50 results on '"Kristian Karstoft"'
Search Results
2. Pharmacological but not physiological GDF15 suppresses feeding and the motivation to exercise
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Mark Lyngbæk, Rasmus Jensen, Andreas M. Fritzen, Anders B. Klein, Sarah Falk, Niels Ørtenblad, Christoffer Clemmensen, Henrik E. Poulsen, Ronni E. Sahl, Maximilian Kleinert, Jens Lund, Randy J. Seeley, Emil List Larsen, Kasper Degn Gejl, Brian Finan, Bente Klarlund Pedersen, Jørn Wulff Helge, Helga Ellingsgaard, Erik A. Richter, Bente Kiens, Trine S. Nicolaisen, Kristian Karstoft, Sebastian Beck Jørgensen, Wei Lu, and Thomas Morville
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Leptin ,Male ,0301 basic medicine ,Time Factors ,General Physics and Astronomy ,Endogeny ,Energy homeostasis ,Mice ,0302 clinical medicine ,Glial cell line-derived neurotrophic factor ,Homeostasis ,Receptor ,Creatine Kinase ,media_common ,Mice, Knockout ,Multidisciplinary ,Molecular medicine ,biology ,Interleukin-10 ,medicine.anatomical_structure ,Liver ,Adult ,medicine.medical_specialty ,Glial Cell Line-Derived Neurotrophic Factor Receptors ,Growth Differentiation Factor 15 ,media_common.quotation_subject ,Science ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Endurance training ,Physical Conditioning, Animal ,Internal medicine ,medicine ,Animals ,Humans ,Exercise physiology ,Muscle, Skeletal ,Exercise ,Motivation ,Appetite Regulation ,Interleukin-6 ,business.industry ,Myocardium ,Skeletal muscle ,Appetite ,Feeding Behavior ,General Chemistry ,030104 developmental biology ,Endocrinology ,Gene Expression Regulation ,Physical Endurance ,biology.protein ,GDF15 ,business ,030217 neurology & neurosurgery - Abstract
Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation., The physiological role of GDF15 remains poorly defined. Here, the authors show that circulating GDF15 increases in response to prolonged exercise, but that this exercise-induced GDF15, unlike pharmacological GDF15, does not affect post-exercise food intake or exercise motivation.
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- 2021
3. Differential time responses in inflammatory and oxidative stress markers after a marathon: An observational study
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Thorkil Ploug, Christina Petersen-Bønding, Cristina Michaelsen, Kristian Karstoft, Niklas Rye Jørgensen, Laura Kofoed Kjær, Emilie S. Andersen, Clara Lemoine, Tina Vilsbøll, Filip K. Knop, Henrik E. Poulsen, Emil List Larsen, Mark Lyngbæk, and Matthew P. Gillum
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Male ,medicine.medical_specialty ,Time Factors ,FGF21 ,030209 endocrinology & metabolism ,Physical Therapy, Sports Therapy and Rehabilitation ,Adaptive change ,Inflammation ,medicine.disease_cause ,Running ,Bone remodeling ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,Chemistry ,030229 sport sciences ,Oxidative Stress ,Endocrinology ,8-Hydroxy-2'-Deoxyguanosine ,Creatinine ,Physical Endurance ,Nucleic acid ,Cytokines ,Bone Remodeling ,medicine.symptom ,Biomarkers ,Oxidative stress - Abstract
Acute and adaptive changes in systemic markers of oxidatively generated nucleic acid modifications (i.e., 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo)) as well as inflammatory cytokines (i.e., C-reactive protein, interleukin-6, interleukin-10, and tumour necrosis factor alpha), a liver hormone (i.e., fibroblast growth factor 21 (FGF21)), and bone metabolism markers (sclerostin, osteocalcin, C-terminal telopeptide, and N-terminal propeptide of type 1 procollagen) were investigated following a marathon in 20 study participants. Immediate changes were observed in inflammatory cytokines, FGF21, and bone metabolism markers following the marathon. In contrast, no immediate changes in urinary excretion of 8-oxodG and 8-oxoGuo were evident. Four days after the marathon, decreased urinary excretion of 8-oxodG (-2.9 (95% CI -4.8;-1.1) nmol/24 h,8-oxodG: 8-oxo-7,8-dihydro-2'-deoxyguanosine; 8-oxoGuo: 8-oxo-7,8-dihydroguanosine; CI: confidence interval; CTX: C-terminal telopeptide of type 1 collagen; DXA: dual-energy X-ray absorptiometry; ELISA: enzyme-linked immunosorbent assay; FGF21: Fibroblast growth factor 21; h: hour; hsCRP: high sensitivity C-reactive protein; IL: interleukin; IQR: interquartile range; MS: mass spectrometry: P1NP: N-terminal propeptide of type 1 procollagen; TNFα: tumour necrosis factor alpha; UPLC: ultra-performance liquid chromatography.
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- 2020
4. Skeletal muscle adaptations to exercise are not influenced by metformin treatment in humans: secondary analyses of 2 randomised, clinical trials
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Grit Elster, Christina Pedersen Bønding, Nanna Skytt Pilmark, Jesper B. Birk, Henriette Pilegaard, Laura Oberholzer, Mark Lyngbæk, Katrine B. Hansen, Niels Frederich Holm, Anne-Kristine Meinild-Lundby, Ida Elkjær, Jonas M. Kristensen, Emil List Larsen, Henrik E. Poulsen, Kristian Karstoft, Christoph Siebenmann, Bente Klarlund Pedersen, Jens Frey Halling, and Jørgen F. P. Wojtaszewski
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Male ,AMPK ,medicine.medical_specialty ,endocrine system diseases ,Interaction ,Physiology ,Endocrinology, Diabetes and Metabolism ,Skeletal muscle ,medicine.disease_cause ,Complex-1 ,law.invention ,Randomized controlled trial ,law ,Physiology (medical) ,Internal medicine ,medicine ,Faculty of Science ,Humans ,Training ,Muscle, Skeletal ,Exercise ,Glycemic ,chemistry.chemical_classification ,Reactive oxygen species ,Nutrition and Dietetics ,business.industry ,nutritional and metabolic diseases ,Impaired glucose tolerance ,ROS ,General Medicine ,Adaptation, Physiological ,Metformin ,Clinical trial ,Healthy lean males ,Glucose ,medicine.anatomical_structure ,Endocrinology ,chemistry ,business ,Prediabetes ,Oxidative stress ,medicine.drug - Abstract
Metformin and exercise both improve glycemic control, but in vitro studies have indicated that an interaction between metformin and exercise occurs in skeletal muscle, suggesting a blunting effect of metformin on exercise training adaptations. Two studies (a double-blind, parallel-group, randomized clinical trial conducted in 29 glucose-intolerant individuals and a double-blind, cross-over trial conducted in 15 healthy lean males) were included in this paper. In both studies, the effect of acute exercise ± metformin treatment on different skeletal muscle variables, previously suggested to be involved in a pharmaco-physiological interaction between metformin and exercise, was assessed. Furthermore, in the parallel-group trial, the effect of 12 weeks of exercise training was assessed. Skeletal muscle biopsies were obtained before and after acute exercise and 12 weeks of exercise training, and mitochondrial respiration, oxidative stress and AMPK activation was determined. Metformin did not significantly affect the effects of acute exercise or exercise training on mitochondrial respiration, oxidative stress or AMPK activation, indicating that the response to acute exercise and exercise training adaptations in skeletal muscle is not affected by metformin treatment. Further studies are needed to investigate whether an interaction between metformin and exercise is present in other tissues, e.g., the gut. Trial registration: ClinicalTrials.gov (NCT03316690 and NCT02951260). Novelty: Metformin does not affect exercise-induced alterations in mitochondrial respiratory capacity in human skeletal muscle. Metformin does not affect exercise-induced alterations in systemic levels of oxidative stress nor emission of reactive oxygen species from human skeletal muscle. Metformin does not affect exercise-induced AMPK activation in human skeletal muscle.
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- 2022
5. Amino Acid Metabolism and Protein Turnover in Lean and Obese Humans During Exercise-Effect of IL-6 Receptor Blockade
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Beckey Trinh, Merel Peletier, Casper Simonsen, Peter Plomgaard, Kristian Karstoft, Bente Klarlund Pedersen, Gerrit van Hall, and Helga Ellingsgaard
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Endocrinology ,Interleukin-6 ,Endocrinology, Diabetes and Metabolism ,Phenylalanine ,Biochemistry (medical) ,Clinical Biochemistry ,Humans ,Single-Blind Method ,Obesity ,Amino Acids ,Muscle, Skeletal ,Biochemistry ,Receptors, Interleukin-6 - Abstract
Context Interleukin-6 (IL-6) is implicated in skeletal muscle wasting and in regulating skeletal muscle hypertrophy in the healthy state. Objective This work aimed to determine the role of IL-6 in regulating systemic protein and amino acid metabolism during rest, exercise, and recovery in lean and obese humans. Methods In a nonrandomized, single-blind design, 12 lean and 9 obese individuals were infused first with 0.9% saline (Saline), secondly with the IL-6 receptor antibody tocilizumab (Acute IL-6R ab), and 21 days later with saline while still under tocilizumab influence (Chronic IL-6R ab). Outcome measures were determined before, during, and after 90 minutes of exercise at 40% Wattmax by isotope dilution technique, using primed continuous infusion of L-[ring-D5]phenylalanine and L-[D2]tyrosine. Main outcomes measures included systemic protein turnover and plasma amino acid concentrations. Results We saw no effect of acute or chronic IL-6 receptor blockade on protein turnover. In lean individuals, chronic IL-6 receptor blockade increased plasma concentrations of total amino acids (rest Δ + 186 μmol/L; 95% CI, 40-332; recovery Δ + 201 μmol/L; 95% CI, 55-347) and essential amino acids (rest Δ + 43 μmol/L; 95% CI, 12-76; recovery Δ + 45 μmol/L; 95% CI, 13-77) independently of exercise but had no such effect in obese individuals (total amino acids rest Δ + 63 μmol/L; 95% CI, –170 to 295, recovery Δ – 23 μmol/L, 95% CI, –256 to 210; essential amino acids rest Δ + 26 μmol/L; 95% CI, –21 to 73, recovery Δ + 11 μmol/L; 95% CI, –36 to 58). Conclusion IL-6 receptor blockade has no effect on protein turnover in fasting lean and obese humans during rest, exercise, and recovery. Chronic IL-6 receptor blockade increases total and essential amino acid concentrations only in lean individuals.
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- 2021
6. The effect of frequency of activity interruptions in prolonged sitting on postprandial glucose metabolism: A randomized crossover trial
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Cecilie Fau Brinkløv, Kristian Karstoft, Bente Klarlund Pedersen, Fabiana Braga Benatti, David W. Dunstan, Nanna Skytt Pilmark, Mette Y. Johansen, Naja Z. Jespersen, Mathias Ried-Larsen, and Ida Kær Thorsen
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Adult ,Blood Glucose ,Male ,0301 basic medicine ,medicine.medical_specialty ,Percentile ,Anaerobic Threshold ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Walking ,Carbohydrate metabolism ,Sitting ,Body Mass Index ,Young Adult ,03 medical and health sciences ,postprandial glucose metabolism ,0302 clinical medicine ,Endocrinology ,substrate oxidation ,cardiometabolic risk ,Internal medicine ,medicine ,Humans ,Insulin ,Prolonged sitting ,Exercise ,Glycated Hemoglobin ,Sitting Position ,Cross-Over Studies ,C-Peptide ,business.industry ,Area under the curve ,Middle Aged ,Postprandial Period ,Crossover study ,030104 developmental biology ,Postprandial ,postprandial lipid metabolism ,Obesity, Abdominal ,Anesthesia ,Every Hour ,Sedentary Behavior ,business - Abstract
Objective The primary objective was to test the hypothesis that increased frequency of interruptions in prolonged sitting reduces postprandial glycemia independent of energy intake and expenditure. Materials/Methods Healthy, sedentary, centrally obese men (n = 14; age*, 28.2 (23.4; 38.3) years; BMI, 31.9 ± 6.7 kg/m2; VO2max*, 39.5 (38.8; 40.9) ml/min/kg; HbA1c, 5.3 ± 0.4% (34.1 ± 4.2 mmol/mol); mean ± SD (*median (25th; 75th percentile)) completed four 8-h interventions in randomized order: 1) uninterrupted sitting (SIT), 2) sitting interrupted by 2 min of walking (~30% of VO2max) every 20th minute (INT20), 3) sitting interrupted by 6 min of walking every hour (INT60), and 4) sitting interrupted by 12 min of walking every second hour (INT120). A standardized test drink was served at the beginning of and 4 h into the intervention (total of 2310 ± 247 kcal; 50% energy from carbohydrate, 50% energy from fat). Outcomes included the difference in the 8-h total area under the curve (tAUC) for primarily plasma glucose, and secondarily plasma insulin and C-peptide during INT20, INT60, and INT120 compared to SIT. Results No difference [95% CI] was observed in the primary outcome, the 8-h tAUC for the plasma glucose, during INT20, INT60, and INT120 compared to SIT (−65.3 mmol/l∗min [−256.3; 125.7], +53.8 mmol/l∗min [−143.1; 250.8], and +18.6 mmol/l∗min [−172.4; 209.6], respectively). Conclusions Interrupting sitting with increasing frequency did not reduce the postprandial plasma glucose response to prolonged sitting in healthy, sedentary, centrally obese men.
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- 2019
7. The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial
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Nanna Skytt Pilmark, Christina Petersen-Bønding, Nielse Frederich Rose Holm, Mette Yun Johansen, Bente Klarlund Pedersen, Katrine Bagge Hansen, and Kristian Karstoft
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Adult ,Male ,Endocrinology, Diabetes and Metabolism ,Physical Exertion ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Placebo ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Endocrinology ,Oxygen Consumption ,Medicine ,Humans ,rate of perceived exertion ,lcsh:RC648-665 ,exercise ,business.industry ,Cardiorespiratory fitness ,Brief Research Report ,medicine.disease ,Treatment period ,Metformin ,Intensity (physics) ,Treatment dose ,Diabetes Mellitus, Type 2 ,Anesthesia ,Exercise intensity ,self-selected exercise intensity ,type 2 diabetes ,business ,metformin ,medicine.drug - Abstract
IntroductionIn general, patients with type 2 diabetes have lower cardiorespiratory fitness levels and perform exercise at lower intensities compared to healthy controls. Since metformin (MET) has been shown to increase the rate of perceived exertion (RPE) during exercise with a fixed intensity, MET per se may reduce self-selected exercise intensity. The aim of this study was to assess the effect of MET on self-selected exercise intensity.MethodsHealthy males were eligible for this crossover, counterbalanced study with two treatment periods: MET and placebo (PLA), each lasting 17 days. Treatment dose was gradually increased and reached 2 g/day on treatment day 9, and continued at that level for the rest of the treatment period. The two periods were performed in randomized order. Two experimental days (A+B) were conducted on Day 15 (A) and Day 17 (B) of each period, respectively. Day A consisted of an exercise bout with self-selected exercise intensity (equal to RPE = 14–15 on the Borg Scale). Day B consisted of an exercise bout with fixed intensity (70% of VO2peak). Oxygen consumption rate was assessed continuously during both exercise bouts.ResultsFifteen males (age 23.7 ± 0.6 years, BMI 22.3 ± 2.0, VO2peak 3.5 ± 0.6 L/min) were included in the study. On Day B, RPE was higher in MET compared to PLA (14.8 ± 0.4 vs. 14.0 ± 0.3, P = 0.045). On Day A, no difference in self-selected exercise intensity measured by oxygen consumption rate (PLA 2.33 ± 0.09 L O2/min, MET 2.42 ± 0.10 L O2/min, P = 0.09) was seen between treatment periods.ConclusionsSelf-selected exercise intensity was not reduced by MET in healthy males, despite the fact that MET increased RPE during an exercise bout with fixed intensity.
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- 2021
8. Editorial:Understanding the Heterogeneity in Exercise-Induced Changes in Glucose Metabolism to Help Optimize Treatment Outcomes
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Kristian Karstoft, John P. Thyfault, Jacob M. Haus, and Thomas P. J. Solomon
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Blood Glucose ,Glucose control ,Endocrinology, Diabetes and Metabolism ,Treatment outcome ,Carbohydrate metabolism ,Bioinformatics ,Diseases of the endocrine glands. Clinical endocrinology ,Endocrinology ,Diabetes mellitus ,Glucose Intolerance ,medicine ,Humans ,Hypoglycemic Agents ,inter-individual ,Exercise ,glucose control ,diabetes ,business.industry ,variability ,medicine.disease ,RC648-665 ,Prognosis ,Metformin ,Editorial ,hyperglycemia ,heterogeneity ,business ,metformin ,exercise training ,medicine.drug - Published
- 2021
9. Il-6 receptor blockade increases circulating adiponectin levels in people with obesity:An explanatory analysis
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Marc Y. Donath, Mark Lyngbæk, Katharina Timper, Helga Ellingsgaard, Daniel Konrad, Eleonora Seelig, Kristian Karstoft, Stephan Wueest, University of Zurich, Ellingsgaard, Helga, and Konrad, Daniel
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0301 basic medicine ,medicine.medical_specialty ,1303 Biochemistry ,Endocrinology, Diabetes and Metabolism ,lcsh:QR1-502 ,Adipokine ,030209 endocrinology & metabolism ,610 Medicine & health ,White adipose tissue ,Type 2 diabetes ,Biochemistry ,lcsh:Microbiology ,03 medical and health sciences ,tocilizumab ,0302 clinical medicine ,Insulin resistance ,Endocrinology ,white adipose tissue ,Internal medicine ,medicine ,1312 Molecular Biology ,Molecular Biology ,Adiponectin ,adipokine ,business.industry ,Leptin ,Brief Report ,nutritional and metabolic diseases ,Tocilizumab ,medicine.disease ,Obesity ,Diabetes and Metabolism ,2712 Endocrinology, Diabetes and Metabolism ,030104 developmental biology ,10036 Medical Clinic ,Homeostatic model assessment ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Human obesity is associated with decreased circulating adiponectin and elevated leptin levels. In vitro experiments and studies in high fat diet (HFD)-fed mice suggest that interleukin-6 (IL-6) may regulate adiponectin and leptin release from white adipose tissue (WAT). Herein, we aimed to investigate whether IL-6 receptor blockade affects the levels of circulating adiponectin and leptin in obese human individuals. To this end, serum samples collected during a multicenter, double-blind clinical trial were analyzed. In the latter study, obese human subjects with or without type 2 diabetes were randomly assigned to recurrent placebo or intravenous tocilizumab (an IL-6 receptor antibody) administration during a 12-week exercise training intervention. Twelve weeks of tocilizumab administration (in combination with exercise training) trend wise enhanced the decrease in circulating leptin levels (−2.7 ± 8.2% in the placebo vs. −20.6 ± 5.6% in tocilizumab, p = 0.08) and significantly enhanced the increase in circulating adiponectin (3.4 ± 3.7% in the placebo vs. 27.0 ± 6.6% in tocilizumab, p = 0.01). In addition, circulating adiponectin levels were negatively correlated with the homeostatic model assessment of insulin resistance (HOMA-IR), indicating that increased adiponectin levels positively affect insulin sensitivity in people with obesity. In conclusion, IL-6 receptor blockade increases circulating adiponectin levels in people with obesity.
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- 2021
10. No effects of dapagliflozin, metformin or exercise on plasma glucagon concentrations in individuals with prediabetes: A post hoc analysis from the randomized controlled PRE-D trial
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Marit E. Jørgensen, Hanan Amadid, Jonas Salling Quist, Dorte Vistisen, Kristian Karstoft, Nicolai J. Wewer Albrechtsen, Martin B. Blond, Frederik Persson, Kristine Færch, Lea Bruhn, Kim K. B. Clemmensen, Signe S. Torekov, Jens J. Holst, and Mathias Ried-Larsen
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Blood Glucose ,Male ,obesity ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,prediabetes ,030204 cardiovascular system & hematology ,Overweight ,Interval training ,GLUCOSE ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Glucosides ,Prediabetes ,Dapagliflozin ,INSULIN-RESISTANCE ,exercise ,Middle Aged ,Metformin ,Drug Therapy, Combination ,Female ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,medicine.drug ,medicine.medical_specialty ,WEIGHT-LOSS ,030209 endocrinology & metabolism ,Glucagon ,Prediabetic State ,03 medical and health sciences ,BETA-CELL FUNCTION ,Double-Blind Method ,exercise, glucagon, metformin, obesity, prediabetes, sodium-glucose co-transporter-2 inhibitor ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Benzhydryl Compounds ,Aged ,COTRANSPORTER 2 INHIBITION ,business.industry ,Insulin ,nutritional and metabolic diseases ,sodium-glucose co-transporter-2 inhibitor ,medicine.disease ,chemistry ,glucagon ,Diabetes Mellitus, Type 2 ,business ,metformin ,GLP-1 ,Body mass index ,RESPONSES - Abstract
Aim: To assess the effects of dapagliflozin, metformin and exercise treatment on changes in plasma glucagon concentrations in individuals with overweight and HbA1c-defined prediabetes.Materials and Methods: One-hundred and twenty individuals with overweight (body mass index >= 25 kg/m(2)) and prediabetes (HbA1c of 39-47 mmol/mol) were randomized to a 13-week intervention with dapagliflozin (10 mg once daily), metformin (850 mg twice daily), exercise (30 minutes of interval training 5 days per week) or control (habitual living). A 75-g oral glucose tolerance test (OGTT) (0, 30, 60 and 120 minutes) was administered at baseline, at 13 weeks (end of intervention) and at 26 weeks (end of follow-up). Linear mixed effects models with participant-specific random intercepts were used to investigate associations of the interventions with fasting plasma glucagon concentration, insulin/glucagon ratio and glucagon suppression during the OGTT.Results: At baseline, the median (Q1; Q3) age was 62 (54; 68) years, median fasting plasma glucagon concentration was 11 (7; 15) pmol/L, mean (SD) HbA1c was 40.9 (2.3) mmol/mol and 56% were women. Compared with the control group, fasting glucagon did not change in any of the groups from baseline to the end of the intervention (dapagliflozin group: -5% [95% CI: -29; 26]; exercise group: -8% [95% CI: -31; 24]; metformin group: -2% [95% CI: -27; 30]). Likewise, there were no differences in insulin/glucagon ratio and glucagon suppression during the OGTT between the groups.Conclusions: In individuals with prediabetes, 13 weeks of treatment with dapagliflozin, metformin or exercise was not associated with changes in fasting or post-OGTT glucagon concentrations.
- Published
- 2020
11. The Impact of Physical Activity on Glycemic Variability Assessed by Continuous Glucose Monitoring in Patients With Type 2 Diabetes Mellitus: A Systematic Review
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Kristian Karstoft, Sebastian L. Bennetsen, Grit Elster Legaard, Mark Lyngbæk, Camilla S. Feineis, and Mathias Ried-Larsen
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0301 basic medicine ,Blood Glucose ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,physical activity ,030209 endocrinology & metabolism ,Type 2 diabetes ,Glycemic Control ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,law.invention ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Statistical significance ,medicine ,Humans ,education ,Glycemic ,Randomized Controlled Trials as Topic ,education.field_of_study ,lcsh:RC648-665 ,exercise ,business.industry ,Blood Glucose Self-Monitoring ,nutritional and metabolic diseases ,medicine.disease ,randomized controlled trials (RCT) ,Crossover study ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Sample size determination ,Hyperglycemia ,diabetes mellitus ,glycemic variability ,continuous glucose monitoring ,Systematic Review ,type 2 diabetes ,business - Abstract
Aim: Patients with Type 2 Diabetes Mellitus (T2DM) have increased risk of developing vascular complications due to chronic hyperglycemia. Glycemic variability (GV) has been suggested to play an even more important role in the risk of developing diabetic complications than sustained hyperglycemia. Physical activity (PA) has shown reducing effects on mean plasma glucose; however, the effect on GV in T2DM needs further description. The objective of this review is to evaluate the effect of PA on GV, assessed by continuous glucose monitoring (CGM) in people with T2DM. Methods: A systematic literature search was conducted on MEDLINE and Embase to find randomized controlled trials (RCTs) covering the aspects T2DM, PA, and CGM. Following eligibility screening, variables of population characteristics, PA interventions, and GV outcomes were extracted and processed through qualitative synthesis. Risk of bias (ROB) was assessed using Cochrane ROB tool v2.0. Results: Of 1,825 identified articles, 40 full texts were screened. In the ten included RCTs matching the eligibility criteria, sample sizes ranged from nine to 63, mean age from 51 (SD 11) to 65 (SD 2) years and mean T2DM duration from four (SD 3) to ten (SD 6) years. Eight RCTs examined GV following single bouts of exercise, while two RCTs examined GV following training interventions. One RCT applied parallel group design, while nine RCTs applied crossover design. Numeric reductions in GV following acute exercise were seen, with four RCTs reaching statistical significance. Numeric reductions in GV were seen following training interventions, with one RCT reaching statistical significance. Numeric reductions of GV after PA appeared independently of intensity and T2DM progression but higher in participants with high baseline HbA1c and GV than with low. 80% of the trials were evaluated as uncertain/high ROB. Conclusion: The systematic literature search revealed limited and biased evidence showing that acute PA numerically reduced GV in patients with T2DM. PA reduced GV independently of PA intensity and T2DM progression. Prolonged RCTs with low ROB are needed to confirm reducing effects of PA on GV and to assess the influence of patient- and intervention characteristics on the effect of PA on GV.
- Published
- 2020
12. Human Brown Adipose Tissue is Active at Thermoneutrality in a Circadian Rhythm and is Highly Regulated in Winter Swimmers
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Marianne Berntsen, Rune D. Nielsen, Annika Loft, Zach Gerhart-Hines, Bente Klarlund Pedersen, Johan Löfgren, Christine Sølling, Adam E. Hansen, Frederik E. Philipsen, Camilla Scheele, Helle Hjorth Johannesen, Kristin B. Nystrup, Esben Ahrens, Kristian Karstoft, Susanna Søberg, Andreas Kjaer, Michal Jensen, and Anne-Sophie Wedell-Neergaard
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medicine.medical_specialty ,animal structures ,Glucose uptake ,Nocturnal ,Biology ,Control subjects ,Crossover study ,Plasma cortisol ,medicine.anatomical_structure ,Endocrinology ,Internal medicine ,Brown adipose tissue ,medicine ,Cold acclimation ,Circadian rhythm - Abstract
To investigate human brown adipose tissue (BAT) physiology, we recruited young healthy men that were either winter swimmers (WS) or controls. We used 2-deoxy-2-[18F]fluoro-D-glucose PET/MRI-scanning, infrared thermography, iButtons and ingestible thermometer pills to assess BAT glucose uptake, and BAT and core temperature. In a crossover design with interventions performed in randomized order, subjects performed individualized cooling and thermoneutral protocols. We monitored a subset for BAT circadian rhythm. In response to cooling, WS increased more in BAT temperature, BAT glucose uptake and energy expenditure compared to control subjects. At thermoneutrality, WS had higher BAT temperature and lower core temperature, despite BAT glucose uptake in controls only. All subjects demonstrated a nocturnal reduction in BAT temperature, while a peak was observed at 4:30-5:30 am in WS, coinciding with rising plasma cortisol levels. In conclusion, WS have highly regulated BAT, and BAT is active at thermoneutrality in a circadian rhythm in humans.
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- 2020
13. Blocking endogenous IL-6 impairs mobilization of free fatty acids during rest and exercise in lean and obese men
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Casper Simonsen, Gerrit van Hall, Peter Plomgaard, Beckey Trinh, Merel Peletier, Bente Klarlund Pedersen, Helga Ellingsgaard, and Kristian Karstoft
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Adult ,Medicine (General) ,IL-6 receptor ,obesity ,medicine.medical_specialty ,Hydrocortisone ,Lipolysis ,Rest ,Carbohydrates ,stable isotopes ,Adipose tissue ,Endogeny ,glycerol ,Antibodies, Monoclonal, Humanized ,fatty acids ,Article ,General Biochemistry, Genetics and Molecular Biology ,tocilizumab ,chemistry.chemical_compound ,R5-920 ,Tocilizumab ,Thinness ,Internal medicine ,medicine ,Humans ,Interleukin 6 ,Beta oxidation ,chemistry.chemical_classification ,exercise ,biology ,Interleukin-6 ,Chemistry ,Fatty acid ,Metabolism ,Glucagon ,Receptors, Interleukin-6 ,Kinetics ,Glucose ,Endocrinology ,lipolysis ,biology.protein ,Oxidation-Reduction ,metabolism - Abstract
Summary Lack of interleukin-6 (IL-6) leads to expansion of adipose tissue mass in rodents and humans. The exact underlying mechanisms have not been identified. In this placebo-controlled, non-randomized, participant-blinded crossover study, we use the IL-6 receptor antibody tocilizumab to investigate the role of endogenous IL-6 in regulating systemic energy metabolism at rest and during exercise and recovery in lean and obese men using tracer dilution methodology. Tocilizumab reduces fatty acid appearance in the circulation under all conditions in lean and obese individuals, whereas lipolysis (the rate of glycerol appearance into the circulation) is mostly unaffected. The fact that fatty acid oxidation is unaffected by IL-6 receptor blockade suggests increased re-esterification of fatty acids. Glucose kinetics are unaffected. We find that blocking endogenous IL-6 signaling with tocilizumab impairs fat mobilization, which may contribute to expansion of adipose tissue mass and, thus, affect the health of individuals undergoing anti-IL-6 therapy (Clinicaltrials.gov: NCT03967691)., Graphical abstract, Highlights IL-6 receptor blockade lowers mobilization of free fatty acids in lean and obese men The lowered fatty acid mobilization occurs during rest, exercise, and recovery IL-6 receptor blockade slightly impairs lipolysis only in obese men, Trinh et al. show that, in humans, less free fatty acids are mobilized when endogenous IL-6 signaling is blocked. Their findings highlight a possible mechanism by which treatment with IL-6 receptor blockade leads to expansion of fat mass and potentially affects the metabolic health of affected individuals.
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- 2021
14. 131-OR: Effects of Dapagliflozin, Metformin, or Exercise on Glucose Metabolism in Individuals with Prediabetes: The PRE-D Trial
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Camilla Hartmann Pedersen, Mathias Ried-Larsen, Dorte Vistisen, Marit E. Jørgensen, Martin B. Blond, Kristian Karstoft, Lea Bruhn Nielsen, Kim K. B. Clemmensen, Kristine Færch, and Hanan Amadid
- Subjects
medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Serum insulin ,Carbohydrate metabolism ,medicine.disease ,Metformin ,chemistry.chemical_compound ,Postprandial ,Endocrinology ,chemistry ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,Medicine ,Prediabetes ,DAPAGLIFLOZIN/METFORMIN ,Dapagliflozin ,business ,medicine.drug - Abstract
Introduction: We assessed the effects of dapagliflozin, metformin or exercise on glucose metabolism in individuals with prediabetes. Methods: 120 participants were randomized to 13 weeks of either: 1) dapagliflozin (DAP, 10 mg once daily); 2) metformin (MET, 1700 mg daily); 3) exercise (EXE, 5x30 min/week); or 4) control (CON, no treatment). Participants were tested at baseline and after 6 and 13 weeks of intervention with oral glucose tolerance tests with 0, 30, 60, 120 min samples performed at baseline and at 13 weeks. Treatments were stopped the day before the last visit (two days before in EXE). Intention-to-treat analyses were conducted (baseline-adjusted). Results: 44% were men. At baseline, the median (Q1;Q3) age was 62 (54;68) years, BMI 30.8 (28.6;34.3) kg/m2, HbA1c 41 (39;43) mmol/mol (5.9 (5.7;6.1)%), fasting plasma glucose (FPG) 5.6 (5.2;5.8) mmol/L, and fasting serum insulin (FSI) 72 (47;99) pmol/L. HbA1c decreased in DAP at 6 weeks (Table 1). All groups showed reductions of around 1 mmol/mol at 13 weeks. MET, and to a lesser extend DAP, decreased FPG. FSI was reduced by 19-25% in all treatment groups, except for EXE at 13 weeks. The iAUCglucose increased by 66% in MET, and iAUCinsulin decreased somewhat in DAP and EXE. Conclusion: All treatments slightly improved HbA1c and fasting measures. Only DAP and EXE showed signs of improvements in postprandial glucose metabolism. Disclosure K. Færch: Research Support; Self; Ascensia Diabetes Care, AstraZeneca, Unilever. Stock/Shareholder; Self; Novo Nordisk A/S. M.B. Blond: None. H. Amadid: None. L.B. Nielsen: None. D. Vistisen: Stock/Shareholder; Self; Novo Nordisk A/S. K.K. Clemmensen: None. C.H. Pedersen: None. K. Karstoft: Employee; Self; Novo Nordisk A/S. M. Ried-Larsen: Other Relationship; Self; Novo Nordisk A/S. M.E. Jørgensen: Research Support; Self; Amgen Inc., AstraZeneca, Danish Diabetes Association, Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S. Funding Novo Nordisk Foundation; AstraZeneca
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- 2019
15. Type 2 diabetes remission 1 year after an intensive lifestyle intervention: A secondary analysis of a randomized clinical trial
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Mathias Ried-Larsen, Kristian Karstoft, Christopher S. MacDonald, Henning Langberg, Mette Y. Johansen, Nanna Skytt Pilmark, Allan Vaag, Anne Sophie Wedell-Neergaard, Bente Klarlund Pedersen, Katrine B. Hansen, and Robin Christensen
- Subjects
Adult ,Male ,medicine.medical_specialty ,Strength training ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,030204 cardiovascular system & hematology ,weight control ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Randomized controlled trial ,law ,dietary intervention ,Internal medicine ,Intervention (counseling) ,Weight Loss ,Internal Medicine ,medicine ,Humans ,exercise intervention ,Life Style ,Aged ,business.industry ,clinical trial ,Odds ratio ,Original Articles ,Middle Aged ,medicine.disease ,Confidence interval ,Diet ,Exercise Therapy ,Clinical trial ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,Original Article ,type 2 diabetes ,business ,Body mass index - Abstract
Aim: To investigate whether an intensive lifestyle intervention induces partial or complete type 2 diabetes (T2D) remission. Materials and methods: In a secondary analysis of a randomized, assessor-blinded, single-centre trial, people with non-insulin-dependent T2D (duration 2. No intervention was provided during the 12-month follow-up period. Results: Of the 98 randomized participants, 93 completed follow-up (mean [SD] age 54.6 [8.9] years; 46 women [43%], mean [SD] baseline glycated haemoglobin 49.3 [9.3] mmol/mol). At follow-up, 23% of participants (n = 14) in the intervention and 7% (n = 2) in the standard care group met the criteria for any T2D remission (odds ratio [OR] 4.4, 95% confidence interval [CI] 0.8-21.4]; P = 0.08). Assuming participants lost to follow-up (n = 5) had relapsed, the OR for T2D remission was 4.4 (95% CI 1.0–19.8; P = 0.048). Conclusions: The statistically nonsignificant threefold increased remission rate of T2D in the lifestyle intervention group calls for further large-scale studies to understand how to implement sustainable lifestyle interventions among people with T2D.
- Published
- 2019
16. Experimental Hyperglycemia Alters Circulating Concentrations and Renal Clearance of Oxidative and Advanced Glycation End Products in Healthy Obese Humans
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Paul J. Beisswenger, Kristian Karstoft, Thomas P. J. Solomon, Jacob M. Haus, Edwin R. Miranda, and Ryan Perkins
- Subjects
Glycation End Products, Advanced ,Male ,0301 basic medicine ,medicine.medical_specialty ,soluble RAGE ,endocrine system diseases ,Receptor for Advanced Glycation End Products ,Enzyme-Linked Immunosorbent Assay ,030209 endocrinology & metabolism ,Inflammation ,lcsh:TX341-641 ,Article ,RAGE (receptor) ,Excretion ,03 medical and health sciences ,chemistry.chemical_compound ,Basal (phylogenetics) ,0302 clinical medicine ,Tandem Mass Spectrometry ,In vivo ,Glycation ,Internal medicine ,medicine ,Humans ,Obesity ,Receptor ,Nutrition and Dietetics ,Methylglyoxal ,nutritional and metabolic diseases ,Middle Aged ,Healthy Volunteers ,RAGE ,3. Good health ,Oxidative Stress ,Renal Elimination ,030104 developmental biology ,Endocrinology ,chemistry ,inflammation ,Glucose Clamp Technique ,Female ,hyperglycemia ,medicine.symptom ,lcsh:Nutrition. Foods and food supply ,Biomarkers ,Chromatography, Liquid ,Food Science - Abstract
The purpose of this investigation was to evaluate the effects of experimental hyperglycemia on oxidative damage (OX), advanced glycation end products (AGEs), and the receptor for AGEs (RAGE) through an in vivo approach. Obese subjects (n = 10, 31.2 ±, 1.2 kg·, m&minus, 2, 56 ±, 3 years) underwent 24 h of hyperglycemic clamp (+5.4 mM above basal), where plasma at basal and after 2 h and 24 h of hyperglycemic challenge were assayed for OX (methionine sulfoxide, MetSO, and aminoadipic acid, AAA) and AGE-free adducts (Ne-carboxymethyllysine, CML, Ne-carboxyethyllysine, CEL, glyoxal hydroimidazolone-1, GH-1, methylglyoxal hydroimidazolone-1, MG-H1, and 3-deoxyglucosone hydroimidazolone, 3DG-H) via liquid chromatography&ndash, tandem mass spectrometry (LC&ndash, MS/MS). Urine was also analyzed at basal and after 24 h for OX and AGE-free adducts and plasma soluble RAGE (sRAGE) isoforms (endogenous secretory RAGE, esRAGE, and cleaved RAGE, cRAGE), and inflammatory markers were determined via enzyme-linked immunosorbent assay (ELISA). Skeletal muscle tissue collected via biopsy was probed at basal, 2 h, and 24 h for RAGE and OST48 protein expression. Plasma MetSO, AAA, CEL, MG-H1, and G-H1 decreased (&minus, 18% to &minus, 47%, p <, 0.05), while CML increased (72% at 24 h, 0.05) and 3DG-H remained unchanged (p >, 0.05) with the hyperglycemic challenge. Renal clearance of MetSO, AAA, and G-H1 increased (599% to 1077%, 0.05), CML decreased (&minus, 30%, 0.05), and 3DG-H, CEL, and MG-H1 remained unchanged (p >, 0.05). Fractional excretion of MetSO, AAA, CEL, G-H1, and MG-H1 increased (5.8% to 532%, 0.05) and CML and 3DG-H remained unchanged (p >, 0.05). Muscle RAGE and OST48 expression, plasma sRAGE, IL-1&beta, IL-1Ra, and TNF&alpha, remained unchanged (p >, 0.05), while IL-6 increased (159% vs. basal, p >, 0.05). These findings suggest that individuals who are obese but otherwise healthy have the capacity to prevent accumulation of OX and AGEs during metabolic stress by increasing fractional excretion and renal clearance.
- Published
- 2019
17. Effect of ecological momentary assessment, goal-setting and personalized phone-calls on adherence to interval walking training using the InterWalk application among patients with type 2 diabetes-A pilot randomized controlled trial
- Author
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Jens Steen Nielsen, Rasmus Tolstrup Larsen, Bente Klarlund Pedersen, Kristian Karstoft, Henning Langberg, Cecilie Fau Brinkløv, Malte Bue Kongstad, Laura Staun Valentiner, Ida Kær Thorsen, and Mathias Ried-Larsen
- Subjects
Male ,Psychological intervention ,Pilot Projects ,Walking ,Type 2 diabetes ,Biochemistry ,law.invention ,Fats ,Endocrinology ,0302 clinical medicine ,Randomized controlled trial ,law ,Medicine and Health Sciences ,Diabetes diagnosis and management ,Public and Occupational Health ,030212 general & internal medicine ,Response rate (survey) ,Multidisciplinary ,Ecology ,Lipids ,Telephones ,Mobile Applications ,Sports Science ,Type 2 Diabetes ,Treatment Outcome ,Health Education and Awareness ,Patient Satisfaction ,Engineering and Technology ,Medicine ,Female ,Goals ,Research Article ,HbA1c ,Patients ,Endocrine Disorders ,Ecological Momentary Assessment ,Science ,Equipment ,030209 endocrinology & metabolism ,03 medical and health sciences ,Patient satisfaction ,Diabetes Mellitus ,medicine ,Humans ,Hemoglobin ,Sports and Exercise Medicine ,Exercise ,Aged ,Communication Equipment ,Text Messaging ,Biology and life sciences ,business.industry ,Proteins ,Usability ,Physical Activity ,Retention rate ,medicine.disease ,Diagnostic medicine ,Health Care ,Diabetes Mellitus, Type 2 ,Physical Fitness ,Metabolic Disorders ,Feasibility Studies ,Patient Compliance ,business ,Body mass index ,Cell Phone ,Follow-Up Studies - Abstract
ObjectivesThe objective was to investigate the feasibility and usability of electronic momentary assessment, goal-setting and personalized phone-calls on adherence to a 12-week self-conducted interval walking training (IWT) program, delivered by the InterWalk smartphone among patients with type 2 diabetes (T2D).MethodsIn a two-arm pilot randomized controlled trial (Denmark, March 2014 to February 2015), patients with T2D (18-80 years with a Body Mass Index of 18 and 40 kg/m2) were randomly allocated to 12 weeks of IWT with (experimental) or without additional support (control). The primary outcome was the difference between groups in accumulated time of interval walking training across 12 weeks. All patients were encouraged to use the InterWalk application to perform IWT for ≥90 minute/week. Patients in the experimental group made individual goals regarding lifestyle change. Once a week inquiries about exercise adherence was made using an ecological momentary assessment (EMA). In case of consistent self-reported non-adherence, the patients would receive a phone-call inquiring about the reason for non-adherence. The control group did not receive additional support. Information about training adherence was assessed objectively. Usability of the EMA was assessed based on response rates and self-reported satisfaction after 12-weeks.ResultsThirty-seven patients with T2D (66 years, 65% female, hemoglobin 1Ac 50.3 mmol/mol) where included (n = 18 and n = 19 in experimental and control group, respectively). The retention rate was 83%. The experimental group accumulated [95%CI] 345 [-7, 698] minutes of IWT more than the control group. The response rate for the text-messages was 83% (68% for males and 90% for females). Forty-one percent of the experimental and 25% of the control group were very satisfied with their participation.ConclusionThe combination inquiry about adherence using EMA, goal-setting with the possibility of follow-up phone calls are considered feasible interventions to attain training adherence when using the InterWalk app during a 12-week period in patients with T2D. Some uncertainty about the effect size of adherence remains.Trial registrationClinicaltrials.gov NCT02089477.
- Published
- 2019
18. Skeletal muscle as a gene regulatory endocrine organ
- Author
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Kristian Karstoft and Bente Klarlund Pedersen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Decorin ,medicine.medical_treatment ,Medicine (miscellaneous) ,Endocrine System ,Biology ,Endocrine System Diseases ,Proinflammatory cytokine ,03 medical and health sciences ,Internal medicine ,Myokine ,medicine ,Animals ,Humans ,Endocrine system ,Healthy Lifestyle ,Muscle, Skeletal ,Exercise ,Gene ,Regulation of gene expression ,Nutrition and Dietetics ,Gene Expression Regulation, Developmental ,Skeletal muscle ,030104 developmental biology ,Cytokine ,medicine.anatomical_structure ,Endocrinology ,Cytokines - Abstract
Purpose of review Skeletal muscle is gaining increased attention as an endocrine organ. Recently, novel myokines and new effects of already established myokines have been identified. The objective of this review is to give an update on the recent advances in the field. Recent findings Several hundred putative myokines have been described, some of which are induced by contraction and differentially regulated between healthy and metabolically diseased individuals. Interleukin-6 (IL-6) is the prototype myokine, which was identified as a muscle-derived cytokine 15 years ago. Recently, IL-6 has been linked to β-cell survival and inhibition of cancer-cell growth. Moreover, trans-signaling appears to determine whether IL-6 acts as a proinflammatory or an anti-inflammatory cytokine. Irisin has been shown to be a secreted myokine, which contribute to circulating concentrations dependent on training status. IL-15 has been established as a cytokine mediating cross-talk between skeletal muscle and skin tissue, and decorin has been characterized as a contraction-induced myokine which apparently is differentially regulated between healthy and dysglycemic individuals. Summary Skeletal muscle is an endocrine organ which, by the release of myokines, may influence metabolism in virtually all organs in the body. This knowledge may potentially open up for the possibility of designing new drugs that mimic the effects of myokine signaling.
- Published
- 2016
19. FGF21 Mediates Endocrine Control of Simple Sugar Intake and Sweet Taste Preference by the Liver
- Author
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Andreas N. Madsen, Aurelie Vandenbeuch, Anthony P. Thompson, Andrew A. Pieper, Martin D. Cassell, Lucas D. BonDurant, Terry C. Yin, Birgitte Holst, Adriana Ibarra Urizar, Cecilia Ratner, Thomas P. J. Solomon, Matthew P. Gillum, Sue C. Kinnamon, Catherine B. Anderson, Stephanie von Holstein-Rathlou, Kristin E. Claflin, Lila Peltekian, Meghan C. Naber, Matthew J. Potthoff, Kristian Karstoft, and Kamal Rahmouni
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Sucrose ,FGF21 ,Physiology ,media_common.quotation_subject ,Endocrine System ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,Food Preferences ,Internal medicine ,Endocrine system ,Medicine ,Ingestion ,Animals ,Sugar ,Molecular Biology ,media_common ,Mice, Knockout ,business.industry ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,digestive, oral, and skin physiology ,Nuclear Proteins ,Appetite ,Feeding Behavior ,Cell Biology ,Carbohydrate ,Fibroblast Growth Factors ,030104 developmental biology ,Endocrinology ,chemistry ,Liver ,Taste ,business ,Hormone ,Signal Transduction ,Transcription Factors - Abstract
Summary The liver is an important integrator of nutrient metabolism, yet no liver-derived factors regulating nutrient preference or carbohydrate appetite have been identified. Here we show that the liver regulates carbohydrate intake through production of the hepatokine fibroblast growth factor 21 (FGF21), which markedly suppresses consumption of simple sugars, but not complex carbohydrates, proteins, or lipids. Genetic loss of FGF21 in mice increases sucrose consumption, whereas acute administration or overexpression of FGF21 suppresses the intake of both sugar and non-caloric sweeteners. FGF21 does not affect chorda tympani nerve responses to sweet tastants, instead reducing sweet-seeking behavior and meal size via neurons in the hypothalamus. This liver-to-brain hormonal axis likely represents a negative feedback loop as hepatic FGF21 production is elevated by sucrose ingestion. We conclude that the liver functions to regulate macronutrient-specific intake by producing an endocrine satiety signal that acts centrally to suppress the intake of "sweets."
- Published
- 2016
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20. Exercise and type 2 diabetes: focus on metabolism and inflammation
- Author
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Kristian Karstoft and Bente Klarlund Pedersen
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Interleukin-1beta ,Immunology ,Inflammation ,Type 2 diabetes ,03 medical and health sciences ,Internal medicine ,Diabetes mellitus ,medicine ,Animals ,Humans ,Immunology and Allergy ,Exercise physiology ,Exercise ,Tumor Necrosis Factor-alpha ,business.industry ,Type 2 Diabetes Mellitus ,Interleukin ,Lipid metabolism ,Cell Biology ,medicine.disease ,Exercise Therapy ,Interleukin 1 Receptor Antagonist Protein ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Tumor necrosis factor alpha ,medicine.symptom ,business - Abstract
Type 2 diabetes mellitus (T2DM) is associated with metabolic dysregulation and chronic inflammation, and regular exercise may provide a strong stimulus for improving both. In this review, we first discuss the link between inflammation and metabolism. Next, we give an update on the clinical metabolic effects of exercise in T2DM patients with special focus on which parameters to consider for optimizing metabolic improvements. We then discuss the mechanisms whereby exercise exerts its anti-inflammatory and related metabolic effects. Evidence exists that interleukin (IL)-1β is involved in pancreatic β-cell damage, whereas tumor necrosis factor (TNF)-α appears to be a key molecule in peripheral insulin resistance. Mechanistic studies in humans suggest that moderate acute elevations in IL-6, as provoked by exercise, exert direct anti-inflammatory effects by an inhibition of TNF-α and by stimulating IL-1ra (IL-1 receptor antagonist), thereby limiting IL-1β signaling. In addition, IL-6 has direct impact on glucose and lipid metabolism. Moreover, indirect anti-inflammatory effects of exercise may be mediated via improvements in, for example, body composition. While waiting for the outcome of long-term randomized clinical training studies with hard end points, it should be emphasized that physical activity represents a natural strong anti-inflammatory and metabolism-improving strategy with minor side effects.
- Published
- 2015
21. Effects of Acute Experimental Hyperglycemia on Oxidative Markers and AGE-RAGE Dynamics in Obese Humans
- Author
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Jacob M. Haus, Paul J. Beisswenger, Ryan Perkins, Edwin R. Miranda, Jr. Kristian Karstoft, and Thomas P. J. Solomon
- Subjects
medicine.medical_specialty ,Creatinine ,medicine.diagnostic_test ,business.industry ,Endocrinology, Diabetes and Metabolism ,Skeletal muscle ,Inflammation ,medicine.disease_cause ,RAGE (receptor) ,chemistry.chemical_compound ,Basal (phylogenetics) ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Western blot ,Internal medicine ,Internal Medicine ,medicine ,Advanced glycation end-product ,medicine.symptom ,business ,Oxidative stress - Abstract
Chronic hyperglycemia promotes oxidative stress and advanced glycation end product (AGE) formation, leading to recognition by the AGE receptor (RAGE). AGE-RAGE binding and inflammation perpetuates diabetic complications, however the study of these phenomenon present inherent challenges in vivo. Therefore, our purpose was to evaluate the effects of acute experimental hyperglycemia on AGEs, oxidative markers, and RAGE expression in healthy, obese subjects (n=10; 31.2±1.2 kg/m2; 56±3 y) subjected to hyperglycemic clamps (+5.4 mM above basal). Plasma was assayed at baseline, 2, and 24 h post glucose-infusion for well-known AGE-free adducts (CML, CEL, G-H1, MG-H1, 3DG-H) and oxidative markers (MethSO, AAA) via LC-MS/MS as well as soluble RAGE (sRAGE) isoforms via ELISA. Urine was also assayed (basal and 24 h) for AGEs and oxidative markers (normalized to creatinine) and skeletal muscle biopsies were used to study RAGE expression via Western blot. Most circulating factors (MethSO, AAA, CEL, MG-H1, and G-H1) decreased (p0.05). In urine, only MethSO was seen to increase at 24 h (p0.05). In skeletal muscle tissue, there was a trend (p Disclosure R. Perkins: None. E.R. Miranda: None. K. Karstoft: None. P.J. Beisswenger: Employee; Self; PreventAGE Health Care, LLC.. T.P. Solomon: None. J.M. Haus: None.
- Published
- 2018
22. Editorial: Optimizing Exercise for the Prevention and Treatment of Type 2 Diabetes
- Author
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Kristian Karstoft, Adeel Safdar, and Jonathan P. Little
- Subjects
lifestyle interventions ,medicine.medical_specialty ,lcsh:RC648-665 ,exercise ,business.industry ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,prediabetes ,030204 cardiovascular system & hematology ,medicine.disease ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Editorial ,type 2 ,motivation ,Diabetes mellitus ,Lifestyle intervention ,diabetes mellitus ,medicine ,Prediabetes ,Intensive care medicine ,business - Published
- 2018
23. Exercise-Induced Changes in Visceral Adipose Tissue Mass are Regulated by IL-6 Signaling: A Randomized Controlled Trial
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Rikke Krogh-Madsen, Grit Elster Legaard, Mathias Ried-Larsen, Sidsel Kofoed Seide, Janus Damm Nybing, Monica Korsager Larsen, Louise Lang Lehrskov, Emma Dorph, Natja Launbo, Stine Nymand, Anne-Sophie Wedell-Neergaard, Nicole Vinum, Bente Klarlund Pedersen, Jaya Birgitte Rosenmeyer, Camilla Noerfelt Dahl, Helga Ellingsgaard, Kristian Karstoft, Robin Christensen, Sabrina Ravn Fagerlind, Regitse Højgaard Christensen, and Maria Ball
- Subjects
medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Skeletal muscle ,Adipose tissue ,Placebo ,law.invention ,Blockade ,Endocrinology ,medicine.anatomical_structure ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Lean body mass ,Lipolysis ,business ,Lipid profile - Abstract
Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade worsened the lipid profile, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade.
- Published
- 2018
24. Why prescribe exercise as therapy in type 2 diabetes? We have a pill for that!
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Christopher S. MacDonald, Mathias Ried-Larsen, Katrine B. Hansen, Thomas Almdal, Mette Y. Johansen, Robin Christensen, Kristian Karstoft, and Bente Klarlund Pedersen
- Subjects
medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Physical activity ,030209 endocrinology & metabolism ,Type 2 diabetes ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pharmacotherapy ,Diabetes mellitus ,Lifestyle intervention ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,030212 general & internal medicine ,Medical prescription ,Intensive care medicine ,Life Style ,business.industry ,nutritional and metabolic diseases ,medicine.disease ,Exercise Therapy ,Diabetes Mellitus, Type 2 ,Pill ,business - Abstract
The majority of T2D cases are preventable through a healthy lifestyle, leaving little room for questions that lifestyle should be the first line of defence in the fight against the development of T2D. However, when it comes to the clinical care of T2D, the potential efficacy of lifestyle is much less clear-cut, both in terms of impacting the pathological metabolic biomarkers of the disease, and long-term complications. A healthy diet, high leisure-time physical activity, and exercise are considered to be cornerstones albeit adjunct to drug therapy in the management of T2D. The prescription and effective implementation of structured exercise and other lifestyle interventions in the treatment of T2D have not been routinely used. In this article, we critically appraise and debate our reflections as to why exercise and physical activity may not have reached the status of a viable and effective treatment in the clinical care of T2D to the same extent as pharmaceutical drugs. We argue that the reason why exercise therapy is not utilized to a satisfactory degree is multifaceted and primarily relates to a "vicious cycle" with lack of proven efficacy on T2D complications and a lack of proven effectiveness on risk factors in the primary care of T2D. Furthermore, there is a lack of experimental research establishing the optimal dose of exercise. This precludes widespread and sustained implementation of physical activity and exercise in the clinical treatment of T2D will not succeed.
- Published
- 2017
25. Interleukin-6 Delays Gastric Emptying in Humans with Direct Effects on Glycemic Control
- Author
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Helga Ellingsgaard, Sarah E Heywood, Mark Lyngbæk, Kristian Karstoft, Bente Klarlund Pedersen, Nicolai J. Wewer Albrechtsen, Line Soederlund, Louise Lang Lehrskov, Grit Elster Legaard, Jens J. Holst, and Jan A. Ehses
- Subjects
0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Type 2 diabetes ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Double-Blind Method ,Glucagon-Like Peptide 1 ,Internal medicine ,Insulin-Secreting Cells ,Insulin Secretion ,medicine ,Glucose homeostasis ,Humans ,Insulin ,Molecular Biology ,Exercise ,Glycemic ,Aged ,Gastric emptying ,business.industry ,Interleukin-6 ,digestive, oral, and skin physiology ,Interleukin ,Cell Biology ,medicine.disease ,Glucagon-like peptide-1 ,Hypoglycemia ,Recombinant Proteins ,030104 developmental biology ,Postprandial ,Endocrinology ,Diabetes Mellitus, Type 2 ,Gastric Emptying ,Case-Control Studies ,business - Abstract
Summary Gastric emptying is a critical regulator of postprandial glucose and delayed gastric emptying is an important mechanism of improved glycemic control achieved by short-acting glucagon-like peptide-1 (GLP-1) analogs in clinical practice. Here we report on a novel regulatory mechanism of gastric emptying in humans. We show that increasing interleukin (IL)-6 concentrations delays gastric emptying leading to reduced postprandial glycemia. IL-6 furthermore reduces insulin secretion in a GLP-1-dependent manner while effects on gastric emptying are GLP-1 independent. Inhibitory effects of IL-6 on gastric emptying were confirmed following exercise-induced increases in IL-6. Importantly, gastric- and insulin-reducing effects were maintained in individuals with type 2 diabetes. These data have clinical implications with respect to the use of IL-6 inhibition in autoimmune/inflammatory disease, and identify a novel target that could be exploited pharmacologically to delay gastric emptying and spare insulin, which may be beneficial for the beta cell in type 2 diabetes.
- Published
- 2017
26. Direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics
- Author
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Thomas P. J. Solomon, Kristian Karstoft, Stefan P. Mortensen, and Sine H. Knudsen
- Subjects
Blood Glucose ,Glycerol ,Male ,Physiology ,Endocrinology, Diabetes and Metabolism ,Hemodynamics ,Incretins/pharmacology ,Blood Pressure ,Regional Blood Flow/drug effects ,chemistry.chemical_compound ,Heart Rate ,Glucose/metabolism ,Medicine ,Glucose kinetics ,Glucose disposal ,Heart Rate/drug effects ,Glucose clamp technique ,Glucagon-like peptide-1 ,Somatostatin ,Hyperglycemia/metabolism ,hormones, hormone substitutes, and hormone antagonists ,Adult ,endocrine system ,medicine.medical_specialty ,Glucose-dependent insulinotropic polypeptide ,Adolescent ,Carotid Artery, Common ,Incretin ,Carbohydrate metabolism ,Incretins ,Blood Pressure/drug effects ,Young Adult ,Blood Glucose/drug effects ,Physiology (medical) ,Internal medicine ,Humans ,Pancreas ,business.industry ,Pancreas/drug effects ,Carotid Artery, Common/drug effects ,Pancreatic clamp ,Hemodynamics/drug effects ,Glucose ,Endocrinology ,Glycerol/metabolism ,chemistry ,Regional Blood Flow ,Hyperglycemia ,Glucose Clamp Technique ,Glucose effectiveness ,business ,Hormone - Abstract
The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under euglycemic and hyperglycemic conditions. Young, healthy men ( n = 10) underwent three trials in a randomized, controlled, crossover study. Each trial consisted of a two-stage (euglycemia and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism was measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial, and common carotid artery blood flow and flow-mediated dilation of the brachial artery) were also measured. The three trials differed as follows: 1) saline [control (CON)], 2) glucagon-like peptide (GLP-1, 0.5 pmol·kg−1·min−1), and 3) glucose-dependent insulinotropic polypeptide (GIP, 1.5 pmol·kg−1·min−1). No between-trial differences in glucose infusion rates (GIR) or glucose or glycerol kinetics were seen during euglycemia, whereas hyperglycemia resulted in increased GIR and glucose rate of disappearance during GLP-1 compared with CON and GIP ( P < 0.01 for all). However, when normalized to insulin levels, no differences between trials were seen for GIR or glucose rate of disappearance. Besides a higher femoral blood flow during hyperglycemia with GIP (vs. CON and GLP-1, P < 0.001), no between-trial differences were seen for the hemodynamic variables. In conclusion, GLP-1 and GIP have no direct effect on whole body glucose metabolism or hemodynamics during euglycemia. On the contrary, during hyperglycemia, GIP increases femoral artery blood flow with no effect on glucose metabolism, whereas GLP-1 increases glucose disposal, potentially due to increased insulin levels.
- Published
- 2015
27. Association Between Cardiorespiratory Fitness and the Determinants of Glycemic Control Across the Entire Glucose Tolerance Continuum
- Author
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Steven K. Malin, Matthew J. Laye, Thomas P. J. Solomon, John P. Kirwan, Jacob M. Haus, Sine H. Knudsen, and Kristian Karstoft
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Cardiovascular and Metabolic Risk ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,Cohort Studies ,Insulin resistance ,Oxygen Consumption ,Internal medicine ,Diabetes mellitus ,Insulin-Secreting Cells ,Insulin Secretion ,Internal Medicine ,Medicine ,Humans ,Insulin ,Glycemic ,Advanced and Specialized Nursing ,Glucose tolerance test ,Analysis of Variance ,medicine.diagnostic_test ,business.industry ,Cardiorespiratory fitness ,Fasting ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Female ,Analysis of variance ,Insulin Resistance ,business ,human activities - Abstract
OBJECTIVE Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum. RESEARCH DESIGN AND METHODS A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined. RESULTS A low VO2max was associated with high HbA1c (r = −0.33), high fasting glucose (r = −0.34), high 2-h OGTT glucose (r = −0.33), low SiOGTT (r = 0.73), and high early-phase (r = −0.34) and late-phase (r = −0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum. CONCLUSIONS The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes.
- Published
- 2015
28. Circulating soluble RAGE isoforms are attenuated in obese, impaired-glucose-tolerant individuals and are associated with the development of type 2 diabetes
- Author
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Sangeeta R. Kashyap, Kristian Karstoft, Jacob T. Mey, Laurie Quinn, John P. Kirwan, Edwin R. Miranda, Ciaran E. Fealy, Edward Wang, Brian K. Blackburn, Jacob M. Haus, Vikram S. Somal, Sarah S. Farabi, and Thomas P. J. Solomon
- Subjects
0301 basic medicine ,Gene isoform ,Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Aging ,endocrine system diseases ,Adolescent ,Physiology ,Endocrinology, Diabetes and Metabolism ,Receptor for Advanced Glycation End Products ,Inflammation ,Type 2 diabetes ,RAGE (receptor) ,Body Mass Index ,03 medical and health sciences ,Young Adult ,Insulin resistance ,Isomerism ,Glycation ,Physiology (medical) ,Internal medicine ,Glucose Intolerance ,Medicine ,Humans ,Obesity ,Receptor ,Aged ,Retrospective Studies ,Glycated Hemoglobin ,business.industry ,nutritional and metabolic diseases ,Glucose Tolerance Test ,Middle Aged ,Overweight ,medicine.disease ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Disease Progression ,Female ,medicine.symptom ,business ,Research Article - Abstract
The soluble receptor for advanced glycation end products (sRAGE) may be protective against inflammation associated with obesity and type 2 diabetes (T2DM). The aim of this study was to determine the distribution of sRAGE isoforms and whether sRAGE isoforms are associated with risk of T2DM development in subjects spanning the glucose tolerance continuum. In this retrospective analysis, circulating total sRAGE and endogenous secretory RAGE (esRAGE) were quantified via ELISA, and cleaved RAGE (cRAGE) was calculated in 274 individuals stratified by glucose tolerance status (GTS) and obesity. Group differences were probed by ANOVA, and multivariate ordinal logistic regression was used to test the association between sRAGE isoform concentrations and the proportional odds of developing diabetes, vs. normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). When stratified by GTS, total sRAGE, cRAGE, and esRAGE were all lower with IGT and T2DM, while the ratio of cRAGE to esRAGE (cRAGE:esRAGE) was only lower ( P < 0.01) with T2DM compared with NGT. When stratified by GTS and obesity, cRAGE:esRAGE was higher with obesity and lower with IGT ( P < 0.0001) compared with lean, NGT. In ordinal logistic regression models, greater total sRAGE (odds ratio, 0.91; P < 0.01) and cRAGE (odds ratio, 0.84; P < 0.01) were associated with lower proportional odds of developing T2DM. Reduced values of sRAGE isoforms observed with both obesity and IGT are independently associated with greater proportional odds of developing T2DM. The mechanisms by which each respective isoform contributes to obesity and insulin resistance may reveal novel treatment strategies for diabetes.
- Published
- 2017
29. Resting Metabolic Rate Does Not Change in Response to Different Types of Training in Subjects with Type 2 Diabetes
- Author
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Kristian Karstoft, Cecilie Fau Brinkløv, Ida Kær Thorsen, Jens Steen Nielsen, and Mathias Ried-Larsen
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Resting metabolic rate ,Physical fitness ,exercise interventions ,030209 endocrinology & metabolism ,Body composition ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Interval training ,Exercise training ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Glycemic control ,Diabetes type 2 ,Medicine ,Exercise interventions ,Treadmill ,resting metabolic rate ,Glycemic ,body composition ,lcsh:RC648-665 ,diabetes type 2 ,business.industry ,VO2 max ,030229 sport sciences ,Continuous training ,Clinical Trial ,Preferred walking speed ,Basal metabolic rate ,Physical therapy ,physical fitness ,glycemic control ,business ,human activities ,exercise training - Abstract
Background and objectives Ambiguous results have been reported regarding the effects of training on resting metabolic rate (RMR), and the importance of training type and intensity is unclear. Moreover, studies in subjects with type 2 diabetes (T2D) are sparse. In this study, we evaluated the effects of interval and continuous training on RMR in subjects with T2D. Furthermore, we explored the determinants for training-induced alterations in RMR. Methods Data from two studies, both including T2D subjects, were encompassed in this manuscript. Study 1 was a randomized, crossover study where subjects (n = 14) completed three, 2-week interventions [control, continuous walking training (CWT), interval-walking training (IWT)] separated by washout periods. Training included 10 supervised treadmill sessions, 60 min/session. CWT was performed at moderate walking speed [aiming for 73% of walking peak oxygen uptake (VO2peak)], while IWT was performed as alternating 3-min repetitions at slow (54% VO2peak) and fast (89% VO2peak) walking speed. Study 2 was a single-arm training intervention study where subjects (n = 23) were prescribed 12 weeks of free-living IWT (at least 3 sessions/week, 30 min/session). Before and after interventions, RMR, physical fitness, body composition, and glycemic control parameters were assessed. Results No overall intervention-induced changes in RMR were seen across the studies, but considerable inter-individual differences in RMR changes were seen in Study 2. At baseline, total body mass (TBM), fat-free mass (FFM), and fat mass were all associated with RMR. Changes in RMR were associated with changes in TBM and fat mass, and subjects who decreased body mass and fat mass also decreased their RMR. No associations were seen between changes in physical fitness, glycemic control, or FFM and changes in RMR. Conclusion Neither short-term continuous or interval-type training, nor longer term interval training affects RMR in subjects with T2D when no overall changes in body composition are seen. If training occurs concomitant with a reduction in fat mass, however, RMR is decreased. Clinical Trials Registration (www.ClinicalTrials.gov) NCT02320526 and NCT02089477.
- Published
- 2017
30. Glucose effectiveness, but not insulin sensitivity, is improved after short-term interval training in individuals with type 2 diabetes mellitus: a controlled, randomised, crossover trial
- Author
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Gerrit van Hall, Ida Jakobsen, Sine H. Knudsen, Thomas P. J. Solomon, Kristian Karstoft, Bente Klarlund Pedersen, and Margaret A Clark
- Subjects
0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Type 2 diabetes ,Walking ,Interval training ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Insulin ,Exercise ,Aged ,Cross-Over Studies ,C-Peptide ,Continuous glucose monitoring ,business.industry ,Center (category theory) ,Type 2 Diabetes Mellitus ,Insulin sensitivity ,Middle Aged ,medicine.disease ,Crossover study ,Preferred walking speed ,Kinetics ,030104 developmental biology ,Endocrinology ,Diabetes Mellitus, Type 2 ,Body Composition ,Female ,Insulin Resistance ,business ,Energy Metabolism - Abstract
The role of glucose effectiveness (S G) in training-induced improvements in glucose metabolism in individuals with type 2 diabetes is unknown. The objectives and primary outcomes of this study were: (1) to assess the efficacy of interval walking training (IWT) and continuous walking training (CWT) on S G and insulin sensitivity (S I) in individuals with type 2 diabetes; and (2) to assess the association of changes in S G and S I with changes in glycaemic control. Fourteen participants with type 2 diabetes underwent three trials (IWT, CWT and no training) in a crossover study. Exclusion criteria were exogenous insulin treatment, smoking, pregnancy, contraindications to structured physical activity and participation in recurrent training (>90 min/week). The trials were performed in a randomised order (computerised-generated randomisation). IWT and CWT consisted of ten supervised treadmill walking sessions, each lasting 60 min, over 2 weeks. IWT was performed as repeated cycles of 3 min slow walking and 3 min fast walking (aiming for 54% and 89% of $$ \overset{\cdotp }{V}{\mathrm{O}}_{2\mathrm{peak}} $$ , respectively, which was measured during the last minute of each interval), and CWT was performed aiming for a moderate walking speed (73% of $$ \overset{\cdot }{V}{\mathrm{O}}_{2\mathrm{peak}} $$ ). A two-step (pancreatic and hyperinsulinaemic) hyperglycaemic clamp was implemented before and after each trial. All data were collected in a hospitalised setting. Neither participants nor assessors were blinded to the trial interventions. Thirteen individuals completed all procedures and were included in the analyses. IWT improved S G (mean ± SEM: 0.6 ± 0.1 mg kg−1 min−1, p 0.05), whereas CWT matched for energy expenditure and time duration improved neither S G nor S I (both p > 0.05). Changes in S G, but not in S I, were associated with changes in mean (β = −0.62 ± 0.23, r 2 = 0.17, p
- Published
- 2017
31. The Acute Effects of Interval- Vs Continuous-Walking Exercise on Glycemic Control in Subjects With Type 2 Diabetes: A Crossover, Controlled Study
- Author
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Bente Klarlund Pedersen, Camilla S. Christensen, Kristian Karstoft, and Thomas P. J. Solomon
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Clinical Biochemistry ,Context (language use) ,Walking ,Type 2 diabetes ,Biochemistry ,law.invention ,Oxygen Consumption ,Endocrinology ,Randomized controlled trial ,law ,Internal medicine ,Dietary Carbohydrates ,medicine ,Humans ,Insulin ,Exercise physiology ,Exercise ,Glycemic ,Cross-Over Studies ,business.industry ,Biochemistry (medical) ,Type 2 Diabetes Mellitus ,Middle Aged ,Glucagon ,medicine.disease ,Crossover study ,Postprandial ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Physical therapy ,Female ,business ,human activities - Abstract
Glycemic control improves with physical activity, but the optimal exercise mode is unknown.The objective of the study was to determine whether interval-based exercise improves postprandial glucose tolerance and free-living glycemia more than oxygen consumption- and time duration-matched continuous exercise.This was a crossover, controlled study with trials performed in randomized order.The study was conducted in hospitalized and ambulatory care.PATIENTS diagnosed with type 2 diabetes mellitus (n=10, no withdrawals) participated in the study.Subjects performed three 1-hour interventions: 1) interval walking (IW; repeated cycles of 3 min of slow and fast walking); 2) continuous walking (CW); and 3) control (CON). Oxygen consumption (VO2) was measured continuously to match mean VO2 between exercise sessions (∼75% VO2peak).A mixed-meal tolerance test (MMTT; 450 kcal, 55% carbohydrate) with stable glucose isotopic tracers was provided after each intervention, and glucose kinetics were measured during the following 4 hours. Free-living glycemic control was assessed for approximately 32 hours after the MMTT using continuous glucose monitoring.VO2 was well matched between the exercise interventions. IW decreased the mean and maximal incremental plasma glucose during the MMTT when compared with the CON (mean 1.2 ± 0.4 vs 2.0 ± 0.5 mmol/L, P.001; maximal 3.7 ± 0.6 vs 4.6 ± 0.7 mmol/L, P = .005) and mean when compared with CW (1.7 ± 0.4 mmol/L, P = .02). No differences in the mean or maximal incremental plasma glucose values were seen between the CW and CON. The metabolic clearance rate of glucose during the MMTT was increased in the IW compared with CW (P = .049) and CON (P.001). Continuous glucose monitoring mean glucose was reduced in IW compared with CW for the rest of the intervention day (8.2 ± 0.4 vs 9.3 ± 0.7 mmol/L, P = .03), whereas no differences were found between IW and CW the following day.One interval-based exercise session improves glycemic control in type 2 diabetes mellitus subjects when compared with an oxygen consumption- and time duration-matched continuous exercise session.
- Published
- 2014
32. Hyperglycemia abolishes meal-induced satiety by a dysregulation of ghrelin and peptide YY3–36 in healthy overweight/obese humans
- Author
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Kristian Karstoft, Sine H. Knudsen, and Thomas P. J. Solomon
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,Endocrinology, Diabetes and Metabolism ,media_common.quotation_subject ,Peptide ,Overweight ,Satiety Response ,Eating ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Insulin ,Peptide YY ,Obesity ,Meals ,media_common ,chemistry.chemical_classification ,Meal ,business.industry ,digestive, oral, and skin physiology ,Overweight obesity ,Appetite ,Middle Aged ,medicine.disease ,Ghrelin ,Peptide Fragments ,Endocrinology ,chemistry ,Health ,Hyperglycemia ,Female ,medicine.symptom ,business ,Hormone - Abstract
Satiety and satiety-regulating gut hormone levels are abnormal in hyperglycemic individuals. We aimed to determine whether these abnormalities are secondary to hyperglycemia. Ten healthy overweight/obese subjects (age: 56 ± 3 yr; BMI: 30.3 ± 1.2 kg/m2) received three equicaloric meals at t = 0, 4, and 8 h in the absence (control trial) and presence of experimental hyperglycemia (hyperglycemia trial; 5.4 mM above basal). Circulating levels of glucose, insulin, ghrelin, and peptide YY (PYY)3–36 and visual analog scale ratings of satiety were measured throughout each trial. In the control trial, glucose, insulin, PYY3–36, and the feeling of fullness were increased in the postprandial periods, whereas ghrelin was decreased. In the hyperglycemia trial, in which plasma glucose was increased to 11.2 ± 0.1 mmol/l, postprandial meal responses (AUC: 0–2, 4–6, and 8–10 h) of PYY3–36 were lower ( meal 1, P < 0.0001; meal 2, P < 0.001; meal 3, P < 0.05), whereas insulin ( meal 1, P < 0.01; meal 2, P < 0.001; meal 3, P < 0.05) and ghrelin ( meal 1, P < 0.05; meal 2, P > 0.05; meal 3, P > 0.05) were higher compared with the control trial. Furthermore, the incremental (Δ0–0.5, 4–4.5, and 8–8.5 h) ghrelin response to the first and third meals was higher in the hyperglycemia trial in contrast to control (Δ: 2.3 ± 8.0, P = 0.05; Δ: 14.4 ± 2.5, P < 0.05). Also, meal-induced fullness was prevented ( meal 1, P = 0.06; meal 2, P = 0.01; meal 3, P = 0.08) by experimental hyperglycemia. Furthermore, trends in ghrelin, PYY3–36, and fullness were described by different polynomial functions between the trials. In conclusion, hyperglycemia abolishes meal-induced satiety and dysregulates postprandial responses of the gut hormones PYY3–36 and ghrelin in overweight/obese healthy humans.
- Published
- 2014
33. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial
- Author
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Mathias Ried-Larsen, Janus Damm Nybing, Emma Dorph, Camilla Noerfelt Dahl, Nicole Vinum, Louise Lang Lehrskov, Grit Elster Legaard, Sidsel Kofoed Seide, Bente Klarlund Pedersen, Anne-Sophie Wedell-Neergaard, Stine Nymand, Rikke Krogh-Madsen, Natja Launbo, Helga Ellingsgaard, Marie Henneberg, Regitse Højgaard Christensen, Kristian Karstoft, Jaya B. Rosenmeier, Robin Christensen, Sabrina Ravn Fagerlind, Monica Korsager Larsen, and Maria Ball
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Physiology ,Adipose tissue ,Intra-Abdominal Fat ,Placebo ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Randomized controlled trial ,law ,Internal medicine ,medicine ,Humans ,Lipolysis ,Exercise physiology ,Exercise ,Molecular Biology ,Interleukin-6 ,business.industry ,Skeletal muscle ,Organ Size ,Cell Biology ,Middle Aged ,Blockade ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Lean body mass ,Female ,business ,Il 6 signaling ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade. Wedell-Neergaard et al. show that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. Given that abdominal fat is metabolically harmful to health, this study raises a potentially important side effect of IL-6 receptor antibodies, such as tocilizumab, used to treat some forms of arthritis.
- Published
- 2019
34. Changes in urinary excretion of oxidative nucleic acid modifications in the week following Copenhagen Marathon 2018, Denmark
- Author
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Christina Petersen-Bønding, Kristian Karstoft, Thorkil Ploug, Tina Vilsbøll, Emilie S. Andersen, Cristina Michaelsen, Emil List Larsen, Laura Kofoed Kjær, Filip K. Knop, Trine Henriksen, Henrik E. Poulsen, and Mark Lyngbæk
- Subjects
medicine.medical_specialty ,business.industry ,RNA ,Cardiorespiratory fitness ,Oxidative phosphorylation ,Urine ,medicine.disease_cause ,Biochemistry ,Excretion ,Endocrinology ,Interquartile range ,Physiology (medical) ,Internal medicine ,medicine ,business ,human activities ,Body mass index ,Oxidative stress - Abstract
Introduction The relationship between oxidative stress and physical activity is very complex. A single bout of exercise seems to induce oxidative stress, whereas regular exercise has been suggested to reduce oxidative stress. Here, we investigated the changes in oxidative RNA and DNA modifications in the week following a single bout of excessive exercise. Methods This observational study was conducted in relation to the Copenhagen Marathon 2018, Denmark. Male, non-professional runners (n=20) were examined before-, immediate after-, four days after-, and seven days after the marathon. Twenty-four-hour (24h) urine excretion of 8-oxo-7,8-dihydro-guanosine(8-oxoGuo) and 8-oxo-7,8-dihydro-2’-deoxyguanosine(8-oxodG) were determined using ultra performance liquid chromatography-tandem mass spectrometry as a measurement of oxidative RNA and DNA modifications, respectively. Results The runners were healthy, non-smokers with cardiorespiratory fitness level above average ((median (inter quartile range(IQR))): Age: 29.6(24.3;37.2) years, body mass index: 24.3(23.8;25.2) kg/m2, VO2max: 52.7(49.5;55.7) ml/min/kg). The baseline level of 8-oxoGuo and 8-oxodG were (median(IQR)): 33.9(29.2; 38.1) and 27.9(21.4; 30.8) nmol/24h, respectively. The level of 8-oxoGuo presented a marginal trend towards increase immediate after the marathon compared to baseline (Δmedian(IQR): 3.9 (-2.4;8.7) nmol/24h, P=0.12), no difference was found in 8-oxodG (-1.8(-4.3;2.6) nmol/24h, P=0.62). On day four, we observed a decrease in both 8-oxoGuo (-2.1(-8.4;0.1) nmol/24h, P=0.02) and 8-oxodG (-2.5(-4.0;0.1) nmol/24h, P Conclusion A single bout of strenuous exercise did not result in immediate increase in oxidative RNA and DNA modifications, however a marginal trend toward increased level of oxidative RNA modifications was observed. Both oxidative RNA and DNA modifications decreased four days after the marathon. The clinical implications of these results remain to be elucidated.
- Published
- 2018
35. Pancreatic β-cell Function Is a Stronger Predictor of Changes in Glycemic Control After an Aerobic Exercise Intervention Than Insulin Sensitivity
- Author
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Kristian Karstoft, Jacob M. Haus, Sangeeta R. Kashyap, Steven K. Malin, John P. Kirwan, and Thomas P. J. Solomon
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Context (language use) ,Type 2 diabetes ,Biochemistry ,Body Mass Index ,Impaired glucose tolerance ,Endocrinology ,Insulin resistance ,Insulin-Secreting Cells ,Internal medicine ,Glucose Intolerance ,Weight Loss ,medicine ,Humans ,Endocrine Research ,Aerobic exercise ,Obesity ,Exercise ,Glycemic ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,Insulin ,Biochemistry (medical) ,Glucose Tolerance Test ,medicine.disease ,Exercise Therapy ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Female ,Insulin Resistance ,business - Abstract
Understanding intersubject variability in glycemic control following exercise training will help individualize treatment.Our aim was to determine whether this variability is related to training-induced changes in insulin sensitivity or pancreatic β-cell function.We conducted an observational clinical study of 105 subjects with impaired glucose tolerance or type 2 diabetes.Individual subject changes in fitness (VO2max), glycemia (glycosylated hemoglobin, fasting glucose, oral glucose tolerance test), insulin sensitivity (hyperinsulinemic-euglycemic clamp), oral glucose-stimulated insulin secretion (GSIS), and disposition index (DI) were measured following 12 to 16 weeks of aerobic exercise training. Regression analyses were used to identify relationships between variables.After training, 86% of subjects increased VO2max and lost weight. Glycosylated hemoglobin, fasting glucose, and 2-hour oral glucose tolerance test were reduced in 69%, 62%, and 68% of subjects, respectively, while insulin sensitivity improved in 90% of the participants. Changes in glycemic control were congruent with changes in GSIS such that 66% of subjects had a reduction in first-phase GSIS, and 46% had reduced second-phase GSIS. Training increased first- and second-phase DI in 83% and 74% of subjects. Training-induced changes in glycemic control were related to changes in GSIS (P.05), but not insulin sensitivity or DI, and training-induced improvements in glycemic control were largest in subjects with greater pretraining GSIS.Intersubject variability in restoring glycemic control following exercise is explained primarily by changes in insulin secretion. Thus, baseline and training-induced changes in β-cell function may be a key determinant of training-induced improvements in glycemic control.
- Published
- 2013
36. Impaired postprandial fullness in Type 2 diabetic subjects is rescued by acute exercise independently of total and acylated ghrelin
- Author
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Kristian Karstoft, Sine H. Knudsen, and Thomas P. J. Solomon
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,Rest ,media_common.quotation_subject ,Type 2 diabetes ,Carbohydrate metabolism ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Insulin ,Exercise physiology ,Exercise ,media_common ,business.industry ,digestive, oral, and skin physiology ,Type 2 Diabetes Mellitus ,Appetite ,Middle Aged ,Overweight ,Postprandial Period ,medicine.disease ,Ghrelin ,Glucose ,Endocrinology ,Postprandial ,Diabetes Mellitus, Type 2 ,business - Abstract
Ghrelin levels are suppressed in obese subjects and subjects with Type 2 diabetes mellitus (T2DM). Exercise-stimulated decreases in plasma ghrelin are a proposed mediator of exercise-induced satiety in healthy subjects. However, exercise-induced satiety and the impact of impaired ghrelin levels in obesity-related disease are poorly understood. Therefore our objective was to investigate exercise-induced postprandial satiety and ghrelin responses in overweight subjects with T2DM ( N = 8) and healthy controls ( N = 7). Visual analog scale satiety questionnaires (assessing hunger, thirst, food that could be eaten, nausea, and fullness) and circulating levels of glucose, insulin, and total and acylated ghrelin were measured at baseline and in response to a 75 g oral glucose load, provided immediately after an aerobic exercise bout (1 h at 50% Wmax) or no exercise (rest trial), on two separate occasions. Baseline levels of total (284.4 ± 15.9 and 397.6 ± 35.2 pmol/l) and acylated ghrelin (7.9 ± 1.0 and 13.7 ± 1.2 pmol/l) were lower in subjects with T2DM compared with healthy subjects ( P < 0.05). In the rest trial, post- vs. preprandial feeling of fullness increased in healthy subjects but decreased in subjects with T2DM (healthy vs. T2DM; P < 0.05). Exercise increased postprandial fullness in the T2DM group ( P < 0.05), while plasma ghrelin levels were unaffected. Our data suggest that the presence of T2DM likely drives suppressed ghrelin levels and poor appetite regulation, but a single exercise bout is sufficient to restore oral glucose-induced fullness independently of ghrelin.
- Published
- 2013
37. The effect of alternate-day caloric restriction on the metabolic consequences of 8 days of bed rest in healthy lean men: a randomized trial
- Author
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Kirsten Møller, Kristian Karstoft, Mark Lyngbæk, Sebastian Porsdam Mann, Bente Klarlund Pedersen, Ian Law, Carsten Thomsen, Signe Tellerup Nielsen, Rikke Krogh-Madsen, Anne-Sophie Wedell-Neergaard, Anne Langkilde, Nina Majlund Harder-Lauridsen, and Fabiana Braga Benatti
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Energy reduction ,030209 endocrinology & metabolism ,Intra-Abdominal Fat ,Bed rest ,law.invention ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Cognition ,Randomized controlled trial ,law ,Physiology (medical) ,Internal medicine ,Intermittent fasting ,Medicine ,Humans ,Insulin ,Exercise ,Caloric Restriction ,Metabolic Syndrome ,business.industry ,Caloric theory ,Fasting ,Glucose Tolerance Test ,Affect ,Endocrinology ,Glucose ,Anesthesia ,Insulin Resistance ,business ,Energy Metabolism ,030217 neurology & neurosurgery ,Bed Rest - Abstract
Physical activity and alternate-day fasting/caloric restriction may both ameliorate aspects of the metabolic syndrome, such as insulin resistance, visceral fat mass accumulation, and cognitive impairment by overlapping mechanisms. The purpose of this study was to test the hypothesis that alternate-day caloric restriction (ADCR) with overall energy balance would reduce insulin resistance and accumulation of visceral fat, in addition to improving cognitive functions, after 8 consecutive days in bed. Healthy, lean men ( n = 20) were randomized to 1) 8 days of bed rest with three daily isoenergetic meals (control group, n = 10); and 2) 8 days of bed rest with 25% of total energy requirements every other day and 175% of total energy requirements every other day (ADCR group). Oral glucose tolerance testing, dual-energy X-ray absorptiometry (DXA) scans, magnetic resonance imaging of the abdomen and brain, V̇o2max, and tests for cognitive function were performed before and after bed rest. In addition, daily fasting blood samples and 24-h glucose profiles by continuous glucose monitoring system were assessed during the 8 days of bed rest period. Bed rest induced insulin resistance, visceral fat accumulation, and worsening of mood. No positive effects emerged from ADCR on these negative health outcomes. Compared with the control group, ADCR was associated with improved and steadier glycemic control on fasting days and higher glycemic fluctuation and indexes of insulin resistance on overeating days. In contrast to our hypothesis, the metabolic impairment induced by 8 days of bed rest was not counteracted by ADCR with overall energy balance. NEW & NOTEWORTHY Alternate-day caloric restriction without overall energy reduction does not ameliorate the metabolic impairment induced in lean men by 8 days of bed rest.
- Published
- 2016
38. The effects of interval- vs. continuous exercise on excess post-exercise oxygen consumption and substrate oxidation rates in subjects with type 2 diabetes
- Author
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Gareth A. Wallis, Thomas P. J. Solomon, Kristian Karstoft, and Bente Klarlund Pedersen
- Subjects
Glycerol ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,chemistry.chemical_element ,030209 endocrinology & metabolism ,Type 2 diabetes ,Walking ,Fatty Acids, Nonesterified ,Oxygen ,Interval training ,Body Mass Index ,03 medical and health sciences ,Eating ,0302 clinical medicine ,Endocrinology ,Oxygen Consumption ,Internal medicine ,Heart rate ,Medicine ,Humans ,Respiratory exchange ratio ,Exercise ,business.industry ,Calorimetry, Indirect ,030229 sport sciences ,Middle Aged ,medicine.disease ,Lipid Metabolism ,Continuous training ,Kinetics ,chemistry ,Diabetes Mellitus, Type 2 ,Basal metabolic rate ,Female ,business ,Energy Metabolism ,Body mass index ,Oxidation-Reduction - Abstract
For unknown reasons, interval training often reduces body weight more than energy-expenditure matched continuous training. We compared the acute effects of time-duration and oxygen-consumption matched interval- vs. continuous exercise on excess post-exercise oxygen consumption (EPOC), substrate oxidation rates and lipid metabolism in the hours following exercise in subjects with type 2 diabetes (T2D).Following an overnight fast, ten T2D subjects (M/F: 7/3; age=60.3±2.3years; body mass index (BMI)=28.3±1.1kg/m(2)) completed three 60-min interventions in a counterbalanced, randomized order: 1) control (CON), 2) continuous walking (CW), 3) interval-walking (IW - repeated cycles of 3min of fast and 3min of slow walking). Indirect calorimetry was applied during each intervention and repeatedly for 30min per hour during the following 5h. A liquid mixed meal tolerance test (MMTT, 450kcal) was consumed by the subjects 45min after completion of the intervention with blood samples taken regularly.Exercise interventions were successfully matched for total oxygen consumption (CW=1641±133mL/min; IW=1634±126mL/min, P0.05). EPOC was higher after IW (8.4±1.3l) compared to CW (3.7±1.4l, P0.05). Lipid oxidation rates were increased during the MMTT in IW (1.03±0.12mg/kg per min) and CW (0.87±0.04mg/kg per min) compared with CON (0.73±0.04mg/kg per min, P0.01 and P0.05, respectively), with no difference between IW and CW. Moreover, free fatty acids and glycerol concentrations, and glycerol kinetics were increased comparably during and after IW and CW compared to CON.Interval exercise results in greater EPOC than oxygen-consumption matched continuous exercise during a post-exercise MMTT in subjects with T2D, whereas effects on substrate oxidation and lipid metabolism are comparable.
- Published
- 2016
39. The Acute Effects of Interval-Type Exercise on Glycemic Control in Type 2 Diabetes Subjects: Importance of Interval Length. A Controlled, Counterbalanced, Crossover Study
- Author
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Kristian Karstoft, Thomas P. J. Solomon, and Ida Jakobsen
- Subjects
Blood Glucose ,Male ,Physiology ,lcsh:Medicine ,Walking ,Type 2 diabetes ,Biochemistry ,Endocrinology ,0302 clinical medicine ,Heart Rate ,Medicine and Health Sciences ,Insulin ,Medicine ,Biomechanics ,Public and Occupational Health ,lcsh:Science ,Multidisciplinary ,Organic Compounds ,Respiration ,Monosaccharides ,Hematology ,Middle Aged ,Sports Science ,Blood Sugar ,Type 2 Diabetes ,Body Fluids ,Exercise Therapy ,Chemistry ,Blood ,Glycemic index ,Postprandial ,Physical Sciences ,Cardiology ,Anatomy ,Research Article ,Adult ,medicine.medical_specialty ,Endocrine Disorders ,Carbohydrates ,030209 endocrinology & metabolism ,03 medical and health sciences ,Oxygen Consumption ,Internal medicine ,Heart rate ,Diabetes Mellitus ,Humans ,Sports and Exercise Medicine ,Exercise physiology ,Exercise ,Aged ,Glycemic ,Diabetic Endocrinology ,Glycated Hemoglobin ,Biological Locomotion ,business.industry ,Organic Chemistry ,lcsh:R ,Chemical Compounds ,Biology and Life Sciences ,Physical Activity ,030229 sport sciences ,medicine.disease ,Crossover study ,Hormones ,Preferred walking speed ,Glucose ,Diabetes Mellitus, Type 2 ,Physical Fitness ,Glycemic Index ,Metabolic Disorders ,Physical therapy ,lcsh:Q ,Physiological Processes ,business ,human activities - Abstract
Interval-type exercise is effective for improving glycemic control, but the optimal approach is unknown. The purpose of this study was to determine the importance of the interval length on changes in postprandial glycemic control following a single exercise bout. Twelve subjects with type 2 diabetes completed a cross-over study with three 1-hour interventions performed in a non-randomized but counter-balanced order: 1) Interval walking consisting of repeated cycles of 3 min slow (aiming for 54% of Peak oxygen consumption rate [VO2peak]) and 3 min fast (aiming for 89% of VO2peak) walking (IW3); 2) Interval walking consisting of repeated cycles of 1 min slow and 1 min fast walking (IW1) and 3) No walking (CON). The exercise interventions were matched with regards to walking speed, and VO2 and heart rate was assessed throughout all interventions. A 4-hour liquid mixed meal tolerance test commenced 30 min after each intervention, with blood samples taken regularly. IW3 and IW1 resulted in comparable mean VO2 and heart rates. Overall mean postprandial blood glucose levels were lower after IW3 compared to CON (10.3±3.0 vs. 11.1±3.3 mmol/L; P < 0.05), with no significant differences between IW1 (10.5±2.8 mmol/L) and CON or IW3 and IW1 (P > 0.05 for both). Conversely blood glucose levels at specific time points during the MMTT differed significantly following both IW3 and IW1 as compared to CON. Our findings support the previously found blood glucose lowering effect of IW3 and suggest that reducing the interval length, while keeping the walking speed and time spend on fast and slow walking constant, does not result in additional improvements. TRIAL REGISTRATION:ClinicalTrials.gov NCT02257190.
- Published
- 2016
40. Effects of acute exercise on pancreatic endocrine function in subjects with type 2 diabetes
- Author
-
Kamilla Winding, Bente Klarlund Pedersen, Jens J. Holst, Kristian Karstoft, Thomas P. J. Solomon, and Sine H. Knudsen
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Arginine ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Glucagon ,Injections ,Endocrinology ,Glucagon-Like Peptide 1 ,Internal medicine ,Insulin Secretion ,Internal Medicine ,medicine ,Endocrine system ,Humans ,Insulin ,Insulin secretion ,Infusions, Intravenous ,Exercise ,Pancreas ,Morning ,business.industry ,Fasting ,medicine.disease ,Clamp ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Cohort ,Glucose Clamp Technique ,Female ,business - Abstract
We determined the effects of exercise on pancreatic endocrine responses to metabolic stimuli in subjects with type 2 diabetes (T2D) and examined the influence of subjects' diabetic status. Fourteen subjects underwent a hyperglycaemic clamp with glucagon-like peptide-1 (GLP-1) infusion and arginine injection, the morning after a 1-h walk or no exercise. Subjects were stratified by high and low fasting plasma glucose (FPG) levels and by glycated haemoglobin (HbA1c) levels, as well as by current use/non-use of antidiabetic medication. In the entire cohort, exercise did not alter insulin secretion, while glucagon levels were increased in all clamp phases (p
- Published
- 2014
41. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test
- Author
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Kristian Karstoft, John P. Kirwan, Steven K. Malin, Bente Klarlund Pedersen, Thomas P. J. Solomon, Maria Pedersen, Matthew J. Laye, Jacob M. Haus, and Sine H. Knudsen
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,endocrine system diseases ,Physiology ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Denmark ,Type 2 diabetes ,Impaired glucose tolerance ,Cohort Studies ,Diagnosis, Differential ,Prediabetic State ,Insulin resistance ,Physiology (medical) ,Internal medicine ,Insulin-Secreting Cells ,Glucose Intolerance ,Insulin Secretion ,medicine ,Humans ,Insulin ,Ohio ,Glycated Hemoglobin ,Glucose tolerance test ,medicine.diagnostic_test ,business.industry ,nutritional and metabolic diseases ,Insulin sensitivity ,Articles ,Glucose clamp technique ,Glucose Tolerance Test ,Middle Aged ,medicine.disease ,Obesity ,Endocrinology ,Diabetes Mellitus, Type 2 ,Allostasis ,Disease Progression ,Glucose Clamp Technique ,Female ,Insulin Resistance ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that β-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT.
- Published
- 2014
42. Mechanisms behind the superior effects of interval vs continuous training on glycaemic control in individuals with type 2 diabetes: a randomised controlled trial
- Author
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Bente Klarlund Pedersen, Maria M Scheel, Kamilla Winding, Jens J. Holst, Thomas P. J. Solomon, Sine H. Knudsen, Noemi G James, Jesper Olesen, and Kristian Karstoft
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,law.invention ,Randomized controlled trial ,Endurance training ,law ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Insulin ,business.industry ,Skeletal muscle ,Middle Aged ,medicine.disease ,Continuous training ,Peripheral ,Exercise Therapy ,Endocrinology ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,Cardiology ,Female ,business - Abstract
Aims/hypothesis By use of a parallel and partly crossover randomised, controlled trial design we sought to elucidate the underlying mechanisms behind the advantageous effects of interval walking training (IWT) compared with continuous walking training (CWT) on glycaemic control in individuals with type 2 diabetes. We hypothesised that IWT, more than CWT, would improve insulin sensitivity including skeletal muscle insulin signalling, insulin secretion and disposition index (DI). Methods By simple randomisation (sequentially numbered, opaque sealed envelopes), eligible individuals (diagnosed with type 2 diabetes, no exogenous insulin treatment) were allocated to three groups: a control group (CON, n=8), an IWT group (n=12) and an energy expenditure-matched CWT group (n=12). Training groups were prescribed free-living training, five sessions per week (60 min/session). A threestage hyperglycaemic clamp, including glucose isotope tracers and skeletal muscle biopsies, was performed before and after a 4 month intervention in a hospitalised setting. No blinding was performed. Results The improved glycaemic control, which was only seen in the IWT group, was consistent with IWT-induced increases in insulin sensitivity index (49.8±14.6%; p
- Published
- 2014
43. Normal physical activity obliterates the deleterious effects of a high-caloric intake
- Author
-
Rikke Krogh-Madsen, Bente Klarlund Pedersen, Maria Pedersen, Jens J. Holst, Louise Seier Hansen, Louise Lehrskov-Schmidt, Kristian Karstoft, Carsten Thomsen, Karin K. Pedersen, Sine H. Knudsen, and Thomas P. J. Solomon
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Intra-Abdominal Fat ,Adolescent ,Physiology ,medicine.medical_treatment ,Carbohydrate metabolism ,Motor Activity ,Young Adult ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Glycemic ,Sedentary lifestyle ,business.industry ,Insulin ,Type 2 Diabetes Mellitus ,VO2 max ,medicine.disease ,Lipid Metabolism ,Obesity ,Endocrinology ,Body Composition ,Exercise Test ,Sedentary Behavior ,business ,Energy Intake ,Risk Reduction Behavior - Abstract
A high-caloric intake combined with a sedentary lifestyle is an important player in the development of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine if the level of physical activity has impact on the metabolic effects of a high-caloric (+2,000 kcal/day) intake. Therefore, healthy individuals on a high-caloric intake were randomized to either 10,000 or 1,500 steps/day for 14 days. Step number, total energy expenditure, dietary records, neuropsychological tests, maximal oxygen uptake (V̇o2max), whole body dual-energy X-ray absorptiometry (DXA) and abdominal magnetic resonance imaging (MRI) scans, continuous glucose monitoring (CGM), and oral glucose tolerance tests (OGTT) with stable isotopes were performed before and after the intervention. Both study groups gained the same amount of body weight. However, the inactive group accumulated significantly more visceral fat compared with the active group. Following the 2-wk period, the inactive group also experienced a poorer glycemic control, increased endogenous glucose production, decreased hepatic insulin extraction, increased baseline plasma levels of total cholesterol and LDL, and a decreased cognitive function with regard to capacity of attention. In conclusion, we find evidence to support that habitual physical activity may prevent pathophysiological symptoms associated with diet-induced obesity.
- Published
- 2013
44. Exercise‐induced increase in beta‐cell function in type 2 diabetics is dependent on fasting glycemia
- Author
-
Kristian Karstoft, Bente Klarlund Pedersen, Thomas P. J. Solomon, Kamilla Winding, and Sine H. Knudsen
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Genetics ,Medicine ,Beta-cell Function ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2013
45. Identifying novel plasma biomarkers of pancreatic beta‐cell function using acute and chronic models of hyperglycemia
- Author
-
Sine H. Knudsen, Kristian Karstoft, Bente Klarlund Pedersen, and Thomas P. J. Solomon
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Genetics ,medicine ,Cancer research ,Beta-cell Function ,Plasma biomarkers ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2013
46. Daily marathon running for a week--the biochemical and body compositional effects of participation
- Author
-
Kristian Karstoft, Bente Klarlund Pedersen, Thomas P. J. Solomon, and Matthew J. Laye
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Time Factors ,Marathon running ,Physical Therapy, Sports Therapy and Rehabilitation ,LIVER CELL DAMAGE ,Running ,Hemoglobins ,Insulin resistance ,Internal medicine ,medicine ,Homeostasis ,Humans ,Insulin ,Orthopedics and Sports Medicine ,Aspartate Aminotransferases ,Adverse effect ,Serum Albumin ,medicine.diagnostic_test ,L-Lactate Dehydrogenase ,business.industry ,Myoglobin ,Alanine Transaminase ,General Medicine ,Fasting ,Lipase ,Orosomucoid ,gamma-Glutamyltransferase ,Middle Aged ,medicine.disease ,Blood Coagulation Factors ,Endocrinology ,C-Reactive Protein ,Cholesterol ,Blood chemistry ,Hematocrit ,Lean body mass ,Body Composition ,Female ,business ,Lipid profile ,Biomarkers - Abstract
Although long-distance running, such as ultramarathons and multistage races, is increasingly popular, it maybe potentially harmful to health, despite sparse evidence. We studied 8 experienced recreational runners participating in a multiple-marathon running event in which 7 marathons were completed on consecutive days. Fasting blood chemistry and body composition were assessed before and 20-24 hours after the race. The total finish time for the 7 marathons ranged between 23:25:42 and 34:25:21 (hours:minutes:seconds). Only minor increases in circulating skeletal muscle cell damage markers, liver cell damage markers, and inflammatory markers occurred after the race. No other significant adverse biochemical effects were observed. The homeostasis model assessment of insulin resistance decreased markedly, and an improved lipid profile was found. A decrease in fat mass and increase in lean body mass was observed, resulting in no overall weight changes. In summary, the race did not cause any major adverse effects, whereas some traditional markers of cardiovascular disease improved acutely after the race.
- Published
- 2013
47. Examining the effects of hyperglycemia on pancreatic endocrine function in humans: evidence for in vivo glucotoxicity
- Author
-
Thomas P. J. Solomon, Kamilla Winding, Jens J. Holst, Kristian Karstoft, Bente Klarlund Pedersen, and Sine H. Knudsen
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Type 2 diabetes ,Biochemistry ,Glucagon ,Islets of Langerhans ,Endocrinology ,Diabetes mellitus ,Internal medicine ,Insulin Secretion ,medicine ,Humans ,Insulin ,Pancreatic hormone ,Cross-Over Studies ,business.industry ,Biochemistry (medical) ,Glucagon secretion ,Glucose clamp technique ,Middle Aged ,medicine.disease ,Pancreatic Hormones ,medicine.anatomical_structure ,Glucose ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Glucose Clamp Technique ,Female ,business ,Pancreas - Abstract
Investigating the impact of hyperglycemia on pancreatic endocrine function promotes our understanding of the pathophysiology of hyperglycemia-related disease.The objective of the study was to test the hypothesis that experimental hyperglycemia impairs insulin and glucagon secretion.A randomized, crossover in healthy controls, compared with type 2 diabetic patients.The study was conducted at a university hospital.Normal glucose-tolerant subjects (n = 10) and patients with type 2 diabetes (n = 10), individually matched by age, sex, and body mass index.Normal glucose-tolerant subjects underwent 24 h of experimental hyperglycemia (+5.4 mm above basal). Subjects with type 2 diabetes did not undergo an intervention.Insulin secretion, glucagon secretion, insulin sensitivity, disposition index, and endogenous glucose production (via [6,6-(2)H(2)]glucose infusion) were measured during hyperglycemic clamps combined with infusion of glucagon-like peptide (GLP)-1(7-36) (0.5 pmol/kg · min) and injection of arginine (5 g).Insulin secretion was correlated with glucagon suppression in subjects with normal glucose tolerance only. Individuals with type 2 diabetes had lower insulin sensitivity (-33 ± 11%) and insulin secretory responses to glucose, GLP-1, and arginine (-40 ± 11, -58 ± 7, and -36 ± 13%, respectively) and higher plasma glucagon and endogenous glucose production compared with normal glucose-tolerant subjects (all P0.05). After 24 h of experimental hyperglycemia, insulin sensitivity (-29 ± 10%), disposition index (-24 ± 16%), and GLP-1- (-19 ± 7%) and arginine-stimulated (-15 ± 10%) insulin secretion were decreased in normal glucose-tolerant subjects (all P0.05). However, plasma glucagon responses were not affected. Furthermore, experimental hyperglycemia abolished the correlation between insulin secretion and glucagon suppression.Experimental hyperglycemia impaired pancreatic β-cell function but did not acutely impair α-cell glucagon secretion in normal glucose-tolerant subjects.
- Published
- 2012
48. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum
- Author
-
Sine H. Knudsen, Thomas P. J. Solomon, Gerrit van Hall, Kristian Karstoft, and Bente Klarlund Pedersen
- Subjects
Glucose kinetics ,medicine.medical_specialty ,endocrine system diseases ,Physiology ,business.industry ,Insulin ,medicine.medical_treatment ,physical activity ,nutritional and metabolic diseases ,Type 2 diabetes ,oral glucose tolerance test ,medicine.disease ,Glucagon ,Impaired glucose tolerance ,Endocrinology ,Postprandial ,Physiology (medical) ,Internal medicine ,medicine ,Ingestion ,Aerobic exercise ,type 2 diabetes ,business ,Original Research ,Glycemic - Abstract
We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty‐four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m2, P > 0.05) underwent a 180‐min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6‐2H2]glucose and ingestion of [U‐13C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials, plasma glucose concentrations and kinetics, insulin, C‐peptide, and glucagon were measured. Rates (mg kg−1 min−1) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; RaOGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, RaOGTT, and Rd (all P < 0.0001) in all groups with a tendency for a greater (~20%) peak RaOGTT value in NGT subjects when compared to IGT and T2D subjects. Accordingly, following exercise, the plasma glucose concentration during the OGTT was increased in NGT subjects (P < 0.05), while unchanged in subjects with IGT and T2D. In conclusion, while a single bout of moderate‐intensity exercise increased the postprandial glucose response in NGT subjects, glucose tolerance following exercise was preserved in the two hyperglycemic groups. Thus, postprandial plasma glucose responses immediately following exercise are dependent on the underlying degree of glycemic control., This study shows that following an exercise bout, plasma glucose concentrations during an oral glucose tolerance test are increased in subjects with normal glucose tolerance, but unchanged in subjects with impaired glucose tolerance or type 2 diabetes. While rates of glucose disappearance and rates of glucose appearance from endogenous sources and from orally ingested glucose were all increased following exercise, there was a 20% greater peak value for the rate of orally ingested glucose appearance in normal glucose tolerant subjects, when compared to IGT and T2D subjects. In summary, postprandial plasma glucose responses immediately following exercise are dependent on the underlying level of glycemic control.
- Published
- 2014
49. The Influence of Hyperglycemia on the Therapeutic Effect of Exercise on Glycemic Control in Patients With Type 2 Diabetes Mellitus
- Author
-
John P. Kirwan, Steven K. Malin, Thomas P. J. Solomon, Kristian Karstoft, and Jacob M. Haus
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Glucose control ,business.industry ,Treatment outcome ,Therapeutic effect ,Type 2 Diabetes Mellitus ,Middle Aged ,Article ,Clinical trial ,Treatment Outcome ,Text mining ,Endocrinology ,Diabetes Mellitus, Type 2 ,Hyperglycemia ,Internal medicine ,Internal Medicine ,medicine ,Humans ,Female ,In patient ,business ,Exercise ,Glycemic - Published
- 2013
50. The direct effect of incretin hormones on glucose metabolism
- Author
-
Sine H. Knudsen, Stefan P. Mortensen, Thomas P. J. Solomon, and Kristian Karstoft
- Subjects
medicine.medical_specialty ,Endocrinology ,Chemistry ,Internal medicine ,Genetics ,medicine ,Incretin ,Carbohydrate metabolism ,Molecular Biology ,Biochemistry ,Biotechnology ,Hormone
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