The effect of exogenous glucagon on circulating amino acids in individuals with and without type 2 diabetes and obesity.

Objective: In obesity and type 2 diabetes, hyperglucagonaemia may be caused by elevated levels of glucagonotropic amino acids due to hepatic glucagon resistance at the level of amino acid turnover. Here, we investigated the effect of exogenous glucagon on circulating amino acids in obese and non-obese individuals with and without type 2 diabetes. Design: This was a post hoc analysis in a glucagon infusion study performed in individuals with type 2 diabetes (n = 16) and in age, sex, and body mass index-matched control individuals without diabetes (n = 16). Each group comprised two subgroups of eight individuals with and without obesity, respectively. Methods: All participants received a 1-h glucagon infusion (4 ng/kg/min) in the overnight fasted state. Plasma amino acid concentrations were measured with frequent intervals. Results: Compared to the control subgroup without obesity, baseline total amino acid levels were elevated in the control subgroup with obesity and in the type 2 diabetes subgroup without obesity. In all subgroups, amino acid levels decreased by up to 20% in response to glucagon infusion, which resulted in high physiological steady-state glucagon levels (mean concentration: 74 pmol/L, 95% CI [68;79] pmol/L). Following correction for multiple testing, no intergroup differences in changes in amino acid levels reached significance. Conclusion: Obesity and type 2 diabetes status was associated with elevated fasting levels of total amino acids. The glucagon infusion decreased circulating amino acid levels similarly in all subgroups, without significant differences in the response to exogenous glucagon between individuals with and without obesity and type 2 diabetes. Significance statement: The hormone glucagon stimulates glucose production from the liver, which may promote hyperglycaemia if glucagon levels are abnormally elevated, as is often seen in type 2 diabetes and obesity. Glucagon levels are closely linked to, and influenced by, the levels of circulating amino acids. To further investigate this link, we measured amino acid levels in individuals with and without obesity and type 2 diabetes before and during an infusion of glucagon. We found that circulating amino acid levels were higher in type 2 diabetes and obesity, and that glucagon infusion decreased amino acid levels in both individuals with and without type 2 diabetes and obesity. The study adds novel information to the link between circulating levels of glucagon and amino acids.

Measuring small-scale plasma irregularities in the high-latitude E- and F-regions simultaneously.

The ionosphere, Earth's space environment, exhibits widespread turbulent structuring, or plasma irregularities, visualized by the auroral displays seen in Earth's polar regions. Such plasma irregularities have been studied for decades, but plasma turbulence remains an elusive phenomenon. We combine scale-dependent measurements from a ground-based radar with satellite observations to characterize small-scale irregularities simultaneously in the bottomside and topside ionosphere and perform a statistical analysis on an aggregate from both instruments over time. We demonstrate the clear mapping of information vertically along the ionospheric altitude column, for field-perpendicular wavelengths down to 1.5 km. Our results paint a picture of the northern hemisphere high-latitude ionosphere as a turbulent system that is in a constant state of growth and decay; energy is being constantly injected and dissipated as the system is continuously attempting an accelerated return to equilibrium. We connect the widespread irregularity dissipation to Pedersen conductance in the E-region, and discuss the similarities between irregularities found in the polar cap and in the auroral region in that context. We find that the effects of a conducting E-region on certain turbulent properties (small-scale spectral index) is near ubiquitous in the dataset, and so we suggest that the electrodynamics of a conducting E-region must be considered when discussing plasma turbulence at high latitudes. This intimate relationship opens up the possibility that E-region conductivity is associated with the generation of F-region irregularities, though further studies are needed to assess that possibility.

Competing interface and bulk anisotropies in Co-rich TbCo amorphous thin films.

We study the magnetic properties of amorphous TbxCo100-xfilms withxin the range 8-12 at% and with a thickness of 5-100 nm. In this range the magnetic properties are shaped by a competition between a perpendicular bulk magnetic anisotropy and an in-plane interface anisotropy, in addition to the changes in magnetization. This results in a temperature controllable spin reorientation transition from in-plane to out-of-plane which is thickness and composition dependent. Furthermore, we show that perpendicular anisotropy is recovered throughout an entire TbCo/CoAlZr multilayer, where neither TbCo nor CoAlZr single layers exhibit perpendicular anisotropy. This illustrates the important role of the TbCo interfaces in the overall effective anisotropy.

Worldwide Assessment of the Mandibular First Molar Second Distal Root and Root Canal: A Cross-sectional Study with Meta-analysis.

INTRODUCTION: This study assessed the prevalence of radix entomolaris and 2 canals at the distal aspect of mandibular first molars among different geographic regions by means of cone-beam computed tomographic imaging. METHODS: Precalibrated observers from 23 worldwide geographic locations followed a standardized screening protocol to assess 5750 cone-beam computed tomographic images of mandibular first molars (250 per region), gathering demographic data and recording the presence of radix entomolaris and a second canal at the distal aspect of teeth. Intra- and interrater reliability tests were conducted and comparisons among groups were performed using proportions and odds ratio forest plots. The significance level was set at 5%. RESULTS: The results of intra- and interrater tests were above 0.79. The prevalence of radix entomolaris varied from 0.9% in Venezuela (95% confidence interval [CI], 0%-1.9%) to 22.4% in China (95% CI, 17.2%-27.6%). Regarding the proportion of a second distal canal, it ranged from 16.4% in Venezuela (95% CI, 11.8%-21.0%) to 60.0% in Egypt (95% CI, 53.9%-66.1%). The East Asia subgroup was associated with a significantly higher prevalence of an extra distolingual root, whereas the American subgroup, the American native ethnic group, and elderly patients were linked to significantly lower percentages of a second canal at the distal aspect of teeth. No significant differences were noted between male or female patients. CONCLUSIONS: The overall worldwide prevalence rates of radix entomolaris and a second canal at the distal aspect of the mandibular first molar were 5.6% and 36.9%, respectively. The East Asia geographic region and Asian ethnic group had a higher prevalence of a second distal root.

Glucagon Clearance is Preserved in Type 2 Diabetes.

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity. Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed. Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T½. Individuals with obesity had neither a significantly decreased MCR, T½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

Glucagon Clearance is Preserved in Type 2 Diabetes.

Hyperglucagonemia is a common observation in both obesity and type 2 diabetes, and the etiology is primarily thought to be hypersecretion of glucagon. We investigated whether altered elimination kinetics of glucagon could contribute to the hyperglucagonemia in type 2 diabetes and obesity. Individuals with type 2 diabetes and preserved kidney function (8 with and 8 without obesity) and matched control individuals (8 with and 8 without obesity) were recruited. Each participant underwent a 1-hour glucagon infusion (4 ng/kg/min), achieving steady-state plasma glucagon concentrations, followed by a 1-hour wash-out period. Plasma levels, the metabolic clearance rate (MCR), half-life (T½) and volume of distribution of glucagon were evaluated and a pharmacokinetic model was constructed. Glucagon MCR and volume of distribution were significantly higher in the type 2 diabetes group compared to the control group, while no significant differences between the groups were found in glucagon T½ Individuals with obesity had neither a significantly decreased MCR, T½, nor volume of distribution of glucagon. In our pharmacokinetic model, glucagon MCR associated positively with fasting plasma glucose and negatively with body weight. In conclusion, our results suggest that impaired glucagon clearance is not a fundamental part of the hyperglucagonemia observed in obesity and type 2 diabetes.

Tuneable exchange-spring stiffness in amorphous magnetic trilayer structures.

We investigate the magnetic properties of amorphous Sm10Co90/Co60(Al70Zr30)40/Co85(Al70Zr30)15exchange-spring magnet trilayers. The magnetically soft Co85(Al70Zr30)15layer is coupled to the magnetically hard Sm10Co90layer through the weakly magnetic low-TcCo60(Al70Zr30)40spacer layer. The strength of the coupling can be controlled with temperature and the coupling persists above the intrinsicTcof the spacer layer due to a long-range magnetic proximity effect. Polarized neutron reflectivity is used to examine the magnetic profile of the trilayers during magnetization reversal. A two-step switching occurs, with the switching angle of the soft layer strongly dependent on the strength of the coupling. In the strong coupling regime a magnetic state can be achieved where the soft layer magnetization is perpendicular to the hard layer whereas in the weak coupling regime the soft layer reverses fully.

Treatment of type 2 diabetes in children: what are the specific considerations?

Introduction: The number of individuals under 18 years of age with type 2 diabetes is increasing at an alarming rate worldwide. These patients are often characterized by obesity and they often experience a more rapid disease progression than adults with type 2 diabetes. Thus, focus on prevention and management of complications and comorbidities is imperative. With emphasis on weight loss and optimal glycemic control, treatment includes lifestyle changes and pharmacotherapy, which in this patient group is limited to metformin, liraglutide and insulin. In selected cases, bariatric surgery is indicated.Areas covered: This perspective article provides an overview of the literature covering pathophysiology, diagnosis, characteristics and treatment of pediatric type 2 diabetes, and outlines the gaps in our knowledge where further research is needed. The paper draws on both mechanistic studies, large scale intervention trials, epidemiological studies and international consensus statements.Expert opinion: Type 2 diabetes in pediatric patients is an increasing health care problem, and the current treatment strategies do not successfully meet the many challenges and obstacles in this patient group. Treatments must be early, intensive, multifaceted and durable. Also, prevention of obesity and type 2 diabetes in at-risk children should be addressed and prioritized on all levels.

Metabolic effects of 1-week binge drinking and fast food intake during Roskilde Festival in young healthy male adults.

AIMS/HYPOTHESIS: Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males. METHODS: Fourteen festival participants (FP) were studied before, during and after 1 week's participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline. RESULTS: The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group. CONCLUSIONS/INTERPRETATION: Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.

Worldwide Prevalence of a Lingual Canal in Mandibular Premolars: A Multicenter Cross-sectional Study with Meta-analysis.

INTRODUCTION: The presence of multiple root canals is an important morphologic aspect of mandibular premolars. This study aimed to perform a worldwide analysis on the prevalence of a lingual canal in mandibular premolars and to evaluate its influence on patients' demographics in 23 countries using cone-beam computed tomographic images. METHODS: Observers from 23 countries were instructed to evaluate cone-beam computed tomographic images of 300 first and 300 second premolars (13,800 teeth) regarding the presence of a lingual canal, canal configuration, and data related to patients' ethnicity, age, and sex following a standardized screening methodology. Intra- and interrater evaluations were performed using the Cohen kappa test and intraclass correlation coefficient. Proportion and odds ratio forest plots were calculated in order to compare groups. Statistical significance was set at 5%. RESULTS: Both kappa and intraclass correlation coefficient values were above 0.60, and the percentage of agreement was 94.9% (first premolar) and 97.8% (second premolar). A significant statistical difference was observed between the worldwide proportion of a lingual canal in mandibular first (23.8%; range, 12.0%-32.7%) and second (5.3%; range, 1.0%-15.3%) premolars (P < .05). Asians and patients over 60 years old were associated with the lowest proportions of a lingual canal (P < .05), whereas Africans and younger groups were associated with the highest proportions (P < .05). The prevalence of a lingual canal in males (27.9%) was higher than females (20.0%) for the first premolar only (P < .05). Males were associated with 1.533 and 1.597 higher odds of presenting a lingual root canal in the first and second premolars, respectively. CONCLUSIONS: The worldwide proportion of a lingual root canal was 23.6% and 5.3% for the first and second premolars, respectively. Ethnicity, geographic region, age, and sex had an influence on the outcomes.

Glucagonostatic Potency of GLP-1 in Patients With Type 2 Diabetes, Patients With Type 1 Diabetes, and Healthy Control Subjects.

Hyperglucagonemia is a well-known contributor to diabetic hyperglycemia, and glucagon-like peptide 1 (GLP-1) suppresses glucagon secretion. Reduced inhibitory effects of glucose and GLP-1 on glucagon secretion may contribute to the hyperglucagonemia in diabetes and influence the success of GLP-1 receptor agonist therapy. We examined the dose-response relationship for GLP-1 on glucose-induced glucagon suppression in healthy individuals and patients with type 2 and type 1 diabetes. In randomized order, 10 healthy individuals with normal glucose tolerance, 10 patients with type 2 diabetes, and 9 C-peptide-negative patients with type 1 diabetes underwent 4 separate stepwise glucose clamps (five 30-min steps from fasting level to 15 mmol/L plasma glucose) during simultaneous intravenous infusions of saline or 0.2, 0.4, or 0.8 pmol GLP-1/kg/min. In healthy individuals and patients with type 2 diabetes, GLP-1 potentiated the glucagon-suppressive effect of intravenous glucose in a dose-dependent manner. In patients with type 1 diabetes, no significant changes in glucagon secretion were observed during the clamps whether with saline or GLP-1 infusions. In conclusion, the glucagonostatic potency of GLP-1 during a stepwise glucose clamp is preserved in patients with type 2 diabetes, whereas our patients with type 1 diabetes were insensitive to the glucagonostatic effects of both glucose and GLP-1.

Estimation of Heart Rate Variability from Finger Photoplethysmography During Rest, Mild Exercise and Mild Mental Stress.

Due to the possibilities in miniaturization and wearability, photoplethysmography (PPG) has recently gained a large interest not only for heart rate measurement, but also for estimating heart rate variability, which is derived from ECG by convention. The agreement between PPG and ECG-based HRV has been assessed in several studies, but the feasibility of PPG-based HRV estimation is still largely unknown for many conditions. In this study, we assess the feasibility of HRV estimation based on finger PPG during rest, mild physical exercise and mild mental stress. In addition, we compare different variants of signal processing methods including selection of fiducial point and outlier correction. Based on five minutes synchronous recordings of PPG and ECG from 15 healthy participants during each of these three conditions, the PPG-based HRV estimation was assessed for the SDNN and RMSSD parameters, calculated based on two different fiducial points (foot point and maximum slope), with and without outlier correction. The results show that HRV estimation based on finger PPG is feasible during rest and mild mental stress, but can give large errors during mild physical exercise. A good estimation is very dependent on outlier correction and fiducial point selection, and SDNN seems to be a more robust parameter compared to RMSSD for PPG-based HRV estimation.

Endurance exercise training volume is not associated with progression of coronary artery calcification.

BACKGROUND: Recent cross-sectional studies have suggested a dose-dependent relationship between lifelong exposure to physical activity and the burden of calcified coronary artery disease (CAD). No longitudinal studies have addressed this concern. HYPOTHESIS: Exercise volume is associated with progression of coronary artery calcium (CAC), defined as ≥10 units increase in CAC score. METHODS: Sixty-one recreational athletes who were assessed by coronary computed tomography angiography (CCTA) as part of the NEEDED 2013/14 study were re-assessed 4-5 years later, in 2018. RESULTS: Subjects were 45.9 ± 9.6 years old at inclusion, and 46 (74%) were male. Between 2013 and 2018, the participants reported median 5 (range: 0-20, 25th-75th percentile: 4-6) hours of high-intensity exercise per week. None of the included subjects smoked during follow-up. At inclusion, 21 (33%) participants had coronary artery calcifications. On follow-up CCTA in 2018, 15 (25%) subjects had progressive coronary calcification (≥10 Agatston units increase in CAC). These subjects were older (53 ± 9 vs 44 ± 9 years old, P = .002) and had higher levels of low-density lipoprotein at baseline (3.5 (2.9-4.3) vs 2.9 (2.3-3.5) mmol/L, P = .031) as compared to subjects with stable condition. No relationship was found between hours of endurance training per week and progression of coronary artery calcification. In multiple regression analysis, age and baseline CAC were the only significant predictors of progressive CAC. CONCLUSION: No relationship between exercise training volume and the progression of coronary artery calcification was found in this longitudinal study of middle-aged recreational athletes.

Occult obstructive coronary artery disease is associated with prolonged cardiac troponin elevation following strenuous exercise.

BACKGROUND: Sudden cardiac death among middle-aged recreational athletes is predominantly due to myocardial ischaemia. This study examined whether measuring cardiac troponin I and T (cTnI and cTnT) after strenuous exercise could identify occult obstructive coronary artery disease. DESIGN: Prospective observational study. METHODS: Subjects were recruited from 1002 asymptomatic recreational cyclists completing a 91-km mountain bike race (North Sea Race Endurance Exercise Study). No subject had known cardiovascular disease or took cardiovascular medication. Blood samples were collected within 24 h before and 3 h and 24 h after the race. Coronary computed tomography angiography was performed in 80 participants with the highest post-exercise cTnI and in 40 reference subjects with moderately elevated cTnI values. RESULTS: Study subjects (N = 120) were 45 (36-52) years old and 74% were male. There were similar demographics in the High-cTnI group and the Reference group. The cTn concentrations were highest at 3 h post-race: cTnI, 224 (125-304) ng/L; cTnT, 89 (55-124) ng/L. Nine subjects had obstructive coronary artery disease on coronary computed tomography angiography, eight of whom were High-cTnI responders. Two subjects had myocardial bridging, both High-cTnI responders. Troponin concentrations at 24 h post-race were higher in subjects with obstructive coronary artery disease than in the rest of the cohort (n = 109): cTnI, 151 (72-233) ng/L vs. 24 (19-82) ng/L, p = 0.005; cTnT, 39 (25-55) ng/L vs. 20 (14-31) ng/L, p = 0.002. The areas under the receiver operating characteristic curves for predicting obstructive coronary artery disease were 0.79, p = 0.005 (cTnI) and 0.82, p = 0.002 (cTnT). CONCLUSION: In subjects with occult obstructive coronary artery disease there was a prolonged elevation of cTn following strenuous exercise.

Worldwide Analyses of Maxillary First Molar Second Mesiobuccal Prevalence: A Multicenter Cone-beam Computed Tomographic Study.

INTRODUCTION: Maxillary first molar second mesiobuccal (MB2) root canal prevalence may change among different populations. The aim of this study was to analyze the worldwide prevalence of the MB2 root canal and understand its possible relation with sex, age, side, and root configuration using in vivo cone-beam computed tomographic (CBCT) assessment. METHODS: Observers from 21 regions were calibrated to achieve a similar CBCT assessment methodology and instructed to collect data from 250 maxillary first molars in previously existing examinations. Intra- and interrater reliability tests were performed. The sample size included 5250 molars and was defined by way of a preliminary trial. Data collected included MB2 presence, sex, age, side, number of roots per tooth, and mesiobuccal root configuration. The z test for proportions in independent groups was used to analyze the differences among subgroups. P < .05 was considered significant. RESULTS: The worldwide CBCT-assessed MB2 prevalence was 73.8%, ranging from 48.0% in Venezuela to 97.6% in Belgium. The prevalence in males and females was 76.3% and 71.8%, respectively (P < .05). Significantly higher MB2 proportions were found in younger patients and 3-rooted molar configurations. The group intraclass correlation coefficient and the percentage of agreement for the MB2 presence were 0.95 and 0.91, respectively. The intrarater Cohen kappa value was above 0.61 for all observers. CONCLUSIONS: MB2 prevalence in the analyzed regions varied widely. The differences may be associated with specificities within each region but also patient demographics. Males, younger patients, and 3-rooted configurations were associated with higher MB2 proportions.

Is glucagon-like peptide-1 fully protected by the dipeptidyl peptidase 4 inhibitor sitagliptin when administered to patients with type 2 diabetes?

AIM: To evaluate the relationship between plasma dipeptidyl-peptidase 4 (DPP-4) activity and its protection of glucagon-like peptide-1 (GLP-1) using the DPP-4 inhibitor sitagliptin. METHODS: On four separate days, patients with type 2 diabetes (T2D) (n = 8; age: 59.9 ±10.8 [mean ±SD] years; body mass index [BMI]: 28.8 ±4.6 kg/m2 ; glycated haemoglobin A1c [HbA1c]: 43.1 ±0.5 mmol/mol [6.6% ±1.7%]) received a 380-minute continuous intravenous infusion of GLP-1 (1.0 pmol × kg bodyweight-1 × minutes-1 ) and a double-blind, single-dose oral administration of sitagliptin in doses of 0 (placebo), 25, 100 and 200 mg. RESULTS: Plasma DPP-4 activity decreased compared to baseline (placebo) with increasing doses of sitagliptin (P < .01), reaching a maximal inhibition with the 100 mg dose. Levels of intact GLP-1 increased with increasing doses of sitagliptin from placebo to 100 mg (area under curve [AUC] 7.2 [95%, CI; 12.1, 16.4] [placebo], 10.7 [16.1, 21.4] [25 mg], 11.7 [17.8, 23.6] [100 mg] nmol/L × 360 minutes [P < .01]), but no further increase in intact GLP-1 levels was observed with 200 mg of sitagliptin (11.5 [17.6, 23.4] nmol/L × 360 minutes) (P = .80). CONCLUSION: Our findings suggest that the sitagliptin dose of 100 mg is sufficient to inhibit both plasma and membrane-bound DPP-4 activity, presumably also leading to complete protection of endogenous GLP-1 in patients with T2D.

Effects of Smoking Versus Nonsmoking on Postprandial Glucose Metabolism in Heavy Smokers Compared With Nonsmokers.

OBJECTIVE: Epidemiological studies suggest that smoking increases the risk of type 2 diabetes. We hypothesized that smoking-derived nicotine and ensuing activation of nicotinic cholinergic receptors in the gastrointestinal tract and the autonomic nervous system would have a detrimental effect on postprandial glucose metabolism and, thus, potentially constitute a link between smoking and the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: We subjected 11 male heavy smokers to two identical 4-h liquid mixed-meal tests: one with concomitant cigarette smoking (immediately before and after meal intake) and one without smoking. Twelve age-, sex-, and BMI-matched nonsmokers underwent an identical meal test without smoking. RESULTS: The smokers were characterized by higher fasting plasma concentrations of glucagon compared with the nonsmokers. Among smokers, cigarette smoking before and after the meal significantly reduced postprandial plasma glucose excursions. There were no differences in gut or pancreatic hormone concentrations between the test days in the smoking group, and the responses were similar to those in the control group. CONCLUSIONS: Our results suggest that smoking in association with meal intake decreases the postprandial plasma glucose concentrations, possibly through decreased gastric emptying, and that elevated fasting glucagon concentrations rather than smoking-induced alterations in postprandial glucose and hormone responses may be associated with the elevated risk of type 2 diabetes in chronic smokers.

The cardiac troponin response following physical exercise in relation to biomarker criteria for acute myocardial infarction; the North Sea Race Endurance Exercise Study (NEEDED) 2013.

BACKGROUND: The aim of this study was to investigate troponin (cTn) dynamics for both genders, compared the different release patterns to the gender specific 99th percentile and to current biomarker criteria for diagnosing myocardial infarction (MI). METHODS: Serum was collected from 97 recreational cyclists 24 h before and immediately, 3 and 24 h following a 91-km bike race. hs-cTnI (Abbott) and hs-cTnT (Roche) were measured. Conventional or CT coronary angiography was performed in the 13 participants with the highest hs-cTnI (>140 ng/L). Three subjects with obstructive coronary artery disease were excluded from the statistical analysis. RESULTS: There was a significant (p < 0.001) post-race increase in cTnI and cTnT; cTnT peaked immediately, cTnI peaked after 3 h. Relative to the gender specific 99th percentile values, women had the largest increase. The biomarker criteria for MI were met in 76-87% for hs-cTnI, and 96-95% for hs-cTnT (p value <0.05), within the first 3 h post-race. CONCLUSION: Post-race cardiac troponin concentrations exceeded diagnostic criteria for MI in the majority of subjects, more often for hs-cTnT than for hs-cTnI, and more pronounced in women than in men. The current biomarker criteria for MI discriminate poorly between an exercise induced troponin increase and acute MI.

The copeptin response after physical activity is not associated with cardiac biomarkers or asymptomatic coronary artery disease: The North Sea Race Endurance Exercise Study (NEEDED) 2013.

BACKGROUND: Copeptin concentrations increase both during acute coronary syndrome and following physical exercise. The relationship between copeptin increase following physical exercise and coronary artery disease (CAD) is uncertain. The aim of this study was to 1) describe the copeptin response following strenuous physical exercise, and 2) investigate the determinants of exercise induced copeptin concentrations, particularly in relation to cardiac biomarkers and CAD. METHODS: Serum samples were collected from 97 recreational cyclists 24h before, and immediately, 3 and 24h after a 91-km bike race. Three subjects were subsequently diagnosed with significant asymptomatic CAD. Delta copeptin concentrations were correlated to patient characteristics and to biomarker concentrations. RESULTS: Participants were 42.8±9.6years, and 76.3% were male. Copeptin concentrations increased to maximal levels immediately after the race and were normalized in >90% after 3h. A total of 53% and 39% exceeded the 95th and 99th percentile of the assay (10 and 19pmol/L) respectively. In multivariate models, race time, serum sodium, creatinine and cortisol were significant predictors of copeptin levels. There was no correlation between changes in copeptin and changes in cardiac biomarkers (hs-cTnI, hs-cTnT and BNP). Copeptin concentrations were normal in the subjects with asymptomatic CAD. CONCLUSIONS: The moderate, short-term, exercise induced copeptin increase observed in the present study was not related to hs-cTn or BNP levels. Copeptin was normal in three asymptomatic recreational athletes with significant CAD.

Current Therapies That Modify Glucagon Secretion: What Is the Therapeutic Effect of Such Modifications?

PURPOSE OF REVIEW: Hyperglucagonemia contributes significantly to hyperglycemia in type 2 diabetes and suppressed glucagon levels may increase the risk of hypoglycemia. Here, we give a brief overview of glucagon physiology and the role of glucagon in the pathophysiology of type 2 diabetes and provide insights into how antidiabetic drugs influence glucagon secretion as well as a perspective on the future of glucagon-targeting drugs. RECENT FINDINGS: Several older as well as recent investigations have evaluated the effect of antidiabetic agents on glucagon secretion to understand how glucagon may be involved in the drugs' efficacy and safety profiles. Based on these findings, modulation of glucagon secretion seems to play a hitherto underestimated role in the efficacy and safety of several glucose-lowering drugs. Numerous drugs currently available to diabetologists are capable of altering glucagon secretion: metformin, sulfonylurea compounds, insulin, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors and amylin mimetics. Their diverse effects on glucagon secretion are of importance for their individual efficacy and safety profiles. Understanding how these drugs interact with glucagon secretion may help to optimize treatment.