Clinical trial NCT02497651: Effect of Smoking on Postprandial Gastric Emptying, Glucose Tolerance and Secretion of Gut and Pancreatic Hormones
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus
Keywords: Smoking
Diabetes
Incretin hormones
Glucose tolerance
Lead sponsor: University Hospital, Gentofte, Copenhagen
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: European Foundation for the Study of Diabetes
First posted: 2015-07-14
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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

Primary outcomes:
measure: Postprandial response of glucagon-like peptide-1 (GLP-1)
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
Secondary outcomes:
measure: Postprandial response of insulin
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Postprandial response of Glukagon
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Postprandial response of CCK
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Postprandial response of Gastrin
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Postprandial response of GIP
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Postprandial increment in plasma glucose
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Blood Inflammatory and metabolic markers (composite)
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min)
measure: Gall bladder volume
timeFrame: -30, 20, 40, 80, 240 minutes (meal tests start at 0 min)
measure: Gastric emptying
timeFrame: -30, -20, -10, 0, 10, 20, 30, 50, 70, 90, 120, 150, 180, 240 minutes (meal tests start at 0 min
measure: GLP-1 receptor expression in the skin
timeFrame: After the 240 minutes
Other outcomes:
Locations:
city: Hellerup
country: Denmark
facility: Center for Diabetes Research, Department of Medicine, Gentofte Hospital
state: Copenhagen
Study officials:
References:
citation: Grondahl MF, Bagger JI, Lund A, Faurschou A, Rehfeld JF, Holst JJ, Vilsboll T, Knop FK. Effects of Smoking Versus Nonsmoking on Postprandial Glucose Metabolism in Heavy Smokers Compared With Nonsmokers. Diabetes Care. 2018 Jun;41(6):1260-1267. doi: 10.2337/dc17-1818. Epub 2018 Mar 30.