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"The Role of the Liver for Interorgan Metabolic Crosstalk in Type 2 Diabetes"

Type2 Diabetes Clinical Trial

Official title:
"Non-invasive Measurement of Hepatic Substrate Flux Rates in Patients With Diabetes Mellitus Type 2"

Clinical Trial Summary

WP 1: Working hypothesis: The gluconeogenic flux rates from pyruvate (lactate, alanine) and glycerol are higher in patients with T2D compared to the healthy control group. WP2: Working Hypothesis: The gluconeogenic flux rates of lactate and glycerol are reduced in patients with T2D by acute inhibition of the redox shuttle.

Clinical Trial Description

Type 2 diabetes (T2D) is characterized by insulin resistance and inadequate insulin secretion leading to hyperglycemia. Current concepts indicate that insulin resistant adipose tissue releases metabolites, which stimulate hepatic gluconeogenesis (GNG), lipid deposition and secretion. Failure of compensation by ß cell function will favour muscle insulin resistance and fasting/postprandial hyperglycemia. The investigators have previously provided evidence for abnormal ATP synthesis and mitochondrial efficiency, but it remains unknown, how and which substrate fluxes account for excessive GNG in T2D. For this reason, the main objective of this project is to adress the multi-system challenges of T2D, by examining interorgan metabolic crosstalk with an emphasis on liver as orchestrator of interorgan substrate fluxes and driver of the transition from normo- to hyperglycemia. This proposal aims at investigating hepatic glucose and energy flux in T2D with focus on gluconeogenic contribution of lactate to hepatic mitochondrial substrate flux, the activity of the redox shuttle and mitochondrial ATP synthase flux, also after inhibition by metformin by using a novel combination of positional isotopomer nuclear magnetic resonance (NMR) analysis (PINTA) with multinuclei magnetic resonance spectroscopy (MRS). ;

Study Design

Related Conditions & MeSH terms

Clinical Trial Details
NCT number NCT04088851
Study type Interventional
Source German Diabetes Center
Contact
Status Enrolling by invitation
Phase N/A
Start date September 11, 2019
Completion date December 31, 2024
View Details
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