Peripheral hormone levels in healthy subjects during controlled fasting

The effect of one week of controlled fasting (31 of fluid containing 50 g of carbohydrate/day) upon the serum levels of hormones, sex hormone binding globulin, and albumin was studied in healthy subjects. Fasting caused decreased levels of prolactin and T3, no changes in the levels of TSH, FSH, LH, dehydroepiandrosterone, 4-androstene-3, 17-dione, total oestrone, and total testosterone, and increased levels of cortisol, dehydroepiandrosterone sulphate and albumin. A significant positive correlation was found between albumin and dehydroepiandrosterone sulphate. Fasting rapidly increased the levels of sex hormone binding globulin and decreased the percentage of free testosterone and the calculated free testosterone level in both sexes. A decreased metabolic clearance of certain steroids (cortisol, dehydroepiandrosterone sulphate) owing to an increased protein binding may be one of the endocrine consequences of fasting. An increased protein binding of testosterone may be outweighed by a decreased gonadal production, thus resulting in an unchanged total testosterone level. The increased sex hormone binding globulin level could not be explained by changes in gonadal and thyroid hormones.     

Effects of oral alanine administration in fasting obese subjects

The effects of administration of oral alanine to therapeutically starved obese subjects is described. Fifty grams of alanine administered daily in divided doses after 2 wk of fasting caused reversal of hypoglycemia and ketosis. Since urinary and blood urea nitrogen increased, these effects appeared secondary to increased hepatic glucose production from alanine. Reduction of muscle catabolism during alanine administration was suggested by decreased plasma levels of essential branched chain amino acids and diminished urinary losses of phosphorus and potassium. Small rises in plasma insulin occurred and may have mediated these effects. Hyperuricemia was diminished, and urinary uric acid excretion was increased by alanine as ketosis disappeared. These data suggest that alanine supply may be one important regulator of hepatic gluconeogenesis during fasting. Additionally, it was observed that a single oral 50-g dose of alanine produced hyperinsulinemia and hypoglycemia in the postabsorptive state. After 2 wk of fasting, the same dose produced hyperglycemia and lesser hyperinsulinemia.     

Colonic myoelectric activity during fasting and postprandial periods in healthy subjects and colonopathic patients

The purpose of this prospective study was to assess colonic myoelectric activity during fasting and after a test meal in patients with the Irritable Bowel Syndrome (IBS) and in control subjects. Colonic electromyographic activity was recorded using an intraluminal probe in 14 patients and in 8 controls. Only rapid electrical activity [i. e. Short Spike Bursts (SSB) and Long Spike Bursts (LSB)] was taken into account. In control subjects the test meal provoked a significant increase in LSB from 46.7 +/- 16.3 to 88.6 +/- 20.3 (p less than 0.001) but not in SSB. In IBS patients rapid myoelectrical activity was not significantly modified by food intake (47.2 +/- 10.3 vs. 62.2 +/- 10.9; NS). The increase of postprandial LSB activity was found to be significantly higher in controls than in IBS patients (41.8 +/- 7.6 vs. 12.9 +/- 8.4; p less than 0.05). These results showed that colonic myoelectrical activity in IBS patients is different from that of controls; such a difference could be useful in classifying IBS patients.     

The effect of Ramadan fasting on spirometry in healthy subjects

OBJECTIVES: Lung function tests are an important investigative tool in diagnosing respiratory diseases, judging their severity and assessing prognosis. The primary aim of the present study was to assess whether Ramadan fasting affected normal lung function values. METHODOLOGY: Forty-six non-smoking healthy males, with a mean age of 24.2 years (SD 6.4 years) were investigated. Spirometry was performed according to the recommendations of the American Thoracic Society. Days between the 15th and 25th of three Islamic months (pre-Ramadan, Ramadan and post-Ramadan) were selected for spirometry. On all three occasions, FVC, FEV(1), FEV(1)/FVC%, maximum voluntary ventilation (MVV(indirect)), PEF, FEF(25--75%) and body mass were measured. Pre- and post-Ramadan readings were compared with the readings during Ramadan fasting. The results were analysed by repeated measures analysis of variance. RESULTS: No significant change was seen in lung function during Ramadan as compared to the pre-Ramadan period. FVC was decreased significantly in the post-Ramadan period compared to Ramadan and this period was associated with a significant increase in body mass. CONCLUSION: Relative to pre-Ramadan baseline values, there was no change in spirometry during Ramadan fasting in these subjects.     

Alterations of sensory perceptions in healthy elderly subjects during fasting and refeeding. A pilot study

BACKGROUND: Sensory perception losses may contribute to age-related malnutrition by affecting food selection and consumption. OBJECTIVE: To determine the effects of a 36-hour fast followed by a 6-hour refeeding period on sensory perceptions in 7 healthy elderly subjects (65-80 years of age) and 6 healthy young subjects (18-35 years of age). METHODS: Self-perceived hunger and olfactory ratings were recorded on visual analogue scales in response to three different classes of odorant stimuli (salt, sweet and sour). Odorant stimuli were administered three times during the study, twice during the fasting period (12 and 24 h fasted) and once at the end of the re-nutrition period. RESULTS: A significant difference was found between the two groups for the self-perceived hunger ratings in response to the sour stimuli. A significant difference was observed between the two groups for olfactory ratings as regards the salt and sour odorant stimuli. Among the metabolic changes associated with fasting and refeeding, blood glucose was significantly related (r(2) = 0.97, p = 0.001) to the perception of hunger in the control group subjects, but no such relationship was found for the elderly subjects (r(2) = 0.16, p = NS). CONCLUSION: (1) Self-perceived hunger and olfactory ratings are specifically affected in healthy elderly. (2) Nutritional status can modulate sensory perceptions in elderly and young during the transition from fasting to refeeding.     

Ghrelin levels are not regulated by recombinant leptin administration and/or three days of fasting in healthy subjects

Ghrelin, a stomach-derived orexigenic peptide, and leptin, a fat-derived anorexigenic hormone, act primarily in the hypothalamus to regulate energy homeostasis and have been reported to be regulated in opposite directions by acute and chronic changes in nutritional state. Nutritional, anthropometric, and hormonal predictors of circulating ghrelin have not yet been fully elucidated, and whether ghrelin is regulated by leptin in humans remains unknown. To address these questions, we performed cross-sectional and interventional studies. In 120 healthy men and women, ghrelin was negatively associated with leptin as well as overall and central adiposity, but not with total energy or specific macronutrient intake. The sexual dimorphism in ghrelin levels (higher levels in women than in men) and the negative correlation between ghrelin and insulin are largely mediated by central adiposity. In six lean men, complete fasting for 3 d resulted in a low leptin state without a major change in fat mass and abolished the meal-related secretory pattern of ghrelin without increasing 24-h ghrelin levels. In addition, recombinant human leptin administration in physiological and pharmacological doses did not regulate ghrelin over several hours to a few days. These data do not support a role for regulation of circulating ghrelin by leptin levels independently of changes in adiposity and suggest that the leptin and ghrelin systems for energy homeostasis function independently of each other in healthy humans.     

Reproducibility of glycaemic thresholds for activation of counterregulatory hormones and hypoglycaemic symptoms in healthy subjects

Summary Nine healthy subjects were studied on two separate occasions, at least two weeks apart, using the glucose clamp technique to produce a gradual hypoglycaemia. Glucose thresholds for neuroendocrine and symptom responses varied up to 1.5 mmol/l between subjects. There was a significant correlation between individual glucose thresholds on day 1 and 2 for adrenaline (p = 0.0008), growth hormone (p = 0.007) and pancreatic polypeptide (p = 0.02), and for autonomic (p = 0.018) and neuroglycopoenic (p = 0.023) symptoms, whereas no significant correlations were found for glucagon and cortisol. The mean intra-individual differences in glucose thresholds between day 1 and 2 were 0.22 mmol/l for the hormones and 0.25 mmol/l for the symptoms. We conclude that healthy subjects differ in hypoglycaemic thresholds, and that the difference reflects individual variation.     

Short-term metabolic effects of prednisone administration in healthy subjects

Aims: Supraphysiologic glucocorticoid activity is well established to cause impaired glucose tolerance and insulin resistance, yet no study has evaluated dose‐dependent effects of low‐dose prednisone during short‐term oral administration. Methods: The objective of this study was to quantify the effects of daily 10 or 25 mg prednisone administration for one week on insulin sensitivity by employing a two‐step hyperinsulinemic euglycemic glucose clamp (Step 1: insulin infusion = 20 mU/m²/min; Step 2: insulin infusion = 80 mU/m²/min) in healthy, lean males. The amount of glucose infused at steady‐state to maintain stable blood glucose [90 mg/dl (4.95 mmol/l)] was used to calculate several indices of insulin sensitivity. Results: During Step 1 of the clamp, whole body glucose disposal (M) was reduced by 35% (p = 0.003) and M/I was reduced by 29% (p = 0.025) for 25 mg prednisone compared to placebo. No appreciable effect of 10 mg prednisone was observed. During Step 2, M was reduced by 33% (p = 0.001) and 15% (p = 0.006) for 25 and 10 mg prednisone compared to placebo; and M/I ratio was reduced by 31% (p < 0.001) and 13% (p = 0.026), respectively. The insulin sensitivity index, Si , calculated as the quotient of augmentation of M/I between Step 1 and 2, was reduced by 35.3% (p < 0.01) and 23.5% (p < 0.05) for 25 and 10 mg prednisone, respectively. Conclusion: Administration of relatively low pharmacological doses of prednisone for one week impaired insulin sensitivity in a dose‐dependent manner in healthy males. These observed changes in insulin sensitivity are likely to be clinically relevant, especially in individuals predisposed to develop glucose intolerance.     

No increased risk of perforation during colonoscopy in patients undergoing Nurse Administered Propofol Sedation

Abstract

Objective. Nurse Administered Propofol Sedation (NAPS) contributes to a deeper sedation of the patients, making them unable to respond to pain and an increased incidence of perforations has been speculated. The objective of this study was to evaluate the risk of perforations during colonoscopies performed with either NAPS or conventional sedation regimes. Material and methods. Data were retrospectively retracted from medical journals from 1 January 2007 to 31 December 2011. All journals were examined and cross-referenced to reveal any perforations. We analyzed all colonoscopies in regard to nature of the procedure (diagnostic vs therapeutic), experience of the endoscopist and ASA-classification of the patients. Results. A total of 6371 colonoscopies were performed, of which 3155 were performed under propofol sedation. There were 16 perforations (0.25%); 10 of these performed during NAPS and 6 during conventional colonoscopy (p = 0.454, OR: 1.7 (95% CI: 0.6–5.7)). There were 4874 diagnostic and 1497 therapeutic colonoscopies, with a majority of the perforations (94%) occurring during a diagnostic procedure (p = 0.389). No statistically difference was found in the incidence of perforations caused by an experienced or less experienced endoscopist (p = 0.589). Conclusion. The risk of colonic perforations during colonoscopy was not found to be significantly higher in patients undergoing NAPS compared to patients undergoing conventional sedation, although a tendency may exist. Furthermore, we found no correlation to neither experience of the endoscopist, nature of the procedure nor sex of the patients. Larger and prospective studies are needed to further evaluate on this subject.     

Determinants of within-subject variation of fasting serum leptin concentrations in healthy subjects.

The hormone leptin is considered to contribute to body weight regulation through modulation of feeding behavior and energy expenditure. The aim of the present study was 1) to assess the day-to-day within-subject variation (biovariability) of serum leptin concentrations in healthy subjects and 2) to investigate whether this variation is associated with food intake, exercise, anthropometric measurements or various metabolic covariates (insulin, C-peptide and glucagon, glucose, lactate, 3-hydroxybutyrate (3-OHB), triglycerides, non-esterified-fatty acids and glycerol). Serum leptin levels were taken daily on 12 consecutive days after an overnight fast in 12 healthy subjects with a mean (SD) age of 22.7 (1.5) yr. and a BMI of 22.8 (1.6) kg/m2. Food intake, exercise, anthropometric measurements and various metabolic covariates were also determined during this period. The overall mean of serum leptin concentration was 33.3 pmol/L with a within-subject SD range of 27-41 pmol/L and a between-subject SD range of 18-61 pmol/L. The within-subject variance of serum leptin as a proportion of total variance was 9.5%. Within-subject variation of serum leptin concentrations is small in relation to between-subject variation in healthy, normal weight subjects. This has implications for the power of interventional or prospective studies. In men, 6.7% of the variation in serum leptin concentration was associated with body weight measured on the same day (p= 0.037). In women, however, 66% of the variation was negatively associated with 3-OHB measured on both the same and the previous day (p=0.0003 and 0.002), and positively associated with triglyceride concentration measured on the previous day (p=0.0017) and insulin measured on the same day (p=0.0002). Within-subject associations in women could be due to phasic changes in unmeasured variables, possibly related to the menstrual cycle or might suggest that energy balance may exert a delayed influence on serum leptin levels, with plasma 3-OHB and triglycerides acting as markers for the state of the fat stores that regulate leptin secretion. The differences between the genders remain unexplained, however.     

Activated platelets in subjects at increased risk of IDDM

Summary Activated platelets respond to activated leukocytes and endothelial cells via adhesion molecules linking inflammation and thrombosis. Platelets of recent-onset insulin-dependent diabetic (IDDM) patients have been shown to be activated independent of metabolic control. This study evaluates the levels of circulating activated platelets exposing adhesion molecules in healthy subjects at increased risk of IDDM (surface markers were: P-selectin (CD62), thrombospondin, lysosomal GP53 (CD63) ). From the DENIS and the ENDIT screening programmes 19 identified islet cell antibody positive (titre ≥ 20 Juvenile Diabetes Foundation units) first degree relatives of IDDM patients (male/female 9/10; age 22 ± 15 years; body mass index (BMI): 20.0 ± 4.3 kg/m²) with clearly normal metabolism (HbA₁: 6.1 ± 0.8 %; fasting blood glucose: 4.95 ± 0.67 mmol/l) were available for this investigation. Platelet CD62 as well as thrombospondin and CD63 expression were determined by flow cytometry. We matched 50 normal volunteers for age (29 ± 6 years), anthropometric measures (male/female 26/24; BMI: 22.3 ± 2.8 kg/m²) and metabolic parameters (HbA₁: 5.8 % ± 0.3; fasting blood glucose: 4.41 ± 0.53 mmol/l) served as control subjects. The mean number of CD62⁺ platelets was increased 3.2-times in prediabetic patients: 1.94 × 2.91^±1 vs 0.60 × 1.83^±1 %, p < 0.0001. Thrombospondin⁺ and CD63⁺ platelet levels were concomitantly increased (1.45 × 2.38^±1/5.97 × 2.89^±1 % vs 0.52 × 2.01^±1/1.64 × 2.26^±1 %, p < 0.0001 for both comparisons). Thus, intravasal platelet activation is already present in potentially prediabetic subjects representing an antecedent, potentially pathogenic feature of IDDM. [Diabetologia (1997) 40: 573–577] Received: 6 September 1996 and in revised form: 16 January 1997     

Prevalence and significance of increased intraventricular velocities in healthy elderly subjects

BACKGROUND: Heart murmurs are common in the elderly and increased intracavitary velocities (IIV) within the left ventricle have been reported to be a cause of systolic murmur. OBJECTIVE: To assess the prevalence and functional significance of IIV in healthy elderly subjects METHODS: Ambulatory healthy elderly subjects were recruited from community centres and seniors' apartments. They were screened using a structured questionnaire and then underwent a comprehensive history and physical examination. Electrocardiogram, echocardiogram and 6-min walk test were performed on the same day. RESULTS: Four of the 88 subjects were excluded because of significant valvular dysfunction. Ten of the remaining 84 subjects had IIV and their demographics were similar to those of the 74 subjects without IIV. Echocardiographic parameters including left ventricular size and mass were similar between the two groups. Left ventricular mass index was lower in subjects with IIV (P=0.02). Both groups had similar 6-min walk results. CONCLUSIONS: In the healthy elderly who do not have valvular disease or left ventricular hypertrophy, IIV is uncommon and does not appear to have functional significance.     

Changes in energy metabolism in response to 48 h of overfeeding and fasting in Caucasians and Pima Indians

OBJECTIVE: Differences in the metabolic response to overfeeding and starvation may confer susceptibility or resistance to obesity in humans. To further examine this hypothesis, we assessed the changes in 24 h energy metabolism in response to short-term overfeeding and fasting in Caucasians (C) and Pima Indians (I), a population with a very high propensity for obesity. METHODS: We measured the changes in 24 h energy expenditure (24 -EE) and 24 h respiratory quotient (24-RQ) in response to 48 h of mixed diet overfeeding (100% above energy requirements) and fasting in a whole body respiratory chamber in 14 male subjects (7 C/7 I, age 30+/-6 y, mean+/-s.d.). Results were compared to a 24 h measurement under eucaloric conditions. RESULTS: Mean 24-EE increased in response to overfeeding and decreased in response to fasting (all changes P<0.01), with no differences between C (+9.1% and -9.1%) and I (+8.6% and -9.6%). Similarly, mean 24-RQ increased/decreased in response to overfeeding/fasting, respectively (all changes P<0.01), again with no differences between C (+0.06 and -0.05) and I (+0.05 and -0.05). The changes in 24-EE in response to overfeeding and fasting were positively correlated (r=0.70, P<0.01), whereas those in 24-RQ were not (r=0.40, NS). CONCLUSIONS: Pima Indians do not appear to have an impaired metabolic response to short-term overfeeding and fasting that could explain their propensity for obesity. Individuals with a large increase in energy expenditure in response to overfeeding appear to have a small decrease in energy expenditure in response to starvation (spendthrift phenotype) and vice versa (thrifty phenotype).     

Physiological role of endothelin-1 in nonworking muscles during exercise in healthy subjects

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. However, the role of ET-1 in exercise-induced physiological responses is still to be investigated. The purpose of the present study was to investigate in healthy volunteers whether the ET-1 plasma concentration in nonworking muscles is changed by exercise and to investigate the physiological role of ET-1 during exercise. Bicycle ergometer cardiopulmonary exercise tests were performed in 36 healthy men (mean age, 22.5 years). Blood samples for measuring ET-1 were drawn from the cubital vein during rest and immediately after the exercise test. The ET-1 change ratio was calculated as ET-1 immediately following exercise/ET-1 during the resting state. Cardiac output (CO) was measured during the exercise test by the impedance method. Arterial venous oxygen difference (AVO2D) when CO reached 10L/min or 15L/min was calculated as AVO2D = VO2/CO. Results were as follows: (1) the ET-1 change ratio correlated inversely with exercise time at the anaerobic threshold (r = -0.37, p = 0.03) and peak exercise time (r = -0.35, p = 0.04); (2) the ET-1 change ratio tended toward an inverse correlation with deltaVO2/deltawork rate (r = -0.29, p = 0.09); (3) the ET-1 change ratio correlated positively with AVO2D when CO reached 10L/min (r = 0.42, p = 0.02) and tended toward a positive correlation with AVO2D when CO reached 15 L/min (r = 0.32, p = 0.08). These results indicate that an increase in ET-1 in nonworking muscles may participate in the exercise-induced redistribution of blood flow and in increasing the blood flow to working muscles.     

Brain energy metabolism during hypoglycaemia in healthy and Type 1 diabetic subjects

Aims/hypothesis This study aimed to examine brain energy metabolism during moderate insulin-induced hypoglycaemia in Type 1 diabetic patients and healthy volunteers.Methods Type 1 diabetic patients (mean diabetes duration 13±2.5 years; HbA₁c 6.8±0.3%) and matched controls were studied before, during (0–120 min) and after (120–240 min) hypoglycaemic (~3.0 mmol/l) hyperinsulinaemic (1.5 mU·kg^–1·min^–1) clamp tests. Brain energy metabolism was assessed by in vivo ³¹P nuclear magnetic resonance spectroscopy of the occipital lobe (3 Tesla, 10-cm surface coil).Results During hypoglycaemia, the diabetic patients showed blunted endocrine counter-regulation. Throughout the study, the phosphocreatine:-ATP ratios were lower in the diabetic patients (baseline: controls 3.08±0.29 vs diabetic patients 2.65±0.43, p<0.01; hypoglycaemia: 2.97±0.38 vs 2.60±0.35, p<0.05; recovery: 3.01±0.28 vs 2.60±0.35, p<0.01). Intracellular pH increased in both groups, being higher in diabetic patients (7.096±0.010 vs. 7.107±0.015, p<0.04), whereas intracellular magnesium concentrations decreased in both groups (controls: 377±33 vs 321±39; diabetic patients: 388±47 vs 336±68 µmol/l; p<0.05).Conclusions/interpretation Despite a lower cerebral phosphocreatine:-ATP ratio in Type 1 diabetic patients at baseline, this ratio does not change in control or diabetic patients during modest hypoglycaemia. However, both groups exhibit subtle changes in intracellular pH and intracellular magnesium concentrations.Abbreviations [Mg²⁺]_i intracellular magnesium - NMR nuclear magnetic resonance - PCr phosphocreatine - pH_i intracellular pH - P_i intracellular inorganic phosphate     

No increased risk of thrombosis in heterozygous congenital dysplasminogenemia

To assess the risk of thrombosis in congenital dysplasminogenemia, we studied 10 unrelated families with this disorder. The probands were excluded from the analysis of data to prevent bias in the selection of subjects. Positive thrombotic histories were found in 1 of the 25 family members determined to have heterozygous congenital dysplasminogenemia and in 2 of their 41 biochemically unaffected relatives. The percentages of family members with no history of thrombosis up to a given age among subjects with and without congenital dysplasminogenemia were analyzed by the Kaplan-Meier method. No significant difference between the 2 groups was observed by generalized Wilcoxon test (P = .32) or Cox-Mantel test (P = .62). These findings suggest that heterozygous congenital dysplasminogenemia is not associated with an increased risk of thrombosis.     

The effects of short-term fasting on the excretion of sulfur compounds in healthy subjects

The urinary excretion of sulfur-containing compounds was studied before, on the third, and on the seventh day of fasting in 10 healthy subjects. The excretion of total sulfur, inorganic sulfate, ester sulfate, “non-sulfate sulfur”, methionine, cystathionine, cysteine, N-acetylcysteine, taurine, thiosulfate and thiocyanate was decreased during fasting, whereas the excretion of mercaptoacetate was unaltered and that of mercaptolactate increased. The excretion of inorganic sulfate, taurine and thiocyanate was also decreased when calculated relative to that of total sulfur, suggesting that these compounds are derived mainly from dietary sulfur amino acids. The output of ester sulfate, methionine, cystathionine, cysteine and thiosulfate was unaltered in relation to that of total sulfur, indicating that these compounds are derived from both dietary and endogenous sulfur amino acids, liberated during protein catabolism. By contrast, the excretion of mercaptolactate and mercaptoacetate was increased relative to that of total sulfur, suggesting that these compounds are derived mainly from endogenous sulfur amino acids formed by the enchanced protein catabolism seen during fasting.