Day-night Rhythm in Muscle Metabolism of Prediabetics

Maastricht University12 enrolled

Overview

This study evaluates the existence of a day-night rhythm in skeletal muscle energy metabolism in prediabetic subjects. Subjects will stay at the research facility for 44 hours with a standardized living protocol during which several measurements of skeletal muscle and whole body energy metabolism will be performed.

Recent evidence from both observational and experimental studies indicates that disobedience of a normal day-night rhythm negatively influences metabolic and cardiovascular health, possibly leading to obesity and type 2 diabetes mellitus (T2DM). An important hallmark of obesity and T2DM is a decreased skeletal muscle mitochondrial function. Interestingly, recent research indicates that also skeletal muscle mitochondrial function is under the influence of a day-night rhythm. In this study, the presence of a day-night rhythm in skeletal muscle energy metabolism (in particular mitochondrial function) of overweight prediabetic participants will be investigated. During this study, subjects will stay at the research unit for 44 hours, with standardized meals and sleeping time. Five muscle biopsies (v. lateralis) and frequent blood draws will be taken. In addition, indirect calorimetry measurements will be performed.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Masking

NONE

Enrollment

Conditions

Diabetes Mellitus, Type 2 Insulin Resistance

Interventions

Standardized living protocolOTHER

Subjects stay at the research facility for 44 hours and adhere to a standard sleeping, eating and activity protocol. During this protocol, multiple measurements will be performed including skeletal muscle biopsies (m. vastus lateralis), blood draws, indirect calorimetry and MRS measurements.

Eligibility

Sex: MALEMin age: 40 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria: * Caucasian * Healthy (as determined by dependent physician) * Overweight: BMI 25 - 35 kg/m2 * Prediabetic based on one or a combination of the following criteria: * Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after glucose drink consumption during OGTT in screening. * Impaired Fasting Glucose (IFG): Fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l. * Insulin Resistance: glucose clearance rate ≤ 360ml/kg/min, as determined using the OGIS120 model. * HbA1c of 5.7-6.4%. * Regular sleeping time (normally 7 - 9h daily) * Stable dietary habits: no weight gain or loss \> 3kg in the last three months. Exclusion criteria: * Use of anticoagulants * Previously diagnosed with type 2 diabetes * Current alcohol consumption \> 20 grams alcohol/day * Extreme early bird or extreme night person (score ≤ 30 or ≥ 70 on MEQ-SA questionnaire) * Heavily varying sleep-wake rhythm * Nightshift work during last 3 months * Travel across \> 1 time zone in the last 3 months * Significant food allergies/intolerance (seriously hampering study meals) * Using \> 400mg caffeine daily (more than 4 coffee or energy drink) * Smoking

Locations (1)

Maastricht University

Maastricht, Limburg, Netherlands