Effect of Smoking on Postprandial Gastric Emptying, Glucose Tolerance and Secretion of Gut and Pancreatic Hormones (SmokinGLP-1)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Dietary supplement: Liquid mixed meal; Other: Skin Biopsy

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen
    • Hellerup, Copenhagen, Denmark, 2900
      • Center for Diabetes Research, Department of Medicine, Gentofte Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy, heavy smoking men; 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; 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.; Other: Skin Biopsy; 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.
Experimental: Healthy, non-smoking men; Twelve healthy, male subjects. Intervention: Will undergo a liquid mixed meal test and a skin biopsy.	Dietary supplement: Liquid mixed meal; 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.; Other: Skin Biopsy; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Gentofte, Copenhagen
• Collaborators: University of Copenhagen; European Foundation for the Study of Diabetes

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 25, 2015
• First Submitted That Met QC Criteria: July 13, 2015
• First Posted (Estimate): July 14, 2015

Study Record Updates

• Last Update Posted (Actual): August 7, 2017
• Last Update Submitted That Met QC Criteria: August 4, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: Diabetes; Smoking; Glucose tolerance; Incretin hormones
• Other Study ID Numbers: h-1-2013-042