c-peptide and Metabolic-Diseases

We investigated the changes in the cardiovascular system [resting blood pressure (BP) and heart rate (HR), measured by means of a 24-h ambulatory BP and a holter-electrocardiogram (ECG)], glycemic parameters, and lipid metabolism of subjects suffering from metabolic syndrome during a 3-week sojourn at 1,700 m in the Austrian Alps. A total of 22 male subjects with metabolic syndrome were selected. Baseline investigations were performed at Innsbruck (500 m above sea level). During the 3-week altitude stay the participants simulated a holiday with moderate sports activities. Examinations were performed on days 1, 4, 9, and 19. After returning to Innsbruck, post-altitude examinations were conducted after 7-10 days and 6-7 weeks, respectively. The 24-h ambulatory BP and holter ECG revealed a decrease in average HR, BP, and rate pressure product (RPP: systolic blood pressure x HR) after 3 weeks of altitude exposure. In some patients, an increase in premature ventricular beats was observed at the end compared to the beginning of the exposure to moderate altitude. The ECG revealed no ischemic ST-segment changes. Maximal physical capacity as measured by symptom-limited maximal cycle ergometry tests remained unchanged during the study. Six weeks after the altitude exposure the blood pressure increased again and returned to pretest levels. The Homeostasis Model Assessment index, which is a measure of insulin resistance, decreased significantly and glucose concentrations obtained after an oral glucose tolerance test were significantly lower after the stay at altitude compared to the basal values. We conclude that after a 3-week exposure to moderate altitude, patients with metabolic syndrome (1) tolerated their sojourn without any physical problems, (2) exhibited short-term favorable effects on the cardiovascular system, and (3) had significant improvements in glycemic parameters that were paralleled by a significant increase in high-density-lipoprotein-cholesterol.

Topics: Adaptation, Physiological; Adult; Aged; Altitude; Austria; Blood Glucose; Blood Pressure; C-Peptide; Cardiovascular Physiological Phenomena; Diastole; Electrocardiography, Ambulatory; Exercise Test; Heart Rate; Hemoglobins, Abnormal; Homeostasis; Humans; Insulin; Insulin Resistance; Male; Metabolic Diseases; Middle Aged; Physical Exertion; Pilot Projects; Systole

Endocrine insufficiency following severe acute pancreatitis (SAP) leads to diabetes of the exocrine pancreas, (type 3c diabetes mellitus), however it is not known how this metabolic phenotype differs from that of type 2 diabetes, or how the two subtypes can be differentiated. We sought to determine the prevalence of diabetes following SAP, and to analyse the behaviour of glucose and pancreatic hormones across a 2-h oral glucose tolerance test (OGTT).. Twenty-six patients following SAP (mean (range) duration of first SAP episode to study time of 119.3 (14.8-208.9) months) along with 26 matched controls underwent an OGTT with measurement of glucose, insulin, c-peptide, glucagon and pancreatic polypeptide (PP) at fasting/15/90/120min. Beta-cell area was estimated using the 15min c-peptide/glucose ratio, and insulin resistance (IR) using homeostasis model assessment (HOMA) and oral glucose insulin sensitivity (OGIS) models.. The prevalence of diabetes/prediabetes was 54% following SAP (38.5% newly-diagnosed compared to 19.2% newly-diagnosed controls). Estimated beta-cell area and IR did not differ between groups. AUC c-peptide was lower in SAP versus controls. AUC insulin and AUC c-peptide were lower in SAP patients with diabetes versus controls with diabetes; between-group differences were observed at the 90 and 120 min time-points only. Half of new diabetes cases in SAP patients were only identified at the 120min timepoint.. Diabetes and pre-diabetes occur frequently following SAP and are difficult to distinguish from type 2 diabetes in controls but are characterised by reduced insulin and c-peptide at later stages of an OGTT. Consistent with this observation, most new post SAP diabetes cases were diagnosed by 2-h glucose levels only.

Topics: Acute Disease; Adult; Aged; Blood Glucose; C-Peptide; Case-Control Studies; Diabetes Mellitus; Female; Follow-Up Studies; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin Resistance; Insulin-Secreting Cells; Male; Metabolic Diseases; Middle Aged; Pancreatic Hormones; Pancreatitis; Prediabetic State; Prevalence

Obesity and late-night food consumption are associated with impaired glucose tolerance. Late-night carbohydrate consumption may be particularly detrimental during late pregnancy because insulin sensitivity declines as pregnancy progresses. Further, women who were obese (Ob) prior to pregnancy have lower insulin sensitivity than do women of normal weight (NW). The aim of this study is to test the hypothesis that night-time carbohydrate consumption is associated with poorer glucose tolerance in late pregnancy and that this association would be exacerbated among Ob women. Forty non-diabetic African American women were recruited based upon early pregnancy body mass index (NW, <25 kg m(-2) ; Ob, ≥30 kg m(-2) ). Third trimester free-living dietary intake was assessed by food diary, and indices of glucose tolerance and insulin action were assessed during a 75-g oral glucose tolerance test. Women in the Ob group reported greater average 24-h energy intake (3055 kcal vs. 2415 kcal, P < 0.05). Across the whole cohort, night-time, but not day-time, carbohydrate intake was positively associated with glucose concentrations after the glucose load and inversely associated with early phase insulin secretion (P < 0.05). Multiple linear regression modelling within each weight group showed that the associations among late-night carbohydrate intake, glucose concentrations and insulin secretion were present only in the Ob group. This is the first study to report an association of night-time carbohydrate intake specifically on glucose tolerance and insulin action during pregnancy. If replicated, these results suggest that late-night carbohydrate intake may be a potential target for intervention to improve metabolic health of Ob women in late pregnancy.

Topics: Adolescent; Adult; Black or African American; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diet; Diet Records; Dietary Carbohydrates; Feeding Behavior; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Linear Models; Metabolic Diseases; Nutrition Assessment; Obesity; Pregnancy; Time Factors; Young Adult

The unbalance of glucose metabolism in humans may cause the excessive formation of methylglyoxal (MG), which can react with various biomolecules to form the precursor of advanced glycation end products (AGEs). Vescalagin (VES) is an ellagitannin that alleviates insulin resistance in cell study. Results showed that VES reduced the value of oral glucose tolerance test, cardiovascular risk index, AGEs, and tumor necrosis factor-α contents while increasing C-peptide and d-lactate contents significantly in rats orally administered MG and VES together. The preventive effect of VES on MG-induced inflammation and carbohydrate metabolic disorder in rats was thus proved. On the basis of the experiment data, a mechanism, which involves the increase in d-lactate to retard AGE formation and the decrease in cytokine release to prevent β-cell damage, is proposed to explain the bioactivities of VES in antiglycation and in the alleviation of MG-induced carbohydrate metabolic disorder in rats.

Topics: Animals; C-Peptide; Carbohydrate Metabolism; Cholesterol; Fruit; Glucose Tolerance Test; Hydrolyzable Tannins; Inflammation; Insulin; Interleukin-6; Male; Metabolic Diseases; Organ Size; Protective Agents; Pyruvaldehyde; Rats; Rats, Wistar; Syzygium; Triglycerides; Tumor Necrosis Factor-alpha

The fasting proinsulin-to-insulin ratio is a currently used marker of beta-cell dysfunction. This ratio is calculated at the basal condition, but its behavior in dynamic conditions, i.e., during glucose stimulation, could be more informative. Given the different kinetics of the peptides, a mathematical model was necessary to analyze the oral glucose tolerance test (OGTT) data of insulin, C-peptide, and proinsulin in 55 healthy (NGT), 30 impaired glucose-tolerant (IGT), and 31 type 2 diabetic (T2DM) subjects. The model provided for secretion and disappearance of the peptides and an index of beta-cell function under dynamic conditions. Total proinsulin secretion during the OGTT was not different (P > 0.053) among NGT (0.17 +/- 0.01 mmol/l in 3 h), IGT (0.22 +/- 0.02), and T2DM (0.21 +/- 0.02) subjects. The proinsulin-to-insulin molar ratio measured from basal samples was higher (P < 0.0001) in T2DM (0.39 +/- 0.05) than in NGT (0.14 +/- 0.01) and IGT (0.13 +/- 0.02) subjects, and similar results (P < 0.003) were found by the dynamic index (0.27 +/- 0.04, 0.14 +/- 0.01, 0.15 +/- 0.01 in T2DM, NGT, IGT subjects, respectively). The basal ratio significantly correlated with the dynamic index, and the regression line slope was lower than 1 (0.43 +/- 0.08, 0.61 +/- 0.10, and 0.56 +/- 0.03 in NGT, IGT, and T2DM subjects, respectively, P < 0.0001). Impaired beta-cell function in T2DM could then be indicated by proinsulin-to-insulin indexes at both basal and dynamic phases.

Topics: Adult; Algorithms; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Kinetics; Metabolic Diseases; Models, Biological; Models, Statistical; Pancreatic Function Tests; Pregnancy; Pregnancy in Diabetics; Proinsulin; Regional Blood Flow

The relationship between parity and risk of diabetes is controversial, and little information is available regarding associations between parity and measures of insulin resistance and beta-cell function. The objective of this study was to investigate the association between parity and risk of glucose intolerance and related metabolic disorders using data from a population-based study in a Native Canadian community.. Female participants (n = 383, aged 12-79 years) provided fasting blood samples for the determination of glucose, insulin, C-peptide, and proinsulin concentrations. A 75-g oral glucose tolerance test was administered, and diabetes and impaired glucose tolerance were diagnosed according to World Health Organization criteria. Waist circumference and percent body fat were determined. Information regarding occurrence of live births and previously diagnosed diabetes was obtained from interviewer-administered questionnaires.. Parity was associated with a significantly reduced risk of diabetes (nulliparous vs. >or=1 birth, odds ratio 0.43, 95% CI 0.19- 0.94, P < 0.05) after adjustment for age and waist circumference. In addition, nondiabetic nulliparous women had significantly elevated concentrations of fasting insulin and proinsulin relative to nondiabetic parous women (all P < 0.05) in analyses adjusted for age and waist circumference.. Our results are consistent with those from other populations experiencing high rates of diabetes and suggest the presence of a diabetes-prone phenotype within the nulliparous subcohort of this population, which may contribute to infertility.

Topics: Adipose Tissue; Adolescent; Adult; Aged; Blood Glucose; C-Peptide; Child; Diabetes Mellitus, Type 2; Female; Glucose Tolerance Test; Homeostasis; Humans; Insulin; Metabolic Diseases; Middle Aged; Parity; Prevalence; Proinsulin; Risk Factors

Many obese middle-aged rhesus monkeys (Macaca mulatta) spontaneously develop noninsulin dependent diabetes mellitus (NIDDM). Basal hyperinsulinemia and increased stimulated plasma insulin levels are associated with this obesity and precede the onset of overt diabetes. The present studies sought to determine the relative contributions of enhanced insulin secretion and of reduced insulin clearance to this early obesity-associated hyperinsulinemia. Direct simultaneous measurement of portal and jugular vein insulin levels in two normal monkeys showed a constant rate of hepatic insulin extraction of 56+/-3% over the range of peripheral insulin levels from 351+/-113 to 625+/-118 pmol/L. In 33 additional monkeys ranging from normal to diabetic, basal C-peptide levels were examined as an indicator of beta-cell secretion and the molar ratio of plasma C-peptide to insulin (C/I ratio) under basal steady state conditions calculated as an index of hepatic insulin extraction. Well in advance of overt diabetes, there was a progressive decline of 67% in the apparent hepatic insulin extraction rate in association with increased obesity and plasma insulin levels. Basal insulin levels and hepatic insulin extraction returned toward normal in monkeys with impaired glucose tolerance and in those with overt diabetes. We conclude that reduced insulin disposal, probably due to reduced hepatic extraction of insulin, in addition to increased beta-cell activity, contributes to the development of basal hyperinsulinemia in obese rhesus monkeys progressing toward NIDDM. In addition, in overt diabetes, normal hepatic insulin extraction in the presence of limited beta-cell secretion may exacerbate the hypoinsulinemic state.

Topics: Adipose Tissue; Animals; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Disease Models, Animal; Female; Glucose Tolerance Test; Hyperinsulinism; Insulin; Insulin-Secreting Cells; Jugular Veins; Liver; Macaca mulatta; Male; Metabolic Diseases; Obesity; Portal Vein; Receptor, Insulin; Time Factors