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 (PoLiFat)

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus Type 2
• Intervention / Treatment: Dietary supplement: Supplementation with Polyphenol Rich Drink; Dietary supplement: Supplementation with Control Drink (Placebo)

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Federico II University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Grape Pomace Polyphenol Rich Drink; Participants consume an experimental drink rich in polyphenols extracted from red grape pomace (RGP) containing 1.5 g/150 ml of Gallic Acid Equivalent (GAE) polyphenols and 28 g/150 ml of soluble sugars (14 g of glucose and 14 g of fructose) during the lunch and dinner for 6 weeks	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 end of the 6 weeks. This standard meal was preceded by the consumption of the RGPD 60 minutes prior.
Placebo Comparator: Placebo Drink; Participants consume a control drink (Placebo), containing zero polyphenol and 28 g of total sugars (14 g of glucose and 14 g of fructose solubilized in 150 ml of drinking water), quantities equivalent to those contained in the experimental drink, during the lunch and dinner for 6 weeks	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 test meal at the end of the 6 weeks. This standard meal was preceded by the consumption of the Control drink (Placebo) 60 minutes prior.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in liver fat content	Differences in liver fat content after the intake of polyphenol rich drink (RGPD) for 6 weeks, as compared to Control drink (Placebo). Liver fat content will be assessed by magnetic resonance spectroscopy (MRI).	At baseline and at the end of 6 weeks of each treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in glycemic variability	Differences in glycemic variability after the intake of polyphenol rich drink (RGPD) for 6 weeks, as compared to control drink (placebo). Glycemic variability will be assessed by Continuos Glucose Monitoring (CGM) during the 7 days before the end of each treatment.	At baseline and at the end of 6 weeks of each treatment
Differences in glucose response	Differences in fasting and postprandial plasma glucose response to a standard test meal at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma glucose concentration will be assessed by enzymatic colorimetric methods.	At the end of 6 weeks of each treatment
Differences in insulin response	Differences in fasting and postprandial plasma insulin response to a standard test meal at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma insulin concentration will be assessed by ELISA method.	At the end of 6 weeks of each treatment
Differences in fasting lipid concentrations	Differences in fasting plasma triglycerides, total cholesterol, HDL-cholesterol and LDL-cholesterol concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma lipid concentrations will be assessed by enzymatic colorimetric methods.	At the end of 6 weeks of each treatment
Differences in postprandial triglyceride response	Differences in postprandial plasma triglycerides concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma triglyceride concentrations will be assessed by enzymatic colorimetric methods.	At the end of 6 weeks of each treatment
Differences in gastrointestinal hormones response	Differences in fasting and postprandial plasma GLP-1, PYY and Ghrelin concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Plasma concentrations of GLP-1, PYY and Ghrelin will be assessed by ELISA methods.	At the end of 6 weeks of each treatment
Differences in inflammatory markers	Differences in fasting and postprandial serum hs-CRP concentration at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Serum concentrations of hs-CRP will be assessed by immunoturbidimetric method.	At the end of 6 weeks of each treatment
Differences in gut microbiota composition	Differences in microbiota composition at the end of the 6-week treatment with polyphenol rich drink (RGPD) as compared to control drink (placebo). Microbiota analysis will be assessed on feacal samples by metagenomics.	At the end of 6 weeks of each treatment

Collaborators and Investigators

• Sponsor: Federico II University
• Collaborators: Consiglio Nationale delle Richerche (CNR)
• Investigators: Principal Investigator: Rosalba Giacco, Senior Researcher, CNR; Study Director: Luigi Russo, Senior Researcher, CNR; Principal Investigator: Lutgarda Bozzetto, Full Professor, Federico II Univerisity

Study record dates

Study Major Dates

• Study Start (Actual): May 3, 2024
• Primary Completion (Estimated): August 8, 2025
• Study Completion (Estimated): October 31, 2025

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Estimated): March 26, 2025

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: lipid metabolism; NAFLD; Gut microbiota; Polyphenols; Glucose metabolism; insulin metabolism; glucose variability; sublinical inflammation; grape pomace
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus, Type 2; Diabetes Mellitus; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 325/20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No