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Insulin Concentrations (insulin + concentration)
Kinds of Insulin Concentrations Selected AbstractsAssociation of Season and Pasture Grazing with Blood Hormone and Metabolite Concentrations in Horses with Presumed Pituitary Pars Intermedia DysfunctionJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2010N. Frank Background: Pituitary pars intermedia dysfunction (PPID) is a risk factor for pasture-associated laminitis, which follows a seasonal pattern. Hypothesis: Hormonal responses to season differ between PPID and unaffected horses. Animals: Seventeen horses aged 8,30 years (14 horses , 20 years of age). Methods: Longitudinal observational study. Blood was collected monthly from August 2007 until July 2008 after pasture grazing and again after overnight stall confinement. Blood hormone and metabolite concentrations were measured and pasture grass samples were analyzed to determine carbohydrate content. Analysis of variance analysis for repeated measures was performed. Results: Mean ACTH concentrations varied significantly over time (P < .001), with higher concentrations detected in August, September, and October compared with November,April. Pasture × time effects were detected for glucose and insulin concentrations, with peaks observed in September. Horses were retrospectively allocated to PPID (n = 8) and control (n = 9) groups on the basis of plasma ACTH concentrations. Changes in insulin concentrations over time differed in the PPID group when compared with the control group. Insulin concentrations were positively correlated with grass carbohydrate composition. Conclusions and Clinical Importance: PPID did not affect the timing or duration of the seasonal increase in ACTH concentrations, but higher values were detected in affected horses. Insulin concentrations differed between groups, but hyperinsulinemia was rarely detected. Glucose and insulin concentrations peaked in September when horses were grazing on pasture, which could be relevant to the seasonal pattern of laminitis. [source] Clustering of cardiovascular risk factors in type 2 diabetes mellitus: prognostic significance and trackingDIABETES OBESITY & METABOLISM, Issue 1 2001J. Kaukua Summary Aim Little attention has been paid to the prognostic significance and tracking effect of risk factor clusters characteristic of type 2 diabetes mellitus. We studied the clustering of eight cardiovascular risk factors (smoking, high body mass index, elevated systolic blood pressure, high serum, low density lipoprotein (LDL) cholesterol, high serum LDL triglycerides, low serum, high density lipoprotein (HDL) cholesterol, high fasting blood glucose and high plasma insulin concentration) and their effect on the prognosis and the tracking effect. Methods This study is a population-based prospective follow-up of newly diagnosed type 2 diabetic subjects (n = 133, aged 45,64 years) in Eastern Finland. The following end points were used: all-cause mortality, cardiovascular mortality, and incidences of first myocardial infarction and first stroke. Furthermore, we studied the ,tracking effect' of the risk factor clusters during the 10-year follow-up period. Results When the clustering of risk factors typical of type 2 diabetes mellitus was taken into account, all-cause mortality increased from 28.6% to 50.0% (p <,0.05) and cardiovascular disease mortality increased from 14.3% to 50.0% (p <,0.01) depending on the number of risk factors present. The incidence of first myocardial infarction increased from 0% to 40.0% (p <,0.05) as the number of risk factors increased from 0 to 5. In survivors, the proportion of individuals with no risk factors decreased and the proportion on individuals with three to four risk factors increased during the 10-year follow-up period despite the high mortality among the group with many risk factors. Conclusions The risk factor clusters among type 2 diabetic subjects are of great predictive value and when not aggressively treated, show a relentless increase despite selective mortality. [source] Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose toleranceDIABETIC MEDICINE, Issue 5 2004S. M. A. Bennett Abstract Aims To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). Methods Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. Results Rosiglitazone significantly improved the insulin sensitivity index by 2.26 µg/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). Conclusions Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects. [source] Prediction of incipient pasture-associated laminitis from hyperinsulinaemia, hyperleptinaemia and generalised and localised obesity in a cohort of poniesEQUINE VETERINARY JOURNAL, Issue 2 2009R. A. CARTER Summary Reasons for performing study: The ability to predict ponies at increased risk of laminitic episodes, when exposed to nutrient dense pasture, would facilitate management to avoid disease. Objectives: To identify variables and clinically useful cut-off values with reproducible diagnostic accuracy for the prediction of ponies that subsequently developed laminitis when exposed to nutrient dense pasture. Methods: A cohort of predominantly Welsh and Dartmoor ponies from a closed herd was evaluated in March 2006 (n = 74) and March 2007 (n = 57). Ponies were categorised as never laminitic or previously laminitic according to reported laminitic history and as clinically laminitic (CL) if laminitis was observed within 3 months following evaluation. Body condition score (BCS), cresty neck score (CNS), girth and neck circumferences (NC), withers height, blood pressure and hoof surface temperature, and plasma insulin, glucose, triglyceride, leptin, cortisol, ACTH, uric acid and TNF-, concentrations were measured. Analysis of sensitivity, specificity and receiver operating characteristic curves was used to evaluate the diagnostic accuracy for a variable to predict CL ponies. Results: Variables with diagnostic accuracy for the prediction of CL ponies included insulin, leptin, BCS, CNS, and NC:height ratio. Specific cut-off values of insulin (>32 mu/l), leptin (>7.3 ng/ml), BCS (,7), CNS (,4) and NC:height ratio (>0.71) had reproducible diagnostic accuracy for the prediction of laminitis. Combining tests did not result in higher diagnostic accuracy than individual tests of insulin or leptin during either evaluation. Conclusions: Tests of insulin and leptin concentrations and measures of generalised (BCS) and localised (CNS or NC:height ratio) obesity were beneficial in the prediction of laminitic episodes. Potential relevance: These results highlight the importance of monitoring and reducing insulin concentration, and generalised and regional obesity in ponies to reduce risk of laminitis. [source] Leptin stimulates uncoupling protein-2 mRNA expression and Krebs cycle activity and inhibits lipid synthesis in isolated rat white adipocytesFEBS JOURNAL, Issue 19 2000Rolando B. Ceddia The treatment of rats and mice with leptin causes dramatic body fat reduction and in some cases even disappearance of fat tissue. Here, we report the effects of leptin (10 and 100 ng·mL,1) on isolated rat adipocytes maintained for 15 h in culture. Leptin decreased the incorporation of acetate into total lipids by 30%. A reduction in this incorporation (42%) was still observed after the leptin-cultivated adipocytes were exposed to a supra-physiological insulin concentration (10 000 µU·mL,1). On the other hand, leptin increased acetate degradation by 69% and the maximal activity of citrate synthase by 50% in isolated adipocytes. It also increased oleate degradation by 35 and 50% at concentrations of 10 and 100 ng·mL,1, respectively. Eventually, leptin upregulated the uncoupling protein-2 (UCP2) mRNA level by 63% and had no effect on uncoupling protein-3 (UCP3) mRNA in isolated adipocytes. The upregulation of UCP2 mRNA might have contributed to the stimulation of acetate and fatty acid degradation by leptin. The peripheral effects of leptin observed in this study are in line with the general energy dissipating role postulated for this hormone and for UCP2. They suggest mechanisms by which adipocytes regulate their fat content by an autocrine pathway without the participation of the central nervous system. [source] Modulation of glycosphingolipid metabolism significantly improves hepatic insulin sensitivity and reverses hepatic steatosis in mice,HEPATOLOGY, Issue 5 2009Nora Bijl Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. The hyperinsulinemia that occurs as a consequence of insulin resistance is thought to be an important contributor to the development of fatty liver. We have shown that the iminosugar N-(5'-adamantane-1'-yl-methoxy)-pentyl-1-deoxynojirimycin (AMP-DNM), an inhibitor of the enzyme glucosylceramide synthase, is a potent enhancer of insulin signaling in rodent models for insulin resistance and type 2 diabetes. The present study was designed to assess the impact of AMP-DNM on insulin levels, liver triglyceride synthesis, and gene expression profile. Treatment of ob/ob mice with AMP-DNM restored insulin signaling in the liver, corrected blood glucose values to levels found in lean mice, and decreased insulin concentration. The expression of sterol regulatory element-binding protein 1c target genes involved in fatty acid synthesis normalized. AMP-DNM treatment significantly reduced liver to body weight ratio and reversed hepatic steatosis, comprising fat as well as inflammatory markers. In addition, AMP-DNM treatment corrected to a large extent the gene expression profile of ob/ob mice livers toward the profile of lean mice. Conclusion: Pharmacological lowering of glycosphingolipids with the iminosugar AMP-DNM is a promising approach to restore insulin signaling and improve glucose homeostasis as well as hepatic steatosis. (HEPATOLOGY 2009.) [source] Effects of oat processing on the glycaemic and insulin responses in horsesJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 3-4 2003I. Vervuert Summary This study was conducted to evaluate the effects of different oat processing techniques on the plasma glucose and insulin response in horses. In a cross-over design, six horses (ages 4,15 years, mean body weight ± SD: 450 ± 37 kg) were fed in random order: untreated oats, finely ground, steam-flaked and popped oats. The total oat intake varied between 1.05,1.5 kg/day, and the amount of diet was adjusted to a starch content of 630 g starch per day and horse (1.2,1.5 g starch/kg BW/day). During the stabilization period of 10 days, horses additionally received 6 kg grass hay. Following this adaptation period, plasma glucose and insulin responses to the respective dietary treatments were tested. Horses were fed their test diet (exclusively oats), and blood samples were collected at defined times to determine glycaemic and insulin response. Oat feeding resulted in a significant increase in mean plasma glucose and insulin concentration. However, glucose and insulin peaks as well as their respective areas under the curves were not clearly influenced by oat processing. The glycaemic index varied between 94.7 ± 11.2% (steam-flaked oats) and 102.6 ± 14.5% (finely ground oats, n.s.), the insulin index ranged between 93.8 ± 18.9% (popped oats) and 150.0 ± 77.6% (finely ground oats, n.s.). The insulin reaction to oat feeding showed a high variability between the horses. The results of this study indicate that the glucose and insulin responses are not clearly altered by the different types of oat processing. However, the glucose and insulin responses tended to be lower in thermally treated oats when compared with untreated or finely ground oats. [source] Effects of dietary protein level and cold exposure on tissue responsiveness and sensitivity to insulin in sheepJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 11-12 2001H. Sano The effects of dietary crude protein (CP) level and cold exposure on tissue responsiveness and sensitivity to insulin were studied in sheep. Nine rams were assigned to one of three isoenergetic diets which contained 70, 100, and 140% of CP for maintenance. They were exposed from a thermoneutral environment (20 °C) to a cold environment (0 °C) for 7 days. A hyperinsulinemic euglycemic clamp approach was applied for the determination of tissue responsiveness to insulin (the maximal glucose infusion rate, GIRmax) and tissue sensitivity to insulin (the plasma insulin concentration at half maximal glucose infusion rate, ED50). Dietary CP level influenced digestibilities of dry matter and CP (P=0.002 and P=0.001, respectively), and cold exposure decreased (P=0.01) CP digestibility. The GIRmax and ED50 tended to be influenced (P=0.08) by dietary CP level. The GIRmax was enhanced (P=0.0001) during cold exposure. Significant interactions between diet and environment were found for the GIRmax (P=0.04), but not for ED50 (P=0.07). It is concluded that in sheep dietary CP level can modify insulin action in response to cold exposure. [source] Blood leucocyte cytokine production after LPS stimulation at different concentrations of glucose and/or insulinACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2009S. BEITLAND Background: Previous studies have indicated that alterations in blood glucose and/or insulin levels modify the inflammatory response. The purpose of this study was to elucidate whether increased levels of glucose and/or insulin influence the activation pattern of blood leucocytes and their production of cytokines in vitro. Methods: Venous blood was obtained from eight healthy male volunteers after an overnight fast. Glucose and/or insulin were added to aliquots of whole blood to increase the blood glucose concentration by 5 or 20 mmol/l and/or the insulin concentration by 6 or 30 nmol/l, respectively, before stimulation with E. coli lipopolysaccharide (LPS) at concentrations of 10, 100 or 1000 ng/ml. The samples were subsequently incubated at 37 °C for 6 h before cytokine measurements. After centrifugation the levels of interleukins (IL)-1,, IL-6, IL-8, IL-10 and tumour necrosis factor (TNF)-, were measured in plasma using enzyme-linked immuno-sorbent assays. The results were compared with cytokine levels in parallel control samples to which only identical amounts of LPS were added. Results: The LPS-stimulated production of IL-1, was significantly reduced by on average 26% in samples to which glucose 20 mmol/l was added; addition of insulin and/or glucose 5 mmol/l had no apparent effect on the IL-1, production at any LPS concentration. The levels of IL-6, IL-8, IL-10 and TNF-, were not manifestly altered by addition of glucose and/or insulin at any LPS concentration. Conclusion: A substantial increase in blood glucose concentration changed the IL-1, production, but not the production of other cytokines, in response to LPS stimulation. [source] Are Hormonal Responses to Exercise in Young Men with Down's Syndrome Related to Reduced Endurance Performance?JOURNAL OF NEUROENDOCRINOLOGY, Issue 5 2008V-A. Bricout The aim of the present study was to analyse whether hormonal responses could explain an exercise limitation in Down's syndrome (DS). Fourteen young men with DS (mean age 22.5 ± 0.7 years) and 15 controls (CONT, mean age 22.5 ± 0.3 years) participated in the study. During a treadmill submaximal incremental test, blood samples were collected for determination of hormonal and metabolic variables. Compared to CONT, DS individuals showed lower VO2max (P < 0.05), and lower duration of submaximal incremental exercise (P < 0.001). At rest, DS individuals showed greater catecholamines, insulin and leptin values (P < 0.05), but lower testosteronemia and cortisolemia (P < 0.05), compared to CONT. During submaximal incremental tests, catecholamines and cortisol were not increased, whereas the insulin concentration of DS individuals was significantly higher (P < 0.01) compared to CONT. Glycaemia increased significantly at the end of submaximal incremental test for CONT but not for DS individuals (P < 0.01). Maximal fat oxidation was lower (P < 0.01), whereas non-esterified fatty acids concentrations rose significantly during submaximal exercise in DS individuals. These results indicate an altered hormonal response to exercise in DS individuals. This endocrine profile at rest and during exercise may limit endurance performance in DS individuals. [source] Costs of managing conditions associated with obesity among Australian teenagersJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 7-8 2009Michael L Booth Aim: To determine the health-care charges associated with monitoring and managing, over 1 year, the cases of elevated insulin concentration, elevated alanine aminotransferase concentration and dyslipidaemia due to overweight or obesity among 15,19-year-old Australian males and females. Methods: Fasting blood samples (n= 500) were collected in 2004 from a representative population sample of adolescents (n= 496; mean age 15.3 years) attending schools in Sydney, Australia. Full service charges and Medicare expenditures for specialist medical and dietary consultations, pathology tests and radiological investigations, over 1 year, under efficient and inefficient health-care delivery models, including and excluding participants in the healthy body mass index (BMI) category. Results: Under an inefficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A305.1 million per annum (M pa). Exclusion of participants in the healthy BMI category resulted in an annual Medicare expenditure of $A170.0M pa. Under an efficient delivery model and including all participants with elevated risk factors, the Medicare expenditure was $A295.5M pa. Exclusion of participants in the healthy BMI category reduced annual Medicare expenditure to $A164.8M pa. Medicare expenditure for 15,19-year-olds would increase by 48% if only cases among overweight and obese adolescents were treated and by 85% if all cases were identified and treated. Conclusions: Short-term management of the health consequences of overweight and obesity among adolescents will increase Medicare expenditure on this group by at least 48%. Failure to treat will delay, but compound, health-care expenditure. [source] Formulation pH modulates the interaction of insulin with chitosan nanoparticlesJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2002Zengshuan Ma Abstract Previous studies on chitosan-insulin nanoparticles have reported diverse encapsulation efficiency and insulin release profiles despite similar formulation and preparation procedures. This study examined the efficiency and mechanism of association of insulin with chitosan nanoparticles in the pH range of 2.3 to 6.3. Nanoparticles of 237 to 235 nm were prepared by ionotropic gelation of chitosan with tripolyphosphate counterions. Insulin was quantified by an RP-HPLC method. The insulin association efficiency (AE) spanned a broad range from 2 to 85%, and was highly sensitive to formulation pH. Highest AE was measured at insulin loading concentrations,,,4.28 U/mL and pH 6.1, close to the pI of native insulin and the pKa of chitosan. This association, attributed to physical adsorption of insulin through hydrophobic interactions with chitosan, was labile, and the associated insulin rapidly and completely released by dilution of the nanoparticles in aqueous media of pH 2 to 7.4. AE obtained at pH 5.3 was less than half that measured at pH 6.1 at corresponding insulin concentration, but the association at pH 5.3 appeared to be based on stronger interactions, because the release of insulin was pH-dependent and recovery was less than 25% even upon disintegration of the chitosan matrix. Interaction of insulin with the chitosan nanoparticles rendered the protein more susceptible to acid and enzymatic hydrolyses, the effects being more predominant in nanoparticles prepared at pH 5.3 than at pH 6.1. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91:1396,1404, 2002 [source] Seasonal Variation in Serum Concentrations of Selected Metabolic Hormones in HorsesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010N.J. Place Background: Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. Objective: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). Animals: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 laminitic horses residing at the same farm/stable were also studied. Methods: Prospective study of healthy and laminitic horses. Plasma/serum samples were analyzed for concentrations of hormones and glucose. Results: ACTH was the only analyte to show a discrete seasonal pattern, with concentrations in healthy and EMS horses frequently outside of the reference range (9,35 pg/mL) in August through October. Insulin was elevated (>40 ,IU/mL) in EMS horses during most months and median serum glucose was generally higher in EMS horses (100 mg/dL, range, 76,163 mg/ dL) than in controls (94 mg/dL, range, 56,110 mg/dL), but no seasonal patterns for insulin or glucose were found. Conclusions and Clinical Importance: An increased ACTH concentration in horses in late summer or autumn should be interpreted with caution. In contrast, insulin concentration is maintained within the reference range throughout the year in healthy horses, thus an increased insulin concentration at any time of year should raise suspicions of EMS, ECD, or both. [source] Comparison of the effect of ketamine added to bupivacaine and ropivacaine, on stress hormone levels and the duration of caudal analgesiaACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2005M. Akbas Background:, The aim of this study was to compare bupivacaine 0.25% and ropivacaine 0.2%, singly and in combination with ketamine, for caudal administration in children. Duration of analgesia, the need for other analgesics and the stress response were measured. Methods:, Eighty children were ramdomized into four groups of twenty. The bupivacaine group received bupivacaine 0.25% and the ketamine/bupivacaine group received bupivacaine 0.25% plus 0.5 mg/kg ketamine. The ropivacaine group received ropivacaine 0.2%, and the ketamine/ropivacaine group received ropivacaine 0.2% plus 0.5 mg/kg ketamine. The duration of analgesia and analgesic requirements were recorded for each group, as were peri-operative and post-operative concentrations of the stress hormones insulin, glucose and cortisol. Results:, Ketamine, added to either bupivacaine or ropivacaine for caudal analgesia, gave a longer duration of analgesia (P < 0.05) than bupivacaine or ropivacaine alone. In all groups, blood insulin concentration was increased, and cortisol concentration reduced. Glucose concentration was significantly increased in all groups (P < 0.05). Conclusions:, Ketamine can safely be added to ropivacaine 0.2% or bupivacaine 0.25% for caudal anesthesia in order to prolong duration of analgesia and reduce the need for additional analgesics. Stress hormone levels are partially attenuated. [source] Effects of castration on insulin levels and glucose tolerance in the mouse differ from those in manTHE PROSTATE, Issue 15 2010Takamitsu Inoue Abstract BACKGROUND Plasma insulin concentration is increased in prostate cancer patients during androgen deprivation therapy (ADT) and hyperinsulinemia has been associated with aggressive prostate cancer behavior. To investigate the possible role of castration-induced hyperinsulinemia as a mechanism that may attenuate the beneficial effects of ADT in patients with prostate cancer, a murine model would be useful. We therefore investigated long-term metabolic effects of castration in several mouse models. METHODS We studied the long-term influence of castration on energy intake, body weight, glucose tolerance, plasma-insulin, plasma insulin-like growth factor-1 (IGF-1), plasma adiponectin, and plasma leptin in C57BL/6, Swiss nu/nu, and CB17 scid mice receiving various diets. In each case, mice were randomized to have either bilateral orchiectomy or a sham operation. RESULTS Energy intake, body weight, blood glucose levels in glucose tolerance test, plasma insulin, plasma IGF-1, and plasma leptin level in all had a trend to be decreased in castrated as compared to sham operated mice. Plasma adiponectin level was increased in the castrated mice. CONCLUSIONS The effects of castration on glucose, insulin, and related markers in several mouse models studied does not coincide with clinical observations; further studies in this area will require clinical research and/or the use of alternate models such as the dog. Prostate 70: 1628,1635, 2010. © 2010 Wiley-Liss, Inc. [source] Influence of Sirolimus on Cyclosporine-Induced Pancreas Islet Dysfunction in RatsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009H. K. Song This study was performed to investigate the effect of sirolimus (SRL) on cyclosporine (CsA)-induced pancreatic islet dysfunction in rats. Three separate studies were performed. First, diabetogenic effect of SRL was evaluated with three different doses (0.15, 0.3 and 0.6 mg/kg). Second, rats were treated with SRL (0.3 mg/kg) with or without CsA (15 mg/kg) for 4 weeks. Third, rats were treated with CsA for 4 weeks, and then switched to SRL for 4 weeks. The effect of SRL on CsA-induced pancreatic islet dysfunction was evaluated by an intraperitoneal glucose tolerance test, plasma insulin concentration, HbA1c level, HOMA-R index, immunohistochemistry of insulin and pancreatic beta islet cell mass. The SRL treatment increased blood glucose concentration in a dose-dependent manner. The combined treatment with SRL and CsA increased blood glucose concentration, Hemoglobin A1c (HbA1c) level, HOMA-R [fasting insulin (mU/mL) x fasting glucose (mmol/L)]/22.5] index and decreased plasma insulin concentration, immunoreactivity of insulin and pancreatic beta islet cell mass compared with rats treated with CsA. CsA withdrawal for 4 weeks improved pancreatic beta-cell function and structure. However, conversion from CsA to SRL further increased blood glucose levels compared with the rats converted from vehicle to SRL. The results of our study demonstrate that SRL is diabetogenic and aggravates CsA-induced pancreatic islet dysfunction. [source] An INSIG2 Polymorphism Affects Glucose Homeostasis in Sardinian Obese Children and AdolescentsANNALS OF HUMAN GENETICS, Issue 5 2010Patrizia Zavattari Summary Allelic variants of a single nucleotide polymorphism (SNP), rs7566605, located approximately 10 kb upstream of the INSIG2 gene have been found in association with body weight and with other clinical features related to obesity in some populations but not in others. Our objective was to test the association of this SNP in obese children and adolescents from the genetically isolated population of Sardinia. We tested the association of rs7566605 with body mass index (BMI) and with serum glucose and insulin concentrations and a surrogate measure of insulin resistance (HOMA-IR) in a cohort of 747 Sardinian obese children and adolescents. A case control analysis was performed using 548 ethnically-matched healthy controls. Allelic frequencies of the SNP were similar between patients and controls. Mean glucose and insulin concentration and mean HOMA-IR values were significantly higher in patients carrying the CC genotype than in the CG and GG carriers. In the patients with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), allele C was significantly more frequent than in controls. Although INSIG2 polymorphisms do not consistently associate with BMI, the observation of an association with glucose concentration would support a role for this gene in the metabolic complications of obesity. [source] Transdermal drug delivery by coated microneedles: geometry effects on drug concentration in bloodASIA-PACIFIC JOURNAL OF CHEMICAL ENGINEERING, Issue 6 2009Barrak Al-Qallaf Abstract Drug administration through transdermal delivery is restricted by the top layer of skin, the stratum corneum. One possible solution to overcome the barrier function of the stratum corneum is to employ microneedle arrays. However, detailed theoretical models relating drug-coated microneedles and their geometry to the drug concentration in the blood are limited. This article aims to address this issue by examining the blood concentration profiles for a model drug, insulin, that has been administered via coated microneedles. A mathematical model is introduced and applied to predict theoretical blood concentrations. Furthermore, the insulin concentration in blood is calculated for a range of different microneedle shapes and dimensions to identify the most effective geometry. The results indicate that the optimum microneedle geometry in terms of maximizing insulin concentration was a rocket-shaped needle with a constant tip angle of 90°. Also, it has been found that the number of microneedles in an array is the most significant factor in determining maximum insulin concentration in the blood (Cb, max). Penetration depth of the microneedle, centre-to-centre spacing and microneedle thickness had a less significant effect on the maximum insulin concentration in the blood. It is envisaged that the current study will help in designing microneedles of optimum size and shape for transdermal drug delivery. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd. [source] Effectiveness of a community-directed ,healthy lifestyle' program in a remote Australian Aboriginal communityAUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 2 2000Kevin G. Rowley Objective: To assess the sustainability and effectiveness of a community-directed program for primary and secondary prevention of obesity, diabetes and cardiovascular disease in an Aboriginal community in north-west Western Australia. Method: Evaluation of health outcomes (body mass index, glucose tolerance, and plasma insulin and triglyceride concentrations) in a cohort of high-risk individuals (n=49, followed over two years) and cross-sectional community samples (n=200 at baseline, 185 at two-year and 132 at four-year follow-ups), process (interventions and their implementation) and impact (diet and exercise behaviour). Results: For the high-risk cohort, involvement in diet and/or exercise strategies was associated with protection from increases in plasma glucose and triglycerides seen in a comparison group; however, sustained weight loss was not achieved. At the community level, significant reductions were observed in fasting insulin concentration but no change in prevalence of diabetes, overweight or obesity. Weight gain remained a problem among younger people. Sustainable improvements were observed for dietary intake and level of physical activity. These changes were related to supportive policies implemented by the community council and store management. Conclusions: Community control and ownership enabled embedding and sustainability of program, in association with social environmental policy changes and long-term improvements in important risk factors for chronic disease. Implications: Developmental initiatives facilitating planning, implementation and ownership of interventions by community members and organisations can be a feasible and effective way to achieve sustainable improvements in health behaviours and selected health outcomes among Aboriginal people. [source] Transient hyperglycaemia in a prediabetic dog treated with prednisone and cyclosporin AAUSTRALIAN VETERINARY JOURNAL, Issue 9 2009SC Murray A dog with immune-mediated haemolytic anaemia developed transient hyperglycaemia and glucosuria requiring insulin therapy in association with prednisone and cyclosporin A therapy. Following short-term therapy with insulin and cyclosporin A, the dog remained on prednisone therapy but required no further insulin therapy for 12 weeks, at which time the dog became permanently diabetic. We hypothesise that prednisone and cyclosporin A contributed to insulin resistance in a prediabetic dog with suboptimal endogenous insulin concentration and that the degree of insulin resistance decreased when cyclosporin A therapy was discontinued. [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] 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] 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] The glucose lowering effect of an oral insulin (Capsulin) during an isoglycaemic clamp study in persons with type 2 diabetesDIABETES OBESITY & METABOLISM, Issue 1 2010S. D. Luzio Aim: Randomized, open, single-centre, two-way crossover study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of subcutaneous (sc) regular human insulin (Actrapid) and oral insulin in a capsule form (Capsulin). Methods: Sixteen persons (12 males) with type 2 diabetes on oral hypoglycaemic agents (OHAs) participated. Mean (s.d.) age 60.2 (5.5) years, BMI 28.3 (3.4) kg/m2, haemoglobin A1c (HbA1c) 7.4% (1.1). Two 6-h isoglycaemic glucose clamp studies were conducted 11 days apart. All subjects received in random order 12U sc Actrapid on one clamp study day and either 150U or 300U Capsulin (Cap) on the other day. Glucose infusion rates (GIRs), plasma insulin and C-peptide concentrations were determined throughout each 6-h isoglycaemic clamp. Between the clamp study days, all patients received 150U Capsulin twice daily, dropping all their standard OHAs apart from metformin. Self-monitored blood glucose (SMBG) levels were taken four times a day between the clamp study days. Results: Administration of either Actrapid or Capsulin (150 and 300U) increased GIRs reaching a maximum values at approximately 280,330 min. Overall values for maximum GIR values were higher for Actrapid than either dose of Capsulin (p < 0.05). The significantly greater systemic insulin concentrations following Actrapid were reflected in the AUC0,6 h (910 ± 270 vs. 472 ± 245 pmol h/L; 950 ± 446 vs. 433 ± 218 pmol h/L; both p < 0.05 for Actrapid vs. 150U Capsulin and 300U Capsulin respectively). No difference was observed between 150U and 300U Capsulin. During the repeat-dosing period, good safety and tolerability were observed with Capsulin, and SMBG levels remained stable. At the poststudy visit, significant falls in HbA1c, weight and triglycerides were observed. Conclusions: Administration of the oral insulin Capsulin preparation demonstrated a significant hypoglycaemic action over a period of 6 h associated with only a small increase in circulating plasma insulin concentrations. [source] Effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjectsDIABETES OBESITY & METABOLISM, Issue 3 2006M. González-Ortiz Aim:, To identify the effect of a nutritional liquid supplement designed for the patient with diabetes mellitus (Glucerna SR) in single administration on the postprandial glucose state, insulin secretion and insulin sensitivity in healthy subjects. Methods:, A randomized, single-blind, cross-over, clinical trial was carried out in 14 young, healthy, non-obese, volunteers. A basal metabolic profile, which included glucose level, insulin, total cholesterol, high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, creatinine, and uric acid, was measured. Subjects received a single administration of 300 kcal, gauged with water at 350 ml, of each of the following (at least 3 days apart): glucose 75 g, polymeric supplement (Ensure high calcium) 315 ml or Glucerna SR 323 ml. At the beginning of each administration and 30, 60, 90 and 120 min later, glucose and insulin concentrations were measured. Areas under the curve of glucose and insulin were calculated. First-phase and total insulin secretions and insulin sensitivity were also estimated. Results:, Glucose level at 120 min was significantly lower after receiving Ensure high calcium or Glucerna SR. Administration of Glucerna SR resulted in a significant reduction in the areas under the curve of glucose and insulin, as well as in total insulin secretion with a tendency to be lower in their first phase. Insulin sensitivity was increased. Conclusions:, A single administration of Glucerna SR to healthy subjects decreased the postprandial glucose and insulin states, as well as the insulin secretion; insulin sensitivity increased. [source] Combination therapy using metformin or thiazolidinediones and insulin in the treatment of diabetes mellitusDIABETES OBESITY & METABOLISM, Issue 6 2005Suzanne M. Strowig The biguanide, metformin, sensitizes the liver to the effect of insulin, suppressing hepatic glucose output. Thiazolidinediones such as rosiglitazone and pioglitazone enhance insulin-mediated glucose disposal, leading to reduced plasma insulin concentrations. These classes of drugs may also have varying beneficial effects on features of insulin resistance such as lipid levels, blood pressure and body weight. Metformin in combination with insulin has been shown to significantly improve blood glucose levels while lowering total daily insulin dose and body weight. The thiazolidinediones in combination with insulin have also been effective in lowering blood glucose levels and total daily insulin dose. Triple combination therapy using insulin, metformin and a thiazolidinedione improves glycaemic control to a greater degree than dual therapy using insulin and metformin or insulin and a thiazolidinedione. There is insufficient evidence to recommend the use of metformin or thiazolidinediones in type 1 diabetic patients. Although these agents are largely well tolerated, some subjects experience significant gastrointestinal problems while using metformin. Metformin is associated with a low risk of lactic acidosis, but should not be used in patients with elevated serum creatinine or those being treated for congestive heart failure. The thiazolidinediones are associated with an increase in body weight, although this can be avoided with careful lifestyle management. Thiazolidinediones may also lead to oedema and are associated with a low incidence of hepatocellular injury. Thiazolidinediones are contraindicated in patients with underlying heart disease who are at risk of congestive heart failure and in patients who have abnormal hepatic function. The desired blood glucose-lowering effect and adverse event profiles of these agents should be considered when recommending these agents to diabetic patients. The potential for metformin or the thiazolidinediones to impact long-term cardiovascular outcomes remains under investigation. [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] Studies of relationships between the GLUT10 Ala206Thr polymorphism and impaired insulin secretionDIABETIC MEDICINE, Issue 7 2005C. S. Rose Abstract Aims This study aimed to investigate if the previously observed association between the GLUT10 Ala206Thr polymorphism and variation in fasting and oral glucose-induced serum insulin concentrations could be replicated in a large-scale population-based cohort of Danish whites. Methods The GLUT10 Ala206Thr polymorphism was genotyped in a case-control study of 880 Type 2 diabetic patients and 4372 glucose-tolerant control subjects. The latter group was also enrolled in an assessment of fasting and post-OGTT circulating levels of plasma glucose and serum insulin in relation to genotype. The variant was genotyped by analysis of PCR-generated primer extension by matrix-assisted laser desorption/ionization time-of-flight analysis. Results The Ala206Thr variant was equally frequent among Type 2 diabetic patients and glucose-tolerant subjects (P = 0.9) and there was no difference in the distribution of genotype groups (P = 1.0). In the 4372 glucose-tolerant subjects there was no statistically significant association between the polymorphism and levels of fasting and post-oral glucose tolerance test plasma glucose and serum insulin along with the insulinogenic index and the homeostasis model of assessment for insulin resistance and insulin secretion. Likewise, in an age-stratified subgroup comprising 1264 subjects, we observed no relationships between the GLUT10 polymorphism and the selected metabolic features. Conclusions The GLUT10 Ala206Thr polymorphism is not associated with Type 2 diabetes in the Danish population. Furthermore, in the present large-scale cohort, the polymorphism does not associate with phenotypes such as fasting and oral glucose-induced levels of plasma glucose and serum insulin. [source] Glycaemia and insulinaemia in elderly European subjects (70,75 years)DIABETIC MEDICINE, Issue 2 2001A. U. Teuscher SUMMARY Aims To determine glycaemia and insulinaemia in elderly subjects aged 70,75 years, living across Europe, who participated in the EURONUT-SENECA (Survey in Europe on Nutrition and the Elderly, a Concerted Action) study. Methods Fasting plasma glucose (FPG) and fasting insulin concentrations were measured in 1830 subjects aged 70,75 years living in 15 traditional towns in 11 European countries. For the diagnosis of diabetes, the recommendations of the 1997 report of the American Diabetes Association ,Expert Committee on the diagnosis and classification of diabetes mellitus' were used. Results A total of 31.6% of the study subjects had either diabetes (17.5%) or impaired fasting plasma glucose (FPG) (14.1%). Fifty-one per cent of the subjects with diabetes were unaware of the disease. No difference in diabetes prevalence was found for sex, but male subjects were more likely to have impaired FPG than female subjects (16.8 vs. 11.5%, P = 0.001). Hyperinsulinaemia (fasting insulin levels in the highest quartile) was associated with increased FPG, body mass index, and waist-to-hip ratio. Conclusions It was found that a substantial number of elderly Europeans have impaired glucose homeostasis, with diabetes and impaired FPG being present in almost a third of European subjects aged 70,75 years. [source] Hepatocyte growth factor is a significant risk factor for white matter lesions in Japanese type 2 diabetic patientsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010Futoshi Anan Eur J Clin Invest 2010; 40 (7): 585,590 Abstract Background, The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke. Elevated hepatocyte growth factor (HGF) levels are associated with a high mortality rate in type 2 diabetic patients. The preliminary study was therefore designed to test the hypothesis that the presence of WML correlates with HGF and insulin resistance in type 2 diabetic patients not receiving insulin treatment. Material and methods, Based on brain magnetic resonance imaging, 92 type 2 diabetic patients were divided into two groups: WML-positive group (age 60 ± 5 years, mean ± SD, n = 35) and WML-negative group (age 59 ± 6 years, mean ± SD, n = 57. The level of blood glucose was assessed by fasting plasma glucose, fasting immunoreactive insulin, homeostasis model assessment (HOMA) index and haemoglobin A1c (HbA1c). Results, The body mass index was higher in the WML-positive group than that in the WML-negative group (P < 0·005). Plasma levels of triglycerides were higher while high-density lipoprotein cholesterol was lower in the WML-positive group than in the WML-negative group (P < 0·01 and P < 0·0001 respectively). Fasting plasma glucose (P < 0·0001), insulin concentrations (P < 0·0001), HOMA index (P < 0·0001) and HGF (< 0·0001) levels were higher in the WML-positive group than in the WML-negative group. Multivariate logistic analysis revealed that WML was independently predicted by the high HGF and insulin resistance (P < 0·0001 and P < 0·0001 respectively). Conclusion, The results of this preliminary study indicate that the presence of WML was associated with the high HGF and insulin resistance in Japanese patients with type 2 diabetes mellitus. [source] | ||||||||||||||||||||||||||||||||||||||||