NCT04088851

"Hepatic Substrate Flux Rates in Type 2 Diabetes"

"Non-invasive Measurement of Hepatic Substrate Flux Rates in People with Diabetes Mellitus Type 2"

• Status: Active Not Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 23 (estimated)
• Sponsor: German Diabetes Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	On Metformin	Oral intake of Metformin (1 g / day) for 2 weeks
DRUG	Off Metformin	No oral intake of Metformin (1 g / day) for 2 weeks

Timeline

• Start date: 2019-09-11
• Primary completion: 2025-12-31
• Completion: 2025-12-31
• First posted: 2019-09-13
• Last updated: 2025-01-13

Locations

1 site across 1 country: Germany