Search Results
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Search for other papers by David P Sonne in
Google Scholar
PubMed
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Search for other papers by Asger Lund in
Google Scholar
PubMed
Search for other papers by Jens Faber in
Google Scholar
PubMed
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Department of Medicine, Department of Biomedical Sciences, Department of Endocrinology, Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900 Hellerup, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Bile acids are possible candidate agents in newly identified pathways through which energy expenditure may be regulated. Preclinical studies suggest that bile acids activate the enzyme type 2 iodothyronine deiodinase, which deiodinates thyroxine (T4) to the biologically active triiodothyronine (T3). We aimed to evaluate the influence of bile acid exposure and incretin hormones on thyroid function parameters in patients with type 2 diabetes. Thyroid-stimulating hormone (TSH) and thyroid hormones (total T3 and free T4) were measured in plasma from two human studies: i) 75 g-oral glucose tolerance test (OGTT) and three isocaloric (500 kcal) and isovolaemic (350 ml) liquid meals with increasing fat content with concomitant ultrasonographic evaluation of gallbladder emptying in 15 patients with type 2 diabetes and 15 healthy age, gender and BMI-matched controls (meal-study) and ii) 50 g-OGTT and isoglycaemic intravenous glucose infusions (IIGI) alone or in combination with glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1) and/or GLP2, in ten patients with type 2 diabetes (IIGI-study). In both studies, TSH levels declined (P<0.01) similarly following all meal and infusion stimuli. T3 and T4 concentrations did not change in response to any of the applied stimuli. TSH levels declined independently of the degree of gallbladder emptying (meal-study), route of nutrient administration and infusion of gut hormones. In conclusion, intestinal bile flow and i.v. infusions of the gut hormones, GIP, GLP1 and/or GLP2, do not seem to affect thyroid function parameters. Thus, the presence of a ‘gut–thyroid–pituitary’ axis seems questionable.
Search for other papers by Nicolai J Wewer Albrechtsen in
Google Scholar
PubMed
NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Department of Science, Faculty of Health Science, University of Copenhagen, Blegdamsvej 3B, 12.2, DK‐2200 Copenhagen N, Denmark
Search for other papers by Monika J Bak in
Google Scholar
PubMed
Search for other papers by Bolette Hartmann in
Google Scholar
PubMed
Search for other papers by Louise Wulff Christensen in
Google Scholar
PubMed
Search for other papers by Rune E Kuhre in
Google Scholar
PubMed
Search for other papers by Carolyn F Deacon in
Google Scholar
PubMed
Search for other papers by Jens J Holst in
Google Scholar
PubMed
To investigate the stability of glucagon-like peptide 1 (GLP-1) and glucagon in plasma under short- and long-term storage conditions. Pooled human plasma (n=20), to which a dipeptidyl peptidase 4 (DPP4) inhibitor and aprotinin were added, was spiked with synthetic GLP-1 (intact, 7–36NH2 as well as the primary metabolite, GLP-1 9–36NH2) or glucagon. Peptide recoveries were measured in samples kept for 1 and 3 h at room temperature or on ice, treated with various enzyme inhibitors, after up to three thawing–refreezing cycles, and after storage at −20 and −80 °C for up to 1 year. Recoveries were unaffected by freezing cycles or if plasma was stored on ice for up to 3 h, but were impaired when samples stood at RT for more than 1 h. Recovery of intact GLP-1 increased by addition of a DPP4 inhibitor (no ice), but was not further improved by neutral endopeptidase 24.11 inhibitor or an inhibitor cocktail. GLP-1, but not glucagon, was stable for at least 1 year. Surprisingly, the recovery of glucagon was reduced by almost 50% by freezing compared with immediate analysis, regardless of storage time. Plasma handling procedures can significantly influence results of subsequent hormone analysis. Our data support addition of DPP4 inhibitor for GLP-1 measurement as well as cooling on ice of both GLP-1 and glucagon. Freeze–thaw cycles did not significantly affect stability of GLP-1 or glucagon. Long-term storage may affect glucagon levels regardless of storage temperature and results should be interpreted with caution.
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Search for other papers by Bjarke R Medici in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Birte Nygaard in
Google Scholar
PubMed
Search for other papers by Jeppe L la Cour in
Google Scholar
PubMed
Department of Clinical Physiology and Nuclear Medicine, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Martin Krakauer in
Google Scholar
PubMed
Department of Clinical Pharmacology, Bispebjerg and Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Andreas Brønden in
Google Scholar
PubMed
Search for other papers by Mette P Sonne in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Search for other papers by Jens F Rehfeld in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens Faber in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Context
In individuals with hypothyroidism and overweight, levothyroxine substitution therapy is often expected to cause weight loss due to its effect on resting energy expenditure. However, despite levothyroxine-induced enhancement of resting energy expenditure, fat mass loss is rarely seen after levothyroxine substitution therapy. The mechanism behind this conundrum is unknown.
Aim
The aim of the study was to assess the effect of levothyroxine therapy on hunger sensations and ad libitum food intake in individuals with hypothyroidism.
Design and setting
Prospective cohort study of 18 newly diagnosed hypothyroid women (thyroid-stimulating hormone (TSH) >10 mU/L). Participants were investigated at diagnosis, after normalization of TSH (<4.0 mU/L), and after 6 months of successful treatment. Eighteen age and body mass index-matched healthy controls were also included.
Intervention
Hypothyroid individuals were treated with levothyroxine according to European Thyroid Association guidelines.
Main outcomes
Changes in hunger sensation were assessed using visual analog scales (cm) before and during a standardized mixed meal test, and food intake was measured during a subsequent ad libitum meal (g).
Results
After 6 months of levothyroxine therapy, mean resting energy expenditure was increased by 144 kcal/day (10%) (P < 0.001). Weight loss was comprised of 0.8 kg fat-free mass while fat mass remained unchanged. Fasting hunger sensation increased from a mean of 4.5 (s.d. 2.2) cm to 5.5 (s.d. 2.2) cm (P = 0.047). The numerical increase in ad libitum meal intake did not reach statistical significance.
Conclusion
Our data suggest that levothyroxine-induced hunger may be a culprit in the lack of fat mass loss from levothyroxine therapy.
Search for other papers by Justyna Modrzynska in
Google Scholar
PubMed
Search for other papers by Christine F Klein in
Google Scholar
PubMed
Search for other papers by Kasper Iversen in
Google Scholar
PubMed
Search for other papers by Henning Bundgaard in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Bolette Hartmann in
Google Scholar
PubMed
Search for other papers by Maike Mose in
Google Scholar
PubMed
Search for other papers by Nikolaj Rittig in
Google Scholar
PubMed
Search for other papers by Niels Møller in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Nicolai J Wewer Albrechtsen in
Google Scholar
PubMed
Objective
Glucagon and glucagon-like peptide-1 (GLP-1) originate from the common precursor, proglucagon, and their plasma concentrations have been reported to be increased during inflammatory conditions. Increased blood glucose levels are frequently observed in septic patients, and therefore we hypothesized that glucagon, but not GLP-1, is increased in individuals with inflammation.
Design
Prospective longitudinal cohort study.
Materials and methods
We measured glucagon and GLP-1 in plasma sampled consecutively in three cohorts consisting of patients with infective endocarditis (n = 16), urosepsis (n = 28) and post-operative inflammation following percutaneous aortic valve implantation or thoracic endovascular aortic repair (n = 5). Correlations between C-reactive protein (CRP), a marker of systemic inflammation, and glucagon and GLP-1 concentrations were investigated. Additionally, glucagon and GLP-1 concentrations were measured after a bolus infusion of lipopolysaccharide (LPS, 1 ng/kg) in nine healthy young males.
Results
Glucagon and CRP were positively and significantly correlated (r = 0.27; P = 0.0003), whereas no significant association between GLP-1 and CRP was found (r = 0.08, P = 0.30). LPS infusion resulted in acute systemic inflammation reflected by increased temperature, pulse, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6) and concomitantly increased concentrations of glucagon (P < 0.05) but not GLP-1.
Conclusions
Systemic inflammation caused by bacterial infections or developed as a non-infected condition is associated with increased plasma concentration of glucagon, but not GLP-1. Hyperglucagonemia may contribute to the impaired glucose control in patients with systemic inflammatory diseases.
Search for other papers by Peter L Kristensen in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Ulrik Pedersen-Bjergaard in
Google Scholar
PubMed
Lægerne på Ellemarksvej, Køge, Denmark
Search for other papers by Rikke Due-Andersen in
Google Scholar
PubMed
Department of Cardiology, Herlev-Gentofte University Hospital, Herlev, Denmark
Search for other papers by Thomas Høi-Hansen in
Google Scholar
PubMed
Novo Nordisk A/S, Søborg, Denmark
Search for other papers by Lise Grimmeshave in
Google Scholar
PubMed
Lund University Diabetes Centre, Skåne University Hospital, Malmø, Sweden
Search for other papers by Valeriya Lyssenko in
Google Scholar
PubMed
Finnish Institute for Molecular Medicine (FIMM), Helsinki University, Helsinki, Finland
Search for other papers by Leif Groop in
Google Scholar
PubMed
Department of Biomedical Sciences, NNF Center for Basic Metabolic Research, The Panum Institute, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Department of Endocrinology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark
Search for other papers by Allan A Vaag in
Google Scholar
PubMed
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Birger Thorsteinsson in
Google Scholar
PubMed
Introduction
In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM).
Material and methods
This is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined.
Results
Incidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion.
Discussion
Patients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.
Zealand Pharma A/S, Søborg, Denmark
Search for other papers by Iben Rix in
Google Scholar
PubMed
Search for other papers by Marie L Johansen in
Google Scholar
PubMed
Search for other papers by Asger Lund in
Google Scholar
PubMed
Search for other papers by Malte P Suppli in
Google Scholar
PubMed
Search for other papers by Elizaveta Chabanova in
Google Scholar
PubMed
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Gerrit van Hall in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Nicolai J Wewer Albrechtsen in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Caroline Kistorp in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Aims
Hyperglucagonaemia contributes to the pathophysiology in type 2 diabetes (T2D), but the mechanisms behind the inappropriate glucagon secretion are not fully understood. Glucagon and amino acids are regulated in a feedback loop referred to as the liver–α cell axis. Individuals with non-alcoholic fatty liver disease (NAFLD) appear to be glucagon resistant, disrupting the liver–α cell axis resulting in hyperglucagonaemia and hyperaminoacidaemia. We investigated the associations between circulating glucagon, amino acids, and liver fat content in a cohort of individuals with T2D.
Methods
We included 110 individuals with T2D in this cross-sectional study. Liver fat content was quantified using 1H magnetic resonance spectroscopy (MRS). Associations between liver fat content and plasma glucagon and amino acids, respectively, were estimated in multivariate linear regression analyses.
Results
Individuals with NAFLD (n = 52) had higher plasma glucagon concentrations than individuals without NAFLD (n = 58). The positive association between plasma glucagon concentrations and liver fat content was confirmed in the multivariable regression analyses. Plasma concentrations of isoleucine and glutamate were increased, and glycine and serine concentrations were decreased in individuals with NAFLD. Concentrations of other amino acids were similar between individuals with and without NAFLD, and no clear association was seen between liver fat content and amino acids in the regression analyses.
Conclusion
MRS-diagnosed NAFLD in T2D is associated with hyperglucagonaemia and elevated plasma concentrations of isoleucine and glutamate and low plasma concentrations of glycine and serine. Whether NAFLD and glucagon resistance per se induce these changes remains to be elucidated.
Search for other papers by Magnus F G Grøndahl in
Google Scholar
PubMed
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Jonatan I Bagger in
Google Scholar
PubMed
Search for other papers by Malte P Suppli in
Google Scholar
PubMed
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Gerrit Van Hall in
Google Scholar
PubMed
Search for other papers by Nicolai J W Albrechtsen in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Pharmacology, Copenhagen University Hospital – Bispebjerg and Frederiksberg, Copenhagen, Denmark
Copenhagen Center for Translational Research, Copenhagen University Hospital – Bispebjerg and Frederiksberg, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Mikkel B Christensen in
Google Scholar
PubMed
Search for other papers by Asger B Lund in
Google Scholar
PubMed
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Objective
In obesity and type 2 diabetes, hyperglucagonaemia may be caused by elevated levels of glucagonotropic amino acids due to hepatic glucagon resistance at the level of amino acid turnover. Here, we investigated the effect of exogenous glucagon on circulating amino acids in obese and non-obese individuals with and without type 2 diabetes.
Design
This was a post hoc analysis in a glucagon infusion study performed in individuals with type 2 diabetes (n = 16) and in age, sex, and body mass index-matched control individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and without obesity, respectively.
Methods
All participants received a 1-h glucagon infusion (4 ng/kg/min) in the overnight fasted state. Plasma amino acid concentrations were measured with frequent intervals.
Results
Compared to the control subgroup without obesity, baseline total amino acid levels were elevated in the control subgroup with obesity and in the type 2 diabetes subgroup without obesity. In all subgroups, amino acid levels decreased by up to 20% in response to glucagon infusion, which resulted in high physiological steady-state glucagon levels (mean concentration: 74 pmol/L, 95% CI [68;79] pmol/L). Following correction for multiple testing, no intergroup differences in changes in amino acid levels reached significance.
Conclusion
Obesity and type 2 diabetes status was associated with elevated fasting levels of total amino acids. The glucagon infusion decreased circulating amino acid levels similarly in all subgroups, without significant differences in the response to exogenous glucagon between individuals with and without obesity and type 2 diabetes.
Significance statement
The hormone glucagon stimulates glucose production from the liver, which may promote hyperglycaemia if glucagon levels are abnormally elevated, as is often seen in type 2 diabetes and obesity. Glucagon levels are closely linked to, and influenced by, the levels of circulating amino acids. To further investigate this link, we measured amino acid levels in individuals with and without obesity and type 2 diabetes before and during an infusion of glucagon. We found that circulating amino acid levels were higher in type 2 diabetes and obesity, and that glucagon infusion decreased amino acid levels in both individuals with and without type 2 diabetes and obesity. The study adds novel information to the link between circulating levels of glucagon and amino acids.
Search for other papers by Amalie R Lanng in
Google Scholar
PubMed
Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Lærke S Gasbjerg in
Google Scholar
PubMed
Search for other papers by Natasha C Bergmann in
Google Scholar
PubMed
Search for other papers by Sigrid Bergmann in
Google Scholar
PubMed
Search for other papers by Mads M Helsted in
Google Scholar
PubMed
Search for other papers by Matthew P Gillum in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Bolette Hartmann in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Background
Ingestion of the calorically dense compound alcohol may cause metabolic disturbances including hypoglycaemia, hepatic steatosis and insulin resistance, but the underlying mechanisms are uncertain. The gastrointestinal tract is well recognised as a major influencer on glucose, protein and lipid metabolism, but its role in alcohol metabolism remains unclear.
Objective
To examine the effects of oral and intravenous alcohol, respectively, on plasma concentrations of several gluco-regulatory hormones including serum/plasma insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF21).
Design and methods
In a double-blinded, randomised, crossover design, we subjected 12 healthy men to intragastric ethanol infusion (IGEI) and an isoethanolaemic intravenous ethanol infusion (IVEI) (0.7 g alcohol per kg body weight), respectively, on two separate experimental days.
Results
Isoethanolaemia during the two alcohol administration forms was obtained (P = 0.38). During both interventions, plasma glucose peaked after ~30 min and thereafter fell below baseline concentrations. GIP and GLP-1 concentrations were unaffected by the two interventions. Insulin concentrations were unaffected by IGEI but decreased during IVEI. C-peptide, insulin secretion rate and glucagon concentrations were lowered similarly during IGEI and IVEI. FGF21 concentrations increased dramatically (nine-fold) and similarly during IGEI and IVEI.
Conclusions
Alcohol does not seem to affect the secretion of incretin hormones but decreased insulin and glucagon secretion independently of gut-derived factors. IGEI as well as IVEI potently stimulate FGF21 secretion indicating a gut-independent effect of alcohol on FGF21 secretion in humans.
Danish Diabetes Academy, Odense University Hospital, Odense, Denmark
Search for other papers by Charlotte Janus in
Google Scholar
PubMed
Search for other papers by Dorte Vistisen in
Google Scholar
PubMed
Department of Public Health, Research Unit of Epidemiology, Aarhus University, Aarhus, Denmark
Search for other papers by Hanan Amadid in
Google Scholar
PubMed
Department of Public Health, Research Unit of Epidemiology, Aarhus University, Aarhus, Denmark
Steno Diabetes Center Aarhus, Aarhus, Denmark
Search for other papers by Daniel R Witte in
Google Scholar
PubMed
Search for other papers by Torsten Lauritzen in
Google Scholar
PubMed
Search for other papers by Søren Brage in
Google Scholar
PubMed
Search for other papers by Anne-Louise Bjerregaard in
Google Scholar
PubMed
Search for other papers by Torben Hansen in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
National Institute of Public Health, University of Southern Denmark, Odense, Denmark
Search for other papers by Marit E Jørgensen in
Google Scholar
PubMed
Search for other papers by Oluf Pedersen in
Google Scholar
PubMed
Search for other papers by Kristine Færch in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Signe S Torekov in
Google Scholar
PubMed
Rationale
The hormone glucagon-like peptide-1 (GLP-1) decreases blood glucose and appetite. Greater physical activity (PA) is associated with lower incidence of type 2 diabetes. While acute exercise may increase glucose-induced response of GLP-1, it is unknown how habitual PA affects GLP-1 secretion. We hypothesised that habitual PA associates with greater glucose-induced GLP-1 responses in overweight individuals.
Methods
Cross-sectional analysis of habitual PA levels and GLP-1 concentrations in 1326 individuals (mean (s.d.) age 66 (7) years, BMI 27.1 (4.5) kg/m2) from the ADDITION-PRO cohort. Fasting and oral glucose-stimulated GLP-1 responses were measured using validated radioimmunoassay. PA was measured using 7-day combined accelerometry and heart rate monitoring. From this, energy expenditure (PAEE; kJ/kg/day) and fractions of time spent in activity intensities (h/day) were calculated. Cardiorespiratory fitness (CRF; mL O2/kg/min) was calculated using step tests. Age-, BMI- and insulin sensitivity-adjusted associations between PA and GLP-1, stratified by sex, were evaluated by linear regression analysis.
Results
In 703 men, fasting GLP-1 concentrations were 20% lower (95% CI: −33; −3%, P = 0.02) for every hour of moderate-intensity PA performed. Higher CRF and PAEE were associated with 1–2% lower fasting GLP-1 (P = 0.01). For every hour of moderate-intensity PA, the glucose-stimulated GLP-1 response was 16% greater at peak 30 min (1; 33%, P rAUC0-30 = 0.04) and 20% greater at full response (3; 40%, P rAUC0-120 = 0.02). No associations were found in women who performed PA 22 min/day vs 32 min/day for men.
Conclusion
Moderate-intensity PA is associated with lower fasting and greater glucose-induced GLP-1 responses in overweight men, possibly contributing to improved glucose and appetite regulation with increased habitual PA.
Search for other papers by Kim K B Clemmensen in
Google Scholar
PubMed
Search for other papers by Jonas S Quist in
Google Scholar
PubMed
Search for other papers by Dorte Vistisen in
Google Scholar
PubMed
Danish Diabetes Academy, Odense, Denmark
Search for other papers by Daniel R Witte in
Google Scholar
PubMed
Search for other papers by Anna Jonsson in
Google Scholar
PubMed
Search for other papers by Oluf Pedersen in
Google Scholar
PubMed
Search for other papers by Torben Hansen in
Google Scholar
PubMed
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens J Holst in
Google Scholar
PubMed
Search for other papers by Torsten Lauritzen in
Google Scholar
PubMed
National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
Search for other papers by Marit E Jørgensen in
Google Scholar
PubMed
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Signe Torekov in
Google Scholar
PubMed
Search for other papers by Kristine Færch in
Google Scholar
PubMed
