The acute effects of different macronutrients on the secretion of glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) and glucose-dependent insulinotropic polypeptide (GIP) were compared in healthy human subjects. Circulating levels of the two hormones were measured over a 24-h period during which subjects consumed a mixed diet. In the first study, eight subjects consumed three equicaloric (375 kcal) test meals of carbohydrate, fat and protein. Small increases in plasma GLP-1(7-36) amide were found after all meals. Levels reached a maximum 30 min after the carbohydrate and 150 min after the fat load. Ingestion of both carbohydrate and fat induced substantial rises in GIP secretion, but the protein meal had no effect. In a second study, eight subjects consumed 75 g glucose or the equivalent portion of complex carbohydrate as boiled brown rice or barley. Plasma GIP, insulin and glucose levels increased after all three meals, the largest increase being observed following glucose and the smallest following the barley meal. Plasma GLP-1(7-36)amide levels rose only following the glucose meal. In the 24-h study, plasma GLP-1(7-36)amide and GIP concentrations were increased following every meal and remained elevated throughout the day, only falling to fasting levels at night. The increases in circulating GLP-1(7-36)amide and GIP levels following carbohydrate or a mixed meal are consistent with their role as incretins. The more sustained rises observed in the daytime during the 24-h study are consistent with an anabolic role in lipid metabolism.
Background-Hypersecretion of insulinotropic factors such as glucose dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36)amide (GLP-1) have been postulated to account for the hyperinsulinaemia of obesity. Aims-To examine the role of GLP-1 and GIP in obese women and matched controls. Subjects-Six lean and six obese women subjects matched for age. Methods-The gut hormone, plasma glucose, and serum triglyceride responses were studied over 180 minutes after oral carbohydrate and fat meals. Heparin (10 000 units) was given intravenously at 120 minutes.Results-There was pronounced attenuation of plasma GLP-1 secretion to oral carbohydrate in the obese compared with lean subjects but no such difference in response to oral fat load. There were no differences in the plasma GIP responses to carbohydrate or fat feeding. There was an apparent fall in plasma GLP-1 values in all subjects after administration of heparin. Conclusion-Postprandial GLP-1 secretion in response to oral carbohydrate is considerably attenuated in obese subjects.The cause of this attenuation of GLP-1 secretion is not known although we suggest that both this fall and the overall reduction in GLP-1 values in obese subjects may be related to an increase in plasma non-esterified fatty acids. (Gut 1996; 38: 916-919) Keywords: GLP-1, obesity, carbohydrate meal, fat meal. strongly stimulates insulin secretion after carbohydrate, fat, and mixed meals. Molecular biology techniques have shown that posttranslational processing of proglucagon in the pancreas and ileum yields several novel glucagon-like peptides.67 Among these, the truncated fragment of GLP-1 (hitherto called GLP-1 in this paper), has been shown to be strongly insulinotropic and its secretion has been shown to increase after oral glucose and mixed meals.8 9 In addition to its insulinotropic effect, GLP-1 inhibits pancreatic glucagon secretion, decreases hepatic gluconeogenesis, and decreases insulin resistance.10 11 It has been postulated that an exaggerated 'incretin' factor may have a pathophysiological role in obesity. A role for GIP has been examined in this regard but has not been conclusively shown.5 In this context, it has been suggested that hypersecretion of GLP-1 may be the long sought 'incretin' factor in obesity. 12 Indeed, Fukase and colleagues have examined this hypothesis in a study where they showed increased secretion of glucagon-like peptide-1 in obese diabetic subjects but the responses in non-diabetic obese and matched controls were very similar.However, the methodology adopted by Fukase and workers for GLP-1 assay was indirect and less specific than that used in this study and included GLP-1(7-37), which is normally present at very low concentrations in plasma, and the two biologically inactive major proglucagon derived fragments. GLP-1 (7-36)amide, measured in this study, is the predominant circulating molecular species of glucagon-like peptides in humans. We undertook this study to clarify the conclusions of Fukase and colleagues that hypers...
The circadian rhythms of many night-shift workers are maladapted to their imposed behavioural schedule, and this factor may be implicated in the increased occurrence of cardiovascular disease (CVD) reported in shift workers. One way in which CVD risk could be mediated is through inappropriate hormonal and metabolic responses to meals. This study investigated the responses to standard meals at different circadian times in a group of night-shift workers on a British Antarctic Survey station at Halley Bay (75 S) in Antarctica.Twelve healthy subjects (ten men and two women) were recruited. Their postprandial hormone and metabolic responses to an identical mixed test meal of 3330 kJ were measured on three occasions: (i) during daytime on a normal working day, (ii) during night-time at the beginning of a period of night-shift work, and (iii) during the daytime on return from nightworking to daytime working. Venous blood was taken for 9 h after the meal for the measurement of glucose, insulin, triacylglycerol (TAG) and non-esterified fatty acids. Urine was collected 4-hourly (longer during sleep) on each test day for assessment of the circadian phase via 6-sulphatoxymelatonin (aMT6s) assay.During normal daytime working, aMT6s acrophase was delayed (7·7 1·0 h (...)) compared with that previously found in temperate zones in a comparable age-group. During the night shift a further delay was evident (11·8 1·9 h) and subjects' acrophases remained delayed 2 days after return to daytime working (12·4 1·8 h). Integrated postprandial glucose, insulin and TAG responses were significantly elevated during the night shift compared with normal daytime working. Two days after their return to daytime working, subjects' postprandial glucose and insulin responses had returned to pre-shift levels; however, integrated TAG levels remained significantly elevated.These results are very similar to those previously found in simulated night-shift conditions; it is the first time such changes have been reported in real shift workers in field conditions. They provide evidence that the abnormal metabolic responses to meals taken at night during unadapted night shifts are due, at least in part, to a relative insulin resistance, which could contribute to the documented cardiovascular morbidity associated with shift work. When applied to the 20% of the UK workforce currently employed on shift work, these findings have major significance from an occupational health perspective.
Forty five women and 10 men with coeliac disease diagnosed in adult life, who were already on a gluten free diet, had serial bone mineral density measurements at the lumbar spine and femoral neck over 12 months. Osteoporosis, defined as a bone mineral density (BMD) ',2 SD below the normal peak bone mass was found in 50° suggest that reduced bone mineral density is common at presentation.9 10 We therefore studied the prevalence of osteoporosis in asymptomatic adults with treated coeliac disease, and utilised serial bone mineral density measurements to detect any change in bone mineral density over 12 months. SubjectsFifty five patients (45 women and 10 men) with coeliac disease diagnosed in adult life (-18 years old at the time of diagnosis) and already established on a gluten free diet were recruited to the study from the gastroenterology outpatients department at the Royal United Hospital, Bath between 24 September 1991 and 21 October 1992. Coeliac disease was defined as small intestinal malabsorption associated with the characteristic small intestinal mucosal lesion together with clinical and histological improvement on a gluten free diet. 1 'The average age of the men was 50.2 years (range 27.0-65.0 years) and that of the women was 51-3 years (range 33.6-69.1 years). With regard to the women, the average age at menarche was 14 years (range 10-20 years; five patients had menarche at age 16 years or older). Five women (no overlap with the delayed menarche group) had a history of an episode of premenopausal amenorrhoea of at least six months. Sixteen women were premenopausal, 11 were perimenopausal, and 18 were postmenopausal (average age at menopause was 46.3 years, range 34 to 57 years, eight patients had had the menopause at age less than 45 years).Seven patients had been previously treated with oral vitamin D preparations, six had been on glucocorticoids in the past, and five of the women were either on, or had previously been on, hormone replacement therapy for more than 12 months. Fourteen patients (two men) had a history of a serious fracture (rib, clavicle, ankle, forearm, sternum, scaphoid).The average weight of the women was 61-7 kg (range 35-92.7 kg) and that of the men was 74.5 kg (range 55-97 kg). The average height of the women was 1.62 m (range 1A40-1.75 m) and that of the men was 1.74 m (range 1-60-1-86 m). The mean times spent on a gluten free diet were 4.25 years (range 0-4-10 years) in men and 9.2 years (range 0.3-40 years) in women. MethodsA dietary assessment was performed, based on a 10 day weighed record'2 of all food consumed, and the dietary intakes of calcium,
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