Clinical trial NCT00364767: Moderate Alcohol Consumption, Fat and Carbohydrate Metabolism and Insulin Sensitivity
Official title: The Effect of Moderate Alcohol Consumption on Markers of Oxidative Phosphorylation and Lipid Oxidation and on Postprandial Glycemic Control in Healthy, Lean and Overweight, Young Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Cardiovascular Disease
Keywords: Moderate alcohol consumption
Fat and carbohydrate oxidative capacity
Postprandial glycemic response
Lead sponsor: TNO
Sponsor class: OTHER
Collaborators: name: Dutch Foundation for alcohol research
First posted: 2006-08-16
Enrollment: 19
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: PREVENTION

Brief summary: Moderate alcohol consumption is associated with a decreased risk of diabetes type 2. This association could be mediated by an improvement of insulin sensitivity with moderate alcohol consumption. Patients with diabetes type 2 or impaired glucose tolerance often may have decreased fat oxidative capacity or oxidative phosphorylation in tissue such as muscle. This could lead to accumulation triglyceride storage in muscle, which could interfere with insulin signaling. Whether such mechanism can also play a role with moderate alcohol consumption is unknown and will be investigated in this study.

In addition, moderate alcohol consumption with a meal can lead to delayed hypoglycemia in type 1 diabetes patients. How moderate alcohol consumption affects postprandial glycemic response in healthy subjects is unknown. This is a secondary objective of this trial.

Detailed description: To investigate the effect of moderate alcohol consumption on

* enzymes involved in fatty acid oxidation, oxidative phosphorylation and glycolysis in skeletal muscle
* transporters of fatty acids and glucose in fat tissue
* post-prandial glycemic response in healthy, lean or overweight, young men

Design : Open, randomized, partially diet-controlled, placebo controlled cross-over design

Participants

* Description : Healthy, lean and overweight young (18-40 years) men
* Number : 20

Study substances

* Test substance : 100 ml whiskey (Famous Grouse, 40% v/v alcohol: ≈ 32 g alcohol)
* Reference substance : 100 ml mineral water (Spa blauw)

Duration: 2 treatment periods of 4 weeks (28 days)

Test parameters:

* Muscle biopsy for activity of 3-hydroxy fatty-acyl CoA dehydrogenase, citrate synthase, cytochrome c oxidase
* Postprandial glycemic response (glucose, insulin, GLP-1, GLP-2, GIP, glucagon, FFA etc.)
* Insulin sensitivity and related factors (oral glucose tolerance test, adiponectin, HbA1c)
* Liver enzymes (safety)
* Body weight
* Urinary ethyl glucuronide (compliance)

Eligibility criteria: Inclusion Criteria:

* Healthy men aged between 18 and 40 years
* Lean subjects BMI 18.5-25 kg/m2 and overweight/obese subjects BMI \>27 kg/m2 (including 18.5, 25 and 27)
* Alcohol consumption between 7 and 28 units/week (including 7 and 28)

Exclusion Criteria:

* Smoking
* Family history of alcoholism
* History of medical or surgical events that may significantly affect the study outcome, particularly metabolic or endocrine disorders and gastrointestinal disorders
* Recent blood donation
* More than 8 hours/week of intense exercise
* Blood haemoglobin concentration below 8.4 mmol/l
* Allergic to betadine or lidocaine.

Primary outcomes:
measure: enzymes involved in fatty acid oxidation, oxidative phosphorylation and glycolysis in skeletal muscle
timeFrame: 4 weeks
Secondary outcomes:
measure: Post-prandial glycemic response
timeFrame: 4 weeks
measure: insulin sensitivity (oral glucose tolerance test) and related factors (adiponectin, HbA1c)
timeFrame: 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: TNO
name: Henk FJ Hendriks, PhD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Beulens JW, van Loon LJ, Kok FJ, Pelsers M, Bobbert T, Spranger J, Helander A, Hendriks HF. The effect of moderate alcohol consumption on adiponectin oligomers and muscle oxidative capacity: a human intervention study. Diabetologia. 2007 Jul;50(7):1388-92. doi: 10.1007/s00125-007-0699-8. Epub 2007 May 11.