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.

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.

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.

Water oxidation by manganese oxides formed from tetranuclear precursor complexes: the influence of phosphate on structure and activity.

Two types of manganese oxides have been prepared by hydrolysis of tetranuclear Mn(iii) complexes in the presence or absence of phosphate ions. The oxides have been characterized structurally using X-ray absorption spectroscopy and functionally by O2 evolution measurements. The structures of the oxides prepared in the absence of phosphate are dominated by di-µ-oxo bridged manganese ions that form layers with limited long-range order, consisting of edge-sharing MnO6 octahedra. The average manganese oxidation state is +3.5. The structure of these oxides is closely related to other manganese oxides reported as water oxidation catalysts. They show high oxygen evolution activity in a light-driven system containing [Ru(bpy)3](2+) and S2O8(2-) at pH 7. In contrast, the oxides formed by hydrolysis in the presence of phosphate ions contain almost no di-µ-oxo bridged manganese ions. Instead the phosphate groups are acting as bridges between the manganese ions. The average oxidation state of manganese ions is +3. This type of oxide has much lower water oxidation activity in the light-driven system. Correlations between different structural motifs and the function as a water oxidation catalyst are discussed and the lower activity in the phosphate containing oxide is linked to the absence of protonable di-µ-oxo bridges.

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.

Glucagon Clearance is Decreased in Chronic Kidney Disease, but Preserved in Liver Cirrhosis.

It is not completely clear which organs are responsible for glucagon elimination in humans, and disturbances in the elimination of glucagon could contribute to the hyperglucagonemia observed in chronic liver disease and chronic kidney disease (CKD). Here, we evaluated kinetics and metabolic effects of exogenous glucagon in individuals with stage 4 CKD (n =16), individuals with Child-Pugh A-C cirrhosis (n = 16) and matched control individuals (n = 16), before, during and after a 60-minute glucagon infusion (4 ng/kg/min). Individuals with CKD exhibited a significantly lower mean metabolic clearance rate of glucagon (14.0 [95% CI 12.2;15.7] mL/kg/min) both compared to individuals with cirrhosis (19.7 [18.1;21.3] mL/kg/min, P < 0.001) and to control individuals (20.4 [18.1;22.7] mL/kg/min, P < 0.001). Glucagon half-life was significantly prolonged in the CKD group (7.5 [6.9;8.2] minutes) compared to individuals with cirrhosis (5.7 [5.2;6.3] minutes, P = 0.002) and control individuals (5.7 [5.2;6.3] minutes, P < 0.001). No difference in the effects of exogenous glucagon on plasma glucose, amino acids, or triglycerides was observed between groups. In conclusion, chronic kidney disease, but not liver cirrhosis leads to a significant reduction in glucagon clearance, supporting the kidneys as a primary site for human glucagon elimination.

Magnetic self-organized atomic laminate from first principles and thin film synthesis.

The first experimental realization of a magnetic M(n+1)AX(n) (MAX) phase, (Cr(0.75)Mn(0.25))(2)GeC, is presented, synthesized as a heteroepitaxial single crystal thin film, exhibiting excellent structural quality. This self-organized atomic laminate is based on the well-known Cr(2)GeC, with Mn, a new element in MAX phase research, substituting Cr. The compound was predicted using first-principles calculations, from which a variety of magnetic behavior is envisaged, depending on the Mn concentration and Cr/Mn atomic configuration within the sublattice. The analyzed thin films display a magnetic signal at room temperature.

Early diagnosis of sepsis-related hepatic dysfunction and its prognostic impact on survival: a prospective study with the LiMAx test.

INTRODUCTION: Liver dysfunction can derive from severe sepsis and might be associated with poor prognosis. However, diagnosis of septic liver dysfunction is challenging due to a lack of appropriate tests. Measurement of maximal liver function capacity (LiMAx test) has been successfully evaluated as a new diagnostic test in liver resection and transplantation. The aim of this study was to evaluate the LiMAx test during sepsis in comparison to biochemical tests and the indocyanin green test (ICG-PDR). METHODS: We prospectively investigated 28 patients (8 female and 20 male, age range 35 to 80 years) suffering from sepsis on a surgical ICU. All patients received routine resuscitation from septic shock (surgery, fluids, catecholamines, antibiotic drugs). The first LiMAx test and ICG-PDR were carried out within the first 24 hours after onset of septic symptoms, followed by day 2, 5 and 10. Other biochemical parameters and scores determining the severity of illness were measured daily. Clinical outcome parameters were examined after 90 days or at the end of treatment. The population was divided into 2 groups (group A: non-survivors or ICU length of stay (ICU-LOS) >30 days versus group B: survivors and ICU-LOS <30 days) for analysis. RESULTS: Epidemiological baseline characteristics of both groups were similar. Group A patients had significant lower LiMAx and ICG-PDR values than patients in group B. Determination of ICG-PDR by finger probe failed in 14.3% of tests due to insufficient peripheral pulses. Respiratory, renal and hepatic dysfunction (LiMAx and ICG-PDR) were associated with prolonged ICU-LOS. Only LiMAx <100 µg/kg/h and respiratory dysfunction were associated with increased mortality. For LiMAx <100 µg/kg/h receiver operating characteristic-analysis revealed a 100% sensitivity and 77% specificity for death. CONCLUSIONS: Sepsis-related hepatic dysfunction can be diagnosed early and effectively by the LiMAx test. The extent of LiMAx impairment is predictive for patient morbidity and mortality. The sensitivity and specificity of the LiMAx test was superior to that of ICG-PDR regarding the prediction of mortality.

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.

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.

Nutrient limitation on terrestrial plant growth--modeling the interaction between nitrogen and phosphorus.

Growth of plants in terrestrial ecosystems is often limited by the availability of nitrogen (N) or phosphorous (P) Liebig's law of the minimum states that the nutrient in least supply relative to the plant's requirement will limit the plant's growth. An alternative to the law of the minimum is the multiple limitation hypothesis (MLH) which states that plants adjust their growth patterns such that they are limited by several resources simultaneously. We use a simple model of plant growth and nutrient uptake to explore the consequences for the plant's relative growth rate of letting plants invest differentially in N and P uptake. We find a smooth transition between limiting elements, in contrast to the strict transition in Liebig's law of the minimum. At N : P supply ratios where the two elements simultaneously limit growth, an increase in either of the nutrients will increase the growth rate because more resources can be allocated towards the limiting element, as suggested by the multiple limitation hypothesis. However, the further the supply ratio deviates from these supply rates, the more the plants will follow the law of the minimum. Liebig's law of the minimum will in many cases be a useful first-order approximation.

Comparing resonant photon tunneling via cavity modes and Tamm plasmon polariton modes in metal-coated Bragg mirrors.

Resonant photon tunneling was investigated experimentally in multilayer structures containing a high-contrast (TiO(2)/SiO(2)) Bragg mirror capped with a semitransparent gold film. Transmission via a fundamental cavity resonance was compared with transmission via the Tamm plasmon polariton resonance that appears at the interface between a metal film and a one-dimensional photonic bandgap structure. The Tamm-plasmon-mediated transmission exhibits a smaller dependence on the angle and polarization of the incident light for similar values of peak transmission, resonance wavelength, and finesse. Implications for transparent electrical contacts based on resonant tunneling structures are discussed.

FTIR study of manganese dimers with carboxylate donors as model complexes for the water oxidation complex in Photosystem II.

The carboxylate stretching frequencies of two high-valent, di-µ-oxido bridged, manganese dimers has been studied with IR spectroscopy in three different oxidation states. Both complexes contain one monodentate carboxylate donor to each Mn ion, in one complex, the carboxylate is coordinated perpendicular to the Mn-(µ-O)(2)-Mn plane, and in the other complex, the carboxylate is coordinated in the Mn-(µ-O)(2)-Mn plane. For both complexes, the difference between the asymmetric and the symmetric carboxylate stretching frequencies decrease for both the Mn(2)(IV,IV) to Mn(2)(III,IV) transition and the Mn(2)(III,IV) to Mn(2)(III,III) transition, with only minor differences observed between the two arrangements of the carboxylate ligand versus the Mn-(µ-O)(2)-Mn plane. The IR spectra also show that both carboxylate ligands are affected for each one electron reduction, i.e., the stretching frequency of the carboxylate coordinated to the Mn ion that is not reduced also shifts. These results are discussed in relation to FTIR studies of changes in carboxylate stretching frequencies in a one electron oxidation step of the water oxidation complex in Photosystem II.

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.

Mechanistic studies on the water-oxidizing reaction of homogeneous manganese-based catalysts: isolation and characterization of a suggested catalytic intermediate.

The synthesis, isolation, and characterization of two high-valent manganese dimers with isomeric ligands are reported. The complexes are synthesized and crystallized from solutions of low-valent precursors exposed to tert-butyl hydroperoxide. The crystal structures display centrosymmetric complexes consisting of Mn(2)(IV,IV)(µ-O)(2) cores, with one ligand coordinating to each manganese. The ligands coordinate with the diaminoethane backbone, the carboxylate, and one of the two pyridines, while the second pyridine is noncoordinating. The activity of these complexes, under water oxidation conditions, is discussed in light of a proposed mechanism for water oxidation, in which this type of complexes have been suggested as a key intermediate.

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.

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.

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.