasting and postprandial metabolic parameters, microbiota composition and continuos glucose monitoring will be assessed.

Energy intake and habitual dietary composition will be evaluated at the end of the run-in, and at 6 weeks after the start of each treatment period using a 7-day food diary.

Interventions

• Dietary supplement Supplementation with Polyphenol Rich Drink
  Participants were instructed to consume, over a 6-week period, within the context of a Mediterranean diet, a polyphenol-rich drink RGPD (150 mL) containing 1.5 g of polyphenols. After this treatment period, participants underwent a two-week washout period before switching to the alternative treatment with control drink (Placebo) devoid of polyphenols. To evaluate metabolic responses during both fasting and postprandial states, participants participants consumed a standardized test meal at the en
• Dietary supplement Supplementation with Control Drink (Placebo)
  Participants were instructed to consume, over a 6-week period, within the context of a Mediterranean diet, a control drink (Placebo) (150 mL) containing 0 g of polyphenols. After this treatment period, participants underwent a two-week washout period before switching to the alternative treatment with a polyphenol-rich drink RGPD (150 mL) containing 1.5 g of polyphenols. To evaluate metabolic responses during both fasting and postprandial states, participants participants consumed a standardized

Primary outcome measures

• Differences in liver fat content [Time frame: At baseline and at the end of 6 weeks of each treatment]

Secondary outcome measures (8)

• Differences in glycemic variability [Time frame: At baseline and at the end of 6 weeks of each treatment]
• Differences in glucose response [Time frame: At the end of 6 weeks of each treatment]
• Differences in insulin response [Time frame: At the end of 6 weeks of each treatment]
• Differences in fasting lipid concentrations [Time frame: At the end of 6 weeks of each treatment]
• Differences in postprandial triglyceride response [Time frame: At the end of 6 weeks of each treatment]
• Differences in gastrointestinal hormones response [Time frame: At the end of 6 weeks of each treatment]
• Differences in inflammatory markers [Time frame: At the end of 6 weeks of each treatment]
• Differences in gut microbiota composition [Time frame: At the end of 6 weeks of each treatment]

Eligibility criteria

Inclusion criteria

• Body Mass Index (BMI) >25 and ≤35 kg/m2
• Cholesterolemia ≤ 250 mg/dl and Triglyceridemia ≤ 200 mg/dl.
• type 2 Diabetes in good glycemic control (Hb1Ac ≤7.5%) treated with diet alone or diet + metformin.

Exclusion criteria

• Cardiovascular events (myocardial infarction and/or stroke)
• Renal insufficiency (serum creatinine >1.5 mg/dl) and liver failure (ALT/AST twice the normal values)
• Anemia (Hb <12 g/dl) or other chronic disease
• Insulin therapy and other hypoglycemic drugs other than metformin
• Habitual intense physical activity

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Federico II University — Naples

Identifiers

NCT: NCT06895018 · 325/20

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗