Copeptin, a surrogate marker for arginine vasopressin secretion, is positively associated with glucagon.

AIM: To explore the association of plasma copeptin, the C-terminal portion of provasopressin and a stable surrogate marker for arginine vasopressin secretion, with plasma glucagon in obese men and men of normal weight. METHODS: We measured fasting blood concentrations of copeptin and glucagon in 102 healthy obese men (mean ± sd age 49.4 ± 10.2 years) and a control group 27 healthy men of normal weight (mean ± sd age 51.5 ± 8.4 years). Differences between groups were evaluated using t-tests, and multiple linear regression analysis, adjusting for age and weight status (normal weight vs obese), was used to calculate unstandardized regression coefficients (ß) with 95% CIs between copeptin and glucagon. Copeptin was (natural) log-transformed. RESULTS: The obese men had higher [median (interquartile range)] plasma copeptin concentrations [6.6 (4.6-9.5) vs 4.9 (3.5-6.8) pmol/l; P = 0.040] and higher mean ± sd plasma glucagon concentrations (8.5 ± 3.8 vs 5.3 ± 1.4 pmol/l; P < 0.001) than the normal-weight men. Adjusted for age and weight status, copeptin was significantly associated with glucagon (ß = 1.35, 95% CI 0.13-2.57; P = 0.031). No significant interaction effect between copeptin and weight status on glucagon was found (P = 0.81). CONCLUSIONS: Obese men had higher concentrations of copeptin and glucagon than men of normal weight. Copeptin was positively associated with glucagon. Our data suggest that increased arginine vasopressin-stimulated glucagon secretion might contribute to higher glucagon concentrations; therefore, increased arginine vasopressin secretion, in addition to other factors, could further aggravate the hyperglucagonaemic state found in obese individuals.

Soluble urokinase plasminogen activator receptor levels are elevated and associated with complications in patients with type 1 diabetes.

OBJECTIVES: Soluble urokinase plasminogen activator receptor (suPAR) is a marker of inflammation and endothelial dysfunction. We investigated the associations between suPAR and diabetes, including diabetes duration and complications, in patients with type 1 diabetes. DESIGN, SETTING AND SUBJECTS: From 2009 to 2011, 667 patients with type 1 diabetes and 51 nondiabetic control subjects were included in a cross-sectional study at Steno Diabetes Center, Gentofte, Denmark. suPAR levels were measured with an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: The investigated diabetic complications were cardiovascular disease (CVD: previous myocardial infarction, revascularisation, peripheral arterial disease and stroke), autonomic dysfunction (heart rate variability during deep breathing <11 beats min(-1) ), albuminuria [urinary albumin excretion rate (UAER) ≥30 mg/24 h] or a high degree of arterial stiffness (pulse wave velocity ≥10 m s(-1) ). Analyses were adjusted for gender, age, systolic blood pressure, estimated glomerular filtration rate, UAER, glycated haemoglobin (HbA1c ), total cholesterol, body mass index, C-reactive protein, antihypertensive treatment and smoking. RESULTS: Soluble urokinase plasminogen activator receptor levels were lower in control subjects versus all patients, in control subjects versus normoalbuminuric patients (UAER <30 mg/24 h), in normoalbuminuric patients with short (<10 years) versus long diabetes duration and were increased with degree of albuminuria (adjusted P < 0.001 for all). Furthermore, suPAR levels were higher in patients with versus without CVD (n = 144; 21.3%), autonomic dysfunction (n = 369; 59.2%), albuminuria (n = 357; 53.1%) and a high degree of arterial stiffness (n = 298; 47.2%) (adjusted P ≤ 0.024). The adjusted odds ratio (95% confidence interval) values per 1 ln unit increase in suPAR were as follows: 2.5 (1.1-5.7) for CVD: 2.7 (1.2-6.2) for autonomic dysfunction; 3.8 (1.3-10.9) for albuminuria and 2.5 (1.1-6.1) for a high degree of arterial stiffness (P ≤ 0.039). CONCLUSION: The suPAR level is higher in patients with type 1 diabetes and is associated with diabetes duration and complications independent of other risk factors. suPAR is a potential novel risk marker for the management of diabetes.

Copeptin, a surrogate marker for arginine vasopressin secretion, is associated with higher glucose and insulin concentrations but not higher blood pressure in obese men.

AIM: To explore the putative associations of plasma copeptin, the C-terminal portion of provasopressin and a surrogate marker for arginine vasopressin secretion, with obesity-related health problems, such as hyperlipidaemia, hyperinsulinaemia, hyperglycaemia, high blood pressure and an android fat distribution. METHODS: In 103 obese men (mean age ± standard deviation: 49.4 ± 10.2 years) and 27 normal weight control men (mean age: 51.5 ± 8.4 years), taking no medication, we measured 24-h ambulatory blood pressure, fasting blood concentrations of copeptin, lipids, glucose and insulin, and determined body composition by dual energy X-ray absorptiometry scanning. RESULTS: The obese men had higher [median (interquartile range)] plasma copeptin concentrations [6.6 (4.6-9.5) vs. 4.9 (3.5-6.8) pmol/l, P = 0.040] compared with the normal weight men. In the obese men, plasma copeptin was not related to 24-h systolic blood pressure (r = 0.11, P = 0.29), 24-h diastolic blood pressure (r = 0.11, P = 0.28), BMI (r = 0.09, P = 0.37), total body fatness percentage (r = 0.10, P = 0.33), android fat mass percentage (r = 0.04, P = 0.66) or serum triglyceride concentrations (r = 0.04; P = 0.68). In contrast, plasma copeptin was associated with higher serum insulin concentrations (r = 0.26, P = 0.0085) and insulin resistance as assessed by the homeostasis assessment model (r = 0.28, P = 0.0051). CONCLUSIONS: Plasma copeptin, a surrogate marker for arginine vasopressin secretion, is higher in obese men compared with normal weight men, and is associated with abnormalities in glucose and insulin metabolism, but not with higher blood pressure or an android fat distribution in obese men.

The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat.

Previous studies suggested that gastrin-releasing peptide (a neuropeptide found in rat oxyntic mucosa) and oxyntomodulin (a glucagon-containing peptide of mammalian gut) could directly affect the acid secretion of the parietal cells. We therefore studied their effect on gastric acid production in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi.

Resistance to insulin-stimulated glucose uptake and dyslipidemia in Asian Indians.

Persons from the Indian subcontinent have elevated coronary heart disease risk. We measured insulin resistance with the insulin suppression test in 22 Asian Indian men and women and an equal number of control subjects of European ancestry matched for age and body mass index. Asian men and women had increased glucose and insulin responses to oral glucose tolerance tests (P < .05 by ANOVA) and had approximately 60% higher steady-state plasma glucose levels during the insulin suppression test (P < .001 by ANOVA), consistent with insulin resistance. In response to mixed meals, Asian women had higher plasma free fatty acids and glycerol concentrations than women of European ancestry (P < .02 by ANOVA), whereas Asian Indian men had similar free fatty acid and glycerol levels compared with men of European ancestry despite higher plasma insulin levels. Thus, results in both sexes were consistent with resistance to insulin suppression of free fatty acid levels in Asian Indians. Asian Indians of both sexes had higher fasting plasma triglyceride (P < .01) and lower high-density lipoprotein cholesterol (P < .01) concentrations than men and women of European ancestry. Resistance to insulin-stimulated glucose uptake and to insulin suppression of free fatty acid levels in Asian Indians is associated with a number of metabolic abnormalities that are demonstrated risk factors for coronary heart disease, including increased glucose, insulin, and triglyceride concentrations and decreased high-density lipoprotein cholesterol concentrations.