Impaired glucose tolerance in healthy men with low body weight.

BACKGROUND: Impaired glucose tolerance (IGT) and high body mass index (BMI) are recognized risk factors for type 2 diabetes mellitus (T2DM). However, data suggest that also underweight predisposes people to develop T2DM. Here, we experimentally tested if already moderate underweight is associated with impaired glucose tolerance as compared to normal weight controls. Obese subjects were included as additional reference group. METHOD: We included three groups of low weight, normal weight, and obese subjects comprising 15 healthy male participants each. All participants underwent a standardized hyperinsulinemic-euglycemic glucose clamp intervention to determine glucose tolerance. In addition, insulin sensitivity index (ISI) was calculated by established equation. RESULTS: ISI values were higher in low and normal weight than in obese subjects (P < 0.010) without any difference between low and normal weight groups (P = 0.303). Comparable to obese participants (P = 0.178), glucose tolerance was found decreased in low weight as compared with normal weight subjects (P = 0.007). Pearson's correlation analysis revealed a positive relationship between glucose tolerance and BMI in low (P = 0.043) and normal weight subjects (P = 0.021), an effect that was found inverse in obese participants (P = 0.028). CONCLUSION: Our study demonstrates that not only obese but also healthy people with moderate underweight display glucose intolerance. It is therefore suggested that all deviations from normal BMI may be accompanied by an increased risk of developing T2DM in later life indicating that the maintenance of body weight within the normal range has first priority in the prevention of this disease.

Evidence for a relationship between VEGF and BMI independent of insulin sensitivity by glucose clamp procedure in a homogenous group healthy young men.

BACKGROUND: This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI) as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed. METHODOLOGY/PRINCIPAL FINDINGS: Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20-25 kg/m(2)), 15 low weight (BMI<20 kg/m(2)), and 15 obese (BMI>30 kg/m(2)) male subjects aged 18-30 years and the insulin sensitivity index (ISI) was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145), cortisol (P = 0.840), and norepinephrine (P = 0.065) levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008) with higher concentrations in obese subjects as compared to normal weight (P = 0.061) and low weight subjects (P = 0.002). Pearson's correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010) but no correlation of VEGF with ISI (r = 0.224; P = 0.175). CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes.

Evidence for a relationship between body mass and energy metabolism in the human brain.

Cerebral energy metabolism has been suggested to have an important function in body weight regulation. We therefore examined whether there is a relationship between body mass and adenosine triphosphate (ATP) metabolism in the human brain. On the basis of our earlier findings indicating a neuroprotective preferential energy supply of the brain, as compared with peripheral muscle on experimentally induced hypoglycemia, we examined whether this physiological response is preserved also in low-weight and obese participants. We included 45 healthy male subjects with a body mass index (BMI) ranging from 17 to 44 kg/m(2). Each participant underwent a hypoglycemic glucose-clamp intervention, and the ATP metabolism, that is, the content of high-energy phosphates phosphocreatine (PCr) and ATP, was measured repeatedly by (31)phosphor magnetic resonance spectroscopy ((31)P-MRS) in the cerebral cortex and skeletal muscle. Results show an inverse correlation between BMI and high-energy phosphate content in the brain (P<0.01), whereas there was no such relationship found between skeletal muscle and BMI. The hypoglycemic clamp intervention did not affect the ATP metabolism in both tissues. Our data show an inverse correlation between BMI and cerebral high-energy phosphate content in healthy humans, suggesting a close relationship between energetic supply of the brain and body weight regulation.

Short Hypoxia Does not Affect Plasma Leptin in Healthy Men under Euglycemic Clamp Conditions.

Leptin is involved in the endocrine control of energy expenditure and body weight regulation. Previous studies emphasize a relationship between hypoxic states and leptin concentrations. The aim of this study was to investigate the effects of acute hypoxia on leptin concentrations in healthy subjects. We examined 14 healthy men. Hypoxic conditions were induced by decreasing oxygen saturation to 75% for 30 minutes. Plasma leptin concentrations were determined at baseline, after 3 hours of euglycemic clamping, during hypoxia, and repeatedly the following 2.5 hours thereafter. Our results show an increase of plasma leptin concentrations in the course of 6 hours of hyperinsulinemic-euglycemic clamping which may reflect diurnal rhythmicity. Notwithstanding, there was no difference between levels of leptin in the hypoxic and the normoxic condition (P = .2). Since we did not find any significant changes in leptin responses upon hypoxia, plasma leptin levels do not seem to be affected by short hypoxic episodes of moderate degree.

Continuous positive airway pressure therapy decreases evening cortisol concentrations in patients with severe obstructive sleep apnea.

Patients with obstructive sleep apnea syndrome (OSAS) show recurrent episodes of nightly hypoxic stress. The purpose of this study is the detection of alterations of the hypothalamic-pituitary-adrenal stress axis in OSAS patients before and after continuous positive airway pressure (CPAP) therapy. An activation of the hypothalamic-pituitary-adrenal axis was proposed because of the nightly hypoxic stress in these patients, but previous studies were not conclusive. Here we hypothesize that CPAP therapy decreases salivary cortisol concentrations in patients with severe OSAS. We performed a clinical within-subject study including 50 patients with newly diagnosed OSAS and an apnea-hypopnea index greater than or equal to 40 h(-1). Diurnal profiles of salivary cortisol concentrations were compiled before and after 3 months of treatment with CPAP. Therefore, 6 cortisol samples were collected: before and after lunch, in the evening, the next morning after awakening, and before and after breakfast. Thirty-eight patients returned after 3 months of CPAP therapy for follow-up. According to the reference range for healthy subjects, cortisol values were not pathologically increased. Analysis of variance revealed a significant effect of CPAP therapy on diurnal cortisol profiles (P = .048). Subjects with severe OSAS showed a decrease (3.04 +/- 0.55 nmol L(-1) pre-CPAP vs 2.48 +/- 0.78 nmol L(-1) post-CPAP, P = .038) of evening cortisol levels after CPAP treatment, whereas prelunch levels were increased after CPAP therapy (7.18 +/- 0.83 nmol L(-1) pre-CPAP vs 10.22 +/- 1.10 nmol L(-1) post-CPAP, P = .044). Our results show that CPAP therapy decreases evening cortisol concentrations in patients with severe OSAS. These data suggest that OSAS may increase the cortisol nadir that is reversed after CPAP therapy.