BACKGROUND: Peripheral administration of glucagon-like peptide-1 (GLP-1) for four hours, to normal weight and obese humans, decreases food intake and suppresses appetite. OBJECTIVE: The aim of this study was to assess the effect of an eight hour infusion of GLP-1 on appetite and energy intake at lunch and dinner in obese subjects. DESIGN: Randomised, blinded cross-over design with intravenous infusion of GLP-1 (0.75 pmol Á kg 71 Á min 71 ) or saline. SUBJECTS: Eight obese (body mass index, BMI, 45.5 AE 2.3 kgam 2 ) male subjects. MEASUREMENTS: Ad libitum energy intake at lunch (12.00 h) and dinner (16.00 h) after an energy ®xed breakfast (2.4 MJ) at 08.00 h. Appetite sensations using visual analogue scales, (VAS) immediately before and after meals and hourly in-between. Blood samples for the analysis of glucose, insulin, C-peptide, GLP-1 and peptide YY. Gastric emptying after breakfast and lunch using a paracetamol absorption technique. RESULTS: Hunger ratings were signi®cantly lower with GLP-1 infusion. The summed ad libitum energy intake at lunch and dinner was reduced by 1.7 AE 0.5 MJ (21 AE 6%) by GLP-1 infusion (P 0.01). Gastric emptying was delayed by GLP-1 infusion, and plasma glucose concentrations decreased (baseline: 6.6 AE 0.35 mmolaL; nadir: 5.3 AE 0.15 mmolaL). No nausea was recorded during GLP-1 infusion. CONCLUSIONS: Our results demonstrate that GLP-1 decreases feelings of hunger and reduces energy intake in obese humans. One possible mechanism for this ®nding might be an increased satiety primarily mediated by gastric vagal afferent signals.

The gut peptide glucagon-like peptide 1(7-36) amide (GLP-1) is released into the circulation after food intake. GLP-1 has been shown to have an incretin effect and inhibits gastrointestinal motility in humans. In rats, intracerebral administration of GLP-1 results in reduced food intake. Obese humans have been found to have an attenuated plasma GLP-1 response to a mixed meal. To approximate the physiologic state, GLP-1 or saline was administered intravenously and randomly at the beginning of a test meal served on a universal eating monitor to 6 obese subjects to test our hypothesis that GLP-1 influences termination of food intake (and thus food intake during a meal) and feelings of satiety in humans. As a marker for gastric emptying, 1.5 g acetaminophen was given at the start of the meal. Blood samples for analysis of acetaminophen, insulin, glucose, glucagon, and C-peptide were obtained. Hunger, fullness, and food choice were assessed with visual analogue scales and food-choice questionnaires. GLP-1 infusion resulted in a prolonged period of reduced feelings of hunger, desire to eat, and prospective consumption after the meal. The rate of gastric emptying was slower during infusion of GLP-1. Postprandial blood glucose concentrations were reduced during the GLP-1 infusion, but the amount of energy consumed, eating rate, and plasma concentrations of insulin, glucagon, and C-peptide were unchanged. GLP-1 given exogenously at the start of a meal did not seem to affect meal termination or the amount of food eaten. However, postprandial feelings of hunger decreased, suggesting that exogenous GLP-1 may influence feelings of hunger and satiety in humans.

OBJECTIVE:To evaluate the diagnostic accuracy of body mass index (BMI, kg/m 2 ), waist-circumference (WC) and waist-hipratio (WHR) as diagnostic tests for detecting fatness in adolescents. DESIGN: A cross-sectional analysis of 474 healthy adolescents aged 17 y was used. Measurements of height, weight, WC, hipcircumference and body fat percentage (%BF) were obtained. The diagnostic accuracy for detecting excess fatness was evaluated through receiver operating characteristics (ROC) analyses with %BF, measured by densitometry (air-displacement plethysmography), as reference test. RESULTS: BMI and WC showed strong positive correlation (r ¼ 0.68-0.73; Po0.0001) with %BF in both sexes, but the correlation was weaker for WHR (r ¼ 0.30-0.41; Po0.0001). For overweight and obesity in boys and obesity in girls, the area under the ROC curve was high (0.96-0.99) for BMI and WC. WHR was not significantly better than chance as diagnostic test for obesity in girls. For BMI and WC, highly sensitive and specific cutoffs for obesity could be derived, while larger trade-offs were needed for detecting overweight in girls. The cutoffs producing equal sensitivity and specificity were lower than the ones minimizing the absolute number of misclassifications. The latter approached internationally recommended reference values, but were still several units lower for BMI in girls and several centimeters lower for WC in boys. CONCLUSION: BMI and WC were found to perform well as diagnostic tests for fatness, while WHR was less useful. The discrepancies between cutoffs producing equal sensitivity and specificity, cutoffs minimizing the absolute number of misclassifications and internationally recommended reference values for overweight and obesity highlight the importance of specifying the characteristics of classification systems for different settings.

Transthyretin (TTR) is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol, mainly existing as a tetramer in vivo. We now demonstrate that TTR tetramer has a positive role in pancreatic ␤-cell stimulus-secretion coupling. TTR promoted glucose-induced increases in cytoplasmic free Ca 2؉ concentration ([Ca 2؉ ]i) and insulin release. This resulted from a direct effect on glucose-induced electrical activity and voltagegated Ca 2؉ channels. TTR also protected against ␤-cell apoptosis. The concentration of TTR tetramer was decreased, whereas that of a monomeric form was increased in sera from patients with type 1 diabetes. The monomer was without effect on glucose-induced insulin release and apoptosis. Thus, TTR tetramer constitutes a component in normal ␤-cell function. Conversion of TTR tetramer to monomer may be involved in the development of ␤-cell failure͞ destruction in type 1 diabetes.type 1 diabetes ͉ Ca 2ϩ channels ͉ insulin release ͉ ␤-cell signal transduction ͉ apoptosis T ransthyretin (TTR) is a protein that is synthesized in the liver, the choroid plexus of the brain, and the endocrine pancreas (1, 2). It is a transport protein for thyroxine and, in association with retinol-binding protein, for retinol. It has been reported that 1-2% of plasma TTR circulates bound to highdensity lipoprotein (HDL) and that the association to the HDL vesicle occurs through binding to apolipoprotein A1 (3). TTR has a complex equilibrium between different quaternary structures in serum (4),but exists mainly as a tetrameric protein of 14-kDa subunits (160-380 mg͞liter) with only a small amount of TTR monomer present in vivo in normal individuals (5, 6). Consequently, measurements of TTR in serum by conventional methods mainly reflect the tetrameric form. The TTR amyloidoses are human diseases in which misfolded TTR protein aggregates in different tissues. Several point mutations in TTR have been related to familial amyloidotic polyneuropathy (FAP) (7). The fact that TTR is also produced within the pancreatic islet made us interested in evaluating a possible role of this protein in ␤-cell stimulus-secretion coupling. MethodsIdentification of TTR in Human Sera. Sera from type 1 diabetes (T1D) patients and control subjects were collected, identically sterile-processed, heat-inactivated by incubation at 56°C for 30 min, and stored frozen at Ϫ20°C until used. Changes in cytoplasmic free Ca 2ϩ concentration ([Ca 2ϩ ] i ) were tested in ␤-cells when they were depolarized with 25 mM KCl. Those diabetic sera that induced a higher increase in [Ca 2ϩ ] i than sera from controls were centrifuged, and the supernatant was passed through a 0.45-mm sterile filter. Samples were loaded on SepPak C 18 preconditioned with 0.1% trifluoroacetic acid. After application, the sample proteins were eluted with 60% acetonitrile in 0.1% trifluoroacetic acid. This procedure was repeated twice. The two fractions were pooled, and the volume was reduced by lyophilization.The lyophilized material was submitted to...