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Plasma Glucose (plasma + glucose)
Kinds of Plasma Glucose Terms modified by Plasma Glucose Selected AbstractsEFFECTS OF ADMINISTRATION OF ORAL MAGNESIUM ON PLASMA GLUCOSE AND PATHOLOGICAL CHANGES IN THE AORTA AND PANCREAS OF DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005Nepton Soltani SUMMARY 1.,Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the complications of diabetes. The purpose of the present study was to determine the relationship between oral Mg supplementation and changes in plasma glucose, calcium, haemogolobin, Ca/Mg ratio, blood pressure and the histology of the pancreas and vascular system in streptozotocin-induced diabetic rats. 2.,Ten days after the induction of diabetes in male Wistar rats, half the diabetic animals were divided into six groups, receiving 0, 1, 3, 10, 30 or 50 g/L MgSO4 added into the drinking water for 8 weeks. Plasma glucose and Mg were measured at days 1, 2, 3, 5, 7, 14 and 21 to find the optimum dose of Mg and the time-course of its effect. In addition, histological observations were undertaken. Eight weeks later, all animals were decapitated, the pancreas and thoracic aorta were removed carefully and immersed immediately in 10% formaldehyde for histological study. 3.,To evaluate the effects of Mg on plasma glucose, calcium, haemoglobin, Mg and blood pressure, another group of animals was divided into four experimental groups, as follows: (i) non-diabetic controls received tap water for 8 weeks; (ii) acute diabetics received tap water for 10 days; (iii) chronic diabetic controls received tap water for 8 weeks; and (iv) Mg-treated chronic diabetic rats received 10 g/L MgSO4 added into the drinking water 10 days after the induction of diabetes for 8 weeks. 4.,Magnesium dose dependently affects plasma glucose levels. The peak effect was reached during the first 24 h following oral administration. Administration of 10 g/L MgSO4 results in the return of normal structure in the diabetic pancreas and aorta. Moreover, this concentration of MgSO4 causes glucose, haemoglobin, calcium, the Ca/Mg ratio and blood pressure to reach normal levels. Although the Mg level increases slightly following the administration of 10 g/L MgSO4 to diabetic rats, it never reaches control levels. 5.,On the basis of the results of the present study, it may be concluded that chronic Mg administration may have beneficial effects on diabetes. [source] Rosiglitazone combined with insulin preserves islet , cell function in adult-onset latent autoimmune diabetes (LADA)DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005Zhiguang Zhou Abstract Background LADA is thought to result from the chronic autoimmune destruction of the insulin-producing pancreatic , cells. In addition to antidiabetic effects, the newly developed insulin sensitizer-thiazolidinediones have the potential to increase the insulin content of islet cells by downregulating local inflammation and autoimmune response. Therefore, we hypothesized that LADA patients might benefit from thiazolidinediones treatment. Methods LADA patients, with a fasting C-peptide (FCP) of 0.3 nmol/L or more, were enrolled and randomly assigned to receive subcutaneous insulin alone (insulin group, n = 12) or rosiglitazone plus insulin (insulin + RSG group, n = 11) to compare the impacts on islet , cell function. Plasma glucose, HbA 1c, fasting C-peptide (FCP) and C-peptide after 2 h 75-g glucose load (PCP) were determined every 6 months. GAD-Ab and C-peptide were measured with radioimmune assays. Islet , cell function was evaluated by PCP and ,CP(,CP = PCP-FCP). Results All of the 23 patients have been followed up for 6 months, 17 cases for 12 months and 14 for 18 months. (1) During 6 months' follow-up, there were no significant changes for ,CP and PCP levels in both groups. (2) PCP and ,CP levels in insulin + RSG group patients stayed steady during the 12 months' observation (P = 0.161 for both PCP and ,CP), while in the insulin alone group, both FCP (P = 0.021) and PCP (P = 0.028) levels decreased significantly. Furthermore, PCP (P = 0.004) and ,CP(P = 0.015) differences between 12th month and baseline were higher in insulin + RSG group than those in the insulin group. (3) When observed up to 18 months, PCP and ,CP levels in insulin + RSG group patients still stayed steady, while PCP and ,CP levels decreased more in the insulin alone group. Conclusions This pilot study suggests that rosiglitazone combined with insulin may preserve islet , cell function in LADA patients. Copyright © 2004 John Wiley & Sons, Ltd. [source] The relationship between depression and diabetes mellitus: findings from the Hertfordshire Cohort StudyDIABETIC MEDICINE, Issue 6 2009R. I. G. Holt Abstract Aims, To assess the relationship between depression scores and diabetes, glucose and insulin in a cross-sectional population-based study. Methods, One thousand, five hundred and seventy-nine men and 1418 women from the Hertfordshire Cohort Study were assessed for diabetes. Plasma glucose and insulin concentrations were measured at 0, 30 and 120 min during a standard 75-g oral glucose tolerance test. Depressive and anxiety symptoms were measured using the Hospital Anxiety and Depression Scale (HADS). Results, Overall, 431 (14.6%) were diagnosed with diabetes [232 men (14.9%) and 199 women (14.3%)]. One hundred and eight (47%) men and 74 (37%) women had known diabetes. The remainder were previously undiagnosed. Fifty-nine (3.7%) men and 65 (4.6%) women had possible depression (HAD-D scores 8,10) and 17 (1.1%) men and 20 (1.4%) women had probable depression (HAD-D scores , 11). Probable depression was associated with an adjusted odds ratio for diabetes of 3.89 [95% confidence interval (CI) 1.28,11.88] in men and 1.51 (95% CI 0.47,4.84) in women. In men without previously diagnosed diabetes, fasting insulin (P = 0.035), 2-h glucose concentrations (P = 0.028) and insulin resistance (P = 0.032) were significantly associated with HAD-D scores. With the exception of 2-h glucose concentrations (P = 0.034), the associations were not significant in women. Conclusions, These data support the hypothesis that depression may increase the risk for diabetes. The relationship between depression score and metabolic variables extends across the whole population and is not confined to those with either diagnosed depression or diabetes. This relationship should lead clinicians to consider screening for diabetes in those with depression and vice versa. [source] Prevalence of the metabolic syndrome among the Inuit in Greenland.DIABETIC MEDICINE, Issue 11 2004A comparison between two proposed definitions Abstract Aims To estimate the prevalence of the metabolic syndrome among Greenland Inuit according to the World Health Organization (WHO) definition and the definition suggested by the National Cholesterol Education Program (NCEP). Methods From 1999 to 2001, 917 adult Inuit participated in a health survey in Greenland. The examination included a 75-g oral glucose tolerance test (OGTT). Body mass index (BMI), waist circumference, waist-to-hip ratio and blood pressure were measured. Plasma glucose, serum insulin, lipids and urine albumin/creatinine ratio were measured. The metabolic syndrome was diagnosed according to the WHO criteria 1999 and to the working definition suggested by the NCEP 2001. Results Using the WHO and the NCEP criteria, 20.7% and 17.9% of the participants had the metabolic syndrome, respectively. There was a moderate agreement between the two definitions, , = 0.56 (95% CI 0.51,0.61). Of those with the WHO metabolic syndrome, 37.9% did not have the NCEP syndrome, and 28.5% of those with the NCEP syndrome were not classified with the metabolic syndrome under the WHO criteria. Compared with the WHO syndrome, men with the NCEP syndrome had higher mean values of waist circumference, BMI and triglycerides, and lower mean values of high-density lipoprotein (HDL) cholesterol; among women, triglycerides were higher with the NCEP syndrome. Conclusion The metabolic syndrome is common among Inuit using either the WHO definition or the proposed NCEP definition. The classification disagreement is considerable and a universally accepted definition is needed. [source] The metabolic effects of once daily extended-release metformin in patients with type 2 diabetes: a multicentre studyINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2008H. Gao Summary Aim:, To investigate the effects of extended-release metformin (MXR) compared with immediate-release metformin (MIR) on post-prandial glycaemic excursion, chronic glycaemia, lipid profiles, insulin resistance and islet function in type 2 diabetes. Methods:, A randomised, open-labelled, positive-controlled multicentre study was conducted on 150 Chinese patients with type 2 diabetes. After 2 weeks of run-in period with MIR, 150 subjects were randomised into MXR group and MIR group. The patients in MXR group were assigned to take MXR 1500 mg once daily after dinner, while the patients in MIR group were assigned to continue MIR 500 mg thrice daily after meals for 12 weeks. Standard meal tests were carried out at baseline and at the end of this study. Plasma glucose, serum insulin, HbA1c and lipid profiles were measured. Homeostasis model assessment (HOMA) was used to evaluate insulin resistance index (HOMA-IR) and islet ,-cell function index (HOMA-B). Results:, Either MIR or MXR modestly, but significantly decreased HbA1c levels and body mass index (BMI) after 12 weeks of treatment. However, there were no significant differences between two groups. The post-prandial glycaemia at 120 min after a standard meal in MXR group was higher than in MIR group (11.02 ± 3.08 mmol/l vs. 9.74 ± 2.61 mmol/l, p < 0.05). Moreover, no differences in the areas under curve of insulin release response, HOMA-B, HOMA-IR and lipid profiles were found within or between groups after 12 weeks of treatment. Conclusion:, The effects of once daily MXR on chronic glycaemia, BMI, lipid profiles, insulin resistance and islet function are comparable with that of thrice daily MIR in oriental population. [source] Effects of glucose polymer with and without potassium and different diets on glycogen repletion after a treadmill exercise test in endurance horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2005T. M. Hess Glycogen repletion involves absorption of glucose and its uptake into the muscle cells through GLUT-4 transporters. In the muscle and adipose tissue GLUT,4 transporters facilitates the glucose transport in the presence of insulin and K+. Potassium supply has been shown to stimulate insulin secretion. This study tested the effects of a glucose polymer added with electrolytes containing potassium (GP+K) compared to a glucose polymer with electrolytes without potassium (GP-K) on glycogen repletion. Also it compared the effect of different diet adaptations on glycogen repletion. Six horses were fed a diet rich in sugar and starch (SS), and six horses a diet rich in fat and fibre (FF) for 6 months before the test. In a crossover designed study, 12 trained Arabian or Arabian cross horses were submitted to a glycogen depleting exercise test on the treadmill. After exercise stopped six horses were supplied with GP-K and six other horses supplied with GP+K, at a dose of 5 g/kg BW, and a rate of 1 g/kg BW/hour through naso-gastric gavage. Muscle biopsies were taken before, just after they stopped exercise, and 16 h after they had been supplied with glycogen replacing formulas, and analysed for muscle glycogen. Blood was taken before, after 3 h of exercise, after the stepwise exercise test, at 0, 1 and 4 h after exercise stopped and analysed for plasma glucose, insulin and [K+]. Muscle glycogen decreased from 516.41 ± 12.92 glucosyl units/kg dry weight muscle to 408.74 ± 12.92 glucosyl units/kg dry weight muscle (79%). Sixteen hours after the repletion protocol horses recovered their muscle glycogen to 458.53 ± 12.91 glucosyl units/kg dry weight muscle (89%). Plasma glucose had a glucose polymer by sampling effect (p = 0.013) and a feed by sampling effect (p = 0.022). Plasma glucose was higher in SS fed horses at 1 and 4 h after exercise. Plasma glucose was lower in GP+K supplied horses 4 h after exercise. Plasma insulin had a trend (p = 0.070) for a glucose polymer effect. No differences were found in muscle glycogen between the two GP treatments. Although the present results demonstrate that intensive nasogastric supplementation with glucose polymer can result in glycogen repletion approaching that following i.v. administration, the addition of potassium conferred no advantage. [source] Responses to handling and confinement stressors in juvenile great sturgeon Huso husoJOURNAL OF FISH BIOLOGY, Issue 4 2009B. Falahatkar The effects of acute stressors on physiological responses of juvenile great sturgeon or beluga Huso huso L. were investigated in two experiments. In the first experiment, fish were handled by placing them in containers at either low density (LD, one fish l,1) or high density (HD, four fish l,1) for 60 s. Concentrations of plasma cortisol, glucose and lactate were determined from blood collected at 0, 1, 3, 6 and 12 h after application of the stressor. Plasma cortisol concentrations increased after the disturbance in H. huso from both handling treatments, but changes were not significant. Plasma glucose rose significantly by 22·9 and 31·6% in LD and HD handling treatments, respectively, after 3 h. Significant increases in plasma lactate occurred within 1 h in both treatment groups, but that of the HD group was much higher. In the second experiment, fish were held at two different densities, LD (2 kg m,2 tank bottom surface area) and HD (7 kg m,2), for 8 weeks and then subjected to an aerial emersion handling stressor in a net for 60 s; blood samples were taken before handling (resting, 0 h) and at 1, 3, 6 and 9 h after handling. Plasma cortisol increased significantly in fish from the HD treatment from 8·8 ± 0·3 to 19·2 ± 2·4 ng ml,1 (mean ±s.e.) by 1 h after stress, but post-handling changes in the LD group were not significant. Significant increases in both plasma glucose and lactate were observed by 1 h in both treatment groups, with peak levels of plasma glucose evident at 3 h [69·4 ± 2·9 and 60·9 ± 1·7 mg dl,1 (mean ±s.e.) in LD and HD groups, respectively]. Plasma glucose levels were significantly higher in the LD group than in the HD group at 3 and 6 h. Post-handling haemoglobin content increased by 1 h and white blood cell numbers were reduced by 3 and 6 h in the HD treatment group compared with resting values, but changes in these blood features in the LD group were not significant. Acute handling did not affect haematocrit in either treatment. The results suggest that H. huso is relatively resistant to handling and confinement, and could tolerate normal hatchery practices associated with aquaculture. Because changes in cortisol concentrations were relatively low compared with those in most teleosts, glucose and lactate concentrations may be more useful as stress indicators in juvenile H. huso. This study also demonstrated that prior exposure to a chronic stressor, specifically high stocking density, could alter the physiological response to subsequent acute handling in H. huso. [source] Plasma cortisol and metabolite level profiles in two isogenic strains of common carp during confinementJOURNAL OF FISH BIOLOGY, Issue 1 2001N. M. Ruane A rapid increase in common carp Cyprinus carpio plasma cortisol levels was noted, in two experiments, after 30 mins of a 3 h net confinement, which was sustained while the fish were held in the nets. After release from the nets, cortisol levels returned to control values in 1 h. Plasma glucose and free fatty acid levels were elevated by the confinement. Glucose was increased after 30 min but returned to basal levels after 22 h of recovery while free fatty acids were not elevated until 3 h of confinement and remained high for the duration of the recovery period. After confinement for 3 h, plasma lactate levels were reduced and remained low for a further 1 h. No change in either plasma triglyceride or cholesterol levels were found during the study. Confinement had no effect on haematocrit levels but blood haemoglobin levels were reduced. In both experiments hypochloraemia occurred in response to confinement. However, values returned to pre-confinement levels 22 h after confinement. These results show that rearing isogenic carp strains, under identical conditions, results in a reproducable response to an acute stressor and that these carp respond in a similar manner to other teleost species. [source] Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humansNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2010Y. Falkén Abstract Background, Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans. Methods, Ghrelin (15 pmol kg,1 min,1) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed. Key Results, The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 ± 3.9 vs 59.9 ± 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin. Conclusions & Inferences, The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders. [source] 47 Effects of retrograde gastric electrical stimulation on gastric motility and plasma hormones in dogsNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2006G SONG Aims:, The aim of this study was to investigate the effect of different parameters of RGES with trains of long pulses in turning gastric slow waves into tachygastria, and evaluate the effects of RGES with the efficient trains of pulses on gastric slow waves, gastric emptying of solids and plasma concentrations of satiety-related peptides and glucose. Methods:, Seven female dogs implanted with four pairs of gastric electrodes were studied in two experiments. The first experiment included a series of sessions with different pacing parameters in the fasting state, each lasting 10 min. The second experiment included two randomized sessions (control and RGES). Gastric emptying of solid was measured by scintigraphy for a period of 4 h. Blood samples were collected at 45 and 15 min before, 30, 60 and 120 min after the meal. Plasma leptin, insulin and glucagon were measured using radioimmunoassay method. Plasma glucose was assessed with a commercially available glucometer. RGES was applied via the distal pair of electrodes (2 cm above the pylorus) with trains of pulses. RGES was initiated 30 min before the first blood sample and maintained for a period of 2.5 h. Gastric slow waves and symptomatic response were also recorded in each session. Results:, (1) RGES with pulse trains (12 trains/min) was able to turn regular gastric slow waves into tachygastria. (2) RGES with the efficient parameters (frequency: 40 Hz; pulse width: 2 ms; amplitude: 5 mA; train on-time, 2 s; off-time, 3 s) was capable of delaying gastric emptying of solids (P < 0.05). (3) Compared with the control session without RGES, the total AUC's of plasma insulin with RGES was significantly decreased in the fasting and postprandial periods (p < 0.05). However, the total area under curves (AUC's) of plasma leptin, glucagon, and glucose were not significantly affected by RGES (p > 0.05). (4) This method of GES induced no noticeable symptoms. Conclusion:, RGES with at a tachygastrial frequency decreases gastric emptying of solids and plasma insulin, but has no effects on plasma leptin, glucagons, and glucose. [source] Sex differences in stress responses to transportation in goats: Effects of gonadal hormonesANIMAL SCIENCE JOURNAL, Issue 6 2003Masato AOYAMA ABSTRACT The present study examined sex differences and the involvement of gonadal hormones in stress responses caused by road transportation in Shiba goats. In experiment 1, we investigated the stress responses of males and females to transportation. Plasma levels of cortisol (Cor) significantly increased during 1 h of transportation, and those in females were significantly higher than those in males. Plasma glucose (Glu) and free fatty acid (FFA) levels also increased similarly in both females and males by transportation, and there were no sex differences. Food intake following transportation decreased only in males compared with that in the basal session, in which the animals were not transported. Experiment 2 examined the involvement of gonadal hormones in stress responses to transportation using castrated males. Goats were given cholesterol (Cho), 5,-dihydrotestosterone (DHT) or 17,-estradiol (Es). The plasma Cor levels increased during transportation regardless of hormone treatment, and those in DHT treated goats were significantly lower than those in Cho or Es treated animals. Plasma Glu and FFA levels also increased during transportation, regardless of hormone treatment, and there were no differences between treatments. Food intake following transportation was significantly lower than that in the basal session only in goats given DHT. In conclusion, gender affects Cor secretion that is increased by transportation and the decrease of food intake following transportation in Shiba goats, and the major cause of these differences is androgen. [source] Dietary protein/lipid level and protein source effects on growth, tissue composition and lipid metabolism of blackspot seabream (Pagellus bogaraveo)AQUACULTURE NUTRITION, Issue 2 2010A.C. FIGUEIREDO-SILVA Abstract A study was carried out to determine the effects of fish meal (FM) replacement by plant protein (PP) on growth, body composition and lipid metabolism of blackspot seabream fed different protein/lipid levels. Four experimental diets were formulated to contain two protein (P) and lipid (L) levels (60P/6L or 50P/10L), varying in their protein source (100% FM or 50% FM: 50% PP). Dietary inclusion of PP did not affect growth of fish fed 60P/6L, although fish fed 50P/10L exhibited lower final body weight and daily growth index. Fish fed 60P/6L presented the highest protein and the lowest lipid content. FM replacement by PP has decreased muscle n-3 whereas the n-6 fatty acids increased. Glucose-6-phosphate dehydrogenase and fatty acid synthetase (FAS) were depressed in fish fed 50P/10L. FAS was significantly increased with 60P/6L PP which was positively correlated with lipid retention data. Those results suggest the conversion of other nutrient than lipid (protein and/or carbohydrates) into corporal fat. Hepatic lipoprotein lipase activity was lowest in fish fed PP diets. Plasma glucose peaked 1,2 h postfeeding, in all groups and was generally higher with 60P/6L FM. This work shown that besides dietary P/L level, protein source has a strong effect on species lipogenesis and lipid retention. Hence, the 50P/10L FM diet was the most cost-effective for blackspot seabream juveniles. [source] Effects of high carbohydrate and high lipid diets on growth, body composition and glucose metabolism in southern catfish at two temperaturesAQUACULTURE RESEARCH, Issue 10 2010Yiping Luo Abstract The effects of high carbohydrate and high lipid diets on the growth, body composition and glucose metabolism in the southern catfish were determined at 17.5 °C and 27.5 °C. At each temperature, the feeding rate, specific growth rate and protein productive value decreased with increasing dietary carbohydrate (P<0.05). Feed efficiency and protein efficiency ratio were lower in the fish fed a high dietary carbohydrate diet at 17.5 °C, but were not significantly different between diets at 27.5 °C. Plasma glucose and activities of pyruvate kinase and glucose-6-phosphate dehydrogenase were higher in fish reared at 27.5 °C than those reared at 17.5 °C, and within each temperature, they were higher in fish fed the high-carbohydrate diet. Hepatosomatic index was higher in fish fed the high-carbohydrate diet than those fed the high-lipid diet at 27.5 °C, but no significant difference was found at 17.5 °C. The results indicate that higher temperatures enhance glycogen deposition and lipogenous enzyme activities when fed with a high-carbohydrate diet; thus, at higher temperatures, this fish uses carbohydrate more efficiently for protein sparing. [source] Transport stress in Atlantic salmon (Salmo salar L.): anaesthesia and recoveryAQUACULTURE RESEARCH, Issue 2 2001R Sandodden Abstract The effects of metomidate anaesthesia on levels of plasma cortisol, glucose, haematocrit and chloride in Atlantic salmon (1+) (Salmo salar L.), after a 2-h transport and during a 48-h recovery period were investigated. The use of metomidate anaesthesia during transport led to a reduced release of cortisol and significantly lower levels of plasma cortisol after a 48-h recovery period. Plasma glucose did not return to basal level after a 48-h recovery period, indicating that even longer recovery may be needed for the fish to return to a pre-stress state. The results show that metomidate anaesthesia combined with a recovery period lessens the stress burden imposed by hauling and transport. [source] Diet in late pregnancy and glucose-insulin metabolism of the offspring 40 years laterBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 7 2000A. W. Shiell Statistician Objective To determine how diets of women in pregnancy influence the glucose-insulin metabolism of their offspring in adult life. Design A follow up study of men and women born during 1948,1954 whose mothers had taken part in a survey of diet in late pregnancy. Setting Aberdeen, Scotland. Population One hundred and sixty-eight men and women born in the Aberdeen Maternity Hospital. Main outcome measure Plasma glucose and insulin concentrations, fasting and after a standard oral glucose challenge. Results The offspring of women who had high intakes of fat and protein in late pregnancy had a reduced plasma insulin increment between fasting and 30 min with a 7.0% decrease in increment (P= 0.007) per 10 g increase in protein intake and a 4.9% decrease (P= 0.002) per 10 g increase in fat intake. This was independent of the mother's body mass index or weight gain in pregnancy. A low maternal body mass index in early or late pregnancy was associated with a raised fasting plasma insulin concentration with a decrease of 2.4% (P= 0.05) per 1 kg/m2 increase of maternal body mass. Conclusion High intakes of protein and fat during pregnancy may impair development of the fetal pancreatic beta cells and lead to insulin deficiency in the offspring. The offspring of thin mothers tend to be insulin resistant. [source] Haemoglobin A1c as a predictor of postoperative hyperglycaemia and complications after major colorectal surgery,BRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 11 2009U. O. Gustafsson Background: Hyperglycaemia following major surgery increases morbidity, but may be improved by use of enhanced-recovery protocols. It is not known whether preoperative haemoglobin (Hb) A1c could predict hyperglycaemia and/or adverse outcome after colorectal surgery. Methods: Some 120 patients without known diabetes underwent major colorectal surgery within an enhanced-recovery protocol. HbA1c was measured at admission and 4 weeks after surgery. All patients received an oral diet beginning 4 h after operation. Plasma glucose was monitored five times daily. Patients were stratified according to preoperative levels of HbA1c (within normal range of 4·5,6·0 per cent, or higher). Results: Thirty-one patients (25·8 per cent) had a preoperative HbA1c level over 6·0 per cent. These had higher mean(s.d.) postoperative glucose (9·3(1·5) versus 8·0(1·5) mmol/l; P < 0·001) and C-reactive protein (137(65) versus 101(52) mg/l; P = 0·008) levels than patients with a normal HbA1c level. Postoperative complications were more common in patients with a high HbA1c level (odds ratio 2·9 (95 per cent confidence interval 1·1 to 7·9)). Conclusion: Postoperative hyperglycaemia is common among patients with no history of diabetes, even within an enhanced-recovery protocol. Preoperative measurement of HbA1c may identify patients at higher risk of poor glycaemic control and postoperative complications. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Metabolic profiles of fat and glucose differ by gender in healthy 8-year-oldsACTA PAEDIATRICA, Issue 1 2010Susanne Eriksson Abstract Objective:, The aim was to investigate if metabolic markers were associated with anthropometry and weight increase in healthy 8-year-olds. Methods:, Ninety-seven healthy children, 66 of whom had been examined at the age of 4 years, were investigated. Dual energy X-ray absorptiometry was performed to determine fat (FM) and lean body mass (LBM). Plasma glucose and serum levels of insulin, cholesterol, triglycerides, adiponectin and leptin were analysed and HOMA-indices were calculated. Results:, Despite similar anthropometry, metabolic markers differed by gender. Sixteen % of the children were overweight or obese. Body mass index (BMI) was strongly correlated to FM. Anthropometric measures except LBM correlated to metabolic markers in the girls. Boys had higher concentrations of plasma glucose than girls. In overweight children, insulin was negatively associated with LBM. Leptin and the ratio between leptin and adiponectin, but not adiponectin, were significantly associated with HOMA-IR and body composition. Conclusion:, The metabolic profile of plasma glucose, serum leptin, fasting insulin and related HOMA indices differed by gender, despite no difference in BMI or FM. LBM, but not FM correlated to the insulin concentration in the overweight children. Leptin was the best marker of overweight. [source] EFFECTS OF ADMINISTRATION OF ORAL MAGNESIUM ON PLASMA GLUCOSE AND PATHOLOGICAL CHANGES IN THE AORTA AND PANCREAS OF DIABETIC RATSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 8 2005Nepton Soltani SUMMARY 1.,Magnesium deficiency has recently been proposed as a novel factor implicated in the pathogenesis of the complications of diabetes. The purpose of the present study was to determine the relationship between oral Mg supplementation and changes in plasma glucose, calcium, haemogolobin, Ca/Mg ratio, blood pressure and the histology of the pancreas and vascular system in streptozotocin-induced diabetic rats. 2.,Ten days after the induction of diabetes in male Wistar rats, half the diabetic animals were divided into six groups, receiving 0, 1, 3, 10, 30 or 50 g/L MgSO4 added into the drinking water for 8 weeks. Plasma glucose and Mg were measured at days 1, 2, 3, 5, 7, 14 and 21 to find the optimum dose of Mg and the time-course of its effect. In addition, histological observations were undertaken. Eight weeks later, all animals were decapitated, the pancreas and thoracic aorta were removed carefully and immersed immediately in 10% formaldehyde for histological study. 3.,To evaluate the effects of Mg on plasma glucose, calcium, haemoglobin, Mg and blood pressure, another group of animals was divided into four experimental groups, as follows: (i) non-diabetic controls received tap water for 8 weeks; (ii) acute diabetics received tap water for 10 days; (iii) chronic diabetic controls received tap water for 8 weeks; and (iv) Mg-treated chronic diabetic rats received 10 g/L MgSO4 added into the drinking water 10 days after the induction of diabetes for 8 weeks. 4.,Magnesium dose dependently affects plasma glucose levels. The peak effect was reached during the first 24 h following oral administration. Administration of 10 g/L MgSO4 results in the return of normal structure in the diabetic pancreas and aorta. Moreover, this concentration of MgSO4 causes glucose, haemoglobin, calcium, the Ca/Mg ratio and blood pressure to reach normal levels. Although the Mg level increases slightly following the administration of 10 g/L MgSO4 to diabetic rats, it never reaches control levels. 5.,On the basis of the results of the present study, it may be concluded that chronic Mg administration may have beneficial effects on diabetes. [source] Interactions of orexins/hypocretins with adrenocortical functionsACTA PHYSIOLOGICA, Issue 3 2010S. M. Kagerer Abstract The neuropeptides orexin A and B (hypocretin-1 and -2) are involved in numerous central regulation processes such as energy homeostasis, sleeping behaviour and addiction. The expression of orexins and orexin receptors in a variety of tissues outside the brain and the presence of orexin A in the circulation indicate the existence of an additional peripheral orexin system. Furthermore, it is well established that orexins exert an influence on the regulation of the hypothalamus,pituitary,adrenal axis, acting both on its central and peripheral branch. In rat and human adrenal cortices the expression of both orexin receptors has been verified with a predominance of OX2R. The local expression of orexin receptors was observed to be gender specific and to be modified by plasma glucose and insulin concentrations, nutritional status as well as gonadal steroids. Various studies consistently demonstrated orexin A to enhance glucocorticoid secretion of rat and human adrenal cortices, while orexin B was found to be either less potent or ineffective. On the contrary, the influence of orexins on adrenocortical aldosterone production and cell proliferation is still more controversial. Recent findings indicate that orexins stimulate adrenocortical steroidogenesis by augmenting transcription of selective steroidogenic enzymes and proteins such as steroidogenic acute regulatory protein. Both, Gq and Gs, signalling pathways with a downstream activation of MAP kinases appear to be involved in this regulation. [source] Greater growth hormone and insulin response in women than in men during repeated bouts of sprint exerciseACTA PHYSIOLOGICA, Issue 2 2009M. Esbjörnsson Abstract Aim:, In a previous study, sprint training has been shown to increase muscle cross-sectional area in women but not in men [Eur J Appl Physiol Occup Physiol 74 (1996) 375]. We hypothesized that sprint exercise induces a different hormonal response in women than in men. Such a difference may contribute to explaining the observed gender difference in training response. Method:, Metabolic and hormonal response to three 30-s sprints with 20-min rest between the sprints was studied in 18 physically active men and women. Results:, Accumulation of blood lactate [interaction term gender (g) × time (t): P = 0.022], and plasma ammonia (g × t: P < 0.001) after sprint exercise was greater in men. Serum insulin increased after sprint exercise more so in women than in men (g × t: P = 0.020), while plasma glucose increased in men, but not in women (g × t: P < 0.001). Serum growth hormone (GH) increased in both women and men reaching similar peak levels, but with different time courses. In women the peak serum GH level was observed after sprint 1, whereas in men the peak was observed after sprint 3 (g × t; P < 0.001). Serum testosterone tended to decrease in men and increase in women (g × t: P = 0.065). Serum cortisol increased approx. 10,15% after sprint exercise, independent of gender (time: P = 0.005). Conclusion:, Women elicited a greater response of serum GH and insulin to sprint exercise. This may contribute to explaining the earlier observed muscle hypertrophy in women in response to sprint training. [source] Reactive hypoglycaemia following GLP-1 infusion in pancreas transplant recipientsDIABETES OBESITY & METABOLISM, Issue 8 2010M. R. Rickels The aim of the study was to determine whether reactive hypoglycaemia in pancreas transplant recipients that followed administration of glucagon-like peptide-1 (GLP-1) was associated with excessive insulin, insufficient glucagon, or both. Methodology involved six portally drained pancreas recipients who received GLP-1 (1.5 pmol/kg/min) or placebo infusion on randomized occasions during glucose-potentiated arginine testing. The second subject developed symptomatic hypoglycaemia [plasma glucose (PG) 42 mg/dl] 1 h after GLP-1 administration; subsequent subjects received intravenous glucose following GLP-1, but not placebo, infusion for PG levels <65 mg/dl. Following GLP-1 vs. placebo infusion, PG was lower (58 ± 4 vs. 76 ± 5 mg/dl; p < 0.05) despite administration of intravenous glucose. During hypoglycaemia, insulin levels and the insulin-to-glucagon ratio were greater after GLP-1 vs. placebo infusion (p < 0.05), while glucagon did not vary. It can be concluded from the study that GLP-1 can induce reactive hypoglycaemia in pancreas transplant recipients through excessive insulin secretion associated with an increased insulin-to-glucagon ratio. [source] Mid- and high-ratio premix insulin analogues: potential treatment options for patients with type 2 diabetes in need of greater postprandial blood glucose controlDIABETES OBESITY & METABOLISM, Issue 2 2010J. S. Christiansen Some patients with type 2 diabetes continue to have high postprandial blood glucose levels on twice-daily regimens of ,low-ratio' premix insulin formulations (up to 30% rapid-acting, with 70% protracted insulin). These patients require intensified insulin therapy, which can be provided by a twice- or thrice-daily regimen of mid-ratio (50% rapid-acting and 50% protaminated intermediate-acting insulin , human or analogue) or high-ratio (70% rapid-acting and 30% protaminated insulin , analogue only) premix insulin. Alternatively, a third daily injection of low-ratio premix insulin can be added to the regimen, with the option of incorporating one or more injections of mid- or high-ratio premix as required, and as an alternative to basal,bolus therapy. How these mid- and high-ratio formulations differ from the low-ratio premix insulins is reviewed here, with the aim of identifying the role of these formulations in diabetes management. Glucose clamp studies have shown that premix analogues give serum insulin levels proportional to their percentage of rapid-acting uncomplexed insulin: the higher the proportion, the greater the maximum level reached. Other pharmacokinetic parameters were not always significantly different between the mid- and high-ratio formulations. In clinical trials, postprandial plasma glucose and glycated haemoglobin A1c (HbA1c) levels were significantly reduced with thrice-daily mid- /high-ratio premix analogue when compared with twice-daily low-ratio biphasic human insulin (BHI) 30/70 or once-daily insulin glargine. Moreover, glycaemic control with mid-/high-ratio premix analogue was found to be similar to that with a basal,bolus therapy. Mid- and high-ratio premix regimens are generally well tolerated. The frequency of minor hypoglycaemia was reportedly higher with mid- /high-ratio premix analogues than with BHI 30, but nocturnal hypoglycaemia was less frequent. Although there is little evidence that clinical outcomes with mid-ratio premix analogues are different from those with high-ratio, they are useful additions to the low-ratio formulations for the management of diabetes, and addressing postprandial hyperglycaemia in particular. [source] Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 2 2010T. Vilsbøll Objective: To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes. Methods: After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c , 7.5% and , 11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24. Results: Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs. 8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m2), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level < 7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group. Conclusion: In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes. [source] Earlier triple therapy with pioglitazone in patients with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 9 2009G. Charpentier Aims: This study assessed the efficacy of add-on pioglitazone vs. placebo in patients with type 2 diabetes uncontrolled by metformin and a sulphonylurea or a glinide. Methods: This multicentre, double-blind, parallel-group study randomized 299 patients with type 2 diabetes to receive 30 mg/day pioglitazone or placebo for 3 months. After this time, patients continued with pioglitazone, either 30 mg [if glycated haemoglobin A1c (HbA1c) ,6.5%] or titrated up to 45 mg (if HbA1c >6.5%), or placebo for a further 4 months. The primary efficacy end-point was improvement in HbA1c (per cent change). Secondary end-points included changes in fasting plasma glucose (FPG), insulin, C-peptide, proinsulin and lipids. The proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of ,-cell function (HOMA-B) were calculated. Results: Pioglitazone add-on therapy to failing metformin and sulphonylurea or glinide combination therapy showed statistically more significant glycaemic control than placebo addition. The between-group difference after 7 months of triple therapy was 1.18% in HbA1c and ,2.56 mmol/l for FPG (p < 0.001). Almost half (44.4%) of the patients in the pioglitazone group who had a baseline HbA1c level of <8.5% achieved the HbA1c target of < 7.0% by final visit compared with 4.9% in the placebo group. When the baseline HbA1c level was , 8.5%, 13% achieved the HbA1c target of < 7.0% in the pioglitazone group and none in the placebo group. HOMA-IR, insulin, proinsulin and C-peptide decreased and HOMA-B increased in the pioglitazone group relative to the placebo group. Conclusions: In patients who were not well controlled with dual combination therapy, the early addition of pioglitazone improved HbA1c, FPG and surrogate measures of ,-cell function. Patients were more likely to reach target HbA1c levels (< 7.0%) with pioglitazone treatment if their baseline HbA1c levels were < 8.5%, highlighting the importance of early triple therapy. [source] Exenatide: a review from pharmacology to clinical practiceDIABETES OBESITY & METABOLISM, Issue 6 2009R. Gentilella Background:, Exenatide is an incretin mimetic that activates glucagon-like-peptide-1 receptors. It blunts the postprandial rise of plasma glucose by increasing glucose-dependent insulin secretion, suppressing inappropriately high glucagon secretion and delaying gastric emptying. Methods:, In seven clinical trials performed in 2845 adult patients with type 2 diabetes mellitus who were inadequately controlled by a sulphonylurea and/or metformin (glycosylated haemoglobin, HbA1c ,11%), or by thiazolidinediones (with or without metformin) and treated for periods from 16 weeks to 3 years, exenatide (5 ,g b.i.d. s.c. for the first 4 weeks of treatment and 10 ,g b.i.d. s.c. thereafter) reduced HbA1c, fasting and postprandial glucose, and body weight dose dependently, and was similar to insulin glargine and biphasic insulin aspart in reducing HbA1c. Body weight diminished with exenatide, whereas it increased with both insulin preparations. Positive effects on the lipid profile and a reduction in C-reactive protein were also recorded with exenatide. Treatment extensions up to 3 years showed that benefits were maintained in the long term. Adverse events were usually mild to moderate in intensity, and generally the frequency decreased with continued therapy. The most common was nausea (whose incidence may be reduced by gradual dose escalation from 5 ,g b.i.d. to 10 ,g b.i.d.), vomiting, diarrhoea, headache and hypoglycaemia (almost exclusively in patients treated with a sulphonylurea). Results and conclusions:, Exenatide is a new, promising therapeutic option for type 2 diabetic patients inadequately controlled by oral agents, before insulin therapy, offering the added benefits of body weight reduction and tight postprandial glucose control. [source] Insulin therapy in type 2 diabetes: what is the evidence?DIABETES OBESITY & METABOLISM, Issue 5 2009Mariëlle J. P. Van Avendonk Aim:, To systematically review the literature regarding insulin use in patients with type 2 diabetes mellitus Methods:, A Medline and Embase search was performed to identify randomized controlled trials (RCT) published in English between 1 January 2000 and 1 April 2008, involving insulin therapy in adults with type 2 diabetes mellitus. The RCTs must comprise at least glycaemic control (glycosylated haemoglobin (HbA1c), postprandial plasma glucose and /or fasting blood glucose (FBG)) and hypoglycaemic events as outcome measurements. Results:, The Pubmed search resulted in 943 hits; the Embase search gave 692 hits. A total of 116 RCTs were selected by title or abstract. Eventually 78 trials met the inclusion criteria. The studies were very diverse and of different quality. They comprised all possible insulin regimens with and without combination with oral medication. Continuing metformin and/or sulphonylurea after start of therapy with basal long-acting insulin results in better glycaemic control with less insulin requirements, less weight gain and less hypoglycaemic events. Long-acting insulin analogues in combination with oral medication are associated with similar glycaemic control but fewer hypoglycaemic episodes compared with NPH insulin. Most of the trials demonstrated better glycaemic control with premix insulin therapy than with a long-acting insulin once daily, but premix insulin causes more hypoglycaemic episodes. Analogue premix provides similar HbA1c, but lower postprandial glucose levels compared with human premix, without increase in hypoglycaemic events or weight gain. Drawing conclusions from the limited number of studies concerning basal,bolus regimen seems not possible. Some studies showed that rapid-acting insulin analogues frequently result in a better HbA1c or postprandial glucose without increase of hypoglycaemia than regular human insulin. Conclusion:, A once-daily basal insulin regimen added to oral medication is an ideal starting point. All next steps, from one to two or even more injections per day should be taken very carefully and in thorough deliberation with the patient, who has to comply with such a regimen for many years. [source] Vildagliptin plus metformin combination therapy provides superior glycaemic control to individual monotherapy in treatment-naive patients with type 2 diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 5 2009E. Bosi Aim:, To compare the efficacy and safety of vildagliptin and metformin initial combination therapy with individual monotherapies in treatment-naive patients with type 2 diabetes mellitus (T2DM). Methods:, This was a 24-week, randomized, double-blind, active-controlled study. Treatment-naive patients with T2DM who had a glycated haemoglobin (HbA1c) of 7.5,11% (N = 1179) were randomized equally to receive vildagliptin plus high-dose metformin combination therapy (50 mg + 1000 mg twice daily), vildagliptin plus low-dose metformin combination therapy (50 mg + 500 mg twice daily), vildagliptin monotherapy (50 mg twice daily) or high-dose metformin monotherapy (1000 mg twice daily). The primary objective was to demonstrate that HbA1c reduction from baseline with either combination therapy is superior to both monotherapies at the week 24 endpoint. Patients who failed glycaemic-screening criteria [HbA1c >11% or fasting plasma glucose (FPG) >15 mmol/l (270 mg/dl)] could enter a 24-week, single-arm substudy. These patients (N = 94) received open-label vildagliptin plus high-dose metformin combination therapy (100 mg + 1000 mg twice daily). Results:, From comparable baseline values (8.6,8.7%), HbA1c decreased in all four treatment groups, to the greatest extent with vildagliptin plus high-dose metformin combination therapy. Mean (SE) HbA1c change from baseline was ,1.8% (0.06%), ,1.6% (0.06%), ,1.1% (0.06%) and ,1.4% (0.06%) with vildagliptin plus high-dose metformin combination therapy, vildagliptin plus low-dose metformin combination therapy, and vildagliptin and metformin monotherapies respectively. The between-group difference was superior with vildagliptin plus high-dose metformin combination therapy (p < 0.001 vs. both monotherapies) and vildagliptin plus low-dose metformin combination therapy (p < 0.001 and p = 0.004, vs. vildagliptin and metformin monotherapies, respectively). Higher baseline HbA1c values were linked to greater HbA1c reductions, with changes of ,3.2% (0.22%), ,2.7% (0.22%), ,1.5% (0.24%) and ,2.6% (0.26%) respectively, occurring in patients with baseline HbA1c,10%. Reductions in FPG were superior with vildagliptin plus high-dose metformin combination therapy [change from baseline ,2.63 (0.13) mmol/l] compared with both monotherapies [,1.26 (0.13) mmol/l and ,1.92 (0.13) mmol/l, respectively; p < 0.001]. There was no incidence of hypoglycaemia or severe hypoglycaemia with either combination therapy, and neither was associated with weight gain. All treatments were well tolerated and displayed a comparable incidence of adverse events overall. Despite superior HbA1c lowering, the vildagliptin plus low-dose metformin combination therapy group demonstrated a favourable gastrointestinal (GI) tolerability profile compared with metformin monotherapy. Conclusions:, In treatment-naive patients, combinations of vildagliptin and both high-dose and low-dose metformin provide superior efficacy to monotherapy treatments with a comparable overall tolerability profile and low risk of hypoglycaemia. The potential dose-sparing effect of adding vildagliptin to low-dose metformin in preference to the up-titration of metformin may allow patients to achieve equivalent or superior HbA1c lowering without the GI tolerability issues associated with higher doses of metformin. [source] Orlistat 120 mg improves glycaemic control in type 2 diabetic patients with or without concurrent weight lossDIABETES OBESITY & METABOLISM, Issue 4 2009S. Jacob Background:, Both obesity and type 2 diabetes are associated with increased morbidity and mortality. Published data suggest that orlistat 120 mg, a lipase inhibitor used to treat obesity, may improve glycaemic parameters through weight loss,independent effects. Aim:, To investigate the effect of orlistat 120 mg on weight loss, and assess whether changes in glycaemic parameters [fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c)] are independent of weight loss. Methods:, This retrospective analysis of pooled data from seven multicentre, double-blind, placebo-controlled studies involved overweight or obese patients with type 2 diabetes (aged 18,70 years). Patients were required to have a body mass index of 27,43 kg/m2, HbA1c of 6.5 to <13%, and stable weight for ,3 months. Subjects received orlistat 120 mg tid or placebo for 6 or 12 months. Results:, A total of 2550 overweight or obese patients with type 2 diabetes were enrolled and randomized to treatment with orlistat 120 mg tid (n = 1279) or placebo (n = 1271). For the whole population, patients treated with orlistat 120 mg had significantly greater mean decreases in FPG compared with placebo-treated patients (,1.39 mmol/l vs. ,0.47 mmol/l; p < 0.0001). In addition, orlistat 120 mg provided significantly larger mean decreases in HbA1c compared with placebo (,0.74% vs. ,0.31%; p < 0.0001). For patients with minimal weight loss (,1% of baseline body weight), orlistat 120 mg still provided a significantly greater decrease in the least squares mean value for both FPG (,0.83 mmol/l vs. ±0.02 mmol/l; p = 0.0052) and HbA1c,0.29% vs. ±0.14%; p = 0.0008). This suggested that the improvement of glycaemic control with orlistat 120 mg was independent of weight loss. Using linear regression analysis, improvement in glycaemic control (FPG and HbA1c) with orlistat 120 mg was less strongly correlated with weight loss than for placebo. Conclusion:, Orlistat 120 mg appears to improve glycaemic control more than would be predicted by weight loss alone in overweight or obese patients with type 2 diabetes. Postulated mechanisms underlying this effect include an improvement of insulin sensitivity, a slower and incomplete digestion of dietary fat, reduction of postprandial plasma non-esterified fatty acids, decreased visceral adipose tissue, and stimulation of glucagon-like peptide-1 secretion in the lower small intestine. [source] Fifty-two-week efficacy and safety of vildagliptin vs. glimepiride in patients with type 2 diabetes mellitus inadequately controlled on metformin monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009E. Ferrannini Aim:, To examine the efficacy and safety of vildagliptin vs. glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus in a 52-week interim analysis of a large, randomized, double-blind, multicentre study. The primary objective was to demonstrate non-inferiority of vildagliptin vs. glimepiride in glycosylated haemoglobin (HbA1c) reduction at week 52. Methods:, Patients inadequately controlled on metformin monotherapy (HbA1c 6.5,8.5%) and receiving a stable dose of metformin (mean dose 1898 mg/day; mean duration of use 36 months) were randomized 1:1 to receive vildagliptin (50 mg twice daily, n = 1396) or glimepiride (titrated up to 6 mg/day; mean dose 4.5 mg/day, n = 1393). Results:, Non-inferiority of vildagliptin was demonstrated (97.5% confidence interval 0.02%, 0.16%) with a mean (SE) change from baseline HbA1c (7.3% in both groups) to week 52 endpoint of ,0.44% (0.02%) with vildagliptin and ,0.53% (0.02%) with glimepiride. Although a similar proportion of patients reached a target HbA1c level of <7% with vildagliptin and glimepiride (54.1 and 55.5%, respectively), a greater proportion of patients reached this target without hypoglycaemia in the vildagliptin group (50.9 vs. 44.3%; p < 0.01). Fasting plasma glucose (FPG) reductions were comparable between groups (mean [SE] ,1.01 [0.06] mmol/l and ,1.14 [0.06] mmol/l respectively). Vildagliptin significantly reduced body weight relative to glimepiride (mean [SE] change from baseline ,0.23 [0.11] kg; between-group difference ,1.79 kg; p < 0.001) and resulted in a 10-fold lower incidence of hypoglycaemia than glimepiride (1.7 vs. 16.2% of patients presenting at least one hypoglycaemic event; 39 vs. 554 hypoglycaemic events, p < 0.01). No severe hypoglycaemia occurred with vildagliptin compared with 10 episodes with glimepiride (p < 0.01), and no patient in the vildagliptin group discontinued because of hypoglycaemia compared with 11 patients in the glimepiride group. The incidence of adverse events (AEs), serious AEs and adjudicated cardiovascular events was 74.5, 7.1 and 0.9%, respectively, in patients receiving vildagliptin, and 81.1, 9.5 and 1.6%, respectively, in patients receiving glimepiride. Conclusions:, When metformin alone fails to maintain sufficient glycaemic control, the addition of vildagliptin provides comparable efficacy to that of glimepiride after 52 weeks and displays a favourable AE profile, with no weight gain and a significant reduction in hypoglycaemia compared with glimepiride. [source] Efficacy and safety of the dipeptidyl peptidase-4 inhibitor alogliptin in patients with type 2 diabetes inadequately controlled by glyburide monotherapyDIABETES OBESITY & METABOLISM, Issue 2 2009R. E. Pratley Aim:, To evaluate the efficacy and safety of alogliptin, a potent and highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor, in combination with glyburide in patients with type 2 diabetes inadequately controlled by sulphonylurea monotherapy. Methods:, After a 2-week screening period, adult patients 18,80 years of age entered a 4-week run-in/stabilization period in which they were switched from their own sulphonylurea medication to an equivalent dose of glyburide (open label) plus placebo (single blind). After the run-in period, patients were randomly assigned to double-blind treatment with alogliptin 12.5 mg (n = 203), alogliptin 25 mg (n = 198), or placebo (n = 99) for 26 weeks. The primary end-point was change from baseline to week 26 in glycosylated haemoglobin (HbA1c). Secondary end-points included clinical response rates and changes in fasting plasma glucose, ,-cell function (fasting proinsulin, insulin, proinsulin/insulin ratio, and C-peptide, and homeostasis model assessment ,-cell function), body weight, and safety end-points [adverse events (AEs), clinical laboratory tests, vital signs and electrocardiographic readings]. Results:, The study population had a mean age of 57 years and a mean disease duration of 8 years; it was well balanced for gender (52% women) and was mainly white (71%). The mean baseline HbA1c was approximately 8.1% in each group. Significantly greater least squares (LS) mean reductions in HbA1c were seen at week 26 with alogliptin 12.5 mg (,0.38%) and 25 mg (,0.52%) vs. placebo (+0.01%; p < 0.001), and more patients in the alogliptin 25-mg group had HbA1c levels ,7.0% at week 26 (34.8%, p = 0.002) vs. placebo (18.2%). Proportionately more patients in the alogliptin 12.5 mg (47.3%) and 25 mg (50.5%) groups had an HbA1c reduction ,0.5% from baseline compared with patients in the placebo group (26.3%; p < 0.001). Minor improvements in individual markers of ,-cell function were seen with alogliptin, but no significant treatment group differences were noted relative to placebo. Minor LS mean changes in body weight were noted across groups (placebo, ,0.20 kg; alogliptin 12.5 mg, +0.60 kg; alogliptin 25 mg, +0.68 kg). AEs were reported for 63,64% of patients receiving alogliptin and 54% of patients receiving placebo. Few AEs were treatment limiting (2.0,2.5% across groups), and serious AEs (2.0,5.6%) were infrequent, similar across groups, and generally considered not related to treatment. The incidences of hypoglycaemia for placebo, alogliptin 12.5 mg and alogliptin 25 mg groups were 11.1, 15.8 and 9.6% respectively. Conclusions:, In patients with type 2 diabetes inadequately controlled by glyburide monotherapy, the addition of alogliptin resulted in clinically significant reductions in HbA1c without increased incidence of hypoglycaemia. [source] | |||||||||||||||||||||||||||||||||||||||||||