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Effect of Smoking on Postprandial Gastric Emptying, Glucose Tolerance and Secretion of Gut and Pancreatic Hormones

Not Applicable
Completed
Conditions
Diabetes Mellitus
Interventions
Dietary Supplement: Liquid mixed meal
Other: Skin Biopsy
Registration Number
NCT02497651
Lead Sponsor
University Hospital, Gentofte, Copenhagen
Brief Summary

The study aims to evaluate the effect of smoking on postprandial responses such as plasma glucose, secretion of gut - and pancreatic hormones and gastric emptying in healthy, heavy smoking men.

Detailed Description

Epidemiological studies show that active smoking increases the risk of type 2 diabetes in a dose-dependent fashion. Smokers seem to be characterized by central obesity, increased inflammatory markers and oxidative stress, which may lead to insulin resistance and irregularities in glucose metabolism. The current study is a meal test study, in which the aim is to examine a number of variables during a liquid mixed meal test (including gastric emptying, glucose tolerance, gut and pancreatic hormone responses, gall bladder emptying, appetite and food intake) performed in healthy non-smoking subjects and in healthy smokers with or without concomitant cigarette smoking.

The investigators hypothesize that smoking-induced increases in circulating nicotine levels and simultaneous activation of nicotinic receptors in the gastrointestinal tract and in the autonomic nervous system would have detrimental effect on postprandial glucose metabolism and, thus, constitute an important link between smoking and the risk of type 2 diabetes. The current study will help to clarify this hypothesis and improve our general understanding of the association between smoking and gut hormone secretion, gastric emptying and glucose metabolism.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
24
Inclusion Criteria
  • Both groups

    • Caucasian ethnicity
    • Healthy males
    • Normal haemoglobin
    • Age above 18 years
    • Informed and written consent
    • BMI >20 kg/m2

Smokers • Minimum 20 cigarettes pr. day for at least 1 year

Non-smokers

• No smoking on a regular basis

Exclusion Criteria
  • Both groups

    • Diabetes or prediabetes (fasting plasma glucose levels >6.5 mM or HbA1c >6.0%)
    • First- or second-degree relatives with diabetes
    • Liver disease (alanine aminotransferase (ALAT) and/or serum aspartate aminotransferase (ASAT) >2 times normal values) or history of hepatobiliary disorder
    • Gastrointestinal disease, previous intestinal resection, cholecystectomy or any major intra-abdominal surgery
    • Hypo- or hyperphosphataemia
    • Nephropathy (serum creatinine >150 µM and/or albuminuria
    • Treatment with medicine that cannot be paused for 12 hours
    • Hypo- or hypercalcaemia
    • Hypo- and hyperthyroidism
    • Treatment with oral anticoagulants
    • Active or recent malignant disease
    • Any treatment or condition requiring acute or sub-acute medical or surgical intervention
    • Any condition considered incompatible with participation by the investigators

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Healthy, heavy smoking menSkin BiopsyTwelve healthy, male subjects. Intervention: Will undergo two separate, identical test days. One absent smoking, and one with concomitant smoking.
Healthy, heavy smoking menLiquid mixed mealTwelve healthy, male subjects. Intervention: Will undergo two separate, identical test days. One absent smoking, and one with concomitant smoking.
Healthy, non-smoking menLiquid mixed mealTwelve healthy, male subjects. Intervention: Will undergo a liquid mixed meal test and a skin biopsy.
Healthy, non-smoking menSkin BiopsyTwelve healthy, male subjects. Intervention: Will undergo a liquid mixed meal test and a skin biopsy.
Primary Outcome Measures
NameTimeMethod
Postprandial response of glucagon-like peptide-1 (GLP-1)-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Secondary Outcome Measures
NameTimeMethod
Postprandial response of Gastrin-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Gastric emptying-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min

Measurement of acetaminophen is taken as a measure of gastric emptying

GLP-1 receptor expression in the skinAfter the 240 minutes

Analysis of the skin cells from the biopsies.

Blood Inflammatory and metabolic markers (composite)-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
Gall bladder volume-30, 20, 40, 80, 240 minutes (meal tests start at 0 min)

Assessment of gall bladder volume will be mediated by ultrasound

Postprandial response of Glukagon-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Postprandial response of CCK-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Postprandial response of GIP-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Postprandial increment in plasma glucose-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Postprandial response of insulin-30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)

Incremental and total area under the Concentration-Time Curve (AUC 0-240 min)

Trial Locations

Locations (1)

Center for Diabetes Research, Department of Medicine, Gentofte Hospital

🇩🇰

Hellerup, Copenhagen, Denmark

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