c-peptide and Starvation

Adaptive thermogenesis (AT) is the fat-free mass (FFM)-independent reduction of resting energy expenditure (REE) to caloric restriction (CR). AT attenuates weight loss and favors weight regain. Its variance, dynamics, and control remain obscure.. Our aims were to address the variance and kinetics of AT, its associations with body composition in the context of endocrine determinants, and its effect on weight regain.. Thirty-two nonobese men underwent sequential overfeeding (1 wk at +50% of energy needs), CR (3 wk at -50% of energy needs), and refeeding (2 wk at +50% of energy needs). AT and its determinants were measured together with body composition as assessed with the use of quantitative magnetic resonance, whole-body MRI, isotope dilution, and nitrogen and fluid balances.. Changes in body weight were +1.8 kg (overfeeding), -6.0 kg (CR), and +3.5 kg (refeeding). CR reduced fat mass and FFM by 114 and 159 g/d, respectively. Within FFM, skeletal muscle (-5%), liver (-13%), and kidneys (-8%) decreased. CR also led to reductions in REE (-266 kcal/d), respiratory quotient (-15%), heart rate (-14%), blood pressure (-7%), creatinine clearance (-12%), energy cost of walking (-22%), activity of the sympathetic nervous system (SNS) (-38%), and plasma leptin (-44%), insulin (-54%), adiponectin (-49%), 3,5,3'-tri-iodo-thyronine (T3) (-39%), and testosterone (-11%). AT was 108 kcal/d or 48% of the decrease in REE. Changes in FFM composition explained 36 kcal, which left 72 kcal/d for true AT. The decrease in AT became significant at ≤3 d of CR and was related to decreases in insulin secretion (r = 0.92, P < 0.001), heart rate (r = 0.60, P < 0.05), creatinine clearance (r = 0.79, P < 0.05), negative fluid balance (r = 0.51, P < 0.01), and the free water clearance rate (r = -0.90, P < 0.002). SNS activity and plasma leptin, ghrelin, and T3 and their changes with CR were not related to AT.. During early weight loss, AT is associated with a fall in insulin secretion and body fluid balance. This trial was registered at clinicaltrials.gov as NCT01737034.

Topics: Adaptation, Physiological; Adiponectin; Adult; Basal Metabolism; Body Composition; Body Mass Index; Body Weight; C-Peptide; Caloric Restriction; Creatinine; Energy Metabolism; Ghrelin; Heart Rate; Humans; Insulin; Insulin Secretion; Leptin; Male; Minnesota; Starvation; Testosterone; Thermogenesis; Triiodothyronine; Young Adult

Adherence to a low-calorie diet often results in a decrease in blood glucose concentration in persons with non-insulin-dependent diabetes mellitus (NIDDM). Whether this is due to the resultant weight loss or to a decrease in caloric intake has been uncertain. We have obtained data previously that indicated a very short-term reduction in caloric intake (5 hours) resulted in a significant decrease in plasma glucose concentration in subjects with NIDDM. The purpose of the present study was to determine if a further decrease in glucose would occur if the fast was extended from 5 to 24 hours. Seven male subjects with untreated NIDDM were studied after an 11-hour overnight fast. For the subsequent 24-hour period, subjects were given only water. Blood was obtained for glucose, insulin, C-peptide, triglycerides, nonesterified fatty acids (NEFA) alpha-amino acid nitrogen, urea nitrogen, and glucagon at hourly intervals for 24 hours beginning at 8 AM. The amount of glycogen degraded was calculated based on the potassium balance. Plasma glucose decreased from 158 mg/dL at 8 AM to a nadir of 104 mg/dL at 7 PM. It then increased by 30 mg/dL. Corresponding changes occurred in insulin and C-peptide. Serum glucagon remained unchanged. Serum alpha-amino acid nitrogen and urea nitrogen decreased. Triglycerides and NEFA increased. The calculated glycogen utilized over this period was approximately 167 g. This would provide approximately 700 kcal energy. The elevated blood glucose concentration in mild to moderately severe untreated NIDDM subjects was normalized following short-term fasting. Plasma insulin concentrations also decreased to within normal limits. These decreases were highly significant. Glycogenolysis is an important source of fuel during this period.

Topics: Aged; Blood Glucose; Blood Urea Nitrogen; C-Peptide; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Insulin; Male; Middle Aged; Nitrogen; Starvation; Time Factors; Triglycerides

Postprandial glucose is reduced in malnourished patients with anorexia nervosa (AN), but the mechanisms and duration for this remain unclear. We examined blood glucose, gastric emptying, and glucoregulatory hormone changes in malnourished patients with AN and during 2 wk of acute refeeding compared with healthy controls (HCs). Twenty-two female adolescents with AN and 17 age-matched female HCs were assessed after a 4-h fast. Patients were commenced on a refeeding protocol of 2,400 kcal/day. Gastric emptying (

Topics: 3-O-Methylglucose; Adolescent; Anorexia Nervosa; Blood Glucose; Breath Tests; C-Peptide; Caprylates; Carbon Isotopes; Case-Control Studies; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Postprandial Period; Starvation; Young Adult

The insulin-like growth factor axis is highly responsive to nutritional status and may be involved as one of the underlying mechanisms through which caloric restriction could affect cancer risk. High levels of circulating insulin-like growth factor (IGF)-I, or IGF-I relative to IGF binding protein (IGFBP)-3 have been related to various human cancer types. In a group of 87 postmenopausal women, we found that childhood exposure to the 1944-1945 Dutch famine was associated with increased plasma levels of IGF-I and IGFBP-3, whereas IGFBP-1 and -2 levels were weakly decreased. These results are opposite to immediate responses seen under starvation and we hypothesize that this could indicate a permanent overshoot upon improvement of nutritional status after the famine.

Topics: Adolescent; Adult; Aged; Body Mass Index; C-Peptide; Caloric Restriction; Child; Child, Preschool; Cohort Studies; Female; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Middle Aged; Netherlands; Postmenopause; Risk Factors; Starvation; Time Factors

In type II diabetic subjects, we previously demonstrated differences in the serum insulin, C-peptide, and glucagon response to ingestion of seven different protein sources when administered with 50 g of glucose. The response was smallest with egg white and greatest with cottage cheese protein. In the present study, we compared the responses to 50 g of the above two proteins ingested without glucose in normal male subjects. We also determined the proportion of each ingested protein converted to urea nitrogen. The incremental area response integrated over 8 hours for serum insulin, C-peptide, glucagon, alpha-amino-nitrogen (AAN), and urea nitrogen were all approximately 50% less following egg white. This was associated with a 50% smaller conversion of protein to urea. Overall, 70% of the cottage cheese but only 47% of the egg white protein could be accounted for by urea formation. Most likely the smaller hormonal response to egg white is due to poor digestibility of this protein.

Topics: Adult; Aminoacetonitrile; Blood Glucose; Blood Urea Nitrogen; C-Peptide; Dairy Products; Dietary Proteins; Egg Proteins; Fatty Acids, Nonesterified; Glucagon; Humans; Insulin; Kinetics; Male; Starvation; Urea

To analyze the mechanisms of fasting-induced glucose intolerance, glucose metabolism was studied before and after the ingestion of 75 g glucose in 24 normal subjects fasted for either 14 h (n = 12) or 4 days (n = 12). The techniques included intravenous infusion of [6-3H]glucose and oral administration of [1-14C]glucose combined with indirect calorimetry. Compared with the controls, the starved subjects exhibited the following differences in glucose metabolism during the 5 h after glucose ingestion. 1) Mean incremental levels were fourfold higher for glucose and 40% higher for insulin. 2) Absorption of oral glucose was delayed and prolonged, but total amount reaching systemic circulation in 5 h was identical in the two groups (approximately 63 g). 3) Suppression of hepatic glucose output was reduced (-12 +/- 1 vs. -22 +/- 2 g). 4) Consequently, the increment in peripheral appearance of total glucose (exogenous plus endogenous) was augmented (+ 52 +/- 2 vs. +41 +/- 2 g). 5) Mean glucose clearance increased significantly less (+28 +/- 7 vs. +96 +/- 10 ml/min). 6) Oxidation of oral glucose was reduced (9 +/- 2 vs. 36 +/- 3 g), and nonoxidative disposal (presumably storage) was enhanced (56 +/- 2 vs. 36 +/- 3 g) in the presence of an elevated fat oxidation (35 +/- 2 vs. 22 +/- 4 g). Thus the alterations in glucose homeostasis responsible for the starvation-induced glucose intolerance are located both at the splanchnic (hepatic) and peripheral levels.

Topics: 3-Hydroxybutyric Acid; Adult; Blood Glucose; C-Peptide; Diabetes Mellitus; Fasting; Fatty Acids, Nonesterified; Glucagon; Humans; Hydroxybutyrates; Insulin; Lactates; Male; Starvation

To examine whether decreased insulin secretion during starvation is related to a change in the ability of insulin to inhibit its own secretion, plasma C-peptide was measured after plasma insulin levels were acutely raised by intravenous (IV) insulin infusion in a dose of 40 and 80 mU/M2/min in obese subjects before and after a 72 hour fast. Plasma glucose concentration was maintained +/- 4% of basal levels by a variable glucose infusion. During the 80 mU infusion, at plasma insulin levels of 200 microU/mL, plasma C-peptide fell by 0.17 pmol/mL in the fed state. In the fasted state, despite basal levels that were 36% lower, C-peptide decreased by 0.21 pmol/mL. Highly significant increases in percent suppression after fasting were noted during both 40 mU and 80 mU studies. The plasma C-peptide response was related to the insulin infusion dose in both the fed and fasted state. In contrast, alpha cell suppression by insulin, as determined by plasma glucagon levels, was not altered by fasting. It is concluded that enhanced inhibitory influences of insulin on the beta cell during starvation may be a physiologically important mechanism for diminished insulin secretion during the transition from the fed to the fasting state.

Topics: Adult; Blood Glucose; C-Peptide; Feedback; Glucagon; Humans; Insulin; Insulin Secretion; Middle Aged; Obesity; Starvation

The usefulness of measurements of urinary C-peptide excretion in indirectly assessing integrated insulin secretion during starvation was studied in eight obese subjects during a 72-h fast. Blood and urine samples were collected at 12-h intervals for measurement of insulin and C-peptide immunoreactivity. After 60 h, serum insulin and plasma C-peptide levels declined 47% and 37%, respectively, and the values were highly correlated (r = 0.8; P less than 0.001). By 72 h, urinary C-peptide excretion had declined to 70% of the level in the first 12-h period. The urinary clearance of C-peptide was not altered by starvation. A highly significant correlation was found between urinary C-peptide and C-peptide secretory rate (P less than 0.001). The molar ratio of plasma C-peptide to insulin remained constant during the fasting period. These data indicate that basal insulin secretion can be added to the list of physiological conditions in which beta-cell secretion can be effectively evaluated by urinary C-peptide measurement.

Topics: Adult; C-Peptide; Creatinine; Humans; Insulin; Insulin Secretion; Metabolic Clearance Rate; Middle Aged; Secretory Rate; Starvation

Rapid oscillations in basal plasma levels of insulin, C-peptide, glucagon, and glucose in rhesus monkeys have been reported previously. We now report large minute-to-minute fluctuations in plasma somatostatinlike immunoreactivity (SLI) in undisturbed, chair-adapted, and chronically cannulated male rhesus monkeys. Plasma samples were drawn from eight monkeys at 1- to 2-min intervals for 30-40 min following an overnight fast. Large fluctuations in SLI levels with periods of 4.4-9.4 min/cycle and possibly secondary periods of 14-18 min/cycle with average amplitudes of +/- 23% relative to the respective mean SLI levels were observed both within a single experiment and across monkeys under basal conditions. No consistent relationship was found between SLI fluctuations and that of insulin or glucagon. When portal and central blood samples were drawn precisely simultaneously no consistent portal-central gradient was found. Patterns of fluctuations in central and portal SLI levels were not correlated. Overfeeding significantly increased insulin levels but did not alter SLI levels. After 5 days of food deprivation basal SLI levels were unchanged. These data indicate the need to exercise care in the interpretation of single samples in the measurement of plasma SLI levels. Somatostatin secreted into the blood under basal, unstimulated conditions appears to be unrelated to nutritional balance.

Topics: Animals; Blood Glucose; C-Peptide; Diet; Glucagon; Humans; Hyperphagia; Insulin; Macaca mulatta; Male; Peptides; Somatostatin; Starvation

Topics: Adult; Arginine; C-Peptide; Female; Glucose; Humans; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Peptides; Proinsulin; Starvation