"Hepatic Substrate Flux Rates in Type 2 Diabetes"

NCT ID: NCT04088851

Last Updated: 2025-01-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-09-11
• Study Completion Date: 2025-12-31

Brief Summary

Investigation of the effects of redox shuttle inhibition by metformin on gluconeogenic flux rates of lactate and glycerol in humans with type 2 diabetes

Detailed Description

Type 2 diabetes (T2D) is characterized by insulin resistance and relative insulin deficiency leading to hyperglycemia. Enhanced endogenous glucose production during fasting is a key feature of hepatic insulin resistance and a major contributor to deterioration of glycemia. Metformin reduces fasting gluconeogenesis (GNG); the underlying mechanisms are still not fully understood, but involve the inhibition of complexes of the electron transport chain and thus the redox shuttle.

The investigators have previously provided evidence for abnormal hepatic ATP synthesis and mitochondrial efficiency in T2D, but it remains unknown, how and which substrate fluxes account for excessive GNG in T2D. For this reason, this proposal aims at investigating hepatic glucose and energy fluxes in T2D with focus on gluconeogenic contribution of lactate and glycerol to hepatic mitochondrial substrate flux, mitochondrial ATP synthase flux and the activity of the redox shuttle, also after metformin intake, by using a novel combination of positional isotopomer nuclear magnetic resonance (NMR) analysis (PINTA) with multinuclei magnetic resonance spectroscopy (MRS).

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Metformin - T2D

Participants with type-2 diabetes will intake metformin 1 g daily for 2 weeks

Group Type: EXPERIMENTAL

On Metformin

Intervention Type: DRUG

Oral intake of Metformin (1 g / day) for 2 weeks

No Metformin - T2D

Participants with type-2 diabetes will pause metformin 1 g daily for 2 weeks

Group Type: PLACEBO_COMPARATOR

Off Metformin

Intervention Type: DRUG

No oral intake of Metformin (1 g / day) for 2 weeks

Interventions

On Metformin

Oral intake of Metformin (1 g / day) for 2 weeks

Intervention Type: DRUG

Off Metformin

No oral intake of Metformin (1 g / day) for 2 weeks

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• type 2 diabetes (duration <7 years),
• age (18-75 years)
• BMI <40 kg/m2
• HbA1c 6-15%

Exclusion Criteria

• uncontrolled hyperglycaemia (>340 mg/dl)
• diabetes types other than type 2 diabetes (ADA criteria)
• thiazolidinedione use during the preceding 6 months
• clinically relevant angiopathy, restrictive or obstructive lung diseases
• other acute or chronic diseases including wounds and the use of pharmacological agents known to affect insulin sensitivity, lipid metabolism or immunological function.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Yale University

OTHER

Sponsor Role: collaborator

German Diabetes Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Roden, Prof., MD

Role: PRINCIPAL_INVESTIGATOR

German Diabetes Center

Locations

German Diabetes Center

Düsseldorf, North Rhine-Westphalia, Germany

Countries

Germany

Other Identifiers

IMPACT

Identifier Type: -

Identifier Source: org_study_id