c-peptide and Weight-Gain

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.. For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.. In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).. UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cesarean Section; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Iran; Leptin; Pregnancy; Pregnancy Outcome; Weight Gain

Atypical antipsychotic drugs have been associated with the development of obesity and diabetes. In particular, olanzapine can induce peripheral insulin resistance and compensatory hyperinsulinemia independent of weight gain or psychiatric disease. To determine if this compensatory increase in insulin is mediated by parasympathetic muscarinic stimulation, we randomized 15 healthy subjects 2:1 to receive double-blind olanzapine or placebo for 9 days under diet- and activity-controlled inpatient conditions. Before and after 7 days of study drug administration, subjects underwent frequently sampled intravenous glucose tolerance tests with either saline or atropine infused on subsequent days to assess insulin secretion and hepatic insulin extraction in the absence or presence of muscarinic blockade. We found that olanzapine led to an increase in the acute insulin response to glucose, which was not seen with placebo, and was attenuated in the olanzapine group by atropine. Deconvolution of C-peptide data confirmed an increase in insulin secretion with olanzapine, which was blocked by atropine, with a modest reduction in hepatic insulin extraction with olanzapine. These results support the contribution of muscarinic augmentation of insulin secretion to olanzapine-induced hyperinsulinemia, and provide a mechanism for the compensatory hyperinsulinemia that normally serves to prevent deterioration of glucose tolerance under conditions of metabolic challenge.

Topics: Adolescent; Adult; Antipsychotic Agents; C-Peptide; Diet; Double-Blind Method; Female; Glucose Tolerance Test; Healthy Volunteers; Humans; Hyperinsulinism; Insulin Secretion; Liver; Male; Muscarinic Antagonists; Olanzapine; Weight Gain; Young Adult

Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring.. Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity.. Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant.. Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Topics: Adiposity; Adult; Anthropometry; Birth Weight; Body Mass Index; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pediatric Obesity; Pregnancy; Weight Gain

To compare maternal characteristics, obstetric outcomes and insulin resistance in a cohort of women subdivided into those who did and those who did not exceed the Institute of Medicine (IOM) gestational weight gain guidelines.. This is a prospective study of 621 women without diabetes. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width (AAW). At delivery birthweight was recorded and fetal glucose, C-peptide and leptin measured in cord blood. Insulin resistance was calculated using the HOMA equation. Outcomes in those who did and did not exceed IOM guidelines were compared.. Overall, 267 women (43%) exceeded IOM guidelines and 354 (57%) did not. On 34-week ultrasound women with excessive weight gain had higher fetal weights (2681 ± 356 g vs. 2574 ± 331, P = 0.001) and fetal adiposity (AAW) (5.29 ± 1.3 vs. 4.8 ± 1.2, P = 0.001). Infant birthweight and birthweight centiles were also higher in those who exceeded the guidelines. There was no difference between the two groups in maternal insulin resistance in early pregnancy, but by 28 weeks those with excessive weight gain had higher maternal HOMA indices and higher maternal leptin concentrations.. Excessive maternal gestational weight gain has significant implications for infant growth and adiposity, with potential implications for later adult health.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; C-Peptide; C-Reactive Protein; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Leptin; Pregnancy; Prospective Studies; United States; Weight Gain

Given that the repetitive loss and regain of body weight, termed weight cycling, is a prevalent phenomenon that has been associated with negative physiological and psychological outcomes, the purpose of this study was to investigate weight change and physiological outcomes in women with a lifetime history of weight cycling enrolled in a 12-month diet and/or exercise intervention.. 439 overweight, inactive, postmenopausal women were randomized to: i) dietary weight loss with a 10% weight loss goal (N=118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week (n=117); ii) both dietary weight loss and exercise (n=117); or iv) control (n=87). Women were categorized as non-, moderate- (≥3 losses of ≥4.5 kg), or severe-cyclers (≥3 losses of ≥9.1 kg). Trend tests and linear regression were used to compare adherence and changes in weight, body composition, blood pressure, insulin, C-peptide, glucose, insulin resistance (HOMA-IR), C-reactive protein, leptin, adiponectin, and interleukin-6 between cyclers and non-cyclers.. Moderate (n=103) and severe (n=77) cyclers were heavier and had less favorable metabolic profiles than non-cyclers at baseline. There were, however, no significant differences in adherence to the lifestyle interventions. Weight-cyclers (combined) had a greater improvement in HOMA-IR compared to non-cyclers participating in the exercise only intervention (P=.03), but no differences were apparent in the other groups.. A history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes.

Topics: Adiponectin; Blood Glucose; Blood Pressure; Body Composition; C-Peptide; C-Reactive Protein; Diet, Reducing; Exercise; Female; Humans; Insulin; Insulin Resistance; Interleukin-6; Leptin; Linear Models; Middle Aged; Overweight; Postmenopause; Weight Gain; Weight Loss

In adults, dietary protein seems to induce weight loss and dairy proteins may be insulinotropic. However, the effect of milk proteins in adolescents is unclear. The objective was to test whether milk and milk proteins reduce body weight, waist circumference, homeostatic model assessment, plasma insulin, and insulin secretion estimated as the plasma C-peptide concentration in overweight adolescents. Overweight adolescents (n = 203) aged 12-15 y with a BMI of 25.4 ± 2.3 kg/m(2) (mean ± SD) were randomized to 1 L/d of skim milk, whey, casein, or water for 12 wk. All milk drinks contained 35 g protein/L. Before randomization, a subgroup of adolescents (n = 32) was studied for 12 wk before the intervention began as a pretest control group. The effects of the milk-based test drinks were compared with baseline (wk 0), the water group, and the pretest control group. Diet and physical activity were registered. Outcomes were BMI-for-age Z-scores (BAZs), waist circumference, plasma insulin, homeostatic model assessment, and plasma C-peptide. We found no change in BAZ in the pretest control and water groups, whereas it was greater at 12 wk in the skim milk, whey, and casein groups compared with baseline and with the water and pretest control groups. The plasma C-peptide concentration increased from baseline to wk 12 in the whey and casein groups and increments were greater than in the pretest control (P < 0.02). There were no significant changes in plasma C-peptide in the skim milk or water group. These data suggest that high intakes of skim milk, whey, and casein increase BAZs in overweight adolescents and that whey and casein increase insulin secretion. Whether the effect on body weight is primary or secondary to the increased insulin secretion remains to be elucidated.

Topics: Adolescent; Animals; Body Mass Index; C-Peptide; Caseins; Cattle; Child; Humans; Insulin; Insulin Resistance; Milk; Milk Proteins; Overweight; Waist Circumference; Weight Gain; Whey Proteins

The purpose of the study was to test prospectively whether healthy individuals with a family history of type 2 diabetes are more susceptible to adverse metabolic effects during experimental overfeeding.. We studied the effects of 3 and 28 days of overfeeding by 5,200 kJ/day in 41 sedentary individuals with and without a family history of type 2 diabetes (FH+ and FH- respectively). Measures included body weight, fat distribution (computed tomography) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp).. Body weight was increased compared with baseline at 3 and 28 days in both groups (p < 0.001), FH+ individuals having gained significantly more weight than FH- individuals at 28 days (3.4 +/- 1.6 vs 2.2 +/- 1.4 kg, p < 0.05). Fasting serum insulin and C-peptide were increased at 3 and 28 days compared with baseline in both groups, with greater increases in FH+ than in FH- for insulin at +3 and +28 days (p < 0.01) and C-peptide at +28 days (p < 0.05). Fasting glucose also increased at both time points, but without a significant group effect (p = 0.1). Peripheral insulin sensitivity decreased in the whole cohort at +28 days (54.8 +/- 17.7 to 50.3 +/- 15.6 micromol min(-1) [kg fat-free mass](-1), p = 0.03), and insulin sensitivity by HOMA-IR decreased at both time points (p < 0.001) and to a greater extent in FH+ than in FH- (p = 0.008). Liver fat, subcutaneous and visceral fat increased similarly in the two groups (p < 0.001).. Overfeeding induced weight and fat gain, insulin resistance and hepatic fat deposition in healthy individuals. However, individuals with a family history of type 2 diabetes gained more weight and greater insulin resistance by HOMA-IR. The results of this study suggest that healthy individuals with a family history of type 2 diabetes are predisposed to adverse effects of overfeeding.. ClinicalTrials.gov NCT00562393. The study was funded by the National Health and Medical Research Council (NHMRC), Australia (no. #427639).

Topics: Adult; Analysis of Variance; Australia; Body Composition; C-Peptide; Diabetes Mellitus, Type 2; Feeding Behavior; Female; Genetic Predisposition to Disease; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Male; Middle Aged; Overnutrition; Risk Factors; Sedentary Behavior; Weight Gain

In type 2 diabetes (T2D), insulin-induced weight gain may stem from a reduction in resting energy expenditure (REE). We sought to determine the early effects of insulin introduction on REE in 20 poorly controlled T2D patients.. After improving the glycaemia, REE was measured on Day 0 and Day 4 during two treatment regimens: bedtime insulin (n=10, group 1); and one off (3-day) intravenous insulin infusion (n=10, group 2).. Both groups were similar in age, gender, BMI, C-peptide, HbA(1c) and initial REE. By Day 4, fasting glycaemia had similarly improved in both groups: group 1: -5.3+/-2.7mmol/L vs group 2: -5.8+/-4.2 mmol/L. In group 2, the second REE was measured 12h after stopping the intravenous insulin infusion, whereas subcutaneous insulin was maintained in group 1. REE did not change in group 2 (-1.3+/-6.5%), whereas it decreased significantly in group 1 (-8.0+/-7.0%; P<0.05).. Bedtime insulin led to an early and specific reduction in REE.

Topics: Adult; Aged; Blood Glucose; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Glycated Hemoglobin; Humans; Infusions, Intravenous; Injections, Subcutaneous; Insulin; Male; Middle Aged; Respiration; Rest; Statistics, Nonparametric; Time Factors; Weight Gain

Muraglitazar is a dual (alpha/gamma) PPAR activator. Dual receptor activation may improve glycaemic and lipid profiles in patients with type 2 diabetes mellitus.This randomised double-blind trial in 1,477 drug-naive patients with type 2 diabetes compared the efficacy and safety of muraglitazar (0.5, 1.5, 5, 10, and 20 mg) with pioglitazone (15 mg). Endpoints included changes in HbA(1C) and plasma lipids, last observation carried forward over 24 weeks. At week 24, mean changes from baseline in HbA(1C) ranged from -0.25% to -1.76% with muraglitazar (p

Topics: Biomarkers; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Edema; Female; Glycated Hemoglobin; Glycine; Humans; Hypoglycemic Agents; Insulin; Lipids; Male; Middle Aged; Oxazoles; Pioglitazone; PPAR alpha; PPAR gamma; Thiazolidinediones; Time Factors; Treatment Outcome; Weight Gain

Ghrelin is a major hormone, regulating the energy balance of the body. Weight gain is a significant side effect of valproic acid, which has not been clearly identified pathogenetically. The aim of this study was to investigate the effect of valproic acid on ghrelin and its potential effects on weight gain and growth. Each patient and control group consisted of 35 children aged 3 to 15 years. Fasting serum glucose, insulin, C-peptide, leptin, ghrelin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 levels were measured in patients treated with valproic acid before and at month 6 of treatment. A significant increase in body weight, body mass index, height, and height standard deviation scores was observed in all patients after 6 months of treatment. Significant increases in growth velocity and weight gain were observed in the patient group compared with controls at 6 months of therapy. A significant increase in serum ghrelin levels (P < .01) was detected at the same time in the study group. A negative correlation of ghrelin with insulin-like growth factor-1 and insulin-like growth factor binding protein-3 was detected. Serum ghrelin levels were significantly increased (P < .05), and insulin-like growth factor-1 and insulin-like growth factor binding protein-3 levels were significantly decreased (P < .01 and P < .05, respectively) in the prepubertal group at 6 months of treatment, but no significant change was observed in the pubertal group. Consequently, ghrelin levels significantly increase in the prepubertal children treated with valproic acid. The weight gain in using valproic acid may be associated with the increase in ghrelin level in the early treatment period.

Topics: Adolescent; Anticonvulsants; Blood Glucose; Body Height; Body Mass Index; Body Weight; C-Peptide; Child; Child, Preschool; Epilepsy; Female; Ghrelin; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Male; Puberty; Valproic Acid; Weight Gain

To evaluate the safety and effectiveness of rosiglitazone in the treatment of overweight subjects with type 1 diabetes.. A total of 50 adult type 1 diabetic subjects with a baseline BMI > or =27 kg/m(2) were randomly assigned in a double-blind fashion to take insulin and placebo (n = 25) or insulin and rosiglitazone 4 mg twice daily (n = 25) for a period of 8 months. Insulin regimen and dosage were modified in all subjects to achieve near-normal glycemic control.. Both groups experienced a significant reduction in HbA(1c) (A1C) level (rosiglitazone: 7.9 +/- 1.3 to 6.9 +/- 0.7%, P < 0.0001; placebo: 7.7 +/- 0.8 to 7.0 +/- 0.9%, P = 0.002) and a significant increase in weight (rosiglitazone: 97.2 +/- 11.8 to 100.6 +/- 16.0 kg, P = 0.008; placebo: 96.4 +/- 12.2 to 99.1 +/- 15.0, P = 0.016). Baseline measures of BMI (P = 0.001), total daily insulin dose (P = 0.002), total cholesterol (P = 0.005), HDL cholesterol (P = 0.001), and LDL cholesterol (P = 0.02) were predictors of improvement in A1C level only in the group treated with rosiglitazone. Total daily insulin dose increased in subjects taking placebo (74.0 +/- 33.8 to 82.0 +/- 48.9 units, P < 0.05 baseline vs. week 32), but it decreased slightly in subjects taking rosiglitazone (77.5 +/- 28.6 to 75.3 +/- 33.1 units). Both systolic blood pressure (137.4 +/- 15.6 vs. 128.8 +/- 14.8 mmHg, baseline vs. week 32, P < 0.02) and diastolic blood pressure (87.2 +/- 9.4 vs. 79.4 +/- 7.2 mmHg, P < 0.0001) improved in the group treated with rosiglitazone. The total incidence of hypoglycemia did not differ between groups.. Rosiglitazone in combination with insulin resulted in improved glycemic control and blood pressure without an increase in insulin requirements, compared with insulin- and placebo-treated subjects, whose improved glycemic control required an 11% increase in insulin dose. Weight gain and hypoglycemia were similar in both groups at the end of the study. The greatest effect of rosiglitazone occurred in subjects with more pronounced markers of insulin resistance.

Topics: Adult; Blood Glucose; Body Mass Index; Body Size; C-Peptide; Diabetes Mellitus, Type 1; Double-Blind Method; Ethnicity; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Male; Obesity; Placebos; Rosiglitazone; Thiazolidinediones; Weight Gain

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker flunarizine are frequently used in the preventive treatment of migraine, but the side-effect of prominent weight gain that frequently emerges during preventive treatment of migraine with these agents often leads to the discontinuation of therapy. In this study, we aimed to investigate the possible relationship between the weight gain associated with the use of these agents and serum levels of leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine patients with a body mass index (BMI) < 25 and without any endocrinological, immunological or chronic diseases were randomly divided into two groups, receiving AMT or flunarizine. There was a statistically significant increase in serum levels of leptin, C-peptide, insulin and measures of BMI in both groups when measured at the 12th week of therapy compared to their respective basal levels. To our knowledge this is the first study investigating the effects of AMT and flunarizine on serum leptin levels in preventive use of migraine treatment. A result from this study indicates that AMT and flunarizine may cause leptin resistance possibly by different mechanisms and thereby result in increase in serum leptin levels and BMI.

Topics: Adult; Amitriptyline; Antidepressive Agents, Tricyclic; Body Mass Index; C-Peptide; Female; Flunarizine; Humans; Insulin; Leptin; Male; Migraine Disorders; Vasodilator Agents; Weight Gain

To study the effect on body weight and glycaemic control of two insulin treatment regimens in patients with Type 2 diabetes and moderate failure to oral hypoglycaemic agents.. Sixteen patients treated with oral hypoglycaemic agents (6 men and 10 women) were included in this open-label, randomized, parallel group study. Their age was 62 +/- 2 (mean +/- SEM) years (range 44-79 years), body weight 71.3 +/- 2.9 kg, body mass index (BMI) 24.6 +/- 0.8 kg/m(2). The patients were switched to insulin treatment with bedtime NPH insulin combined with daytime sulphonylurea (combination group) or twice daily injections of a premixed combination of regular human and NPH insulin (insulin twice daily group) with measurements as given below before and after 12 and 24 weeks of treatment.. HbA(1c) was lowered from 8.3 +/- 0.3% to 7.0 +/- 0.2% in the insulin twice daily group (p<0.05) and from 8.3 +/- 0.3% to 6.8 +/- 0.5% in the combination group (p<0.03; ns between treatment groups). Body weight increased from 71.7 +/- 4.0 kg to 77.6 +/- 4.4 kg in the insulin twice daily group (p<0.001) and from 70.8 +/- 4.6 kg to 72.7 +/- 5.1 kg in the combination group (ns; p<0.02 between groups). The dose of insulin at 24 weeks in the insulin twice daily group was 45.8 +/- 4.2 U and 29.4 +/- 5.4 U in the combination group (p=0.03). Combination treatment reduced fasting and stimulated C-peptide levels.. Both treatments improved glycaemic control to the same extent but the combination of bedtime NPH insulin and daytime sulphonylurea gave a very small increase of body weight over a 6 months period. We conclude that combination therapy is an attractive alternative when starting insulin treatment in patients with Type 2 diabetes as this is a critical period for weight gain in such patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin, Isophane; Middle Aged; Sulfonylurea Compounds; Weight Gain

To examine the effects of improved glycaemic control over 20 weeks on the type and distribution of weight change in patients with type 2 diabetes who at baseline have poor glycaemic control.. Forty-three patients with type 2 diabetes and HbA1c > 8.9% were randomised to either intensive glycaemic control (IC) n = 21 or usual glycaemic control (UC) n = 22 for 20 weeks. Dual energy X-ray absorptiometry was used to assess the type and distribution of weight change during the study.. After 20 weeks HbA1c was significantly lower in patients randomised to IC than UC (HbA1c IC 8.02 +/- 0.25% vs. UC 10.23 +/- 0.23%, p < 0.0001). In the IC group weight increased by 3.2 +/- 0.8 kg after 20 weeks (fat-free mass increased by 1.8 +/- 0.3 kg) compared to 0.02 +/- 0.70 kg in UC (p = 0.003). The gain in total body fat mass comprised trunk fat mass (IC 0.94 +/- 0.5 kg vs. UC 0.04 +/- 0.4 kg, p = 0.18) and peripheral fat mass (total body fat - trunk fat) (IC 0.71 +/- 0.32 kg vs. UC -0.21 +/- 0.28 kg, p = 0.04). Blood pressure and serum lipid concentrations did not change over time in either group.. Intensive glycaemic control was associated with weight gain which was distributed in similar proportions between the central and peripheral regions and consisted of similar proportions of fat and fat-free mass. Blood pressure and serum lipid concentrations were not adversely affected.

Topics: Absorptiometry, Photon; Adipose Tissue; Blood Glucose; Body Composition; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Electrocardiography; Ethnicity; Female; Humans; Lipids; Male; Middle Aged; New Zealand; Weight Gain

The insulin-sensitizing action of troglitazone may be mediated through the activation of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) and the promotion of preadipocyte differentiation in adipose tissue on which troglitazone has depot-specific effects. We investigated the relationship between efficacy of the drug and body fat distribution. Changes in body fat distribution were also investigated by long-term administration of the drug.. Troglitazone was given at a dose of 400 mg/day to 20 patients with type 2 diabetes whose diet and sulfonylurea therapy produced unsatisfactory glycemic control (HbA(1c) >7.8%) and whose insulin secretory capacity was found to be preserved (postprandial C-peptide >3 ng/ml). HbA(1c) values, serum lipid levels, and body weight were measured monthly Body fat distribution was evaluated in subcutaneous (SC) and visceral fat using a computed tomography scan at umbilical levels before and after troglitazone therapy. During the 1-year troglitazone treatment, HbA(1c) was significantly decreased (from 9.2 +/- 0.2 to 7.1 +/- 0.2%, P < 0.01), showing lowest values at 4-6 months, whereas body weight was significantly increased (BMI 24.6 +/- 0.6 to 25.7 +/- 0.6 kg/m2, P < 0.01). Reduction of HbA(1c) (deltaHbA(1c)) from the baseline value during treatment was significantly greater in obese patients (BMI >26 kg/m2) than in nonobese patients (-3.2 +/- 0.4 vs. -2.1 +/- 0.3%, P < 0.05) and was more significant in women than in men (-3.2 +/- 0.2 vs. - 1.4 +/- 0.2%, P < 0.01). The level of deltaHbA(1c) during treatment showed a significant negative correlation with SC fat area (r = -0.742, P < 0.01) but not with visceral fat area. Weight gain during troglitazone treatment resulted in increased accumulation of SC fat without a change in visceral fat area and, consequently. in a significant decrease in the visceral-to-SC fat ratio.. Predominant accumulation of SC fat for the visceral fat tissue was an important predictor of the efficacy of troglitazone therapy in patients with type 2 diabetes. Greater efficacy of troglitazone was observed in women who were characterized by more accumulation of SC adipose tissue than men. Long-term administration of the drug resulted in weight gain with increased accumulation of SC adipose tissue, probably because of the activation of PPAR-gamma in the region.

Topics: Adipose Tissue; Body Mass Index; C-Peptide; Chromans; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Secretion; Male; Middle Aged; Obesity; Sex Characteristics; Thiazoles; Thiazolidinediones; Tomography, X-Ray Computed; Troglitazone; Viscera; Weight Gain

Treatment with small doses of subcutaneous insulin is being investigated as a possible approach to prevent type 1 diabetes in humans. The mechanism of prophylactic insulin therapy could involve the inhibition of beta-cell secretory activity and/or the initiation of an active immunoregulatory process. To evaluate the pure metabolic effect of exogenous insulin, the present study assessed whether daily subcutaneous administration of ultralente insulin alters beta-cell function in normal adults. Fourteen healthy adults were randomized to receive 0.2 U/kg x d ultralente insulin (Ultratard; Novo Nordisk, Bagsvaerd, Denmark) or placebo subcutaneously once daily for 30 days. Plasma glucose, C-peptide, and insulin concentrations were measured in the fasting state and 1 hour after a standardized breakfast, during treatment and during a recovery period of 10 days. Insulin administration induced a 15% to 40% decrease of fasting plasma C-peptide. In contrast, postbreakfast plasma C-peptide increased by 40% to 90% in subjects receiving insulin. Fasting and postbreakfast C-peptide concentrations were significantly different between groups during the injection period after adjustment for baseline concentrations (P < .05, ANOVA with repeated measures). These alterations disappeared 3 days after cessation of insulin treatment. The present regimen of exogenous insulin alters endogenous insulin secretion in normal subjects. Instead of the expected beta-cell rest, the effect appeared to be dual, with insulin secretion decreasing in the basal state and increasing after meals.

Topics: Adult; C-Peptide; Fasting; Female; Humans; Insulin, Long-Acting; Islets of Langerhans; Male; Postprandial Period; Weight Gain

Compared with other insulin regimens, combination therapy with oral hypoglycemic agents and bedtime insulin produces similar improvement in glycemic control but induces less weight gain.. To determine whether bedtime insulin regimens differ with respect to their effects on weight gain in patients with type 2 diabetes.. Randomized, controlled trial.. Four outpatient clinics at central hospitals.. 96 patients (mean age, 58 +/- 1 years; mean body mass index, 29 +/- 1 kg/m2) whose type 2 diabetes was poorly controlled with sulfonylurea therapy (mean glycosylated hemoglobin value, 9.9% +/- 0.2%; mean fasting plasma glucose level, 11.9 +/- 0.3 mmol/L [214 +/- 5 mg/dL]).. Random assignment to 1 year of treatment with bedtime intermediate-acting insulin plus glyburide (10.5 mg) and placebo, metformin (2 g) and placebo, glyburide and metformin, or a second injection of intermediate-acting insulin in the morning. Patients were taught to adjust the bedtime insulin dose on the basis of fasting glucose measurements.. Body weight, biochemical and symptomatic hypoglycemias, and indices of glycemic control.. At 1 year, body weight remained unchanged in patients receiving bedtime insulin plus metformin (mean change, 0.9 +/- 1.2 kg; P < 0.001 compared with all other groups) but increased by 3.9 +/- 0.7 kg, 3.6 +/- 1.2 kg, and 4.6 +/- 1.0 kg in patients receiving bedtime insulin plus glyburide, those receiving bedtime insulin plus both oral drugs, and those receiving bedtime and morning insulin, respectively. The greatest decrease in the glycosylated hemoglobin value was observed in the bedtime insulin and metformin group (from 9.7% +/- 0.4% to 7.2% +/- 0.2% [difference, -2.5 +/- 0.4 percentage points] at 1 year; P < 0.001 compared with 0 months and P < 0.05 compared with other groups). This group also had significantly fewer symptomatic and biochemical cases of hypoglycemia (P < 0.05) than the other groups.. Combination therapy with bedtime insulin plus metformin prevents weight gain. This regimen also seems superior to other bedtime insulin regimens with respect to improvement in glycemic control and frequency of hypoglycemia.

Topics: Albuminuria; Blood Glucose; Blood Pressure; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Follow-Up Studies; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Lipids; Metformin; Middle Aged; Weight Gain

To investigate the effects on serum lipids, plasma fibrinogen, plasma insulin, plasma C-peptide and blood glucose, of smoking cessation after 4 months. To develop a group-based smoking intervention programme in primary health care.. Twenty health centres in primary health care in southern Sweden.. Four hundred habitual smokers (> 10 cigarettes per day-1, > 10 years), recruited by advertisement in local papers.. The smokers were randomized, after stratification for age and sex, to one intervention group (n = 200) and one control group (n = 200). The intervention group was offered supportive group sessions and free nicotine supplementation (patches, chewing gum).. All participants were investigated at the start and after 4 months (medical history, physical examination, laboratory evaluation). Blood samples were drawn for determination of glucose, insulin and C-peptide, both in the fasting state and during an oral glucose tolerance test (OGTT), and for measurement of lipoproteins, fibrinogen, nicotine and cotinine.. In the intervention group 98 of the subjects (48%) had quit smoking after 4 months. They were compared with the 156 subjects in the control group (91%) who were still daily smokers during the whole period. There were no significant differences in any variable between the two (total) experimental groups at baseline. Plasma nicotine and cotinine decreased (P < 0.001) in the intervention group following smoking cessation, and weight increased by 2.7 kg. In the intervention group HDL-cholesterol increased by 11% (P < 0.001), whereas HbA1c increased by 2% (P < 0.05) only in the control group. No changes occurred in levels of glucose, insulin, C-peptide and fibrinogen.. The smoking cessation programme had a success rate of almost 50% over 4 months. Smoking cessation was associated with a marked increase in HDL-cholesterol levels but did not affect glucose tolerance. A concomitant weight increase may have blunted any independent beneficial effect of smoking cessation on glucose metabolism.

Topics: Adult; Blood Glucose; C-Peptide; Cardiovascular Diseases; Feasibility Studies; Female; Fibrinogen; Humans; Insulin; Lipids; Male; Middle Aged; Psychotherapy, Group; Risk Factors; Smoking; Smoking Cessation; Weight Gain

A randomized prospective study was conducted to determine whether the insulin regimen for NIDDM subjects poorly controlled on oral therapy should be designed primarily to control basal metabolism or to control mealtime hyperglycaemia. Grossly obese subjects were excluded. After a 2-month run-in phase involving intensive education, subjects were randomized to therapy with twice daily isophane or three times daily soluble insulin. Both Protaphane and Actrapid brought about similar improvement in HbA1 (9.5 +/- 0.5 and 9.7 +/- 0.4%) compared with baseline (11.7 +/- 0.5%; p < 0.001). Diurnal blood glucose profiles showed that despite the good post-prandial control achieved by pre-meal soluble insulin, loss of control occurred overnight, resulting in higher fasting blood glucose levels compared with Protaphane therapy (8.0 +/- 0.8 vs 10.6 +/- 0.8 mmol l-1; p < 0.05). The overall rate of hypoglycaemia was 0.44 patient-1 year-1. Thirty-two mild hypoglycaemic episodes occurred on Protaphane therapy and 79 on Actrapid therapy. Using formal psychometric tests it was shown that insulin therapy was associated with improved treatment satisfaction and that this was greater on Protaphane therapy (p < 0.05). Overall well-being increased similarly in the two groups. All subjects wished to continue with insulin therapy after the conclusion of the study. The insulin regimen for moderately or poorly controlled non-insulin-dependent diabetes should primarily be designed to correct the basal insulin deficiency rather than to mimic normal meal-induced insulin secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Cholesterol; Circadian Rhythm; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Administration Schedule; Eating; Glycated Hemoglobin; Humans; Insulin; Insulin, Isophane; Insulin, Regular, Pork; Middle Aged; Patient Education as Topic; Patient Satisfaction; Prospective Studies; Quality of Life; Surveys and Questionnaires; Triglycerides; Weight Gain

To determine if glipizide could enhance remission induction in new onset type 1 diabetes compared to intensive insulin treatment alone, 27 patients with type 1 diabetes were intensively treated in an open randomized trial with subcutaneous injections for one month. The insulin was randomly either discontinued (Group A) or the insulin discontinued and glipizide begun (Group B) Three patients in Group A (22%) and 7 in Group B (54%, p < .05) underwent insulin-free remissions for 10.3 +/- 4.4 and 8.7 +/- 2.6 months, respectively (p = NS). Mean blood glucose levels during insulin treatment were lower in patients entering remissions (94 +/- 3 mg/dl versus 102 +/- 5 mg/dl, p < 0.05). C-peptide levels were performed 0, 4, 8, and 24 weeks after insulin treatment. When all patients were examined, mean stimulated C-peptide levels at 4 weeks (0.58 +/- 0.09 pm/ml) were increased compared to time 0 (0.32 +/- 0.05 pm/ml, p < 0.02). Patients not entering remission had higher 4-week stimulated values (0.67 +/- 0.12 pm/ml) compared to time 0 values (0.29 +/- 0.06 pm/ml, p < .01), whereas remission patients' mean C-peptide levels remained similar at 0, 4, 8 and 24 weeks. These data indicate that a) insulin treatment plus glipizide induces higher rates of remission compared to intensive insulin treatment alone, b) the intensity of initial metabolic control may be an important determinant for remission induction, and c) endogenous insulin secretion is not associated with remission induction, suggesting that glipizide alters insulin sensitivity or is immunomodulatory in the context of new onset type 1 diabetes.

Topics: Adult; Age of Onset; Algorithms; Blood Glucose; C-Peptide; Combined Modality Therapy; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Glipizide; Glycated Hemoglobin; Humans; Injections, Subcutaneous; Insulin; Male; Remission Induction; Weight Gain

The prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.. We assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients' levels of selected inflammatory cytokines at baseline.. Subjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS <1 and BMI-SDS >1 groups and were significantly higher within BMI-SDS >1 group.. Higher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines.

Topics: Body Mass Index; Body Weight; C-Peptide; Child; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Obesity; Weight Gain

This prospective cohort study was aimed at investigating the associations between cord blood metabolic factors and early-childhood growth, further elucidating the relationships between cord blood metabolites and overweight and obesity in early life.. A total of 2,267 pairs of mothers and offspring were recruited in our study. Cord blood plasma was assayed for triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), C-peptide, insulin, and glycosylated hemoglobin type A1C (HbA1c) levels. Data of anthropometric measurements were collected from offspring at birth, 6 months, 12 months, and 18 months. Multiple linear regression models were used to evaluate the correlations between cord blood metabolic factors and weight Z-scores, body mass index (BMI) Z-scores, and weight gains at the early stage of life. Forward stepwise logistic regression analyses were applied to explore the associations between cord blood metabolic factors and early-childhood overweight and obesity. Receiver operating characteristic (ROC) curve analyses were applied to determine the optimal cutoff points for cord blood metabolic factors in predicting early-childhood overweight and obesity.. After adjustments for covariates, cord blood TG concentrations and TG/TC ratios were negatively associated with weight Z-scores from birth to 18 months. Cord blood C-peptide and HbA1c levels were inversely associated with weight Z-scores at 6 months and 18 months. Cord blood TG concentrations and TG/TC ratios were negatively correlated with BMI Z-scores up to 18 months. Cord blood C-peptide levels and HbA1c levels were inversely correlated with BMI Z-scores at 18 months. Cord blood TG, TG/TC ratios, C-peptide, and HbA1c had negative correlations with weight gains from birth to 6 months, but the correlations attenuated as time went on. Increase in cord blood TG and HbA1c levels and TG/TC ratios were significantly associated with decreased risks of overweight and obesity at 6 months, 12 months, and 18 months.. Cord blood metabolic factors were significantly associated with early-childhood growth patterns.

Topics: C-Peptide; Child; Cholesterol, HDL; Fetal Blood; Glycated Hemoglobin; Humans; Infant, Newborn; Overweight; Pediatric Obesity; Prospective Studies; Weight Gain

Weight gain after pancreas transplant is a poorly understood phenomenon thought to be related to increased posttransplant insulin production, immunosuppressive medications, and appetite changes. No study has investigated the effect of increased exocrine secretion posttransplant.. We hypothesized that exocrine function, measured by fecal elastase-1 (FE-1), was normal posttransplant and not correlated with weight gain. Our primary aim was to investigate changes in FE-1 levels with pancreas transplantation and to correlate this with weight gain. Establishing weight trends and identifying additional correlating factors were secondary aims.. Forty-two patients that underwent simultaneous pancreas and kidney or pancreas after kidney transplant at a single center between 2013 and 2021 were included. Fecal elastase was measured prospectively in each patient at a single time point, with >500 µg/g categorized as high. Weight and C-peptide values were obtained. All the patients were on steroid-free immunosuppression.. Nineteen patients (45%) had fecal elastase levels >500 µg/g, with a maximum of 3910 µg/g; 43% had levels greater than twice the upper limit of normal. The biggest increase in weight occurred between years 1 and 2, which continued to a median weight gain of 14% at 3 years. There was no correlation between weight gain and FE-1, pretransplant C-peptide levels, or duration of diabetes.. This study demonstrated supranormal fecal elastase levels and weight gain posttransplant; however, there was no correlation. Future study with serial FE-1 before and after transplant is needed to better assess its correlation with weight gain.

Topics: C-Peptide; Humans; Pancreas; Pancreas Transplantation; Pancreatic Elastase; Weight Gain

Oxidative stress and apoptosis are involved in the pathogenesis of obesity-related diseases. This observational study investigates the antioxidant and apoptotic markers response to an oral glucose tolerance test (OGTT) in a population of overweight children and adolescents, with normal (NGT) or impaired glucose tolerance (IGT). Glucose, insulin, and C-peptide concentrations, as well as oxidative stress (SOD, GPx3) and apoptotic markers (Apo1fas, cck18), were determined at T = 0, 30, 60, 90, 120, and 180 min after glucose intake during OGTT. The lipid profile, thyroid function, insulin-like growth factor1, leptin, ghrelin, and adiponectin were also measured at baseline. The 45 participants, with a mean age of 12.15 (±2.3) years old, were divided into two subcategories: those with NGΤ (n = 31) and those with IGT (n = 14). The area under the curve (AUC) of glucose, insulin, and C-peptide was greater in children with IGT; however, only glucose differences were statistically significant. SOD and GPx3 levels were higher at all time points in the IGT children. Apo1fas and cck18 levels were higher in the NGT children at most time points, whereas Adiponectin was lower in the IGT group. Glucose increased during an OGTT accompanied by a simultaneous increase in antioxidant factors, which may reflect a compensatory mechanism against the impending increase in oxidative stress in children with IGT.

Topics: Adiponectin; Adolescent; Antioxidants; Blood Glucose; C-Peptide; Child; Glucose; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Obesity; Superoxide Dismutase; Weight Gain

The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10.9 ± 5.5 kg) was greatest among those of younger age and lower body mass index and 58% of women exceeded the Institute of Medicine GWG recommendations of 5-9 kg for obese pregnancy. GWG was significantly positively associated with increased risk of birthweight >4 kg, cord c-peptide levels and inversely associated with cord total cholesterol. This study identified that higher GWG in obese pregnancy may increase the risk of macrosomia and neonatal hyperinsulinaemia, within a euglycaemic maternal cohort. Impact statement Excess gestational weight gain (GWG) and maternal obesity frequently co-occur with adverse consequences for maternal and neonatal health; however, little is known of the underlying biological pathways which may be affected to contribute to adverse outcomes. Greater understanding of the biological mechanisms involved may help guide future studies to develop targeted interventions for more effective clinical outcomes. This study identified that higher GWG among obese pregnant women resulted in foetal hyperinsulinaemia even in the absence of maternal hyperglycaemia, potentially representing a biological pathway for larger birthweight babies. These results may highlight the need for more intensive dietary and lifestyle interventions among obese women who would not normally receive additional counselling beyond standard antenatal care if not diagnosed with glucose intolerance in pregnancy.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Fetal Blood; Humans; Insulin; Lipids; Obesity; Pregnancy; Pregnancy Complications; Prospective Studies; Weight Gain

Experimental bone marrow transplantation (BMT) in mice is commonly used to assess the role of immune cell-specific genes in various pathophysiological settings. The application of BMT in obesity research is hampered by the significant reduction in high-fat diet (HFD)-induced obesity. We set out to characterize metabolic tissues that may be affected by the BMT procedure and impair the HFD-induced response. Male C57BL/6 mice underwent syngeneic BMT using lethal irradiation. After a recovery period of 8 weeks they were fed a low-fat diet (LFD) or HFD for 16 weeks. HFD-induced obesity was reduced in mice after BMT as compared to HFD-fed control mice, characterized by both a reduced fat (-33%; p<0.01) and lean (-11%; p<0.01) mass, while food intake and energy expenditure were unaffected. As compared to control mice, BMT-treated mice had a reduced mature adipocyte volume (approx. -45%; p<0.05) and reduced numbers of preadipocytes (-38%; p<0.05) and macrophages (-62%; p<0.05) in subcutaneous, gonadal and visceral white adipose tissue. In BMT-treated mice, pancreas weight (-46%; p<0.01) was disproportionally decreased. This was associated with reduced plasma insulin (-68%; p<0.05) and C-peptide (-37%; p<0.01) levels and a delayed glucose clearance in BMT-treated mice on HFD as compared to control mice. In conclusion, the reduction in HFD-induced obesity after BMT in mice is at least partly due to alterations in the adipose tissue cell pool composition as well as to a decreased pancreatic secretion of the anabolic hormone insulin. These effects should be considered when interpreting results of experimental BMT in metabolic studies.

Topics: Adipocytes; Adipose Tissue, White; Animals; Bone Marrow Transplantation; C-Peptide; Diet, Fat-Restricted; Diet, High-Fat; Eating; Energy Metabolism; Fatty Acids, Nonesterified; Feces; Glucose Tolerance Test; Insulin; Insulin Secretion; Macrophages; Male; Mice; Mice, Inbred C57BL; Obesity; Pancreas; Triglycerides; Weight Gain

The connecting peptide in insulin has been associated with cardiovascular risk and overall mortality in the adult population. However, its early determinants are unknown. Assess the association of exposures during pregnancy, delivery, and childhood with C-peptide among 22-23 years old individuals prospectively followed since birth, in a southern Brazilian city.. In 1982, all hospital births in the city were identified and those livebirths whose families lived in the urban area were evaluated (n = 5914). The 1982 Pelotas Birth Cohort has prospectively followed these subjects at different moments. In this study, we evaluated the association of C-peptide with exposures occurring during pregnancy, delivery and childhood. In the 22-23 years follow-up visit, we tried to follow the whole cohort and the subjects were interviewed, examined and donated a blood sample. C-peptide was measured using the chemiluminescence immunoassay technique (Immulite®-Siemens, Germany).. In the 22-23 years visit, 4297 subjects were interviewed and the C-peptide was measured in 3807. The geometric mean of C-peptide was 0.83 ng/mL and the mean was higher among women. In the adjusted analysis, C-peptide was positively associated with family income at birth, lower among children of non-white mothers (0.90; CI95% 0.84-0.96), higher among females (1.22; CI95% 1.16-1.28), and positively associated with rapid weight gain between two and four years of age (1.18; CI95% 1.05-1.32).. Family income at birth, non-white maternal skin color, and rapid weight gain between two and four years of age were associated with high levels of C-peptide.

Topics: Age Factors; Biomarkers; Brazil; C-Peptide; Female; Follow-Up Studies; Humans; Immunoassay; Income; Luminescent Measurements; Male; Mothers; Parturition; Pregnancy; Prognosis; Prospective Studies; Risk Factors; Skin Pigmentation; Time Factors; Up-Regulation; Urban Health; Weight Gain; Young Adult

Topics: Birth Weight; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Humans; Incidence; Infant, Newborn; Metabolic Syndrome; Overweight; Pregnancy; Pregnancy Complications; Weight Gain

The effect of exocrine pancreatic function on the glucose-mediated insulin response and glucose utilization were studied in an exocrine pancreas-insufficient (EPI) pig model. Five 10-week-old EPI pigs after pancreatic duct ligation and 6 age-matched, non-operated control pigs were used in the study. Blood glucose, plasma insulin and C-peptide concentrations were monitored during meal (MGTT), oral (OGTT) and intravenous (IVGTT) glucose tolerance tests. Upon post-mortem examination, the pancreatic remnants of the EPI pigs showed acinar fibrotic atrophy but normal islets and β-cell morphology. The EPI pigs displayed increased fasting glucose concentrations compared with control animals (6.4 ± 0.4 versus 4.8 ± 0.1 mmol l(-1) , P < 0.0001) but unchanged insulin concentrations (2.4 ± 0.6 versus 2.1 ± 0.2 pmol l(-1) ). During the OGTT and IVGTT, the EPI pigs showed slower, impaired glucose utilization, with the disruption of a well-timed insulin response. Plasma C-peptide concentrations confirmed the delayed insulin response during the IVGTT in EPI pigs. Oral pancreatic enzyme supplementation (PES) of EPI pigs improved glucose clearance during IVGTT [AUC(glucose) 1295 ± 70 mmol l(-1) × (120 min) in EPI versus 1044 ± 32 mmol l(-1) × (120 min) in EPI + PES, P < 0.0001] without reinforcing the release of insulin [AUC(C-peptide) 14.4 ± 3.8 nmol l(-1) × (120 min) in EPI versus 6.4 ± 1.3 nmol l(-1) × (120 min) in EPI + PES, P < 0.002]. The results suggest the existence of an acino-insular axis regulatory communication. The presence of pancreatic enzymes in the gut facilitates glucose utilization in an insulin-independent manner, indicating the existence of a gut-derived pancreatic enzyme-dependent mechanism involved in peripheral glucose utilization.

Topics: Animals; Atrophy; Blood Glucose; C-Peptide; Eating; Fibrosis; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Ligation; Pancreas, Exocrine; Pancreatic Ducts; Sus scrofa; Swine; Weight Gain

It is widely accepted that lifestyle plays a crucial role on the quality of life in individuals, particularly in western societies where poor diet is correlated to alterations in behavior and the increased possibility of developing type-2 diabetes. While exercising is known to produce improvements to overall health, there is conflicting evidence on how much of an effect exercise has staving off the development of type-2 diabetes or counteracting the effects of diet on anxiety. Thus, this study investigated the effects of voluntary wheel-running access on the progression of diabetes-like symptoms and open field and light-dark box behaviors in C57BL/6J mice fed a high-fat diet. C57BL/6J mice were placed into either running-wheel cages or cages without a running-wheel, given either regular chow or a high-fat diet, and their body mass, food consumption, glucose tolerance, insulin and c-peptide levels were measured. Mice were also exposed to the open field and light-dark box tests for anxiety-like behaviors. Access to a running-wheel partially attenuated the obesity and hyperinsulinemia associated with high-fat diet consumption in these mice, but did not affect glucose tolerance or c-peptide levels. Wheel-running strongly increased anxiety-like and decreased explorative-like behaviors in the open field and light-dark box, while high-fat diet consumption produced smaller increases in anxiety. These results suggest that voluntary wheel-running can assuage some, but not all, of the physiological problems associated with high-fat diet consumption, and can modify anxiety-like behaviors regardless of diet consumed.

Topics: Animals; Anxiety; C-Peptide; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Eating; Exploratory Behavior; Insulin; Male; Mice, Inbred C57BL; Obesity; Running; Volition; Weight Gain

Dogs consuming a hypercaloric high-fat and -fructose diet (52 and 17% of total energy, respectively) or a diet high in either fructose or fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) and glycogen deposition in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery. The effect of a hypercaloric diet containing neither fructose nor excessive fat has not been examined. Dogs with an initial weight of ≈25 kg consumed a chow and meat diet (31% protein, 44% carbohydrate, and 26% fat) in weight-maintaining (CTR; n = 6) or excessive (Hkcal; n = 7) amounts for 4 wk (cumulative weight gain 0.0 ± 0.3 and 1.5 ± 0.5 kg, respectively, P < 0.05). They then underwent clamp studies with infusions of somatostatin and intraportal insulin (4× basal) and glucagon (basal). The hepatic glucose load was doubled with peripheral (Pe) glucose infusion for 90 min (P1) and intraportal glucose at 4 mg·kg(-1)·min(-1) plus Pe glucose for the final 90 min (P2). NHGU was blunted (P < 0.05) in Hkcal during both periods (mg·kg(-1)·min(-1); P1: 1.7 ± 0.2 vs. 0.3 ± 0.4; P2: 3.6 ± 0.3 vs. 2.3 ± 0.4, CTR vs. Hkcal, respectively). Terminal hepatic glucokinase catalytic activity was reduced nearly 50% in Hkcal vs. CTR (P < 0.05), although glucokinase protein did not differ between groups. In Hkcal vs. CTR, liver glycogen was reduced 27% (P < 0.05), with a 91% increase in glycogen phosphorylase activity (P < 0.05) but no significant difference in glycogen synthase activity. Thus, Hkcal impaired NHGU and glycogen synthesis compared with CTR, indicating that excessive energy intake, even if the diet is balanced and nutritious, negatively impacts hepatic glucose metabolism.

Topics: Animals; Blood Glucose; C-Peptide; Chronic Disease; Dogs; Eating; Glucose; Glucose Clamp Technique; Hyperphagia; Insulin; Liver; Male; Weight Gain

Weight gain in breast cancer patients during treatment is prevalent; the metabolic implications of this weight gain are poorly understood. We aimed to characterize glucose metabolism in breast cancer patients near the initiation of chemotherapy.. Stage I-II breast cancer patients (n = 8) were evaluated near the initiation of chemotherapy and compared with a group of age- and body mass index-matched, as well as a group of young healthy, non-malignant females. Fasting blood samples (analyzed for lipids and cytokines) were taken and an oral glucose tolerance test was performed. Body composition, waist circumference, diet, cardiovascular fitness and muscle strength were evaluated.. Breast cancer patients were abdominally obese (mean ± SD: 94.6 ± 14.0 cm), overweight (28.8 ± 6.0 kg/m(2)) and dyslipidemic (triacylglycerides: 1.84 ± 1.17 mM; high-density lipoprotein cholesterol: 1.08 ± 0.23 mM). Compared to non-malignant matched females, fasting glucose and insulin concentrations were similar but fasting c-peptide was greater in patients (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). Glucose was elevated to a greater extent in patients during the oral glucose tolerance test compared with all non-malignant females. During the glucose tolerance test, c-peptide, but not insulin, remained elevated in patients compared with all non-malignant females. No differences in body composition, serum cytokines, nutrition or exercise capacity between patients and matched, non-malignant females emerged.. Breast cancer patients present with unhealthy metabolic features early in the disease trajectory. Future investigations need to examine the underlying mechanisms and the potential longitudinal changes following chemotherapy.

Topics: Adolescent; Adult; Blood Glucose; Body Composition; Body Mass Index; Breast Neoplasms; C-Peptide; Cholesterol, HDL; Cytokines; Diet Records; Dyslipidemias; Energy Intake; Energy Metabolism; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Middle Aged; Motor Activity; Muscle Strength; Obesity; Waist Circumference; Weight Gain; Young Adult

To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.. GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as >90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.. Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds >90th percentile (OR = 1.75 and 4.77, respectively) and percentage body fat >90th percentile (OR = 2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight >90th percentile (OR = 2.80 and 1.93, respectively) compared to women who gained within the recommendation.. This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.

Topics: Adiposity; Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Female; Gestational Age; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Male; North America; Obesity; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Outcome; United States; Weight Gain

Current literature lacks data on markers of non-alcoholic fatty liver disease (NAFLD) in newly diagnosed type 2 diabetes mellitus (T2DM) patients. We therefore, conducted a cross-sectional study to examine modifiable clinical and lifestyle factors associated with elevated alanine aminotransferase (ALT) levels as a marker of NAFLD in new T2DM patients.. Alanine aminotransferase levels were measured in 1026 incident T2DM patients enrolled in the nationwide Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. We examined prevalence of elevated ALT (>38 IU/L for women and >50 IU/L for men) and calculated prevalence ratios associated with clinical and lifestyle factors using Poisson regression. We examined the association with other biomarkers by linear regression.. The median value of ALT was 24 IU/L (interquartile range: 18-32 IU/L) in women and 30 IU/L (interquartile range: 22-41 IU/L) in men. Elevated ALT was found in 16% of incident T2DM patients. The risk of elevated ALT was increased in patients who were <40 years old at diabetes debut [adjusted prevalence ratio (aPR): 1.96, 95% confidence interval (CI): 1.15-3.33], in those with alcohol overuse (>14/>21 drinks per week for women/men) (aPR: 1.60, 95% CI: 1.03-2.50), and in those with no regular physical activity (aPR: 1.42, 95% CI: 1.04-1.93). Obesity and metabolic syndrome per se showed no association with elevated ALT when adjusted for other markers, whereas we found positive associations of ALT with increased C-peptide (β = 0.14, 95% CI: 0.06-0.21) and fasting blood glucose (β = 0.07, 95% CI: 0.03-0.11).. Among newly diagnosed T2DM patients, several modifiable clinical and lifestyle factors are independent markers of elevated ALT levels.

Topics: Adult; Alanine Transaminase; Alcohol Drinking; Biomarkers; C-Peptide; Cohort Studies; Cross-Sectional Studies; Denmark; Diabetes Mellitus, Type 2; Female; Humans; Linear Models; Male; Non-alcoholic Fatty Liver Disease; Poisson Distribution; Prevalence; Sedentary Behavior; Sex Factors; Weight Gain; Young Adult

The contraceptive skin patch (CSP) accepted by the U.S. FDA in 2001 includes ethinylestradiol and norelgestromine, whereas the subdermal contraceptive implant (SCI) has etonogestrel and is also approved by the FDA. In Mexico, both are now widely used for contraception but their effects on Mexican population are unknown. The objective of the study was to evaluate if these treatments induce metabolic changes in a sample of indigenous and mestizo Mexican women.. An observational, prospective, longitudinal, non-randomized study of women between 18 and 35 years of age assigned to CSP or SCI. We performed several laboratory tests: clinical chemistry, lipid profile, and liver and thyroid function tests. Also, serum levels of insulin, C-peptide, IGF-1, leptin, adiponectin, and C reactive protein were assayed.. Sixty-two women were enrolled, 25 used CSP (0 indigenous; 25 mestizos) and 37 used SCI (18 indigenous; 19 mestizos). Clinical symptoms were relatively more frequent in the SCI group. Thirty-four contraceptive users gained weight without other clinical significant changes. After 4 months of treatment, significant changes were found in some biochemical parameters in both treatment groups. Most were clinically irrelevant. Interestingly, the percentage of users with an abnormal atherogenic index diminished from 75% to 41.6% after follow-up.. The CSP slightly modified the metabolic variables. Most changes were nonsignificant, whereas for SCI users changes were more evident and perhaps beneficial. Results of this attempt to evaluate the effects of contraceptives in mestizo and native-American populations show that clinical symptoms are frequent in Mexican users of CSP and SCI. Although these medications may affect some metabolic variables, these changes seem clinically irrelevant. Induction of abnormalities in other physiological pathways cannot be ruled out.

Topics: Adiponectin; Adult; C-Peptide; C-Reactive Protein; Contraceptive Agents, Female; Desogestrel; Drug Combinations; Ethinyl Estradiol; Female; Humans; Insulin; Insulin-Like Growth Factor I; Leptin; Lipid Metabolism; Liver Function Tests; Longitudinal Studies; Mexico; Norgestrel; Oximes; Thyroid Function Tests; Transdermal Patch; Weight Gain

Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy.

Topics: Amino Acids; Amino Acids, Branched-Chain; Animals; Blood Glucose; Body Mass Index; Breast Feeding; C-Peptide; Dietary Proteins; Humans; Infant; Infant Formula; Infant Nutritional Physiological Phenomena; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Milk; Milk, Human; Nutritional Status; Obesity; Risk Factors; RNA-Binding Proteins; Urea; Weight Gain

With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.. Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.. Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice.. This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

Topics: Animals; C-Peptide; Chemokine CCL2; Diet, Fat-Restricted; Diet, High-Fat; Energy Intake; Gastric Inhibitory Polypeptide; Insulin; Interleukin-6; Leptin; Longevity; Male; Mice; Mice, Inbred C57BL; Obesity; Peptide Fragments; Resistin; Time Factors; Weight Gain; Weight Loss

Topics: Aged, 80 and over; Blood Glucose; C-Peptide; Confusion; Diazoxide; Epilepsy, Tonic-Clonic; Female; Humans; Hypoglycemia; Insulin; Insulinoma; Pancreatic Neoplasms; Vasodilator Agents; Weight Gain

Topics: Antipsychotic Agents; Blood Glucose; C-Peptide; Cholesterol; Cooperative Behavior; Diabetes Mellitus, Type 2; Health Promotion; Humans; Hyperlipidemias; Insulin; Insulin Resistance; Interdisciplinary Communication; Metabolic Syndrome; Mind-Body Relations, Metaphysical; Patient Admission; Patient Care Team; Psychotic Disorders; State Medicine; Triglycerides; Weight Gain

The effects of long-term dietary supplementation of fish oil (n-3 PUFA-rich) in adult male pigs on body condition as well as insulin sensitivity and secretion were examined. Fifteen Duroc boars aged 204.5 (sd 9.4) d (body weight 145.8 (sd 16.8) kg) received daily 2.5 kg basal diet with a supplement of: (1) 62 g hydrogenated animal fat (n 5); (2) 60 g menhaden oil containing 10.8 g DHA and 9.0 g EPA (n 6); (3) 60 g tuna oil containing 19.8 g DHA and 3.9 g EPA (n 4). Rations were balanced to be isoenergetic. After 7 months of treatments, oral glucose and meal tolerance tests were conducted after insertion of a catheter into the jugular vein. Dietary supplementation with n-3 PUFA altered the blood plasma profile: DHA and EPA increased whereas arachidonic acid decreased (P < 0.01). Plasma glucose, insulin and C-peptide responses to oral glucose and the test meal were not affected by treatments (P>0.34). For all animals, total body fat estimated from body weight and back fat thickness was correlated with both beta-cell function (by homeostasis model assessment (HOMA); r+0.63) and insulin sensitivity (index of whole-body insulin sensitivity and by HOMA; r - 0.63 and r+0.66, respectively). In conclusion, long-term supplementation with dietary n-3 PUFA did not affect insulin metabolism in healthy adult male pigs. The relationship between body fat and insulin sensitivity, well documented in human subjects, suggests that the adult male pig could be a promising animal model for studies on insulin metabolism.

Topics: Adipose Tissue; Animal Feed; Animals; Body Weight; C-Peptide; Dietary Fats; Dietary Supplements; Eating; Fatty Acids; Fatty Acids, Nonesterified; Fish Oils; Glucose Tolerance Test; Insulin; Insulin Secretion; Male; Swine; Weight Gain

Ghrelin and GH secretagogues, including GH-releasing peptide (GHRP)-6, stimulate food intake and adiposity. Because insulin modulates the hypothalamic response to GH secretagogues and acts synergistically with ghrelin on lipogenesis in vitro, we analyzed whether insulin plays a role in the metabolic effects of GHRP-6 in vivo. Streptozotocin-induced diabetic rats received saline, GHRP-6, insulin, or insulin plus GHRP-6 once daily for 8 wk. Rats receiving saline suffered hyperglycemia, hyperphagia, polydipsia, and weight loss. Insulin, but not GHRP-6, improved these parameters (P < 0.001 for all), as well as the diabetes-induced increase in hypothalamic mRNA levels of neuropeptide Y and agouti-related peptide and decrease in proopiomelanocortin. Cocaine amphetamine-related transcript mRNA levels were also reduced in diabetic rats, with GHRP-6 inducing a further decrease (P < 0.03) and insulin an increase. Diabetic rats receiving insulin plus GHRP-6 gained more weight and had increased epididymal fat mass and serum leptin levels compared with all other groups (P < 0.001). In epididymal adipose tissue, diabetic rats injected with saline had smaller adipocytes (P < 0.001), decreased fatty acid synthase (FAS; P < 0.001), and glucose transporter-4 (P < 0.001) and increased hormone sensitive lipase (P < 0.001) and proliferator-activated receptor-gamma mRNA levels (P < 0.01). Insulin normalized these parameters to control values. GHRP-6 treatment increased FAS and glucose transporter-4 gene expression and potentiated insulin's effect on epididymal fat mass, adipocyte size (P < 0.001), FAS (P < 0.001), and glucose transporter-4 (P < 0.05). In conclusion, GHRP-6 and insulin exert an additive effect on weight gain and visceral fat mass accrual in diabetic rats, indicating that some of GHRP-6's metabolic effects depend on the insulin/glucose status.

Topics: Adipocytes; Agouti-Related Protein; Animals; Blood Glucose; Body Weight; C-Peptide; Diabetes Mellitus, Experimental; Epididymis; Fats; Fatty Acid Synthases; Gene Expression; Ghrelin; Glucose Transporter Type 4; Growth Hormone; Insulin; Insulin-Like Growth Factor I; Leptin; Male; Neuropeptide Y; Oligopeptides; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; Weight Gain

The purpose of this study was to investigate whether pregnancy induces increased insulin production as a marker of improved beta-cell function in women with long-term type 1 diabetes.. This was a prospective study of 90 consecutive pregnant women with type 1 diabetes. At 8, 14, 21, 27, and 33 weeks blood samples were drawn for measurements of A1C, C-peptide, and serum glucose. C-peptide (detection limit: 6 pmol/l) was considered stimulated at a corresponding serum glucose concentration >or=5.0 mmol/l. GAD antibody concentration was determined at 8 and 33 weeks in 35 women.. C-peptide concentrations gradually increased throughout pregnancy regardless of serum glucose concentrations in the 90 women with a median duration of diabetes of 17 years (range 1-36 years). Among 35 women with paired recordings of stimulated C-peptide, C-peptide production was detectable in 15 (43%) at 8 weeks and in 34 (97%) at 33 weeks (P < 0.0001), and median C-peptide gradually increased from 6 to 11 pmol/l (P = 0.0004) with a median change of 50% (range -50 to 3,271%) during pregnancy. GAD antibodies were present in 77% with no change from 8 to 33 weeks (P = 0.85). Multivariate regression analysis revealed a positive association between the absolute increase in C-peptide concentrations during pregnancy and decreased A1C from 8 to 33 weeks (P = 0.003).. A pregnancy-induced increase in C-peptide concentrations in women with long-term type 1 diabetes was demonstrated, even in women with undetectable C-peptide concentrations in early pregnancy. This increase is suggestive of improved beta-cell function and was associated with improvement in glycemic control during pregnancy.

Topics: Adult; Age of Onset; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Secretion; Insulin-Secreting Cells; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Prospective Studies; Weight Gain

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m(2) BMI within 4(1/2) mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.

Topics: Adult; Blood Glucose; Body Mass Index; C-Peptide; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin Secretion; Kinetics; Male; Weight Gain

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity, hyperleptinemia, insulin resistance, and type 2 diabetes. Although the mechanisms are unclear, this "programming" has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition (UN) during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Using this model of maternal UN, we have recently shown that neonatal leptin treatment in females reverses the postnatal sequelae induced by developmental programming. To examine possible gender-related effects of neonatal leptin treatment, the present study investigated the effect of neonatal leptin treatment on the metabolic phenotype of adult male offspring. Leptin treatment (recombinant rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring. Neonatal leptin treatment of male offspring from normally nourished mothers caused an increase in diet-induced weight gain and related metabolic sequelae, including hyperinsulinemia and increased total body adiposity compared with saline-treated controls. This occurred without an increase in caloric intake. These effects were specific to offspring of normal pregnancies and were not observed in offspring of mothers after UN during pregnancy. In the latter, neonatal leptin treatment conferred protection against the development of the programmed phenotype, particularly in those fed the chow diet postnatally. These data further reinforce the importance of leptin in determining long-term energy homeostasis, and suggest that leptin's effects are modulated by gender and both prenatal and postnatal nutritional status.

Topics: Adipose Tissue; Animals; Animals, Newborn; Blood Glucose; Bone Density; C-Peptide; Eating; Female; Insulin; Leptin; Male; Malnutrition; Maternal Nutritional Physiological Phenomena; Pregnancy; Rats; Rats, Wistar; Weight Gain

Topics: C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Glucagon-Like Peptide 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin-Secreting Cells; Insulin, Long-Acting; Metformin; Peptides; Randomized Controlled Trials as Topic; Risk Factors; Time Factors; Venoms; Weight Gain; Weight Loss

To describe the outcome of 35 patients with type 2 diabetes prospectively followed for 6 years after the addition of a thiazolidinedione (TZD) to a failing regimen of a sulphonylurea and metformin -- triple oral therapy.. Study patients were assessed for the need for the addition of insulin to their regimen, and follow-up clinical and laboratory findings were analysed.. At a mean follow-up of 72 +/- 1.5 months (range 53-80), 18 (51%) of patients remained well controlled on triple oral therapy with a mean glycosylated haemoglobin (HbA1c) value of 6.9 +/- 0.2% (upper limit of normal 6.2%). In 17 other patients, triple oral therapy failed and the use of insulin was necessary after a mean duration of 38 (range 18-68) months. The mean HbA1c in these patients was 8.0 +/- 0.3%. The group that was maintained on triple oral therapy gained 15.2 +/- 1.9 lbs over the 6-year study which was significantly higher than the baseline weight. Alternatively, the group that failed and had insulin added to their therapy gained 20.2 +/- 4.5 lbs over the same period which was also significantly different from baseline but not from the triple oral therapy group. Although after 3 years a trend towards weight loss occurred in the triple oral therapy group, the insulin-added group continued to gain weight. Stimulated C-peptide levels increased significantly in the triple therapy group from 3.6 +/- 0.9 to 4.3 +/- 1.2 ng/ml and had not increased or decreased non-significantly from 3.7 +/- 0.8 to 3.2 +/- 0.6 ng/ml at the time of insulin initiation in the insulin-requiring group.. When used late in the course of type 2 diabetes, TZDs result in improved and prolonged glycaemic control which persisted for a median time of 6 years. Weight gain with TZDs peaks and then plateaus (and even trends downwards) at 3 years, although the addition of insulin to a failing oral therapy regimen results in a further and continuing weight gain in spite of inferior glycaemic control. Continuing glycaemic control with triple oral therapy is dependent on preservation or augmentation of endogenous insulin production.

Topics: Administration, Oral; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Follow-Up Studies; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections; Insulin; Insulin Resistance; Long-Term Care; Metformin; Middle Aged; Sulfonylurea Compounds; Thiazolidinediones; Treatment Failure; Treatment Outcome; Weight Gain

Recent experimental and clinical data suggest that C-peptide replacement during type 1 diabetes exerts beneficial effects on diabetic nephropathy. The aim of this study was to determine if physiological C-peptide administration in replacement dose during 28 days had beneficial effects on metabolic status and renal functions in type-1 diabetic rats.. Four groups of rats were investigated: a non diabetic group treated with buffer (C group, n=6), three streptozotocin diabetic-induced groups treated with either buffer (D group, n=6), insulin (D-I group, n=6) or rat homologous C-peptide (D-C group, n=6). Weight gain was measured every week. All animals were housed in metabolic cages on day 28 for assessment of metabolic data. Blood and urine samples were collected to allow measurement of plasmatic osmolality, C-peptide concentration, sodium, and glucose losses and proteinuria. Glomerular filtration rate (GFR) was determined by creatinine clearance.. All streptozotocin-treated animals were diabetic. Glycaemic control (mg/dl), was markedly improved in D-I (133+/-65) when compared with either D (547+/-49, P<0.05) or D-C (520+/-48, P<0.05) groups. Conversely, weight gain during the study, was improved in D-I and D-C as compared with D animals (135+/-13 and 41+/-18 vs 18+/-21 respectively), despite different glycaemic control. Diabetes-induced glomerular hyperfiltration (ml/min/kg), urinary protein leakage (g/kg/day), and Na urinary losses (mmol/100 g/day) respectively, were significantly (P<0.05) reduced in D-C (3.95+/-0.6; 0.08+/-0.06; 1.5+/-0.9) in comparison with D (4.95+/-0.8; 0.18+/-0.16; 3.7+/-2.1) and D-I (5+/-0.9; 0.19+/-0.11; 2.7+/-0.8) animals. Plasmatic osmolality was significantly increased in D group whereas there were no differences between C group and D-C group. Food and water intakes, urinary volume as well as urinary glucose losses were not significantly different between D-C and D groups.. C-peptide administration in replacement dose to streptozotocin diabetic rats induces weight gain regardless hyperglycaemia or glycosuria. Diabetic animals supplemented with C-peptide exhibit better renal function resulting in reduced urinary sodium waste and protein excretion together with reduction of the diabetes-induced glomerular hyperfiltration.

Topics: Animals; Blood Glucose; C-Peptide; Diabetes Mellitus, Experimental; Diabetic Angiopathies; Insulin; Kidney; Male; Proteinuria; Rats; Rats, Sprague-Dawley; Sodium; Weight Gain

Valproate (VPA) treatment has been reported to be associated with obesity and high fasting serum insulin concentrations in parallel with an unfavorable serum lipid profile and hyperandrogenism and polycystic ovaries in women. The pathogenetic mechanism underlying these changes has remained unknown, although several mechanisms have been implicated.. Fifty-one patients receiving monotherapy (31 male and 20 female patients) were included in this study, with 45 (23 male and 22 female) healthy control subjects. These participants were interviewed, clinically examined, and blood samples for fasting plasma glucose, serum insulin, proinsulin, and C-peptide concentrations were taken after an overnight fast.. The valproate-treated patients had fasting hyperinsulinemia (11.30 +/- 6.23 pM vs. 6.28 +/- 4.66 pM in the control subjects; p < 0.001), although the fasting serum proinsulin and C-peptide concentrations were not significantly higher in the patients than in the control subjects. In addition, proinsulin/insulin (0.30 +/- 0.14) and C-peptide/insulin ratios (35.48 +/- 24.09) were lower (p < 0.001) in the VPA-treated patients when compared with the control subjects (0.53 +/- 0.36 and 94.27 +/- 61.85, respectively), and they also had lower fasting plasma glucose concentrations (4.72 +/- 0.35 mM) than the control subjects (5.12 +/- 0.58 mM; p < 0.01).. This study suggests that valproate does not induce insulin secretion but might interfere with the insulin metabolism in the liver, resulting in higher insulin concentrations in the peripheral circulation. These changes are seen irrespective of concomitant weight gain, suggesting that increased insulin concentrations induce weight gain and not vice versa.

Topics: Adult; Anticonvulsants; Blood Glucose; C-Peptide; Epilepsy; Fasting; Female; Humans; Hyperinsulinism; Insulin; Insulin Secretion; Liver; Male; Obesity; Proinsulin; Secretory Rate; Valproic Acid; Weight Gain

Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds.. To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin.. In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1-2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control.. Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 +/- 0.3 mg/day (mean +/- standard error of the mean), and a total daily insulin dose of 24.1 +/- 2.6 IU. Fasting glucose levels decreased from 12.7 +/- 0.6 mmol/l to 8.1 +/- 0.3 mmol/l (p < 0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 +/- 0.4 to 7.7 +/- 0.2% (p < 0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 +/- 3.6 kg vs. 85.7 +/- 3.3 kg, p = 0.99).. The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.

Topics: Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Insulin; Male; Metformin; Middle Aged; Pilot Projects; Sulfonylurea Compounds; Weight Gain

Insulin resistance as well as marked changes in body weight and energy metabolism are associated with pregnancy. Its impact on plasma leptin is not known and was determined in this longitudinal study in both diabetic and normal pregnancy.. At 28 gestational weeks plasma concentrations of leptin and B-cell hormones were measured at fasting and after an oral glucose load (OGTT:75 g) in women with gestational diabetes and pregnant women with normal glucose tolerance and compared with women who were not pregnant (C).. Plasma leptin (ng/ml) was higher (p < 0.001) in women with gestational diabetes (24.9 +/- 1.6) than in women with normal glucose tolerance (18.2 +/- 1.5) and increased in both groups when compared with the non-pregnant women (8.2 +/- 1.3; p < 0.0005). No change in plasma leptin concentrations was induced by OGTT in any group. Basal insulin release was higher (p < 0.05) in women with gestational diabetes compared with the pregnant women with normal glucose tolerance. Marked insulin resistance was confirmed by a 20 % lower (p < 0.05) insulin sensitivity in subgroup analysis and a decrease of almost 40% in fasting glucose/insulin ratio (p < 0.005) in women with gestational diabetes. Leptin correlated in women with gestational diabetes with basal plasma concentrations of glucose (p < 0.02), insulin (p < 0.004) and proinsulin (p < 0.01) as well as with BMI (p < 0.001) and overall pregnancy induced maternal weight gain (p < 0.009). With normalisation of blood glucose 8 weeks after delivery in women with gestational diabetes their plasma leptin decreased (p < 0.0005) to 17.3 +/- 1.9 ng/ml but did not completely normalize (p < 0.05 vs non-pregnant women).. Our data show that women with gestational diabetes without any change in plasma leptin upon oral glucose loading have increased plasma leptin concentrations during and after pregnancy, a clear association of plasma leptin with the respective concentration of glucose and insulin resistance as well as with changes in body weight, and a failure to normalize spontaneously BMI to the same extent as pregnant women with normal glucose tolerance when compared with matched control subjects.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Fasting; Female; Gestational Age; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Postpartum Period; Pregnancy; Proinsulin; Regression Analysis; Weight Gain

The effect of insulin-like growth factor I (IGF-I) on insulin-stimulated glucose uptake was studied in adipose and muscle tissues of hypophysectomized female rats. IGF-I was given as a subcutaneous infusion via osmotic minipumps for 6 or 20 days. All hypophysectomized rats received L-thyroxine and cortisol replacement therapy. IGF-I treatment increased body weight gain but had no effect on serum glucose or free fatty acid levels. Serum insulin and C-peptide concentrations decreased. Basal and insulin-stimulated glucose incorporation into lipids was reduced in adipose tissue segments and isolated adipocytes from the IGF-I-treated rats. In contrast, insulin treatment of hypophysectomized rats for 7 days increased basal and insulin-stimulated glucose incorporation into lipids in isolated adipocytes. Pretreatment of isolated adipocytes in vitro with IGF-I increased basal and insulin-stimulated glucose incorporation into lipids. These results indicate that the effect of IGF-I on lipogenesis in adipose tissue is not direct but via decreased serum insulin levels, which reduce the capacity of adipocytes to metabolize glucose. Isoproterenol-stimulated lipolysis, but not basal lipolysis, was enhanced in adipocytes from IGF-I-treated animals. In the soleus muscle, the glycogen content and insulin-stimulated glucose incorporation into glycogen were increased in IGF-I-treated rats. In summary, IGF-I has opposite effects on glucose uptake in adipose tissue and skeletal muscle, findings which at least partly explain previous reports of reduced body fat mass, increased body cell mass, and increased insulin responsiveness after IGF-I treatment.

Topics: Adipocytes; Adipose Tissue; Animals; Blood Glucose; C-Peptide; Female; Glucose; Glycogen; Hypoglycemic Agents; Hypophysectomy; Insulin; Insulin-Like Growth Factor I; Lipid Metabolism; Lipolysis; Muscle, Skeletal; Organ Size; Rats; Rats, Sprague-Dawley; Spleen; Weight Gain

Twenty Landrace x Yorkshire cross pigs (body wt, 47.9+/-2.9 kg) were used to evaluate effects of dietary high chromium (Cr) yeast supplementation on plasma kinetics of glucose, insulin and C-peptide. Pigs were provided free access to either a control diet (C) containing 204 microg Cr/kg or a diet supplemented with an additional 200 microg Cr/kg as high Cr yeast (CR) for between 23 and 30 d. After overnight food deprivation, dextrose (500 g/L) was infused through a jugular vein catheter at a dose of 0.5 g glucose/kg body weight with an infusion rate of 10 g glucose/min within 6 min. High Cr yeast supplementation did not affect body weight gain or food intake. There were no differences in fasting plasma concentrations of either glucose or C-peptide, although basal plasma concentration of insulin tended to be higher in pigs fed CR (P<0.10). Plasma glucose concentrations were lower (P<0.01) at postinfusion times 5, 10, 15 and 20 min in pigs fed CR. Plasma insulin concentrations in pigs fed CR were higher (P<0.05) at 2 and 0 min before the completion of dextrose infusion. However, the increase in plasma insulin concentrations was not accompanied by a comparable elevation in plasma C-peptide concentrations. The 30-min (postinfusion) area of plasma glucose concentrations tended to be lower (P<0.10) in pigs fed CR, but there were no differences in 30-min areas of either plasma insulin or plasma C-peptide concentrations between treatments. Plasma clearance rates of glucose, insulin and C-peptide were higher and their half-lives shorter (P<0.05) in pigs fed CR. In conclusion, dietary high Cr yeast supplementation improved glucose tolerance, possibly through a decrease in hepatic extraction of insulin.

Topics: Animals; Blood Glucose; C-Peptide; Chromium; Diet; Female; Glucose; Glucose Tolerance Test; Half-Life; Infusions, Intravenous; Insulin; Liver; Male; Metabolic Clearance Rate; Saccharomyces cerevisiae; Swine; Weight Gain

To investigate the independent and combined effects of the Trp64Arg polymorphism of the beta3-adrenergic receptor (beta3AR) gene and the (-3826) A-->G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10y follow-up study.. Controlled 10y follow-up study with baseline, 5 and 10y examinations.. 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland.. Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA1c. Genotypes by polymerase chain reaction followed by enzymatic digestion.. No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n = 103; change in weight 6.5 +/- 2.5% vs -0.2 +/- 0.8%, P=0.036, and change in Body Mass Index 8.5 +/- 2.6% vs 2.0 +/- 0.8%, P= 0.060, mean +/- s.e.m.).. The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain.

Topics: Anthropometry; C-Peptide; Carrier Proteins; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Genotype; Glycated Hemoglobin; Humans; Insulin; Ion Channels; Male; Membrane Proteins; Middle Aged; Mitochondrial Proteins; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Receptors, Adrenergic, beta; Receptors, Adrenergic, beta-3; Uncoupling Protein 1; Weight Gain

The present study was conducted in order to analyze the relationship existing between leptin and insulin levels in massive weight loss and weight recovery. Thirteen patients with severe obesity, 14 patients with anorexia nervosa and 13 healthy control subjects were studied. The patients with severe obesity underwent a vertical banded gastroplasty followed by an 800 kcal/day diet for 12 weeks. They were evaluated prior to (body mass index [BMI] 51.2 +/- 8.8 Kg/m2) and after drastic weight loss (BMI 40.6 +/- 6.7 Kg/m2). Patients with anorexia nervosa were treated exclusively with nutritional therapy during 12 weeks, and they were evaluated at their lowest weight status (BMI 16.2 +/- 2.2 Kg/m2) and after weight recovery (BMI 17.9 +/- 2.3 Kg/m2). The BMI of the normal subjects was in the normal range of 20 to 27 Kg/m2 (average 22.8 +/- 2.6 Kg/m2). BMI, percentage of body fat, waist circumference, and serum levels of leptin, insulin, and C-peptide were determined in each patient and normal subject. In severely obese patients, serum leptin and insulin decreased significantly after drastic weight reduction (leptin: from 51.8 +/- 22.3 to 23.7 +/- 10.2 ng/ml; insulin: from 27.1 +/- 13.3 to 17.2 +/- 7.2 mU/ml). In patients with anorexia nervosa, the mean serum leptin levels were significantly higher after weight recovery (5.5 +/- 3.2 vs 7.6 +/- 6 ng/ml). Serum leptin in the severe obesity group correlated positively with BMI, percentage body fat and waist circumference before and after weight loss. In those patients suffering from anorexia nervosa, serum leptin correlated positively with the BMI, percentage of body fat, and waist circumference in the low weight state and after weight recovery. In addition, their serum insulin correlated with BMI and waist circumference after weight recovery. These data reveal that serum leptin concentration correlates significantly with the BMI and body fat content 1) in subjects with a range of weight and caloric intake, 2) in obese patients after drastic weight loss; 3) in anorexic patients after weight gain; and that hyper- or normoinsulinemia do not seem to have any influence on the leptin changes caused by weight loss or gain.

Topics: Adipose Tissue; Adolescent; Adult; Anorexia Nervosa; Anthropometry; Body Mass Index; C-Peptide; Combined Modality Therapy; Female; Gastroplasty; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Weight Gain; Weight Loss

Treatment of catabolic conditions with insulin-like growth factor I (IGF-I), the peptide that mediates some of the anabolic growth-promoting effects of GH, offers potential advantages of avoiding the hyperglycemia caused by treatment with GH. A state of moderate catabolism was produced in six normal, young adult volunteers by restricting their daily dietary intake to 20 kilocalories/kg/day. During the last 6 days of two 2-week diet-study periods, they received either IGF-I (12 micrograms/kg/h by i.v. infusion over 16 h) or GH (0.05 mg/kg/day by sc injection). IGF-I improved nitrogen balance from -236 +/- 45 mmol/day (+/- SE) during diet alone, to -65 +/- 40 mmol/day (P less than 0.001) during the last 4 days of IGF-I infusion. A similar effect was produced by GH. IGF-I infusion decreased fasting blood glucose from 4.94 +/- 0.91 mmol/L to 3.13 +/- 0.44 mmol/L (P less than 0.001), while GH raised blood glucose values (4.75 +/- 1.01 mmol/L on diet alone, to 5.48 +/- 1.00 during the period of GH treatment; P less than 0.05). Despite these differences in blood glucose, IGF-I infusions decreased serum insulin (74.9 +/- 26.8 pmol/L on diet alone, to 16.7 +/- 1.5 pmol/L during IGF-I) and serum connecting-peptide concentrations (2.14 +/- 0.89 mmol/L on diet alone, to 0.97 +/- 0.14 during IGF-I), while GH raised insulin (109.4 +/- 31.3 pmol/L, P less than 0.05 during GH) and connecting-peptide (3.12 +/- 0.59 mmol/L, P less than 0.02). At the dose of each hormone used, the attenuation of nitrogen wasting produced by infusions of IGF-I was similar in magnitude and timing to that produced by injections of GH. The reduction in serum glucose concentrations produced by IGF-I compared with the increase in glucose noted during GH treatment, could benefit hyperglycemic catabolic patients.

Topics: Adult; Blood Glucose; C-Peptide; Carbohydrate Metabolism; Diet; Energy Intake; Energy Metabolism; Fasting; Female; Growth Hormone; Humans; Infusions, Intravenous; Insulin; Insulin-Like Growth Factor I; Male; Nitrogen; Recombinant Proteins; Weight Gain

Topics: Adolescent; Adult; Appetite; Blood Glucose; C-Peptide; Dietary Carbohydrates; Female; Flunarizine; Humans; Insulin; Male; Middle Aged; Migraine Disorders; Time Factors; Weight Gain