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

Study Overview
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Brief Summary
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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
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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.

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Dietary Supplement: Liquid mixed meal
* Other: Skin Biopsy


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy, heavy smoking men<br>Twelve healthy, male subjects. Intervention: Will undergo two separate, identical test days. One absent smoking, and one with concomitant smoking. | Dietary Supplement: Liquid mixed meal<br>* The subjects will ingest a 400 ml chocolate drink, rich on carbohydrates, fat and lipids. In the following 4 hours, blood samples will be drawn from a PVC for the measurement of plasma glucose, gut- and pancreatic hormones, acetaminophen etc. After the 4 hours, the subjects will be offered an ad libitum meal.<br>Other: Skin Biopsy<br>* All subjects will undergo a skin biopsy procedure. Two small (3 mm) biopsies will be taken from the hip area under local anaesthesia. Standard wound treatment will follow.<br>|
| Experimental: Healthy, non-smoking men<br>Twelve healthy, male subjects. Intervention: Will undergo a liquid mixed meal test and a skin biopsy. | Dietary Supplement: Liquid mixed meal<br>* The subjects will ingest a 400 ml chocolate drink, rich on carbohydrates, fat and lipids. In the following 4 hours, blood samples will be drawn from a PVC for the measurement of plasma glucose, gut- and pancreatic hormones, acetaminophen etc. After the 4 hours, the subjects will be offered an ad libitum meal.<br>Other: Skin Biopsy<br>* All subjects will undergo a skin biopsy procedure. Two small (3 mm) biopsies will be taken from the hip area under local anaesthesia. Standard wound treatment will follow.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial response of glucagon-like peptide-1 (GLP-1) | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postprandial response of insulin | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| Postprandial response of Glukagon | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| Postprandial response of CCK | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| Postprandial response of Gastrin | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| Postprandial response of GIP | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| Postprandial increment in plasma glucose | Incremental and total area under the Concentration-Time Curve (AUC 0-240 min) | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min) | 
| 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 | Assessment of gall bladder volume will be mediated by ultrasound | -30, 20, 40, 80, 240 minutes (meal tests start at 0 min) | 
| Gastric emptying | Measurement of acetaminophen is taken as a measure of gastric emptying | -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min | 
| GLP-1 receptor expression in the skin | Analysis of the skin cells from the biopsies. | After the 240 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Smoking, Diabetes, Incretin hormones, Glucose tolerance