Isotretinoin 5 mg daily for low-grade adult acne vulgaris--a placebo-controlled, randomized double-blind study.

BACKGROUND: Despite acne persisting into adulthood in up to 50% of the population, very few therapeutic studies have been performed in this age group. OBJECTIVES: To assess the efficacy of 5 mg/day isotretinoin in adult acne. METHODS: An investigator initiated, industry-sponsored, randomized, double-blind, placebo-controlled, parallel-group clinical study of isotretinoin 5 mg/day in the treatment of low-grade adult acne for 16 weeks followed by an open-label phase of 16 weeks. Group 1 received 32 weeks of 5 mg isotretinoin/day; Group 2 first received 16 weeks of placebo, followed by 16 weeks open-label 5 mg isotretinoin/day. Patients were followed for a further 10 weeks off treatment. The primary end-point was the difference in acne lesion count and disability score after 16 weeks isotretinoin compared to placebo. Secondary end-points included differences in these counts/scores after 32 weeks of isotretinoin compared to baseline, and after 10 weeks off treatment, compared to end of treatment (week 32). RESULTS: There were highly significant differences (P < 0.0001) in acne lesion count, Dermatology Life Quality Index and self-assessment after 16 weeks of isotretinoin, compared to placebo (both per protocol and intention to treat). Acne lesions fell significantly, within 4 weeks of 5 mg isotretinoin/day (Group 1) and continued to fall during 32 weeks of treatment [acne lesion count (mean ± SD): 11.3 ± 8.1 (baseline), 3.6 ± 5.5 (week 16), 1.3 ± 3.1 (week 32), P < 0.0001)]. There was a similar significant reduction in acne lesion count in Group 2, but only from week 20, 4 weeks after starting open-label 5 mg isotretinoin. Adverse effects were minimal. CONCLUSIONS: Isotretinoin 5 mg/day is effective in reducing the number of acne lesions, and improving patients dermatologic quality of life, with minimal adverse effects.

A randomised trial of enteric-coated nutrient pellets to stimulate gastrointestinal peptide release and lower glycaemia in type 2 diabetes.

AIMS/HYPOTHESES: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. METHODS: Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was sampled frequently for blood glucose (the primary outcome) and hormone assays. RESULTS: Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. CONCLUSIONS/INTERPRETATION: Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000600842. FUNDING: The study was funded by Meyer Nutriceuticals.

Effects of variations in duodenal glucose load on glycaemic, insulin, and incretin responses in type 2 diabetes.

AIMS: Postprandial glucagon-like peptide-1 (GLP-1) secretion and the 'incretin effect' have been reported to be deficient in Type 2 diabetes, but most studies have not controlled for variations in the rate of gastric emptying. We evaluated blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose in Type 2 diabetes, and compared these with data from healthy controls. METHODS: Eight males with well-controlled Type 2 diabetes, managed by diet alone, were studied on four occasions in single-blind, randomized order. Blood glucose, and plasma insulin, GLP-1, and GIP were measured during 120-min intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2) and 4 kcal/min (G4) or saline control. RESULTS: Type 2 patients had higher basal (P < 0.0005) and incremental (P < 0.0005) blood glucose responses to G2 and G4, when compared with healthy controls. In both groups, the stimulation of insulin and GLP-1 by increasing glucose loads was not linear; responses to G1 and G2 were minimal, whereas responses to G4 were much greater (P < 0.005 for each) (incremental area under the GLP-1 curve 224 ± 65, 756 ± 331 and 2807 ± 473 pmol/l.min, respectively, in Type 2 patients and 373 ± 231, 505 ± 161 and 1742 ± 456 pmol/l.min, respectively, in healthy controls). The GLP-1 responses appeared comparable in the two groups. In both groups there was a load-dependent increase in plasma GIP with no difference between them. CONCLUSIONS: In patients with well-controlled Type 2 diabetes, blood glucose, insulin and GLP-1 responses are critically dependent on the small intestinal glucose load, and GLP-1 responses are not deficient.

How conserved are the bacterial communities associated with aphids? A detailed assessment of the Brevicoryne brassicae (Hemiptera: Aphididae) using 16S rDNA.

Aphids harbor a community of bacteria that include obligate and facultative endosymbionts belonging to the Enterobacteriaceae along with opportunistic, commensal, or pathogenic bacteria. This study represents the first detailed analysis of the identity and diversity of the bacterial community associated with the cabbage aphid, Brevicoryne brassicae (L.). 16S rDNA sequence analysis revealed that the community of bacteria associated with B. brassicae was diverse, with at least four different bacterial community types detected among aphid lines, collected from widely dispersed sites in Northern Britain. The bacterial sequence types isolated from B. brassicae showed little similarity to any bacterial endosymbionts characterized in insects; instead, they were closely related to free-living extracellular bacterial species that have been isolated from the aphid gut or that are known to be present in the environment, suggesting that they are opportunistic bacteria transmitted between the aphid gut and the environment. To quantify variation in bacterial community between aphid lines, which was driven largely by differences in the proportions of two dominant bacterial orders, the Pseudomonales and the Enterobacteriales, we developed a novel real-time (Taqman) qPCR assay. By improving our knowledge of aphid microbial ecology, and providing novel molecular tools to examine the presence and function of the microbial community, this study forms the basis of further research to explore the influence of the extracellular bacterial community on aphid fitness, pest status, and susceptibility to control by natural enemies.

Radiation and radical chemistry of NO3(-), HNO3, and dialkylphosphoric acids in room-temperature ionic liquids.

Hydrophobic room-temperature ionic liquids (ILs) are considered as possible replacements for molecular diluents for nuclear separations, as well as the basis of new separations processes. Such applications may put the solvents both in high radiation fields and in contact with aqueous raffinate containing 1-6 M HNO(3). In this study, we address the effect of the extracted nitrate and nitric acid on the radiation chemistry of hydrophobic ILs composed of 1-alkyl-3-methylimidazolium cations (and closely related systems). We demonstrate that the nitrate anion competes with the solvent cation as an electron scavenger, with most of the primary radical species converted to NO(3)(•2-) and NO(2)(•) that initiate a complex sequence of radical reactions. In hydrophobic ILs equilibrated with 3 M HNO(3), nearly all electrons released by the ionizing radiation are converted to NO(2)(•). While the reductive pathway is strongly affected by the nitrate and there is also some N-O bond scission via direct excitation, the extent of interference with the oxidative pathway is relatively small; the cation damage is not dramatically affected by the presence of nitrate as most of the detrimental radiolytic products are generated via the oxidative pathway. These results are contrasted with the behavior of dialkylphosphoric acids (a large class of extraction agents for trivalent metal ions). We demonstrate that IL solvents protect these dialkylphosphoric acids against radiation-induced dealkylation.

Social cognition in children with Down's syndrome: challenges to research and theory building.

Characterising how socio-cognitive abilities develop has been crucial to understanding the wider development of typically developing children. It is equally central to understanding developmental pathways in children with intellectual disabilities such as Down's syndrome. While the process of acquisition of socio-cognitive abilities in typical development and in autism has received considerable attention, socio-cognitive development in Down's syndrome has received far less scrutiny. Initial work in the 1970s and 1980s provided important insights into the emergence of socio-cognitive abilities in the children's early years, and recently there has been a marked revival of interest in this area, with research focusing both on a broader range of abilities and on a wider age range. This annotation reviews some of these more recent findings, identifies outstanding gaps in current understanding, and stresses the importance of the development of theory in advancing research and knowledge in this field. Barriers to theory building are discussed and the potential utility of adopting a transactional approach to theory building illustrated with reference to a model of early socio-cognitive development in Down's syndrome. The need for a more extensive model of social cognition is emphasised, as is the need for larger-scale, finer-grained, longitudinal work which recognises the within-individual and within-group variability which characterises this population. The value of drawing on new technologies and of adapting innovative research paradigms from other areas of typical and atypical child psychology is also highlighted.

The nitric oxide synthase inhibitor, Ng-nitro-L-arginine-methyl-ester, attenuates the delay in gastric emptying induced by hyperglycaemia in healthy humans.

The aim of this study was to determine whether the nitric oxide (NO) synthase inhibitor, N(g)-nitro-L-arginine-methyl-ester (L-NAME), reverses the effects of acute hyperglycaemia on gastric emptying and antropyloroduodenal (APD) motility. The study had a four-way randomized crossover (hyperglycaemia vs euglycaemia; L-NAME vs placebo) design in a clinical laboratory setting. Seven healthy volunteers [four males; age 30.3 +/- 3.8 years; body mass index (BMI) 23.6 +/- 1.2 kg m(-2)] were the study subjects. After positioning a transnasal manometry catheter across the pylorus, the blood glucose concentration was maintained at either 15 or 5 mmol L(-1) using a glucose/insulin clamp. An intravenous infusion of L-NAME (180 microg kg(-1 )h(-1)) or placebo (0.9% saline) was commenced (T = -30 min) and continued for 150 min. At T = -2 min, subjects ingested a drink containing 50 g of glucose made up to 300 mL with water. Gastric emptying was measured using 3D ultrasound, and APD motility using manometry. Hyperglycaemia slowed gastric emptying (P < 0.05), and this effect was abolished by L-NAME. L-NAME had no effect on gastric emptying during euglycaemia. Hyperglycaemia suppressed fasting antral motility [motility index: 3.9 +/- 0.8 (hyperglycaemia) vs 6.5 +/- 0.6 (euglycaemia); P < 0.01]; l-NAME suppressed postprandial antral motility [motility index: 3.6 +/- 0.2 (L-NAME) vs 5.1 +/- 0.2 (placebo); P < 0.001]. Postprandial basal pyloric pressure was higher during hyperglycaemia (P < 0.001), and lower after administration of L-NAME (P < 0.001). Slowing of gastric emptying induced by hyperglycaemia is mediated by NO, and may involve the modulation of tonic pyloric activity.

Relationship between calcium absorption and plasma dehydroepiandrosterone sulphate (DHEAS) in healthy males.

CONTEXT: Impaired gut sensitivity to 1,25-dihydroxyvitamin D (1,25(OH)(2)D), leading to reduced intestinal calcium absorption, has been reported in older men and women. While this phenomenon in postmenopausal women has been attributed to oestrogen deficiency, it is unclear whether the same observation in older men correlates with the age-related decline in androgen concentrations. OBJECTIVE: To examine the relationship between androgens and intestinal calcium absorption in older men. DESIGN: Cross-sectional study on 55 healthy male volunteers, divided into younger (n = 27) and older (n = 28) groups separated according to the median age of 59 years. MAIN OUTCOME MEASURES: Calcium absorption, total and free (calculated) testosterone, dehydroepiandrosterone sulphate (DHEAS), SHBG, and 1,25(OH)(2)D, among others, were measured. RESULTS: Calcium absorption, free testosterone and DHEAS, but not 1,25(OH)(2)D, declined significantly with age. After adjusting for age and body mass index, stepwise regression showed that 1,25(OH)(2)D and serum albumin were the only significant determinants of calcium absorption in younger men, while the sole determinant in older men was DHEAS, not testosterone. Residual deviations from the regression of calcium absorption on 1,25(OH)(2)D, reflecting the efficiency of 1,25(OH)(2)D-induced calcium absorption, was positively correlated with DHEAS (r = 0.27, P = 0.027). CONCLUSIONS: DHEAS is an independent determinant of calcium absorption in older men, although its manner of influence is, as yet, undefined. The age-related decline of DHEAS may, partly, account for the observed 'intestinal resistance to 1,25(OH)(2)D' in older men.

Socio-cognitive understanding: a strength or weakness in Down's syndrome?

BACKGROUND: Social understanding is often thought to be relatively 'protected' in children with Down's syndrome (DS) and to underlie the outgoing personality characteristically attributed to them. This paper draws together findings from our studies of behaviours during object concept testing, generally considered a theoretically 'pure' measure of early cognitive ability, and from more recent work focusing on two key socio-cognitive skills: recognising facial expressions of emotion and collaborative learning. Age range of children studied was 4 months to 18 years. METHODS: Using standardised hiding tasks, object concept ability was assessed cross-sectionally and longitudinally in children with DS and in age- or stage-matched typically developing (TD) children. Stability of cognitive advances was assessed and similarities/differences in developmental pathways explored. In the emotion recognition studies, the ability to distinguish six primary emotions was measured, with performance compared with that of developmentally-matched TD children and age-matched children with intellectual disabilities of similar severity but differing aetiology [non-specific intellectual disability (NSID) or fragile X syndrome (FXS)]. In the collaborative learning study, the impact on sorting skills of working with a peer on a conceptually related task was measured, with outcomes compared in DS, NSID and TD child pairings. RESULTS: Evidence of counterproductive, socially-based strategies being inappropriately applied by children with DS in learning contexts was found in both the object concept and collaborative learning studies, along with inefficient use of current cognitive and linguistic abilities. Emotion recognition weaknesses were also identified, although deficits were relative rather than absolute and individual variability was marked. CONCLUSIONS: In line with emerging evidence from other research teams, findings suggest possible difficulties in some core aspects of interpersonal functioning in DS, with both qualitative and quantitative differences in how social cognition develops and is applied in learning contexts. Implications for development and for behavioural phenotype theory are briefly discussed.

Collaborative learning: comparison of outcomes for typically developing children and children with intellectual disabilities.

Collaborative learning is widely used in mainstream education but rarely utilized with children who have intellectual disabilities, possibly on the assumption that the metacognitive skills on which it capitalizes are less likely to be available. Effects of collaborative learning experience on a core cognitive skill, sorting by category, were investigated in three child groups: typically developing (TD) children, children with nonspecific intellectual disabilities (NSID) and children with Down syndrome (DS). Following collaboration, sorting performance improved significantly in lower ability partners in TD-TD pairings, with this pattern reversed in NSID-NSID pairings. Neither partner improved significantly in DS-NSID pairings, suggesting that the sociability attributed to children with DS did not necessarily support either their or their partner's learning in this social context.

Understanding of facial expressions of emotion by children with intellectual disabilities of differing aetiology.

BACKGROUND: Interpreting emotional expressions is a socio-cognitive skill central to interpersonal interaction. Poor emotion recognition has been reported in autism but is less well understood in other kinds of intellectual disabilities (ID), with procedural differences making comparisons across studies and syndromes difficult. This study aimed to compare directly facial emotion recognition skills in children with fragile X syndrome (FXS), Down's syndrome (DS) and non-specific intellectual disability (NSID), contrasting ability and error profiles with those of typically developing (TD) children of equivalent cognitive and linguistic status. METHODS: Sixty children participated in the study: 15 FXS, 15 DS, 15 NSID and 15 TD children. Standardised measures of cognitive, language and socialisation skills were collected for all children, along with measures of performance on two photo-matching tasks: an 'identity-matching' task (to control for basic face-processing ability) and an 'emotion-matching' task (happiness, sadness, anger, surprise, fear or disgust). RESULTS: Identity-matching ability did not differ across the four child groups. Only the DS group performed significantly more poorly on the emotion-matching task and only in comparison to the TD group, with fear recognition an area of particular difficulty. CONCLUSION: Findings support previous evidence of emotion recognition abilities commensurate with overall developmental level in children with FXS or NSID, but not DS. They also suggest, however, that syndrome-specific difficulties may be subtle and detectable, at least in smaller-scale studies, only in comparison with TD matches, and not always across syndromes. Implications for behavioural phenotype theory, educational interventions and future research are discussed.

Effect of pramlintide on satiety and food intake in obese subjects and subjects with type 2 diabetes.

AIMS/HYPOTHESIS: Long-term trials in insulin-treated subjects with type 2 diabetes have shown that adjunctive treatment with the amylin analogue pramlintide reduces HbA(1)c levels and elicits weight loss. While amylin reduces food intake in rodents, pramlintide's effect on satiety and food intake in humans has not yet been assessed. METHODS: In this randomised, double-blind, placebo-controlled crossover study, 11 insulin-treated men with type 2 diabetes (age 60+/-9 years, BMI 28.9+/-4.8 kg/m(2)) and 15 non-diabetic obese men (age 41+/-21 years, BMI 34.4+/-4.5 kg/m(2)) underwent two standardised meal tests. After fasting overnight, subjects received single subcutaneous injections of either pramlintide (120 microg) or placebo, followed by a preload meal. After 1 h, subjects ate an ad libitum buffet meal. Energy intake and meal duration were measured, as were hunger ratings (using visual analogue scales), and plasma cholecystokinin, glucagon-like peptide-1 and peptide YY concentrations over time. RESULTS: Compared with placebo, pramlintide reduced energy intake in both the type 2 diabetes (Delta-202+/-64 kcal, -23+/-8%, p<0.01) and obese (Delta-170+/-68 kcal, -16+/-6%, p<0.02) groups, without affecting meal duration. Hunger and hormonal analyte profiles provided evidence that pramlintide may exert a primary satiogenic effect, independently of other anorexigenic gut peptides. CONCLUSIONS/INTERPRETATION: The results indicate that enhanced satiety and reduced food intake may explain the weight loss observed in long-term pramlintide trials.

Relation between calcium absorption and serum calcitriol in normal men: evidence for age-related intestinal resistance to calcitriol.

OBJECTIVE: To obtain information on the causes of age-related bone loss in men and the concomitant decline in calcium absorption. DESIGN: Cross-sectional study. SETTING: Adelaide, South Australia, Australia. SUBJECTS: A total of 95 healthy, Caucasian men (age range 27-87 y). RESULTS: Calcium absorption declined with age (r=-0.46, P<0.0001), as did 24-h urine calcium, phosphate and creatinine (r>-0.21, P<0.05 for all); serum calcitriol and 25 hydroxyvitamin D did not change with age. Calcium absorption was related to serum calcitriol (r=0.20, P=0.05). An inverse relation between the residual deviations in calcium absorption, after allowing for its dependence on calcitriol, and age (F=5.4, P<0.005) was observed. The 24-h urinary calcium, phosphate and creatinine were all related to calcium absorption (r>0.41, P<0.0001). Forearm bone density fell with age (r=-0.45, P<0.0001) but was not related to calcium absorption, or markers of bone turnover. CONCLUSIONS: In healthy Caucasian males (i) calcium absorption falls, but serum calcitriol does not change with age, (ii) the relation between calcium absorption and serum calcitriol changes with age, indicative of an intestinal resistance to calcitriol and (iii) calcium absorption is a significant determinant of 24-h urinary calcium excretion.

Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes.

AIMS/HYPOTHESES: We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients. METHODS: Eight type 2 diabetic patients, who were aged 62 years (median range: 49-68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq (99m)Tc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device. RESULTS: Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean +/- SEM], 61+/-8 min vs 98+/-5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not. CONCLUSIONS/INTERPRETATION: Inhibition of fat digestion by orlistat may-as a result of more rapid gastric emptying-exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.

Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus.

This study examined the effects of the lipase inhibitor, orlistat, on gastric emptying of, and the glycemic and incretin hormone responses to, a drink containing oil and glucose components in patients with type 2 diabetes. Seven patients (aged 58 +/- 5 yr), managed by diet alone, consumed 60 ml olive oil (labeled with 20 MBq (99m)Tc-V-thiocyanate) and 300 ml water containing 75 g glucose (labeled with 6 MBq (67)Ga-EDTA), on two occasions, with and without 120 mg orlistat, positioned in the left lateral decubitus position with their back against a gamma camera. Venous blood samples, for measurement of blood glucose and plasma insulin, glucagon-like peptide-1 and glucose-dependent insulintropic polypeptide were obtained immediately before, and after, the drink. Gastric emptying of both oil (P < 0.001) and glucose (P < 0.0005) was faster after orlistat compared with control. Postprandial blood glucose (P < 0.001) and plasma insulin (P < 0.05) were substantially greater after orlistat compared with control. In contrast, plasma glucagon-like peptide-1 (P < 0.005) and glucose-dependent insulintropic polypeptide (P < 0.05) were less after orlistat. In conclusion, inhibition of fat digestion, by orlistat, may exacerbate postprandial glycemia, as a result of more rapid gastric emptying and a diminished incretin response.

The Son-Rise Program intervention for autism: an investigation into family experiences.

BACKGROUND: Despite the increasing involvement of parents as therapists in interventions for their children with autism, research to date has focused almost exclusively on the outcome for the child, and little is known about the effects of involvement on the whole family. This is true even of highly intensive home-based approaches such as the Son-Rise Program (SRP), the focus of the present paper. A longitudinal questionnaire-based study is reported which investigated a number of potential positive and negative effects for the family, how these changed over time, and their relation to child characteristics and patterns of intervention implementation. METHODS: Questionnaires examining family demographics, patterns of intervention use and perceived family effects were distributed three times over the course of a year to families who had attended an initial training course in the use of the SRP. RESULTS: The results indicated that, although involvement led to more drawbacks than benefits for the families over time, family stress levels did not rise in all cases. Few relationships were found between family effects and patterns of intervention use, although there was a strong connection with parental perceptions of intervention efficacy. CONCLUSIONS: The findings of the present study emphasize the need for those supporting families using home-based interventions to consider the needs of the whole family. This may be especially important if there are periods during which the family find the intervention to be less effective. Families embarking on such intensive approaches may also benefit from considering ways in which any disruption to family life can be minimized.

High-fat diet effects on gut motility, hormone, and appetite responses to duodenal lipid in healthy men.

There is evidence that gastrointestinal function adapts in response to a high-fat (HF) diet. This study investigated the hypothesis that an HF diet modifies the acute effects of duodenal lipid on appetite, antropyloroduodenal pressures, plasma CCK and plasma glucagon-like peptide-1 (GLP-1) levels in humans. Twelve healthy men were studied twice in randomized, crossover fashion. The effects of a 90-min duodenal lipid infusion (6.3 kJ/min) on the above parameters were assessed immediately following 14-day periods on either an HF or a low-fat (LF) diet. After the HF diet, pyloric tonic and phasic pressures were attenuated, and the number of antropyloroduodenal pressure-wave sequences was increased when compared with the LF diet. Plasma CCK and GLP-1 levels did not differ between the two diets. Hunger was greater during the lipid infusion following the HF diet, but there was no difference in food intake. Therefore, exposure to an HF diet for 14 days attenuates the effects of duodenal lipid on antropyloroduodenal pressures and hunger without affecting food intake or plasma hormone levels.

The effects of miglitol on glucagon-like peptide-1 secretion and appetite sensations in obese type 2 diabetics.

BACKGROUND: Previous studies reported that administration of first generation alpha-glucosidase inhibitors (AGIs), such as voglibose or acarbose, produced exaggerated and sustained postprandial responses of glucagon-like peptide-1 (GLP-1), an incretin hormone from the enteroinsular axis, in healthy humans. Little is known about the postprandial release of GLP-1 after AGI therapy in diabetics. GLP-1 plays a role to mediate satiety. Any agent that substantially elevates GLP-1 levels may theoretically reduce hunger, increase satiation and limit food intake. OBJECTIVES: This study was performed to analyse the effect of miglitol, a more potent second generation AGI with fewer gastrointestinal side-effects, on the regulation of meal-related GLP-1 secretion and on the change of insulin-glucose dynamics as well as the release of gastric inhibitory polypeptide (GIP), another incretin hormone, after stimulation by an ordinary meal in obese type-2-diabetic subjects. Miglitol's subsequent influences on appetite sensations and food intake were also measured. DESIGN: In total, 8 obese type-2-diabetic women were randomized to receive treatment with 100 mg of miglitol or placebo three times a day for 2 days (six doses total) in a double-blind fashion. On day 3 of each treatment period (miglitol or placebo), measurements of GLP-1, GIP, insulin and glucose were taken periodically during 3 h after eating a 720 kcal breakfast. Appetite ratings with visual analogue scales (VASs) were used to assess ingestive behaviour hourly just before breakfast and hourly after for 6 h until immediately before lunch. The number of tuna sandwiches eaten at lunch was used to measure food consumption. RESULTS: The plasma GLP-1, glucose, insulin and GIP levels in response to the mixed meal were compared after the miglitol and placebo treatment. Miglitol effectively enhanced postprandial GLP-1 release and suppressed plasma GIP secretion. The ingestion of a mixed meal induced a remarkable rise in GLP-1 after miglitol as compared with placebo in overweight diabetic subjects. The meal-related rise in GLP-1 after miglitol was significantly greater at all time-points between 30 and 180 min than after the placebo. The postprandial incremental area under the curve for GLP-1 with miglitol treatment was about twofold that with the placebo. The GLP-1 level reached a maximum at 120 min after the mixed meal and steadily rose throughout the rest of the 3-h study period. In the miglitol-treated condition, the average caloric intake at lunch during a 30-min eating period was 12% lower (p < 0.05) as compared with that after the placebo in six out of the eight subjects who exhibited a GLP-1 rise after the breakfast meal by greater than 30% from the placebo-treated condition. Correspondingly, the average rating scores were significantly lower for hunger feelings and markedly greater for sensations of satiety under the miglitol treatment; beginning 2 and 3 h, respectively, before the lunch test. CONCLUSIONS: Miglitol induced an enhanced and prolonged GLP-1 release at high physiological concentrations after ingesting an ordinary meal in glycaemic-controlled diabetics. The excessive postprandial GLP-1 elevation after miglitol therapy modified feeding behaviour and food intake, and thereby has potential value in regulating appetite and stabilizing body weight in obese type-2-diabetic patients.

Bone density and bone-related biochemical variables in normal men: a longitudinal study.

BACKGROUND: The objective of this study was to determine the pattern of forearm bone loss and its relationship to markers of bone turnover and sex steroids in normal men. This was a longitudinal study over a median interval of 41 months. The study was conducted in Adelaide, Australia. Study participants were 123 healthy male subjects, between the ages of 20 and 83 years. METHODS: Fat-corrected forearm bone mineral content (fcBMC), markers of bone formation (alkaline phosphatase, osteocalcin, procollagen type 1 C-terminal extension peptide) and bone resorption (collagen type I cross-linked telopeptide, hydroxyproline/creatinine, pyridinoline/creatinine, and deoxypyridinoline/creatinine), calculated serum bioavailable testosterone, and serum estradiol were measured. RESULTS: The mean time-weighted rate of change in forearm fcBMC was -0.33% +/- 0.72 (SD) per year. Bone loss commenced after 30 years of age and increased with age (p <.001), particularly after age 70 years. There was no relationship between the rate of change in fcBMC and either markers of bone turnover or serum sex steroids. CONCLUSIONS: In normal men, bone loss increases with age; there does not appear to be any relationship between this loss and either markers of bone turnover or levels of free androgen or estrogen.