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Sample records for impaired glucose tolerance the

  1. Role of the Transcription Factor Sox4 in Insulin Secretion and Impaired Glucose Tolerance

    PubMed Central

    Goldsworthy, Michelle; Hugill, Alison; Freeman, Helen; Horner, Emma; Shimomura, Kenju; Bogani, Debora; Pieles, Guido; Mijat, Vesna; Arkell, Ruth; Bhattacharya, Shoumo; Ashcroft, Frances M.; Cox, Roger D.

    2008-01-01

    OBJECTIVES— To identify, map, clone, and functionally validate a novel mouse model for impaired glucose tolerance and insulin secretion. RESEARCH DESIGN AND METHODS— Haploinsufficiency of the insulin receptor and associated mild insulin resistance has been used to sensitize an N-ethyl-N-nitrosourea (ENU) screen to identify novel mutations resulting in impaired glucose tolerance and diabetes. The new impaired glucose tolerance 4 (IGT4) model was selected using an intraperitoneal glucose tolerance test and inheritance of the phenotype confirmed by generation of backcross progeny. Segregation of the phenotype was correlated with genotype information to map the location of the gene and candidates sequenced for mutations. The function of the SRY-related high mobility group (HMG)-box 4 (Sox4) gene in insulin secretion was tested using another ENU allele and by small interfering RNA silencing in insulinoma cells. RESULTS— We describe two allelic autosomal dominant mutations in the highly conserved HMG box of the transcription factor Sox4. Previously associated with pancreas development, Sox4 mutations in the adult mouse result in an insulin secretory defect, which exhibits impaired glucose tolerance in association with insulin receptor+/−–induced insulin resistance. Elimination of the Sox4 transcript in INS1 and Min6 cells resulted in the abolition of glucose-stimulated insulin release similar to that observed for silencing of the key metabolic enzyme glucokinase. Intracellular calcium measurements in treated cells indicate that this defect lies downstream of the ATP-sensitive K+ channel (KATP channel) and calcium influx. CONCLUSIONS— IGT4 represents a novel digenic model of insulin resistance coupled with an insulin secretory defect. The Sox4 gene has a role in insulin secretion in the adult β-cell downstream of the KATP channel. PMID:18477811

  2. Sleep restriction acutely impairs glucose tolerance in rats.

    PubMed

    Jha, Pawan K; Foppen, Ewout; Kalsbeek, Andries; Challet, Etienne

    2016-06-01

    Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID:27354542

  3. Retrospective study on the efficacy of a low-carbohydrate diet for impaired glucose tolerance

    PubMed Central

    Maekawa, Satoshi; Kawahara, Tetsuya; Nomura, Ryosuke; Murase, Takayuki; Ann, Yasuyoshi; Oeholm, Masayuki; Harada, Masaru

    2014-01-01

    Background In recent years, the number of people with impaired glucose tolerance (IGT) has increased steadily worldwide. It is clear that the prevention of diabetes is important from the perspective of public health, medical care, and economics. It was recently reported that a low-carbohydrate diet (LCD) is useful for achieving weight loss and glycemic control, but there is no information about the effects of the LCD on IGT. We designed a 7-day in-hospital educational program focused on the LCD for IGT. Methods The subjects were 72 patients with IGT (36 in the LCD group and 36 in the control group) who were enrolled from April 2007–March 2012 and followed for 12 months. We retrospectively compared the LCD group with the control group. Results In 69.4% of the LCD group, blood glucose was normalized at 12 months and the 2-hour plasma glucose level in the oral glucose tolerance test (OGTT) was reduced by 33 mg/dL. In addition, the incidence of diabetes was significantly lower in the LCD group than in the control group at 12 months (0% versus 13.9%, P=0.02). The LCD group showed a significant decrease in fasting plasma glucose, hemoglobin A1c, the homeostasis model of assessment of insulin resistance value, body weight and serum triglycerides (TGs) at 12 months, while there was a significant increase of the serum high-density lipoprotein (HDL) cholesterol level. Conclusion The LCD is effective for normalizing blood glucose and preventing progression to type 2 diabetes in patients with IGT. PMID:24966689

  4. The role of physical activity in the management of impaired glucose tolerance: a systematic review

    PubMed Central

    Khunti, K.; Bull, F.; Gorely, T.; Davies, M. J.

    2007-01-01

    Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966–2006) and EMBASE (1980–2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42–63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal. PMID:17415549

  5. Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

    PubMed Central

    Annema, Wijtske; Dikkers, Arne; de Boer, Jan Freark; van Greevenbroek, Marleen M. J.; van der Kallen, Carla J. H.; Schalkwijk, Casper G.; Stehouwer, Coen D. A.; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    2016-01-01

    Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I. PMID:27270665

  6. Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study.

    PubMed

    Annema, Wijtske; Dikkers, Arne; de Boer, Jan Freark; van Greevenbroek, Marleen M J; van der Kallen, Carla J H; Schalkwijk, Casper G; Stehouwer, Coen D A; Dullaart, Robin P F; Tietge, Uwe J F

    2016-01-01

    Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I. PMID:27270665

  7. Impact of the American Diabetes Association diagnosis criteria on high-risk Spanish population. IGT Research Group. Impaired glucose tolerance.

    PubMed

    Costa, B; Franch, J; Martín, F; Morató, J; Donado, A; Basora, J; Daniel, J

    1999-10-01

    To research into the impact of the new American Diabetes Association (ADA) diagnostic criteria on high risk Spanish population, two cross-sectional studies involving seven primary health care centers in Catalonia (Spain) were revised. Individuals aged > 40 years with any major risk factor for diabetes were screened according to the World Health Organization (WHO) rules using a 75 g oral glucose tolerance test to measure fasting plasma glucose (FPG) and 2 h plasma glucose. The changes on diabetes prevalence and on epidemiological characteristics were evaluated applying the ADA criteria on the basis of FPG alone. A total of 970 individuals, 453 males (46.7%), mean age 59 years and mean body mass index (BMI) 30.6 kg/m2 were screened. Among the 459 diabetic subjects according to either the WHO or the ADA criteria, 314 (68.4%) were classified as having diabetes with respect to both sets of criteria (WHO and ADA). The overlap between impaired glucose tolerance (WHO) and impaired fasting glucose (ADA) diagnoses was 20.7%. Using the ADA criteria results in a decrease of the prevalence of diabetes by 1.5% (95% confidence interval (CI) = -2.2 to -0.8%). No changes in the diabetic phenotype (age, sex and BMI) were found. Impaired fasting glucose prevalence was 18.4% (95% CI = 16-21%). Overall concordance in terms of crude and weighted kappa-value was only acceptable (kappa = 0.51 and kappa = 0.61, respectively). To apply the new ADA diagnostic criteria on high risk Spanish population evidenced a decrease on diabetes prevalence. Nevertheless, the change of criteria undervalued the risk of postprandial hyperglycaemia related to impaired glucose tolerance. PMID:10580619

  8. Variations in the Ghrelin Receptor Gene Associate with Obesity and Glucose Metabolism in Individuals with Impaired Glucose Tolerance

    PubMed Central

    Mager, Ursula; Degenhardt, Tatjana; Pulkkinen, Leena; Kolehmainen, Marjukka; Tolppanen, Anna-Maija; Lindström, Jaana; Eriksson, Johan G.; Carlberg, Carsten; Tuomilehto, Jaakko; Uusitupa, Matti

    2008-01-01

    Background Ghrelin may influence the development of obesity through its role in the control of energy balance, food intake, and regulation of body weight. The effects of ghrelin are mediated via the growth hormone secretagogue receptor (GHSR). Methodology/Principal Findings We genotyped 7 single nucleotide polymorphisms (SNPs) in the GHSR gene and assessed the association between those SNPs and obesity and type 2 diabetes-related phenotypes from 507 middle-aged overweight persons with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Additionally, we performed in silico screening of the 5′-regulatory region of GHSR and evaluated SNPs disrupting putative transcription factor (TF) binding sites in vitro with gelshift assays to determine differences in protein binding between different alleles of SNPs. Rs9819506 in the promoter region of GHSR was associated with body weight (p = 0.036); persons with rs9819506-AA genotype having the lowest body weight. Individuals with rs490683-CC genotype displayed highest weight loss in the whole study population (p = 0.032). The false discovery rate for these results was <10%. Rs490683 and rs509035 were associated with several measures of glucose and insulin metabolism during the follow-up. Rs490683 may be a functional SNP, since gelshift experiments showed differential protein binding between the alleles, with higher binding to the G-allele. Rs490683-C may disrupt a putative binding site for the TF nuclear factor 1 (NF-1), thus rs4906863-GG genotype where the NF-1 site is intact may lead to a higher GHSR gene expression. Conclusion/Significance Polymorphisms in the GHSR promoter may modify changes in body weight during long-term lifestyle intervention and affect ghrelin receptor signalling through modulation of GHSR gene expression. PMID:18698404

  9. Chinese herbal medicines for people with impaired glucose tolerance or impaired fasting blood glucose

    PubMed Central

    Grant, Suzanne J; Bensoussan, Alan; Chang, Dennis; Kiat, Hosen; Klupp, Nerida L; Liu, Jian Ping; Li, Xun

    2011-01-01

    Background Around 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease. Objectives The objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG). Search strategy We searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials. Selection criteria Randomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered. Data collection and analysis Two authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias. Main results This review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the

  10. Unpredictable Feeding Impairs Glucose Tolerance in Growing Lambs

    PubMed Central

    Jaquiery, Anne L.; Oliver, Mark H.; Landon-Lane, Nina; Matthews, Samuel J.; Harding, Jane E.; Bloomfield, Frank H.

    2013-01-01

    Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24) or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21). Intravenous glucose tolerance tests (IVGTT), insulin tolerance tests (ITT), and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18±2%; U 16±2% of initial body weight). Glucose area under the curve (AUC) was unchanged in C (AUC pre 818±34, post 801±33 mmol.min.l−1), but increased by 20% in U (pre 830±25, post 1010±19 mmol.min.l−1; p<0.0001), with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes) post intervention C 1.49±0.04 vs U 1.36±0.04 ng.min.ml−1; p = 0.03). Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism. PMID:23613779

  11. Insulin Secretory Defect and Insulin Resistance in Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance

    PubMed Central

    Aoyama-Sasabe, Sae; Fukushima, Mitsuo; Xin, Xin; Taniguchi, Ataru; Nakai, Yoshikatsu; Mitsui, Rie; Takahashi, Yoshitaka; Tsuji, Hideaki; Yabe, Daisuke; Yasuda, Koichiro; Kurose, Takeshi; Inagaki, Nobuya; Seino, Yutaka

    2016-01-01

    Objective. To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. Methods. We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. Results. In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = −0.245, p < 0.0001) and had the strongest correlation with 2 h PG (β = −0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = −0.162, p < 0.0001) and had the strongest correlation with FPG (β = −0.214). Conclusions. We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects. PMID:26788515

  12. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    PubMed

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations. PMID:15613917

  13. Differences by sex in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa: a systematic review and meta-analysis

    PubMed Central

    Yatsuya, Hiroshi; Kawaguchi, Leo; Aoyama, Atsuko

    2013-01-01

    Abstract Objective To assess differences between men and women in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa. Methods In September 2011, the PubMed and Web of Science databases were searched for community-based, cross-sectional studies providing sex-specific prevalences of any of the three study conditions among adults living in parts of sub-Saharan Africa (i.e. in Eastern, Middle and Southern Africa according to the United Nations subregional classification for African countries). A random-effects model was then used to calculate and compare the odds of men and women having each condition. Findings In a meta-analysis of the 36 relevant, cross-sectional data sets that were identified, impaired fasting glycaemia was found to be more common in men than in women (OR: 1.56; 95% confidence interval, CI: 1.20–2.03), whereas impaired glucose tolerance was found to be less common in men than in women (OR: 0.84; 95% CI: 0.72–0.98). The prevalence of diabetes mellitus – which was generally similar in both sexes (OR: 1.01; 95% CI: 0.91–1.11) – was higher among the women in Southern Africa than among the men from the same subregion and lower among the women from Eastern and Middle Africa and from low-income countries of sub-Saharan Africa than among the corresponding men. Conclusion Compared with women in the same subregions, men in Eastern, Middle and Southern Africa were found to have a similar overall prevalence of diabetes mellitus but were more likely to have impaired fasting glycaemia and less likely to have impaired glucose tolerance. PMID:24101783

  14. Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay

    PubMed Central

    Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Barr, David; Herndon, David N.

    2013-01-01

    Objective Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months post burn. The purpose of this study was to measure insulin sensitivity in severely burned children prior to discharge when wounds are 95% healed. Methods Twenty-four children, aged 4–17 years, with burns ≥ 40% total body surface area (TBSA) underwent a 2 hour oral glucose tolerance test (OGTT) prior to discharge from the acute pediatric burn unit. Plasma glucose and insulin levels, as well as the Homeostasis Model Assessment for Insulin Resistance (HOMAIR) were compared to published OGTT data from healthy, non-burned children. Results There was a significant difference between severely burned children and non-burned, healthy children with respect to the HOMAIR. Severely burned children had a HOMAIR of 3.53±1.62 compared to the value in non-burned healthy children was 1.28±0.16 (p<0.05). Conclusion Insulin resistance secondary to the hypermetabolic stress response persists in severely burned children when burn wounds are at least 95% healed. The results of this study warrant future investigations into therapeutic options for the burned child during the rehabilitative phase of their care after injury. PMID:20634704

  15. Noninvasive fat quantification of the liver and pancreas may provide potential biomarkers of impaired glucose tolerance and type 2 diabetes

    PubMed Central

    Dong, Zhi; Luo, Yanji; Cai, Huasong; Zhang, Zhongwei; Peng, Zhenpeng; Jiang, Mengjie; Li, Yanbing; Li, Chang; Li, Zi-Ping; Feng, Shi-Ting

    2016-01-01

    Abstract The aim of the study is to investigate if the fat content of the liver and pancreas may indicate impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). A total of 83 subjects (34 men; aged 46.5 ± 13.5 years) were characterized as T2DM, IGT, or normal glucose tolerant (NGT). NGT individuals were stratified as <40 or ≥40 years. Standard laboratory tests were conducted for insulin resistance and β-cell dysfunction. The magnetic resonance imaging Dixon technique was used to determine fat distribution in the liver and pancreas. Correlations among liver and pancreatic fat volume fractions (LFVFs and PFVFs, respectively) and laboratory parameters were analyzed. Among the groups, fat distribution was consistent throughout sections of the liver and pancreas, and LFVFs closely correlated with PFVFs. LFVFs correlated more closely than PFVFs with insulin resistance and β-cell function. Both the LFVFs and PFVFs were the highest in the T2DM patients, less in the IGT, and least in the NGT; all differences were significant. The PFVFs of the NGT subjects ≥40 years were significantly higher than that of those <40 years. The fat content of the liver and pancreas, particularly the liver, may be a biomarker for IGT and T2DM. PMID:27281097

  16. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Geneviève; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical Aβ accumulation (2- and 3.5-fold increase in Aβ42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  17. A Novel Animal Model of Impaired Glucose Tolerance Induced by the Interaction of Vitamin E Deficiency and 60Co Radiation

    PubMed Central

    Guan, Yue; Cheng, Yan; Yin, Ying; Duan, Jialin; Wei, Guo; Weng, Yan; Guo, Chao; Zhu, Yanrong; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2015-01-01

    Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually induced by habits of life or environmental factors. Established IGT animal models are mostly conducted with chemical compounds such as streptozocin or genetic modification. However, the occasion of exposure to these factors in daily life is seldom. The objective of this study was to establish a new animal model of IGT induced by VE deficiency in diet and exposure to radiation. SD rats were treated individually or in combination of these two factors. In the combination group, the calculated insulin sensitivity index decreased; then HOMA-β value increased. Oxidative damage and IGT were observed. Insulin secretion level in perfusate from pancreas response to glucose was characterized by a rapid but reduced first phase and an obviously defective second phase upon pancreas perfusion. Histopathological images demonstrated the pathological changes. Western blotting analysis showed that the insulin signaling pathway was downregulated. The interaction of VE deficiency in diet and exposure to radiation could break the equilibrium of oxidation and antioxidation and result in IGT. More importantly, a new IGT model was successfully established which may be conducive to further research into development of drugs against human IGT. PMID:25954750

  18. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects. PMID:23982154

  19. Prevalence of diabetes mellitus and impaired glucose tolerance in a group of urban adults in Nigeria.

    PubMed Central

    Olatunbosun, S. T.; Ojo, P. O.; Fineberg, N. S.; Bella, A. F.

    1998-01-01

    This survey was undertaken to determine the prevalence of diabetes mellitus and impaired glucose tolerance in a group of urban adults in Ibadan, Nigeria. A total of 998 subjects randomly selected from five main ministries and departments in the Government Secretariat participated in the survey. Each subject was asked to fast overnight and ingested 75 g of glucose dissolved in 250 mL of water after answering a questionnaire. Relevant anthropometric measurements such as weight, height, waist and hip diameters, and blood pressure also were taken. After 2 hours, of blood was drawn and plasma glucose concentration measured. Diagnosis of diabetes or impaired glucose tolerance was based on 1985 World Health Organization (WHO) cut-off values. Blood glucose results were available in 875 subjects. Seven subjects were found to be diabetic for a prevalence of 0.8%, with the majority (5 subjects) being newly diagnosed. Nineteen were found to have impaired glucose tolerance for a prevalence of 2.2%. There were no sex differences between the two groups. All of the newly diagnosed diabetics were asymptomatic. Multivariate analysis revealed that subjects with a family history of diabetes, higher body mass index, and higher systolic blood pressure had higher blood glucose levels. The prevalence of diabetes in this survey is lower than rates reported in recent surveys in Nigeria that used less stringent criteria and different methodologies. The rate is comparable to that of a Tanzanian study that used WHO criteria. However, the rate of impaired glucose tolerance in this study, first to be reported in Nigeria, is lower than that obtained in the Bantu population. PMID:9617070

  20. Physicochemical characteristics of polysaccharide conjugates prepared from fresh tea leaves and their improving impaired glucose tolerance.

    PubMed

    Chen, Xiaoqiang; Fang, Yapeng; Nishinari, Katsuyoshi; We, Heng; Sun, Chaochao; Li, Jianrong; Jiang, Yongwen

    2014-11-01

    Hot-water extracts were prepared from fresh tea leaves and fractionated by DEAE-cellulose DE-52 column chromatography to yield one unexplored polysaccharide-conjugate fraction TPC-L (tea polysaccharide conjugates). Chemical components, molecular weight and its distribution, water vapor sorption properties, zeta potentials and optical characteristics of TPC-L were investigated. As compared with injured cell group, the two dosages of TPC-L (150 and 300 μg/mL) were discovered to possess remarkably protective effect on human umbilical vein endothelial cells against impairments induced by high glucose in a dose-dependent manner (p < 0.05, p < 0.001, respectively). Compared with group NC (normal control), the ingestion of 40 mg/kg of TPC-L could significantly reduce blood glucose levels of normal mice ingesting starch, and significant difference of AUC (area under the curve of blood glucose) and ΔAUC (p < 0.05, p < 0.01) at the postprandial time point of 0.5 and 1.0 h were observed. The three dosages of TPC-L (10, 40 and 160 mg/kg) did not significantly lower postprandial blood glucose levels of normal mice ingesting glucose. TPC-L could improve starch tolerance to prevent impaired glucose tolerance (IGT) from developing into diabetes as well as protective effects on HUVE cells against impairments induced by high glucose It was suggested that TPC-L improved IGT through its capability of inhibition on digestive enzymes. PMID:25129719

  1. Diabetes mellitus and impaired glucose tolerance are underdiagnosed in intensive care units

    PubMed Central

    Ladeira, Renata Teixeira; Simioni, Ana Cinthia Marques; Bafi, Antonio Tonete; Nascente, Ana Paula Metran; Freitas, Flavio Geraldo Resende; Machado, Flávia Ribeiro

    2012-01-01

    Objective To evaluate the presence of diabetes mellitus and impaired glucose tolerance in intensive care unit inpatients. Methods The study included patients in post-surgical care for elective and emergency surgery and excluded those patients with known diabetes mellitus. To diagnose prior serum glucose level disorders, we considered the value of glycated hemoglobin (HbA1c) at the time of admission, classifying the patients as normal (<5.7%), glucose intolerant (5.7-6.4%) or diabetic (>6.4%). During the first 3 days of the patient's hospital stay, glycemic control and clinical complications were assessed. Mortality was monitored for 28 days. For the statistical analyses, chi-square, ANOVA, student's t, Kruskal-Wallis or Mann Whitney tests were used. Results Thirty patients were included in the present study, 53% of whom were women; the patients had a mean age of 53.4±19.7 years and an APACHE II score of 13.6±6.6. The majority of patients were admitted for severe sepsis or septic shock followed by post-operative care for elective surgery, oncological surgery, multiple traumas and emergency surgery. When classifying these patients according to HbA1c, despite the absence of a prior history of diabetes mellitus, only 13.3% had a normal HbA1c level, 23.3% had levels compatible with the diagnosis of diabetes mellitus and 63.3% had levels compatible with impaired glucose tolerance. We found a significant association between the diagnosis of diabetes mellitus or impaired glucose tolerance and the use of vasoactive drugs (p=0.04). Conclusion A high prevalence of undiagnosed diabetes mellitus and impaired glucose tolerance was observed in inpatients at a general intensive care unit. PMID:23917931

  2. Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice.

    PubMed

    Zeidler, A; Tosco, C; Kumar, D; Slavin, B; Parker, J

    1982-09-01

    Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P less than 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P less than 0.05). We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice. The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems. PMID:6761217

  3. The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study.

    PubMed

    Krysiak, Robert; Okrzesik, Joanna; Okopien, Boguslaw

    2015-05-01

    Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55-3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy. PMID:25239203

  4. Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats.

    PubMed

    Kim, Yonwook J; Bi, Sheng

    2016-01-15

    Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes. PMID:26561644

  5. Neurogenin 3-Specific Dipeptidyl Peptidase-2 Deficiency Causes Impaired Glucose Tolerance, Insulin Resistance, and Visceral Obesity

    PubMed Central

    Danilova, Olga V.; Tai, Albert K.; Mele, Deanna A.; Beinborn, Martin; Leiter, Andrew B.; Greenberg, Andrew S.; Perfield, James W.; DeFuria, Jason; Singru, Praful S.; Lechan, Ronald M.; Huber, Brigitte T.

    2009-01-01

    The control of glucose metabolism is a complex process, and dysregulation at any level can cause impaired glucose tolerance and insulin resistance. These two defects are well-known characteristics associated with obesity and onset of type 2 diabetes. Here we introduce the N-terminal dipeptidase, DPP2, as a novel regulator of the glucose metabolism. We generated mice with a neurogenin 3 (NGN3)-specific DPP2 knockdown (kd) to explore a possible role of DPP2 in maintaining metabolic homeostasis. These mice spontaneously developed hyperinsulinemia, glucose intolerance, and insulin resistance by 4 months of age. In addition, we observed an increase in food intake in DPP2 kd mice, which was associated with a significant increase in adipose tissue mass and enhanced liver steatosis but no difference in body weight. In accordance with these findings, the mutant mice had a higher rate of respiratory exchange than the control littermates. This phenotype was exacerbated with age and when challenged with a high-fat diet. We report, for the first time, that DPP2 enzyme activity is essential for preventing hyperinsulinemia and maintaining glucose homeostasis. Interestingly, the phenotype of NGN3-DPP2 kd mice is opposite that of DPP4 knockout mice with regard to glucose metabolism, namely the former have normal glucagon-like peptide 1 levels but present with glucose intolerance, whereas the latter have increased glucagon-like peptide 1, which is accompanied by augmented glucose tolerance. PMID:19819973

  6. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose.

    PubMed

    Goossens, Gijs H; Moors, Chantalle C M; Jocken, Johan W E; van der Zijl, Nynke J; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E

    2016-03-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [²H₂]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-(13)C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  7. [Optimization of diet therapy in patients with gallstones complicated with obesity and impaired glucose tolerance].

    PubMed

    Kurbanov, S K

    2003-01-01

    It was investigated the influence of a diet with lower glycaemic index on clinico-metabolic parameters in obese patients with gallstones and impaired glucose tolerance. The results investigations indicated that the lowering of glycaemic index and the caloric reduction of diet have a beneficial effects on dynamic of parameters of functional status of liver and gallbladder. It was noted the increase of medical effect of diet in correction of obesity and impaired parameters of carbohydrate and lipid metabolism in this patients in process of dietotherapy. PMID:14619611

  8. Sustained Decrease of Early-Phase Insulin Secretion in Japanese Women with Gestational Diabetes Mellitus Who Developed Impaired Glucose Tolerance and Impaired Fasting Glucose Postpartum

    PubMed Central

    Katayama, Hiroko; Tachibana, Daisuke; Hamuro, Akihiro; Misugi, Takuya; Motoyama, Koka; Morioka, Tomoaki; Fukumoto, Shinya; Emoto, Masanori; Inaba, Masaaki; Koyama, Masayasu

    2015-01-01

    OBJECTIVE The aim of this study was to compare glucose intolerance in the antenatal and the postpartum periods using a 75-g oral glucose tolerance test (OGTT) in the Japanese women with gestational diabetes mellitus (GDM) using a retrospective design. PATIENTS AND METHODS Data were obtained from 85 Japanese women with GDM who delivered from April 2011 through April 2015 and who underwent an OGTT 6–14 weeks postpartum. The women were divided into two groups based on the results of the postpartum OGTT: one group with normal glucose tolerance (NGT) and the other with impaired glucose tolerance (IGT) as well as impaired fasting glucose (IFG). We analyzed the associations between postpartum IGT–IFG and various factors. RESULTS Antenatally, a significant difference was observed between the groups only in the 1-hour plasma glucose level of the 75-g OGTT. Postpartum results of plasma glucose level were significantly higher at 0.5, 1, and 2 hours in the IGT–IFG group than those in the NGT group. Moreover, a significant decrease in the levels of 0.5-hour immunoreactive insulin and insulinogenic index was observed in the IGT–IFG group compared to those in the NGT group. Homeostasis model assessment-insulin resistance and homeostasis model assessment β-cell function of both groups were found to significantly decrease in the postpartum period; however, there was no significant change in the insulinogenic index of either group. CONCLUSIONS Our study clearly showed that the postpartum IGT and IFG levels of Japanese women with GDM are affected by impaired early-phase insulin secretion; however, insulin resistance promptly improves. PMID:26688669

  9. Effects of Different Proportion of Carbohydrate in Breakfast on Postprandial Glucose Excursion in Normal Glucose Tolerance and Impaired Glucose Regulation Subjects

    PubMed Central

    Kang, Xin; Wang, Chun; Lifang, Lv; Chen, Dawei; Yang, Yanzhi; Liu, Guanjian; Wen, Hu; Chen, Lihong; He, Liping; Li, Xiujun; Tian, Haoming; Jia, Weiping

    2013-01-01

    Abstract Background The variability of postprandial plasma glucose is an independent risk factor for diabetes. The type and amount of carbohydrate may be important determinants of glycemic control. The aim of the study was to compare the effects of different proportions of carbohydrate in breakfast on postprandial blood glucose fluctuations in impaired glucose regulation (IGR) and normal glucose tolerance (NGT) subjects. Subjects and Methods This is a cross-sectional study of two groups including 55 subjects with IGR and 78 individuals with NGT. Their recorded breakfast was sorted into low-carbohydrate (LC) (carbohydrate <45%), medium-carbohydrate (MC) (carbohydrate 45–65%), and high-carbohydrate (HC) (carbohydrate >65%) meals according to the proportion of carbohydrate. Glucose concentrations were continuously measured with a continuous glucose monitoring system, and parameters such as the incremental area under the curve (iAUC) of glucose and postprandial glucose excursion (PPGE) were calculated to evaluate postprandial glucose fluctuations. Results The postprandial fluctuations of glucose increased gradually with increased proportions of carbohydrate in breakfast in both IGR and NGT subjects. For the MC and HC meals, iAUC, PPGE, postprandial glucose spike (PGS), and mean blood glucose were significantly greater than those in the NGT group (P<0.05), respectively. The median time to PGS and the time period in which glucose concentrations decreased to baseline after the MC and HC meals in the IGR group were significantly longer than those in the NGT group (P<0.01), respectively. Compared with the NGT subjects for the HC meal, the IGR subjects consuming the MC meal had greater PGS, range of glucose concentrations, SD, and PPGE (P<0.05). Conclusions The proportion of carbohydrate in breakfast contributes to glucose excursions in the NGT and IGR subjects. In the IGR subjects, a HC meal should be avoided and a LC meal should be recommended to prevent development of

  10. Poor sleep quality is associated with impaired glucose tolerance in women after gestational diabetes.

    PubMed

    Ferrari, U; Künzel, H; Tröndle, K; Rottenkolber, M; Kohn, D; Fugmann, M; Banning, F; Weise, M; Sacco, V; Hasbargen, U; Hutter, S; Parhofer, K G; Kloiber, S; Ising, M; Seissler, J; Lechner, A

    2015-06-01

    We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM. PMID:25930074

  11. Endothelin-1 as a predictor of impaired glucose tolerance and type 2 diabetes - A longitudinal study in the Vara-Skövde Cohort.

    PubMed

    Olausson, Josefin; Daka, Bledar; Hellgren, Margareta I; Larsson, Charlotte A; Petzold, Max; Lindblad, Ulf; Jansson, Per-Anders

    2016-03-01

    We addressed whether endothelin-1, a marker of endothelial dysfunction, predicts impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in a population study in south-western Sweden. Follow-up after 9.7 years showed an association between circulating endothelin-1 levels at baseline and development of IGT/T2DM in women but not in men. PMID:26972958

  12. Dosakaya Juice Assuages Development of Sucrose Induced Impaired Glucose Tolerance and Imbalance in Antioxidant Defense

    PubMed Central

    Kumar, Dommati Anand; Sweeya, Pisupati S. R.; Shukla, Srishti; Anusha, Sanga Venkata; Akshara, Dasari; Madhusudana, Kuncha; Tiwari, Ashok Kumar

    2015-01-01

    Objective: The objective was to explore the effect of Dosakaya (DK) (Cucumis melo var. chito) juice on sucrose induced dysglycemia and disturbances in antioxidant defense in rats. Materials and Methods: Rats were preconditioned with DK juice before administration of sucrose beverage continuously for 1-month. Blood glucose tolerance test and glutathione (GSH) homeostasis pathways in kidney were analyzed in different group of animals at the end of the study. Results: DK juice diffused (P < 0.001) hypertriglyceridemia inducing effect of sucrose and arrested sucrose induced weight gain. It improved glucose tolerance ability by significantly reducing (P < 0.05) first-hour glycemic excursion and decreasing 2 h glycemic load (P < 0.05) following oral glucose tolerance test in sucrose fed animals. Furthermore, disturbances in antioxidant defense mechanisms in terms of GSH homeostasis in kidney were restored due to juice feeding. DK juice administration checked reduction in GSH-S-transferase and glyoxalase-I activity, thus, significantly mitigated lipid peroxidation (P < 0.05), and formation of advanced glycation end-products (P < 0.001) in kidney and serum (P < 0.01). Quantitative analysis of juice found it a rich source of protein and polyphenols. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the presence of multiple protein bands in whole fruit juice. Therefore, SDS-PAGE protein fingerprint of DK juice may serve as a quality control tool for standardization of juice. Conclusion: The whole fruit juice of DK may become cost-effective, affordable health beverage in extenuating ill-health effects of sugar consumption. This is the first report identifying DK juice in preventing development dysglycemia, dyslipidemia, and oxidative stress induced due to chronic sucrose feeding in rats. SUMMARY Chronic sucrose consumption induced development of dysglycemia and also impaired antioxidant defense mechanism in rats. The oral administration of

  13. The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance.

    PubMed

    Krysiak, R; Gilowski, W; Okopien, B

    2015-11-01

    No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone. PMID:26600057

  14. Frequency of impaired glucose tolerance and diabetes mellitus in subjects with fasting blood glucose below 6.1 mmol/L (110 mg/dL).

    PubMed

    Khan, S H; Ijaz, A; Bokhari, S A Raza; Hanif, M S; Azam, N

    2013-02-01

    The diagnosis of diabetes mellitus by the available criteria is controversial and relies heavily on fasting glucose results. This cross-sectional study in 2010-2011 aimed to measure the frequency of impaired glucose tolerance and diabetes mellitus in 127 subjects having fasting blood glucose < 7.0 mmol/L and to measure the agreement between different standard diagnostic criteria. Subjects presenting to a laboratory for analysis of fasting blood glucose for excluding diabetes mellitus underwent a 2-hour 75 g oral glucose challenge. A total of 40.6% of subjects with fasting blood glucose from 5.6-6.0 mmol/L had abnormal glucose regulation on the basis ofthe gold standard glucose challenge. Agreement between American Diabetes Association and World Health Organization diagnostic criteria was only fair (kappa = 0.32). Abnormalities of glucose metabolism including impaired glucose tolerance and diabetes mellitus can exist at fasting blood glucose results < 6.1 mmol/L (110 mg/dL). PMID:23516829

  15. Overexpression of a proton-coupled vacuolar glucose exporter impairs freezing tolerance and seed germination.

    PubMed

    Klemens, Patrick A W; Patzke, Kathrin; Trentmann, Oliver; Poschet, Gernot; Büttner, Michael; Schulz, Alexander; Marten, Irene; Hedrich, Rainer; Neuhaus, H Ekkehard

    2014-04-01

    Arabidopsis vacuoles harbor, besides sugar transporter of the TMT-type, an early response to dehydration like 6 (ERDL6) protein involved in glucose export into the cytosol. However, the mode of transport of ERDL6 and the plant's feedback to overexpression of its activity on essential properties such as, for example, seed germination or freezing tolerance, remain unexplored. Using patch-clamp studies on vacuoles expressing AtERDL6 we demonstrated directly that this carrier operates as a proton-driven glucose exporter. Overexpression of BvIMP, the closest sugar beet (Beta vulgaris) homolog to AtERDL6, in Arabidopsis leads surprisingly to impaired seed germination under both conditions, sugar application and low environmental temperatures, but not under standard conditions. Upon cold treatment, BvIMP overexpressor plants accumulated lower quantities of monosaccharides than the wild-type, a response in line with the reduced frost tolerance of the transgenic Arabidopsis plants, and the fact that cold temperatures inhibits BvIMP transcription in sugar beet leaves. With these findings we show that the tight control of vacuolar sugar import and export is a key requisite for cold tolerance and seed germination of plants. PMID:24329902

  16. Effects of sugar-sweetened beverage intake on the development of type 2 diabetes mellitus in subjects with impaired glucose tolerance: the Mihama diabetes prevention study.

    PubMed

    Teshima, Nobuko; Shimo, Miho; Miyazawa, Kae; Konegawa, Sachi; Matsumoto, Aki; Onishi, Yuki; Sasaki, Ryoma; Suzuki, Toshinari; Yano, Yutaka; Matsumoto, Kazutaka; Yamada, Tomomi; Gabazza, Esteban Cesar; Takei, Yoshiyuki; Sumida, Yasuhiro

    2015-01-01

    In Japan, the incidence of type 2 diabetes mellitus (T2DM) is increasing for several reasons, including increased consumption of sugar-sweetened beverages (SSBs). However, whether SSBs cause T2DM by excess of energy production resulting in obesity remains unclear. Therefore, the present study was designed to evaluate the effects of SSB intake on the development of T2DM in subjects with impaired glucose tolerance (IGT). Ninety-three subjects (30 males and 63 females) with IGT aged 40-69 y and residing in the Mihama district (southern Mie Prefecture, Japan) were included in the study. The mean observational period was 3.6 y. All subjects underwent the 75-g oral glucose tolerance test (OGTT) and completed a lifestyle questionnaire survey related to SSB intake. OGTT results and SSB intake were evaluated before and after the observational period. In addition, the correlation between SSB intake and development of T2DM was investigated. Of the 93 subjects, 20 (21.5%) developed T2DM (T2DM group) and demonstrated a significantly high SSB intake compared with the group that did not develop the disease (non-T2DM group). The odds ratio for the incidence of T2DM based on SSB intake was 3.26 (95% confidence interval, 1.17-9.06). The body mass index (BMI; kg/m(2)) and the homeostasis model assessment for insulin resistance (HOMA-R) values was significantly higher in the T2DM group than in the non-T2DM group, while the insulinogenic indices were significantly lower in the former than in the latter group. The sum of insulin secretion levels during OGTT was not significantly different between groups. SSB intake correlated with the predisposition for developing T2DM, possibly by influencing body weight, insulin resistance, and the ability of the pancreatic beta cells to effectively compensate for the insulin resistance. PMID:25994135

  17. Impaired glucose tolerance plus hyperlipidaemia induced by diet promotes retina microaneurysms in New Zealand rabbits

    PubMed Central

    Helfenstein, Tatiana; Fonseca, Francisco A; Ihara, Sílvia S; Bottós, Juliana M; Moreira, Flávio T; Pott, Henrique; Farah, Michel E; Martins, Maria C; Izar, Maria C

    2011-01-01

    With the increasing prevalence of diabetes mellitus and metabolic syndrome worldwide, experimental models are required to better understand the pathophysiology and therapeutic approaches to preserve pancreatic beta cells, attenuate atherosclerosis and protect target organs. The aims of this study were to develop an experimental model of impaired glucose tolerance combined with hypercholesterolaemia induced by diet and assess metabolic alterations and target organ lesions. New Zealand male rabbits were fed high-fat/high-sucrose (10/40%) and cholesterol-enriched diet for 24 weeks, when they were sacrificed. Biochemistry, fundus photographs with fluorescein angiography and pathological analyses were performed. Cholesterol-fed and normal animals of same age were compared. Results: The animals with diet-induced impaired glucose tolerance combined with hypercholesterolaemia gained weight, increased blood glucose, total cholesterol, LDL-C and triglycerides and decreased HDL-C (P<0.05 vs. baseline). Fructosamine levels and the homeostasis model assessment of insulin resistance (HOMA-IR) index were increased, while there was a reduction in the HOMA-β (P<0.05 for all vs. baseline). Histomorphologic findings of this model were aortic atherosclerosis, hepatic steatofibrosis and glomerular macrophage infiltration. Early clinical features of diabetic retinopathy with hyperfluorescent dots consistent with presence of retina microaneurysms were seen since week 12, progressing up to the end of the experiment (P<0.0005 vs. baseline and 12 weeks). Our model reproduced several metabolic characteristics of human diabetes mellitus and promoted early signs of retinopathy. This non-expensive model is suitable for studying mechanistic pathways and allowing novel strategic approaches. PMID:21272105

  18. Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study

    PubMed Central

    2014-01-01

    Background Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. Methods In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). Results 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients

  19. MR Quantification of Total Liver Fat in Patients with Impaired Glucose Tolerance and Healthy Subjects

    PubMed Central

    Zhang, Zhongwei; Cai, Huasong; Li, Yanbing; Chan, Tao; Wu, Ling; Li, Zi-Ping; Feng, Shi-Ting

    2014-01-01

    Objective To explore the correlations between liver fat content and clinical index in patients with impaired glucose tolerance (IGT) and healthy subjects. Materials and Methods 56 subjects were enrolled and each of them underwent upper-abdominal MRI examination that involved a T1 VIBE Dixon sequence. 14 was clinically diagnosed with IGT (collectively as IGT group ) while 42 showed normal glucose tolerance,(collectively as NGT group). NGT group was further divided into NGTFat (BMI≥25, 18 subjects) and NGTLean (BMI<25, 24 subjects). The total liver fat contents was measured and compared with clinical findings and laboratory results in order to determine statistical correlations between these parameters. Differences among IGT, NGTFat and NGTLean groups were evaluated. Results For all the subjects, fat volume fractions (FVFs) ranged from 4.2% to 24.2%, positive correlations was observed with BMI, waist hip ratio(WHR), low density lipoprotein(LDL), fasting plasma insulin(FPI), homeostasis model assessment insulin resistance (HOMA-IR) and homeostasis model assessment β(HOMAβ). FVFs of IGT group (p = 0.004) and NGTFat group (p = 0.006) were significantly higher than those of NGTLean group. Conclusions People with higher BMI, WHR and LDL levels tend to have higher liver fat content. Patients with BMI≥25 are more likely to develop IGT. Patients with higher FVF showed higher resistance to insulin, thus obtained a higher risk of developing type 2 diabetes mellitus. PMID:25343445

  20. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test. PMID:25342307

  1. Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg{sup 65}{yields}His) not associated with impaired glucose tolerance: The contribution of mutant proinsulin to insulin bioactivity

    SciTech Connect

    Roder, M.E.; Vissing, H.; Nauck, M.A.

    1996-04-01

    Familial hyperproinsulinemia is a genetic abnormality characterized by an increased proportion of proinsulin immunoreactivity in the circulation due to mutations affecting the posttranslational processing of proinsulin. In affected Japanese families, this has been associated with noninsulin-dependent diabetes mellitus or impaired glucose tolerance. A three-generation Caucasian family with hyperproinsulinemia was identified through unexplained hyperinsulinemia in a normal volunteer participating in a metabolic study. High pressure liquid chromatography analysis of fasting plasma revealed a major peak eluting close to the position of proinsulin. Direct sequencing of the proinsulin gene exon 3 showed a heterozygous point mutation (CGT{yields}CAT) resulting in the substitution of Arg{yields}His in position 65 (corresponding to the AC cleavage site) in the index case, his mother, and his maternal grandmother. All affected subjects had normal oral glucose tolerance. In the basal state and after oral glucose administration, their proinsulin responses were slightly reduced. However, when calculating insulin bioactivity by assuming 9% activity for mutant Arg{sup 65}{yields}His proinsulin, responses in affected subjects were comparable to those in normal subjects. In conclusion, our data demonstrate hyperproinsulinemia in a three-generation Caucasian family due to heterozygous mutant Arg{sup 65}{yields}His proinsulin. This was not associated with impaired glucose tolerance. These results suggest that this mutation in the heterozygous state per se does not affect glucose tolerance and that the biological activity of mutant proinsulin contributes to glucose homeostasis in this family. The association of the same mutation with impaired glucose tolerance or diabetes in previous studies may be the result of selection bias or associated conditions (e.g. the genetic background of the kindreds examined). 29 refs., 5 figs., 3 tabs.

  2. The Preventive Effect of Zuogui Wan on Offspring Rats' Impaired Glucose Tolerance Whose Mothers Had Gestational Diabetes Mellitus

    PubMed Central

    Feng, Qianjin; Niu, Xin; Xu, Kaixia; Wang, Yingli; Wang, Jinlong; Mao, Yingqiu; Gao, Shuangrong

    2016-01-01

    In this experiment, we used streptozotocin (STZ) to establish a model of gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats. After pregnancy, offspring rats were divided into 4 groups: control group, high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were fed with high fat and sugar diet. Rats in control group were fed the basic diet. The means of 2hPG were higher than 7.8 mmol·L−1 and lower than 11.1 mmol·L−1 on the rats of GDM group on week 15, and IGT models were successful. Body weight, abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM group. The level of adiponectin in Zuogui Wan GDM group was significantly higher than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a preventive effect on the offsprings' IGT induced by high fat and sugar diet. PMID:27034700

  3. The Preventive Effect of Zuogui Wan on Offspring Rats' Impaired Glucose Tolerance Whose Mothers Had Gestational Diabetes Mellitus.

    PubMed

    Wang, Yuwei; Feng, Qianjin; Niu, Xin; Xu, Kaixia; Wang, Yingli; Wang, Jinlong; Li, Qiuju; Mao, Yingqiu; Gao, Shuangrong

    2016-01-01

    In this experiment, we used streptozotocin (STZ) to establish a model of gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats. After pregnancy, offspring rats were divided into 4 groups: control group, high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were fed with high fat and sugar diet. Rats in control group were fed the basic diet. The means of 2hPG were higher than 7.8 mmol·L(-1) and lower than 11.1 mmol·L(-1) on the rats of GDM group on week 15, and IGT models were successful. Body weight, abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM group. The level of adiponectin in Zuogui Wan GDM group was significantly higher than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a preventive effect on the offsprings' IGT induced by high fat and sugar diet. PMID:27034700

  4. Effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance related to beta-3 adrenergic receptor gene polymorphism Trp64Arg(C/T): Results from the Japan Diabetes Prevention Program.

    PubMed

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Takahashi, Kaoru; Kuzuya, Hideshi

    2016-05-01

    The beta-3 adrenergic receptor (ADRB3), primarily expressed in adipose tissue, is involved in the regulation of energy metabolism. The present study hypothesized that ADRB3 (Trp64Arg, rs4994) polymorphisms modulate the effects of lifestyle intervention on weight and metabolic parameters in patients with impaired glucose tolerance. Data were analyzed from 112 patients with impaired glucose tolerance in the Japan Diabetes Prevention Program, a lifestyle intervention trial, randomized to either an intensive lifestyle intervention group or usual care group. Changes in weight and metabolic parameters were measured after the 6-month intervention. The ADRB3 polymorphisms were determined using the polymerase chain reaction restriction fragment length polymorphism method. Non-carriers showed a greater weight reduction compared with the carriers in both the lifestyle intervention group and usual care group, and a greater increase of high-density lipoprotein cholesterol levels than the carriers only in the lifestyle intervention group. ADRB3 polymorphisms could influence the effects of lifestyle interventions on weight and lipid parameters in impaired glucose tolerance patients. PMID:27330719

  5. Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

    PubMed Central

    Reinert-Hartwall, Linnea; Honkanen, Jarno; Salo, Harri M.; Nieminen, Janne K.; Luopajärvi, Kristiina; Härkönen, Taina; Veijola, Riitta; Simell, Olli; Ilonen, Jorma; Peet, Aleksandr; Tillmann, Vallo; Knip, Mikael; Knip, Mikael; Koski, Katriina; Koski, Matti; Härkönen, Taina; Ryhänen, Samppa; Hämäläinen, Anu-Maaria; Ormisson, Anne; Peet, Aleksandr; Tillmann, Vallo; Ulich, Valentina; Kuzmicheva, Elena; Mokurov, Sergei; Markova, Svetlana; Pylova, Svetlana; Isakova, Marina; Shakurova, Elena; Petrov, Vladimir; Dorshakova, Natalya V.; Karapetyan, Tatyana; Varlamova, Tatyana; Ilonen, Jorma; Kiviniemi, Minna; Alnek, Kristi; Janson, Helis; Uibo, Raivo; Salum, Tiit; von Mutius, Erika; Weber, Juliane; Ahlfors, Helena; Kallionpää, Henna; Laajala, Essi; Lahesmaa, Riitta; Lähdesmäki, Harri; Moulder, Robert; Nieminen, Janne; Ruohtula, Terhi; Vaarala, Outi; Honkanen, Hanna; Hyöty, Heikki; Kondrashova, Anita; Oikarinen, Sami; Harmsen, Hermie J. M.; De Goffau, Marcus C.; Welling, Gjalt; Alahuhta, Kirsi; Virtanen, Suvi M.

    2015-01-01

    Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions. PMID:25480564

  6. Progression to Impaired Glucose Regulation and Diabetes in the Population-Based Inter99 Study

    PubMed Central

    Engberg, Susanne; Vistisen, Dorte; Lau, Cathrine; Glümer, Charlotte; Jørgensen, Torben; Pedersen, Oluf; Borch-Johnsen, Knut

    2009-01-01

    OBJECTIVE The purpose of this study was to estimate the progression rates to impaired glucose regulation (impaired fasting glucose or impaired glucose tolerance) and diabetes in the Danish population–based Inter99 study and in a high-risk subpopulation, separately. RESEARCH DESIGN AND METHODS From a population-based primary prevention study, the Inter99 study, 4,615 individuals without diabetes at baseline and with relevant follow-up data were divided into a low- and a high-risk group based on a risk estimate of ischemic heart disease or the presence of risk factors (smoking, hypertension, hypercholesterolemia, obesity, or impaired glucose tolerance). High-risk individuals (57.1%) were examined with an oral glucose tolerance test at 1 and 3 years, and all of the participants were reexamined at the 5-year follow-up. Person-years at risk were calculated. Progression rates to impaired glucose regulation and diabetes were estimated directly from baseline to the 5-year follow-up for all the participants and from baseline through the 1- and 3- to 5-year follow-up examinations for the high-risk individuals, separately. RESULTS In the combined low- and high-risk group, 2.1 individuals per 100 person-years progressed from normal glucose tolerance (NGT) to impaired glucose regulation or diabetes. Among high-risk individuals, 5.8 per 100 person-years with NGT progressed to impaired glucose regulation or diabetes, and 4.9 per 100 person-years progressed from impaired glucose regulation to diabetes. CONCLUSIONS Progression rates to impaired glucose regulation using the current World Health Organization classification criteria were calculated for the first time in a large European population-based study. The progression rates to diabetes show the same pattern as seen in the few similar European studies. PMID:19114617

  7. Autonomic Neuropathy and Endothelial Dysfunction in Patients With Impaired Glucose Tolerance or Type 2 Diabetes Mellitus.

    PubMed

    Tiftikcioglu, Bedile Irem; Bilgin, Sule; Duksal, Tarik; Kose, Sukran; Zorlu, Yasar

    2016-04-01

    Autonomic neuropathy is one of the most common complications of diabetes mellitus (DM). The etiology of autonomic impairment is not well-understood, yet. There is need for studies to investigate the cause-effect relationships of inflammation and/or endothelial dysfunction and diabetic autonomic neuropathy. Only a few reports have mentioned autonomic neuropathy in individuals with impaired glucose tolerance (IGT), previously. Furthermore, the association between the plasma markers of endothelial dysfunction (von Willebrand factor (vWF), soluble E-selectin) and autonomic neuropathy in patients with IGT or DM has not been studied before. In this study, we aimed to investigate the correlation between plasma markers of endothelial dysfunction and autonomic neuropathy in patients with IGT or type 2 DM (T2DM).In this case-control study, 25 IGT patients, 25 T2DM patients with autonomic symptoms, and 30 controls were included. Demographical data, HbA1c, vWF, and soluble E-selectin (sE-selectin) levels were analyzed. Sympathetic skin response (SSR) and heart rate variability (HRV) were used as the indicator of autonomic activity.Plasma levels of HbA1c, vWF, and sE-selectin were higher in patients with IGT than the controls; patients with T2DM had higher levels than both the controls and the patients with IGT. SSR measures were similar among the groups. However, higher number of T2DM patients had absent plantar SSR than controls. HRV analysis at rest revealed lower standard deviation of R-R interval, coefficient of variation of R-R interval, low-frequency (LF) power and total power in patients with IGT and T2DM than the controls. In addition, HRV analysis at deep breathing showed lower high-frequency (HF) power in IGT group. LF:HF ratio was lower in both patient groups at rest. No strong correlation was found between the levels of HbA1c, vWF, sE-selectin, HRV, and SSR measures.Our results support that endothelial dysfunction is evident in individuals with IGT or T2DM and HRV

  8. [HbA1c is not enough in screening for impaired glucose metabolism. Glucose tolerance tests are also needed, as shown in Swedish prospective epidemiological study].

    PubMed

    Hellgren, Margareta; Daka, Bledar; Larsson, Charlotte

    2015-01-01

    An HbA1c threshold of ≥ 42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended. PMID:26418933

  9. The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance.

    PubMed

    Hsu, Tai-Hao; Lee, Chien-Hsing; Lin, Fang-Yi; Wasser, Solomon P; Lo, Hui-Chen

    2014-01-01

    The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance. PMID:24872934

  10. Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

    PubMed Central

    George, Anish; Bhatia, Raghav T.; Buchanan, Gill L.; Whiteside, Anne; Moisey, Robert S.; Beer, Stephen F.; Chattopadhyay, Sudipta; Sathyapalan, Thozhukat; John, Joseph

    2015-01-01

    Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. PMID:26571120

  11. The relationship of plasma glucose and electrocardiographic parameters in elderly women with different degrees of glucose tolerance.

    PubMed

    Solini, A; Passaro, A; D'Elia, K; Calzoni, F; Alberti, L; Fellin, R

    2000-08-01

    Plasma glucose has been regarded as a risk factor for macrovascular complications in diabetes, but less is known about its role in the development of cardiac impairment other than coronary heart disease (CHD). The aim of our study was to determine the relationship between basal and post-OGTT (Oral Glucose Tolerance Test) plasma glucose levels and some ECG parameters in a group of elderly women with normal or impaired glucose tolerance (IGT). One-hundred and one women with normal fasting glucose (<6.0 mmol/L) and no familial history or clinical signs of CHD and diabetes underwent an OGTT and a resting ECG. Based on the degree of glucose tolerance, we identified 24 women with a diagnostic OGTT for either IGT or diabetes; the 77 women (age range 52-88 years) with normal glucose tolerance were further divided into two groups according to their post-OGTT area under the curve (AUCG): below and above the median value (32 and 45 women, respectively). Basal plasma glucose and insulin levels, as well as lipid profile and percent of hypertensive patients were similar in the three groups. Mean corrected QT (QTc) was prolonged as a function of progressive worsening of glucose tolerance even after adjustment for possible confounding factors (p=0.03). A similar relationship was apparent when post-OGTT plasma glucose peak (GP) was considered. In a multiple regression analysis, AUCG and GP were the only factors independently related to both QTc and Sokolow index. Our observations suggest that, even in the presence of a normal glucose tolerance, plasma glucose concentrations during an OGTT are associated with peculiar ECG signs potentially combined with an increased risk of sudden death, arrhythmias, or cardiovascular mortality. PMID:11073343

  12. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

    PubMed Central

    SAITO, Mikako; KANEDA, Asako; SUGIYAMA, Tae; IIDA, Ryousuke; OTOKUNI, Keiko; KABURAGI, Misako; MATSUOKA, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk+/− mice ranged from 0.41–0.68 versus that in wild (Gk+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk+/− strain fed the CD, and Gk+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk+/− strain developed in this study. PMID:25765873

  13. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men

    PubMed Central

    Yokokawa, Hirohide; Naito, Toshio; Sasabe, Noriko; Okumura, Mitsue; Iijima, Kimiko; Shibuya, Katsuhiko; Hisaoka, Teruhiko; Fukuda, Hiroshi

    2016-01-01

    Background Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. Methods The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan’s metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Results Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). Conclusions It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders

  14. Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research)

    PubMed Central

    Yang, Guang; Li, Chunlin; Gong, Yanping; Fang, Fusheng; Tian, Hui; Li, Jian; Cheng, Xiaoling

    2016-01-01

    Aim. To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM). Methods. 5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed. Results. The M values of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg·kg−1·min−1, 6.23 ± 1.73 mg·kg−1·min−1, 6.37 ± 2.12 mg·kg−1·min−1, and 6.19 ± 1.89 mg·kg−1·min−1, respectively. M values in HINS, IGT, and T2DM groups were lower than those in the NGT group (P = 0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P = 0.835). The independent factors influencing the M value were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with the M value (P < 0.01). Conclusion. IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS. PMID:26770991

  15. Long-Term Feeding of Chitosan Ameliorates Glucose and Lipid Metabolism in a High-Fructose-Diet-Impaired Rat Model of Glucose Tolerance

    PubMed Central

    Liu, Shing-Hwa; Cai, Fang-Ying; Chiang, Meng-Tsan

    2015-01-01

    This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF) diet (63.1%). Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups: (1) normal group (normal); (2) HF group; (3) chitosan + HF group (HF + C). The rats were fed the experimental diets and drinking water ad libitum for 21 weeks. The results showed that chitosan (average molecular weight was about 3.8 × 105 Dalton and degree of deacetylation was about 89.8%) significantly decreased body weight, paraepididymal fat mass, and retroperitoneal fat mass weight, but elevated the lipolysis rate in retroperitoneal fats of HF diet-fed rats. Supplementation of chitosan causes a decrease in plasma insulin, tumor necrosis factor (TNF)-α, Interleukin (IL)-6, and leptin, and an increase in plasma adiponectin. The HF diet increased hepatic lipids. However, intake of chitosan reduced the accumulation of hepatic lipids, including total cholesterol (TC) and triglyceride (TG) contents. In addition, chitosan elevated the excretion of fecal lipids in HF diet-fed rats. Furthermore, chitosan significantly decreased plasma TC, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), the TC/high-density lipoprotein cholesterol (HDL-C) ratio, and increased the HDL-C/(LDL-C + VLDL-C) ratio, but elevated the plasma TG and free fatty acids concentrations in HF diet-fed rats. Plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected by the HF diet, but it was significantly increased in chitosan-supplemented, HF-diet-fed rats. The high-fructose diet induced an increase in plasma glucose and impaired glucose tolerance, but chitosan supplementation decreased plasma glucose and improved impairment of glucose tolerance and insulin tolerance. Taken together, these results indicate that supplementation with chitosan can improve the impairment of

  16. Impaired glucose tolerance after brief heat exposure: a randomized crossover study in healthy young men.

    PubMed

    Faure, Cécile; Charlot, Keyne; Henri, Stéphane; Hardy-Dessources, Marie-Dominique; Hue, Olivier; Antoine-Jonville, Sophie

    2016-06-01

    A high demand on thermoregulatory processes may challenge homoeostasis, particularly regarding glucose regulation. This has been understudied, although it might concern millions of humans. The objective of this project was to examine the isolated and combined effects of experimental short-term mild heat exposure and metabolic level on glucoregulation. Two experimental randomized crossover studies were conducted. Ten healthy young men participated in study A, which comprises four sessions in a fasting state at two metabolic levels [rest and exercise at 60% of maximal oxygen uptake (O2) for 40 min] in two environmental temperatures (warm: 31°C and control: 22°C). Each session ended with an ad libitum meal, resulting in similar energy intake across sessions. In study B, 12 healthy young men underwent two 3 h oral glucose tolerance tests (OGTTs) in warm and control environmental temperatures. Venous blood was sampled at several time points. In study A, repeated measure ANOVAs revealed higher postprandial serum glucose and insulin levels with heat exposure. Glycaemia following the OGTT was higher in the warm temperature compared with control. The kinetics of the serum glucose response to the glucose load was also affected by the environmental temperature (temperature-by-time interaction, P=0.030), with differences between the warm and control conditions observed up to 90 min after the glucose load (all P<0.033). These studies provide evidence that heat exposure alters short-term glucoregulation. The implication of this environmental factor in the physiopathology of Type 2 diabetes has yet to be investigated. PMID:26980346

  17. Evaluation of Fasting State-/Oral Glucose Tolerance Test-Derived Measures of Insulin Release for the Detection of Genetically Impaired β-Cell Function

    PubMed Central

    Heni, Martin; Ketterer, Caroline; Guthoff, Martina; Kantartzis, Konstantinos; Machicao, Fausto; Stefan, Norbert; Häring, Hans-Ulrich; Fritsche, Andreas

    2010-01-01

    Background To date, fasting state- and different oral glucose tolerance test (OGTT)-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced) fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. Methodology/Principal Findings A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs) known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05). The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset) were summed up resulting in a final ranking. This approach revealed area under the curve (AUC)Insulin(0-30)/AUCGlucose(0-30) as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUCInsulin(0-30)/AUCGlucose(0-30), corrected insulin response (CIR), AUCC-Peptide(0-30)/AUCGlucose(0-30), AUCC-Peptide(0-120)/AUCGlucose(0-120), two different formulas for the incremental insulin response from 0–30 min, i.e., the insulinogenic indices (IGI)2 and IGI1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05). AUCC-Peptide(0-120)/AUCGlucose(0-120) was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. Conclusions/Significance With AUCInsulin(0-30)/AUCGlucose(0

  18. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance

    PubMed Central

    Eriksson, Maria J.; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R.; Caidahl, Kenneth

    2015-01-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima–media thickness in the radial and carotid arteries, echogenicity of the carotid intima–media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  19. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance.

    PubMed

    Ring, Margareta; Eriksson, Maria J; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R; Caidahl, Kenneth

    2015-09-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima-media thickness in the radial and carotid arteries, echogenicity of the carotid intima-media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  20. Change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance.

    PubMed

    Popp Switzer, Maryna; Elhanafi, Sherif; San Juan, Zinnia T

    2015-03-01

    Patients with pre-diabetes have a tenfold higher risk of developing Type 2 DM and a twofold higher risk of developing coronary heart disease compared to non-diabetics. Interventions targeted at those in an early stage of impaired glucose metabolism can delay or prevent diabetes. Effects of these interventions on cardiovascular outcome are unknown. This article aims to review current and available data on lifestyle intervention, specifically physical activity, on cardiovascular outcomes in populations at risk for diabetes. We searched PubMed database from 1990 to present with focus on more recent literature published over the last 2 years. Various permutations of keywords used included glucose intolerance, pre-diabetes, diabetes, lifestyle modifications, physical activity, and cardiovascular disease. Intensive glycemic control, specific medications, and lifestyle intervention including increase in physical activity have been evaluated in diabetes and pre-diabetes. Most studies we reviewed showed that these interventions prevented progression of pre-diabetes to diabetes and improved cardiovascular risk surrogate measures. Direct decrease in cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarctions was shown in one recent trial. Increase in physical activity has a positive effect on decreasing cardiovascular risk by modifying several important risk factors and may decrease risk of events in pre-diabetics. More randomized high power trials are needed to verify and characterize these effects. PMID:25638410

  1. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  2. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis

    PubMed Central

    Abrams, Keith R; Lambert, Paul C; Cooper, Nicola J; Sutton, Alex J; Hsu, Ron T; Khunti, Kamlesh

    2007-01-01

    Objective To quantify the effectiveness of pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance. Data sources Medline, Embase, and the Cochrane library searched up to July 2006. Expert opinions sought and reference lists of identified studies and any relevant published reviews checked. Study selection Randomised controlled trials that evaluated interventions to delay or prevent type 2 diabetes in individuals with impaired glucose tolerance. Results 21 trials met the inclusion criteria, of which 17, with 8084 participants with impaired glucose tolerance, reported results in enough detail for inclusion in the meta-analyses. From the meta-analyses the pooled hazard ratios were 0.51 (95% confidence interval 0.44 to 0.60) for lifestyle interventions v standard advice, 0.70 (0.62 to 0.79) for oral diabetes drugs v control, 0.44 (0.28 to 0.69) for orlistat v control, and 0.32 (0.03 to 3.07) for the herbal remedy jiangtang bushen recipe v standard diabetes advice. These correspond to numbers needed to treat for benefit (NNTB) and harm (NNTH) of 6.4 for lifestyle (95% credible interval, NNTB 5.0 to NNTB 8.4), 10.8 for oral diabetes drugs (NNTB 8.1 to NNTB 15.0), 5.4 for orlistat (NNTB 4.1 to NNTB 7.6), and 4.0 for jiangtang bushen (NNTH 16.9 to NNTB 24.8). Conclusions Lifestyle and pharmacological interventions reduce the rate of progression to type 2 diabetes in people with impaired glucose tolerance. Lifestyle interventions seem to be at least as effective as drug treatment. PMID:17237299

  3. Glucose tolerance test - non-pregnant

    MedlinePlus

    Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test ... The most common glucose tolerance test is the oral glucose tolerance test (OGTT). Before the test begins, a sample of blood will be taken. You will then ...

  4. Cost-Effectiveness of a Short Message Service Intervention to Prevent Type 2 Diabetes from Impaired Glucose Tolerance

    PubMed Central

    Wong, Carlos K. H.; Jiao, Fang-Fang; Siu, Shing-Chung; Fung, Colman S. C.; Fong, Daniel Y. T.; Wong, Ka-Wai; Yu, Esther Y. T.; Lo, Yvonne Y. C.; Lam, Cindy L. K.

    2016-01-01

    Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider's perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880. PMID:26798647

  5. Cost-Effectiveness of a Short Message Service Intervention to Prevent Type 2 Diabetes from Impaired Glucose Tolerance.

    PubMed

    Wong, Carlos K H; Jiao, Fang-Fang; Siu, Shing-Chung; Fung, Colman S C; Fong, Daniel Y T; Wong, Ka-Wai; Yu, Esther Y T; Lo, Yvonne Y C; Lam, Cindy L K

    2016-01-01

    Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider's perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880. PMID:26798647

  6. DEXA MEASURED VISCERAL ADIPOSE TISSUE PREDICTS IMPAIRED GLUCOSE TOLERANCE AND METABOLIC SYNDROME IN OBESE CAUCASIAN AND AFRICAN AMERICAN WOMEN

    PubMed Central

    Bi, X; Seabolt, L; Shibao, C; Buchowski, M; Kang, H; Keil, CD; Tyree, R; Silver, HJ

    2016-01-01

    Background and Aims New methods to measure visceral adipose tissue (VAT) by DEXA may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed to: a) compare relationships between cardiometabolic risk factors and DEXA-VAT, anthropometric and body composition measures; b) determine thresholds for DEXA-VAT by race; and c) determine the most robust predictors of impaired glucose tolerance (IGT) and metabolic syndrome (MetSx) in obese women. Methods VAT area (cm2) was measured using Lunar iDXA scanner in 229 obese (BMI 30-49.9) women age 21–69 years of European American (EA = 123) and African American (AA = 106) descent. Linear regression modeling and areas under the curve (AUC) compared relationships with cardiometabolic risk. Bootstrapping with LASSO regression modeling determined thresholds and predictors of IGT and MetSx. Results DEXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and HOMA-IR compared to anthropometric and body composition variables. DEXA-VAT had the highest AUC for IGT (0.767) and MetSx (0.749). Including race and interactionXrace terms in modeling did not significantly change results. Thresholds at which probability was ≥ 50% for IGT or MetSx were lower in AA women (IGT: 2120cm2 AA vs 2550cm2 EA; MetSx: 1320cm2 AA vs 1713cm2 EA). The odds for IGT or MetSx was 3-fold greater with each standard deviation increase in DEXA-VAT. Conclusion DEXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA women and has great potential in risk reduction efforts. PMID:25335442

  7. Association between blood glucose level derived using the oral glucose tolerance test and glycated hemoglobin level

    PubMed Central

    Kim, Hyoung Joo; Kim, Young Geon; Park, Jin Soo; Ahn, Young Hwan; Ha, Kyoung Hwa; Kim, Dae Jung

    2016-01-01

    Background/Aims: Glycated hemoglobin (HbA1c) is widely used as a marker of glycemic control. Translation of the HbA1c level to an average blood glucose level is useful because the latter figure is easily understood by patients. We studied the association between blood glucose levels revealed by the oral glucose tolerance test (OGTT) and HbA1c levels in a Korean population. Methods: A total of 1,000 subjects aged 30 to 64 years from the Cardiovascular and Metabolic Diseases Etiology Research Center cohort were included. Fasting glucose levels, post-load glucose levels at 30, 60, and 120 minutes into the OGTT, and HbA1c levels were measured. Results: Linear regression of HbA1c with mean blood glucose levels derived using the OGTT revealed a significant correlation between these measures (predicted mean glucose [mg/dL] = 49.4 × HbA1c [%] − 149.6; R2 = 0.54, p < 0.001). Our linear regression equation was quite different from that of the Alc-Derived Average Glucose (ADAG) study and Diabetes Control and Complications Trial (DCCT) cohort. Conclusions: Discrepancies between our results and those of the ADAG study and DCCT cohort may be attributable to differences in the test methods used and the extent of insulin secretion. More studies are needed to evaluate the association between HbA1c and self monitoring blood glucose levels. PMID:26898598

  8. Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance.

    PubMed

    Méndez-Del Villar, Miriam; Puebla-Pérez, Ana M; Sánchez-Peña, María J; González-Ortiz, Luis J; Martínez-Abundis, Esperanza; González-Ortiz, Manuel

    2016-05-01

    To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P < .05), A1C (5.8 ± 0.3 vs. 5.6% ± 0.4%, P < .05), AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P < .05), and total insulin secretion (0.45 ± 0.23 vs. 0.35 ± 0.18, P < .05), with a significant increase in high-density lipoprotein cholesterol (HDL-C) (1.3 ± 0.3 vs. 1.4 ± 0.3 mmol/L, P < .05). There were no significant differences after placebo administration. A. dracunculus administration for 90 days in patients with IGT significantly decreased SBP, A1C, AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels. PMID:27097076

  9. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    PubMed

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice. PMID:27255361

  10. Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status

    PubMed Central

    Schöttl, Theresa; Kappler, Lisa; Fromme, Tobias; Klingenspor, Martin

    2015-01-01

    Objective Several human and rodent obesity studies speculate on a causal link between altered white adipocyte mitochondria in the obese state and changes in glucose homeostasis. We here aimed to dissect whether alterations in white adipocyte mitochondrial respiratory function are a specific phenomenon of obesity or impaired glucose tolerance or both. Methods Mature white adipocytes were purified from posterior subcutaneous and intraabdominal epididymal fat of four murine obesity models characterized by either impaired or normal oral glucose tolerance. Bioenergetic profiles, including basal, leak, and maximal respiration, were generated using high-resolution respirometry. Cell respiratory control ratios were calculated to evaluate mitochondrial respiratory function. Results Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance. Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat. Conclusion Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance. PMID:26413469

  11. Acarbose for the prevention of Type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data.

    PubMed

    Chiasson, J-L; Josse, R G; Gomis, R; Hanefeld, M; Karasik, A; Laakso, M

    2004-06-01

    The STOP-NIDDM Trial has shown that acarbose treatment in subjects with impaired glucose tolerance is associated with a significant risk reduction in the development of diabetes, hypertension and cardiovascular complications. Kaiser and Sawicki have accused the investigators of the STOP-NIDDM Trial of major biases in the conduct of the study, of manipulating the data and of conflict of interest. The aim of this paper is to present data and explanations refuting these allegations. In the STOP-NIDDM Trial, 61 subjects were excluded from the efficacy analysis before unblinding for legitimate reasons: failure to satisfy major entry criteria (n=17) and lack of post-randomisation data (n=44). Blinding and randomisation were carried out by an independent biostatistician. Titration of placebo/acarbose is well described in the protocol and in the study design paper. Of the study population, 9.3% had a fasting plasma glucose of > or =7.0 mmol/l at screening and could have been diabetic according to the new diagnostic criteria. However, even if these subjects are excluded, patients having acarbose treatment still saw a significant risk reduction in the development of diabetes (p=0.0027). The changes in weight are consistent in different publications and are related to different times of follow-up and assessment. Weight change does have an effect on the development of diabetes, but acarbose treatment is still effective even after adjusting for this (p=0.0063). The cardiovascular endpoints were a clearly designated assessment in the original protocol, and only those defined in the protocol and ascertained by the independent Cardiovascular Event Adjudication Committee were used in the analysis. Hypertension was defined according to the most recent diagnostic criteria. The STOP-NIDDM Trial results are scientifically sound and credible. The investigators stand strongly behind these results demonstrating that acarbose treatment is associated with a delay in the development of

  12. Efficacy of bofu-tsusho-san, an oriental herbal medicine, in obese Japanese women with impaired glucose tolerance.

    PubMed

    Hioki, Chizuko; Yoshimoto, Kanji; Yoshida, Toshihide

    2004-09-01

    1. In the present study, we conducted the first randomized, double-blind, placebo-controlled study of bofu-tsusho-san (BF), an oriental herbal medicine (24 mg/day ephedrine in Ephedrae Herba and an efficacy equivalent of 280 mg caffeine, judging from the phosphodiesterase-inhibitory effect of Glycyrrhizae Radix, Forsythiae Fructus and Schizonepetae Spica and another 14 crude drugs) in obese women with impaired glucose tolerance (IGT). 2. The aim of the present study was to determine whether BF was effective in decreasing visceral adiposity and insulin resistance. Eighty-one Japanese women (body mass index (BMI) 36.5 +/- 4.8 kg/m2) with IGT and insulin resistance (IR), who had been treated with a low-calorie diet (5016 kj/day: 1200 kcal) and an exercise regimen (1254 kj/day: 300 kcal), were randomized to receive either placebo (n=40) or BF treatment (n=41) three times a day. 3. After 24 weeks treatment, the BF group lost significantly (P <0.01) more bodyweight and abdominal visceral fat without a decrease in the adjusted resting metabolic rate (RMR), whereas the placebo group lost bodyweight (P <0.05) and had no significant change in abdominal visceral fat. The BF group had a lower fasting serum insulin level (P <0.05), a lower insulin area under the curve (P <0.05) and a lower level of the homeostasis model assessment of insulin resistance (P <0.01) compared with values before treatment. 4. We conclude that BF could be a useful herbal medicine in treating obesity with IGT. PMID:15479169

  13. Seven-Day Caloric and Saturated Fat Restriction Increases Myocardial Dietary Fatty Acid Partitioning in Impaired Glucose-Tolerant Subjects.

    PubMed

    Noll, Christophe; Kunach, Margaret; Frisch, Frédérique; Bouffard, Lucie; Dubreuil, Stéphanie; Jean-Denis, Farrah; Phoenix, Serge; Cunnane, Stephen C; Guérin, Brigitte; Turcotte, Eric E; Carpentier, André C

    2015-11-01

    Subjects with impaired glucose tolerance (IGT) have increased myocardial partitioning of dietary fatty acids (DFAs) with left ventricular dysfunction, both of which are improved by modest weight loss over 1 year induced by lifestyle changes. Here, we determined the effects of a 7-day hypocaloric diet (-500 kcal/day) low in saturated fat (<7% of energy) (LOWCAL study) versus isocaloric with the usual amount saturated fat (∼10% of energy) diet (ISOCAL) on DFA metabolism in subjects with IGT. Organ-specific DFA partitioning and cardiac and hepatic DFA fractional uptake rates were measured in 15 IGT subjects (7 males/8 females) using the oral 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid positron emission tomography method after 7 days of an ISOCAL diet versus a LOWCAL diet using a randomized crossover design. The LOWCAL diet led to reductions in weight and postprandial insulin area under the curve. Myocardial DFA partitioning over 6 h was increased after the LOWCAL diet (2.3 ± 0.1 vs. 1.9 ± 0.2 mean standard uptake value, P < 0.04). However, the early (90-120 min) myocardial DFA fractional uptake was unchanged after the LOWCAL diet (0.055 ± 0.025 vs. 0.046 ± 0.009 min(-1), P = 0.7). Liver DFA partitioning was unchanged, but liver fractional uptake of DFA tended to be increased. Very short-term caloric and saturated fat dietary restrictions do not lead to the same changes in organ-specific DFA metabolism as those associated with weight loss in subjects with IGT. PMID:26224886

  14. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

  15. Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.

    PubMed

    Leandro, João G B; Espindola-Netto, Jair M; Vianna, Maria Carolina F; Gomez, Lilian S; DeMaria, Thaina M; Marinho-Carvalho, Monica M; Zancan, Patricia; Paula Neto, Heitor A; Sola-Penna, Mauro

    2016-03-28

    Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity. PMID:26863933

  16. Glucose screening and tolerance tests during pregnancy

    MedlinePlus

    Oral glucose tolerance test - pregnancy (OGTT); Glucose challenge test - pregnancy ... For the glucose screening test: You do not need to prepare or change your diet in any way. You will be asked to drink a ...

  17. Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues.

    PubMed

    Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

    2016-01-01

    Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months' supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake. PMID:27194405

  18. Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

    PubMed Central

    Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

    2016-01-01

    Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months’ supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake. PMID:27194405

  19. Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin

    PubMed Central

    Eastwood, S. V.; Tillin, T.; Mayet, J.; Shibata, D. K.; Wright, A.; Heasman, J.; Beauchamp, N.; Forouhi, N. G.; Hughes, A. D.; Chaturvedi, N.

    2015-01-01

    Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South-Asian origin. Methods For 682 European and 520 South-Asian men and women, aged 58–85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist–hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P=0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the

  20. Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

    PubMed

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2016-06-01

    The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. PMID:27160199

  1. PICK1 and ICA69 control insulin granule trafficking and their deficiencies lead to impaired glucose tolerance.

    PubMed

    Cao, Mian; Mao, Zhuo; Kam, Chuen; Xiao, Nan; Cao, Xiaoxing; Shen, Chong; Cheng, Kenneth K Y; Xu, Aimin; Lee, Kwong-Man; Jiang, Liwen; Xia, Jun

    2013-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which blocks vesicle budding from the Golgi, increased the amount of PICK1 and ICA69 at TGN. On the other hand, mature secretory granules were associated with PICK1 only, not ICA69. PICK1 deficiency in mice caused the complete loss of ICA69 and led to increased food and water intake but lower body weight. Glucose tolerance tests demonstrated that these mutant mice had high blood glucose, a consequence of insufficient insulin. Importantly, while the total insulin level was reduced in PICK1-deficient beta cells, proinsulin was increased. Lastly, ICA69 knockout mice also displayed similar phenotype as the mice deficient in PICK1. Together, our results indicate that PICK1 and ICA69 are key regulators of the formation and maturation of insulin granules. PMID:23630453

  2. Glucose tolerance test - non-pregnant

    MedlinePlus

    ... have pre-diabetes or diabetes: A 2 hour value between 140 and 200 mg/dL is called impaired glucose tolerance. Your doctor may call this "pre-diabetes." It means you are at increased risk of developing diabetes over time. A glucose level ...

  3. High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers

    PubMed Central

    Roujun, Chen; Yanhua, Yi; Bixun, Li

    2016-01-01

    Objective: The prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were hypothesised to be different among different tumor patients. This study aimed to study the association between the prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer, cervical cancer, nasopharyngeal cancer and benign tumor. Methods:  A hospital based retrospective study was conducted on 4610 patients admitted to the Internal Medical Department of the Affiliated Tumor Hospital of Guangxi Medical University, China. Logistic regression was used to examine the association between gender, age group, ethnicity , cancer types or benign tumors and prevalence of DM, IFG, IGT. Results: Among 4610 patients, there were 1000 liver cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients, 230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7% and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%, respectively, in colorectal cancer patients, significantly higher than that of benign cancers. After adjusting for gender, age group, and ethnicity, the prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66) and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively. Conclusion: There was a high prevalence of DM and IGT in liver cancer patients. PMID:27610222

  4. Comparison of Glucose Tolerance Categories in the Korean Population According to World Health Organization and American Diabetes Association Diagnostic Criteria

    PubMed Central

    Park, Kyong Soo; Park, Young Joo; Kim, Sun Wook; Shin, Chan Soo; Park, Do Joon; Koh, Jae Joon; Kim, Seong Yeon; Kim, No Keyong; Lee, Hong Kyu

    2000-01-01

    Objectives To compare the prevalence and metabolic profiles of glucose tolerance categories according to World Health Organization(WHO) and 1997 American Diabetes Association (ADA) fasting criteria for the diagnosis of diabetes mellitus and impaired glucose metabolism in the Korean population. Methods 2251 subjects without previous history of diabetes, who participated in the Yonchon diabetes epidemiology survey in 1993, were classified according to both criteria. The prevalence of glucose tolerance categories and the agreement across all categories of glucose tolerance were calculated. Metabolic characteristics of different glucose tolerance categories were compared. Results The prevalence of diabetes and impaired fasting glucose (IFG) according to ADA fasting criteria was similar to those of diabetes and impaired glucose tolerance (IGT) according to WHO criteria, respectively. However, 35.5 % of the subjects who were diagnosed as diabetes by WHO criteria were reclassified as either IFG or normal fasting glucose (NFG), and 38.5 % of diabetic patients according to ADA fasting criteria were IGT or normal glucose tolerance (NGT) by WHO criteria. Only 31.3 % of IGT subjects remained as IFG and 62.1 % were reclassified as NFG. Similarly, 69.4 % of IFG subjects were NGT by WHO criteria. The agreement between the two criteria was poor (K =0.31). Discordant diabetes groups had higher WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than concordant non-diabetes group. Non-diabetes(WHO)/diabetes(ADA) group had higher WHR than diabetes (WHO)/non-diabetes (ADA) group. There were no differences in other metabolic characteristics between the two discordant diabetes groups. IGT/NFG and NGT/IFG group showed higher BMI, WHR, systolic and diastolic blood pressure, cholesterol and triglyceride levels than NGT/NFG group. Metabolic characteristics of IGT/NFG group were not different from those of NGT/IFG group except IGT/NFG subjects were older than NGT

  5. β-Cell Function, Incretin Effect, and Incretin Hormones in Obese Youth Along the Span of Glucose Tolerance From Normal to Prediabetes to Type 2 Diabetes

    PubMed Central

    Michaliszyn, Sara F.; Mari, Andrea; Lee, SoJung; Bacha, Fida; Tfayli, Hala; Farchoukh, Lama; Ferrannini, Ele

    2014-01-01

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired β-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled β-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. β-Cell function parameters were derived from established mathematical models yielding β-cell glucose sensitivity (βCGS), rate sensitivity, and insulin sensitivity in 255 obese adolescents (173 with normal glucose tolerance [NGT], 48 with impaired glucose tolerance [IGT], and 34 with type 2 diabetes [T2D]). The incretin effect was calculated as the ratio of the OGTT-βCGS to the 2-h hyperglycemic clamp-βCGS. Incretin and glucagon concentrations were measured during the OGTT. Compared with NGT, βCGS was 30 and 65% lower in youth with IGT and T2D, respectively; rate sensitivity was 40% lower in T2D. Youth with IGT or T2D had 32 and 38% reduced incretin effect compared with NGT in the face of similar changes in GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) in response to oral glucose. We conclude that glucose sensitivity deteriorates progressively in obese youth across the spectrum of glucose tolerance in association with impairment in incretin effect without reduction in GLP-1 or GIP, similar to that seen in adult dysglycemia. PMID:24947360

  6. PICK1 and ICA69 Control Insulin Granule Trafficking and Their Deficiencies Lead to Impaired Glucose Tolerance

    PubMed Central

    Kam, Chuen; Xiao, Nan; Cao, Xiaoxing; Shen, Chong; Cheng, Kenneth K. Y.; Xu, Aimin; Lee, Kwong-Man; Jiang, Liwen; Xia, Jun

    2013-01-01

    Diabetes is a metabolic disorder characterized by hyperglycemia. Insulin, which is secreted by pancreatic beta cells, is recognized as the critical regulator of blood glucose, but the molecular machinery responsible for insulin trafficking remains poorly defined. In particular, the roles of cytosolic factors that govern the formation and maturation of insulin granules are unclear. Here we report that PICK1 and ICA69, two cytosolic lipid-binding proteins, formed heteromeric BAR-domain complexes that associated with insulin granules at different stages of their maturation. PICK1-ICA69 heteromeric complexes associated with immature secretory granules near the trans-Golgi network (TGN). A brief treatment of Brefeldin A, which blocks vesicle budding from the Golgi, increased the amount of PICK1 and ICA69 at TGN. On the other hand, mature secretory granules were associated with PICK1 only, not ICA69. PICK1 deficiency in mice caused the complete loss of ICA69 and led to increased food and water intake but lower body weight. Glucose tolerance tests demonstrated that these mutant mice had high blood glucose, a consequence of insufficient insulin. Importantly, while the total insulin level was reduced in PICK1-deficient beta cells, proinsulin was increased. Lastly, ICA69 knockout mice also displayed similar phenotype as the mice deficient in PICK1. Together, our results indicate that PICK1 and ICA69 are key regulators of the formation and maturation of insulin granules. Author Summary Insulin is a key regulator of blood glucose and insufficient insulin leads to diabetes. Insulin is synthesized as proinsulin, processed in endoplasmic reticulum and Golgi, and eventually packaged into insulin granules, a type of dense core vesicles. Despite its importance, the molecular mechanisms governing the biogenesis and maturation of insulin granules are not fully understood. In this study, we identified two cytosolic proteins, PICK1 and ICA69, as important regulators of insulin granule

  7. Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene

    PubMed Central

    2015-01-01

    The G-protein-coupled sweet taste receptor dimer T1R2/T1R3 is expressed in taste bud cells in the oral cavity. In recent years, its involvement in membrane glucose sensing was discovered in endocrine cells regulating glucose homeostasis. We investigated importance of extraorally expressed T1R3 taste receptor protein in age-dependent control of blood glucose homeostasis in vivo, using nonfasted mice with a targeted mutation of the Tas1r3 gene that encodes the T1R3 protein. Glucose and insulin tolerance tests, as well as behavioral tests measuring taste responses to sucrose solutions, were performed with C57BL/6ByJ (Tas1r3+/+) inbred mice bearing the wild-type allele and C57BL/6J-Tas1r3tm1Rfm mice lacking the entire Tas1r3 coding region and devoid of the T1R3 protein (Tas1r3-/-). Compared with Tas1r3+/+ mice, Tas1r3-/- mice lacked attraction to sucrose in brief-access licking tests, had diminished taste preferences for sucrose solutions in the two-bottle tests, and had reduced insulin sensitivity and tolerance to glucose administered intraperitoneally or intragastrically, which suggests that these effects are due to absence of T1R3. Impairment of glucose clearance in Tas1r3-/- mice was exacerbated with age after intraperitoneal but not intragastric administration of glucose, pointing to a compensatory role of extraoral T1R3-dependent mechanisms in offsetting age-dependent decline in regulation of glucose homeostasis. Incretin effects were similar in Tas1r3+/+ and Tas1r3-/- mice, which suggests that control of blood glucose clearance is associated with effects of extraoral T1R3 in tissues other than the gastrointestinal tract. Collectively, the obtained data demonstrate that the T1R3 receptor protein plays an important role in control of glucose homeostasis not only by regulating sugar intake but also via its extraoral function, probably in the pancreas and brain. PMID:26107521

  8. [Diabetes in the Belgian province of Luxembourg: frequency, importance of the oral glucose tolerance test and a modestly increased fasting blood glucose].

    PubMed

    Hortulanus-Beck, D; Lefebvre, P J; Jeanjean, M F

    1990-01-01

    A sample of 1949 subjects aged 35-64 years has been studied in the Belgian Province of Luxembourg according with the MONICA project (MONItoring of Trends and Determinants in CArdiovascular Diseases) elaborated by the World Health Organization. Among the data collected, were a fasting glycaemia and a glycaemia at the second hour of a 75 grams oral glucose load. Analysis of these two parameters has allowed to divide the individuals of the study into: 4.1% of diabetic subjects which half of them being unknown, 5.2% of subjects presenting an impaired glucose tolerance, 3.4% of subjects with an early reactive hypoglycaemia and 87.3% of normoglycaemic subjects. The measurement of the fasting glycaemia alone has allowed to display 15 glucidic abnormalities (that is to say 0.8%) whereas the complementary realization of the oral glucose tolerance test has disclosed about 10% of additional abnormalities. The fact to consider a borderline fasting glycaemia (included between 110 and 140 mg/dl on venous plasma) result in a greater probability to find an abnormal blood glucose value at the second hour of the oral glucose tolerance test. PMID:2265736

  9. The effect of fat removal on glucose tolerance is depot specific in male and female mice.

    PubMed

    Shi, Haifei; Strader, April D; Woods, Stephen C; Seeley, Randy J

    2007-10-01

    Energy is stored predominately as lipid in white adipose tissue (WAT) in distinct anatomical locations, with each site exerting different effects on key biological processes, including glucose homeostasis. To determine the relative contributions of subcutaneous and visceral WAT on glucose homeostasis, comparable amounts of adipose tissue from abdominal subcutaneous inguinal WAT (IWAT), intra-abdominal retroperitoneal WAT (RWAT), male gonadal epididymal WAT (EWAT), or female gonadal parametrial WAT (PWAT) were removed. Gonadal fat removal in both male and female chow-fed lean mice resulted in lowered glucose levels across glucose tolerance tests. Female lean C57BL/6J mice as well as male and female lean FVBN mice significantly improved glucose tolerance, indicated by decreased areas under glucose clearance curves. For the C57BL/6J mice maintained on a high-fat butter-based diet, glucose homeostasis was improved only in female mice with PWAT removal. Removal of IWAT or RWAT did not affect glucose tolerance in either dietary condition. We conclude that WAT contribution to glucose homeostasis is depot specific, with male gonadal EWAT contributing to glucose homeostasis in the lean state, whereas female gonadal PWAT contributes to glucose homeostasis in both lean and obese mice. These data illustrate both critical differences among various WAT depots and how they influence glucose homeostasis and highlight important differences between males and females in glucose regulation. PMID:17652151

  10. Decreased thioredoxin-1 and increased HSP90 expression in skeletal muscle in subjects with type 2 diabetes or impaired glucose tolerance.

    PubMed

    Venojärvi, M; Korkmaz, A; Aunola, S; Hällsten, K; Virtanen, K; Marniemi, J; Halonen, J-P; Hänninen, O; Nuutila, P; Atalay, M

    2014-01-01

    In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) (n = 10) were compared with subjects with impaired glucose tolerance (IGT) (n = 8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower (P = 0.031) and HSP90 was 380% higher (P < 0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research. PMID:24689038

  11. Circulating MiRNAs of ‘Asian Indian Phenotype’ Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes

    PubMed Central

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians—an ethnic population characterized to represent ‘Asian Indian phenotype’ known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a ‘New Lead’ in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes. PMID:26020947

  12. Circulating MiRNAs of 'Asian Indian Phenotype' Identified in Subjects with Impaired Glucose Tolerance and Patients with Type 2 Diabetes.

    PubMed

    Prabu, Paramasivam; Rome, Sophie; Sathishkumar, Chandrakumar; Aravind, Sankaramoorthy; Mahalingam, Balakumar; Shanthirani, Coimbatore Subramanian; Gastebois, Caroline; Villard, Audrey; Mohan, Viswanathan; Balasubramanyam, Muthuswamy

    2015-01-01

    Several omics technologies are underway worldwide with an aim to unravel the pathophysiology of a complex phenotype such as type 2 diabetes mellitus (T2DM). While recent studies imply a clinically relevant and potential biomarker role of circulatory miRNAs in the etiology of T2DM, there is lack of data on this aspect in Indians--an ethnic population characterized to represent 'Asian Indian phenotype' known to be more prone to develop T2DM and cardiovascular disease than Europeans. We performed global serum miRNA profiling and the validation of candidate miRNAs by qRT-PCR in a cohort of subjects comprised of normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and patients with T2DM. Our study revealed 4 differentially expressed miRNAs (miR-128, miR-130b-3p, miR-374a-5p, miR-423-5p) in subjects with IGT and T2DM patients compared to control subjects. They were positively or negatively correlated to cholesterol levels, HbA1C, HOMA-IR and fasting insulin. Interestingly, circulating level of miR-128 and miR-130b-3p were also altered in serum of diet-induced diabetic mice compared to control animals. Among the altered circulating miRNAs, miR-128 had never been described in previous studies/populations and appeared to be a 'New Lead' in Indians. It was positively correlated with cholesterol both in prediabetic subjects and in diet-induced diabetic mice, suggesting that its increased level might be associated with the development of dyslipedemia associated with T2DM. Our findings imply directionality towards biomarker potential of miRNAs in the prevention/diagnosis/treatment outcomes of diabetes. PMID:26020947

  13. Involvement of pregnane X receptor in the impaired glucose utilization induced by atorvastatin in hepatocytes.

    PubMed

    Ling, Zhaoli; Shu, Nan; Xu, Ping; Wang, Fan; Zhong, Zeyu; Sun, Binbin; Li, Feng; Zhang, Mian; Zhao, Kaijing; Tang, Xiange; Wang, Zhongjian; Zhu, Liang; Liu, Li; Liu, Xiaodong

    2016-01-15

    Accumulating evidences demonstrated that statins impaired glucose utilization. This study was aimed to investigate whether PXR was involved in the atorvastatin-impaired glucose utilization. Rifampicin/PCN served as PXR activator control. Glucose utilization, glucose uptake, protein levels of GLUT2, GCK, PDK2, PEPCK1 and G6Pase in HepG2 cells were measured. PXR inhibitors, PXR overexpression and PXR siRNA were applied to verify the role of PXR in atorvastatin-impaired glucose utilization in cells. Hypercholesterolemia rats induced by high fat diet feeding, orally received atorvastatin (5 and 10 mg/kg), pravastatin (10 mg/kg) for 14 days, or intraperitoneally received PCN (35 mg/kg) for 4 days. Results showed that glucose utilization was markedly inhibited by atorvastatin, simvastatin, pitavastatin, lovastatin and rifampicin. Neither rosuvastatin nor pravastatin showed the similar effect. Atorvastatin and pravastatin were selected for the following study. Atorvastatin and rifampicin significantly inhibited glucose uptake and down-regulated GLUT2 and GCK expressions. Similarly, overexpressed PXR significantly down-regulated GLUT2 and GCK expressions and impaired glucose utilization. Ketoconazole and resveratrol attenuated the impaired glucose utilization by atorvastatin and rifampicin in both parental and overexpressed PXR cells. PXR knockdown significantly up-regulated GLUT2 and GCK proteins and abolished the decreased glucose consumption and uptake by atorvastatin and rifampicin. Animal experiments showed that atorvastatin and PCN significantly elicited postprandial hyperglycemia, leading to increase in glucose AUC. Expressions of GLUT2 and GCK in rat livers were markedly down-regulated by atorvastatin and PCN. In conclusion, atorvastatin impaired glucose utilization in hepatocytes via repressing GLUT2 and GCK expressions, which may be partly due to PXR activation. PMID:26616219

  14. Postprandial Differences in the Amino Acid and Biogenic Amines Profiles of Impaired Fasting Glucose Individuals after Intake of Highland Barley

    PubMed Central

    Liu, Liyan; Wang, Xinyang; Li, Ying; Sun, Changhao

    2015-01-01

    The aim of this study was to measure the postprandial changes in amino acid and biogenic amine profiles in individuals with impaired fasting glucose (IFG) and to investigate the changes of postprandial amino acid and biogenic amine profiles after a meal of highland barley (HB). Firstly, 50 IFG and 50 healthy individuals were recruited for the measurement of 2 h postprandial changes of amino acid and biogenic amine profiles after a glucose load. Secondly, IFG individuals received three different loads: Glucose (GL), white rice (WR) and HB. Amino acid and biogenic amine profiles, glucose and insulin were assayed at time zero and 30, 60, 90 and 120 min after the test load. The results showed fasting and postprandial amino acid and biogenic amine profiles were different between the IFG group and the controls. The level of most amino acids and their metabolites decreased after an oral glucose tolerance test, while the postprandial level of γ-aminobutyric acid (GABA) increased significantly in IFG individuals. After three different test loads, the area under the curve for glucose, insulin, lysine and GABA after a HB load decreased significantly compared to GL and WR loads. Furthermore, the postprandial changes in the level of GABA between time zero and 120 min during a HB load were associated positively with 2 h glucose and fasting insulin secretion in the IFG individuals. Thus, the HB load produced low postprandial glucose and insulin responses, which induced changes in amino acid and biogenic amine profiles and improved insulin sensitivity. PMID:26184292

  15. The influence on cognition of the interaction between the macro-nutrient content of breakfast and glucose tolerance.

    PubMed

    Nabb, Samantha; Benton, David

    2006-01-30

    Previously it has been found that both missing breakfast and having poorer glucose tolerance were associated with better memory. The present study therefore examined the impact of eight breakfasts, in a factorial design, that contained either high or low levels of carbohydrate, fat or protein. The meals were designed to vary the rate of release of glucose into the blood stream. Memory, reaction times and vigilance were assessed 30, 75 and 120 min following breakfast. Using fasting blood glucose levels as a measure of glucose tolerance, better memory was found to be associated with better glucose tolerance and the consumption of meals that more slowly release glucose into the blood. The effects of the meals on reaction times and vigilance were opposite to those with memory in that higher levels of blood glucose tended to be associated with better performance. It was concluded that individual differences in glucose tolerance interact with the glycaemic load of a meal to influence cognitive functioning. PMID:16225896

  16. Metabolic Syndrome Components and Their Response to Lifestyle and Metformin Interventions are Associated with Differences in Diabetes Risk in Persons with Impaired Glucose Tolerance

    PubMed Central

    Florez, Hermes; Temprosa, Marinella G; Orchard, Trevor J; Mather, Kieren J; Marcovina, Santica M; Barrett-Connor, Elizabeth; Horton, Edward; Saudek, Christopher; Pi-Sunyer, Xavier F; Ratner, Robert E; Goldberg, Ronald B

    2013-01-01

    Aims To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. Methods We used the NCEP/ATP III revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. Results In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95%CI) for diabetes in those with MetS (versus no MetS) at baseline were 1.7(1.3-2.3), 1.7(1.2-2.3), and 2.0(1.3-3.0) for placebo, metformin, and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favorable changes in WC (placebo and lifestyle) and HDLc (placebo and metformin) contributed to reduced diabetes risk. Conclusions MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycemia, the most predictive factors for diabetes were baseline hypertriglyceridemia and both baseline and lifestyle-associated changes in waist circumference. Targeting these cardio-metabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence. PMID:24118860

  17. Relationship of impaired brain glucose metabolism to learning deficit in the senescence-accelerated mouse.

    PubMed

    Ohta, H; Nishikawa, H; Hirai, K; Kato, K; Miyamoto, M

    1996-10-11

    The relationship between brain glucose metabolism and learning deficit was examined in the senescence-accelerated-prone mouse (SAMP) 8, which has been proven to be a useful murine model of age-related behavioral disorders. SAMP8, 7 months old, exhibited marked learning impairment in the passive avoidance task, as compared with the control strain, senescence-accelerated-resistant mice (SAMR) 1. SAMP8 also exhibited a reduction in brain glucose metabolism, as indicated by a reduction in [14C]2-deoxyglucose accumulation in the brain following the intravenous injection impaired glucose metabolism correlated significantly with the learning impairment in all brain regions in SAMR1 and SAMP8. In the SAMP8, a significant correlation was observed in the posterior half of the cerebral cortex. These results suggest that the SAMP8 strain is a useful model of not only age-related behavioral disorders, but also glucose hypometabolism observed in aging and dementias. PMID:8905734

  18. Maternal inheritance of severe hypertriglyceridemia impairs glucose metabolism in offspring.

    PubMed

    Ma, Ya-Hong; Yu, Caiguo; Kayoumu, Abudurexiti; Guo, Xin; Ji, Zhili; Liu, George

    2015-04-01

    Maternally inherited familial hypercholesterolemia (FH) impairs glucose metabolism and increases cardiovascular risks in the offspring to a greater degree than paternal inherited FH. However, it remains unknown whether hypertriglyceridemia affects glucose metabolism via inheritance. In this study, we sought to compare the impact of maternally and paternally inherited hypertriglyceridemia on glucose and lipid metabolism in mice. ApoCIII transgenic mice with severe hypertriglyceridemia were mated with non-transgenic control mice to obtain 4 types of offspring: maternal non-transgenic control and maternal transgenic offspring, and paternal control and paternal transgenic offspring. Plasma triglycerides (TG), total cholesterol (TC), fasting plasma glucose (FPG) and fasting insulin (FINS) were measured. ApoCIII overexpression caused severe hypertriglyceridemia, but the transgenic female mice had unaltered fertility with normal pregnancy and birth of pups. The 4 groups of offspring had similar birth weight and growth rate. The plasma TG of maternal and paternal transgenic offspring were nearly 40-fold higher than maternal and paternal control mice, but there was no difference in plasma TG between maternal and paternal transgenic offspring. Although the FPG of the 4 groups of animals had no difference, the maternal transgenic mice showed impaired glucose tolerance, increased FINS levels and higher homeostasis model assessment insulin resistance index (HOMA-IR) than the other 3 groups. In conclusion, maternally inherited hypertriglyceridemia in ApoCIII transgenic mice displayed impaired glucose tolerance, hyperinsulinemia and increased HOMA-R, while paternally inherited hypertriglyceridemia did not have such impacts. PMID:25859267

  19. Association Between Cardiorespiratory Fitness and the Determinants of Glycemic Control Across the Entire Glucose Tolerance Continuum

    PubMed Central

    Malin, Steven K.; Karstoft, Kristian; Knudsen, Sine H.; Haus, Jacob M.; Laye, Matthew J.; Kirwan, John P.

    2015-01-01

    OBJECTIVE Cardiorespiratory fitness (VO2max) is associated with glycemic control, yet the relationship between VO2max and the underlying determinants of glycemic control is less clear. Our aim was to determine whether VO2max is associated with insulin sensitivity, insulin secretion, and the disposition index, a measure of compensatory pancreatic β-cell insulin secretion relative to insulin sensitivity, in subjects representing the entire range of the glucose tolerance continuum. RESEARCH DESIGN AND METHODS A cohort of subjects (N = 313) with heterogeneous age, sex, BMI, and glycemic control underwent measurements of body composition, HbA1c, fasting glucose, oral glucose tolerance (OGTT), and VO2max. OGTT-derived insulin sensitivity (SiOGTT), glucose-stimulated insulin secretion (GSISOGTT), and the disposition index (DIOGTT) (the product of SiOGTT and GSISOGTT) were measured, and associations between VO2max and these determinants of glycemic control were examined. RESULTS A low VO2max was associated with high HbA1c (r = −0.33), high fasting glucose (r = −0.34), high 2-h OGTT glucose (r = −0.33), low SiOGTT (r = 0.73), and high early-phase (r = −0.34) and late-phase (r = −0.36) GSISOGTT. Furthermore, a low VO2max was associated with low early- and late-phase DIOGTT (both r = 0.41). Interestingly, relationships between VO2max and either glycemic control or late-phase GSISOGTT deteriorated across the glucose tolerance continuum. CONCLUSIONS The association between poor cardiorespiratory fitness and compromised pancreatic β-cell compensation across the entire glucose tolerance continuum provides additional evidence highlighting the importance of fitness in protection against the onset of a fundamental pathophysiological event that leads to type 2 diabetes. PMID:25784661

  20. Peptide hormones in saliva. I. Insulin in saliva during the oral glucose tolerance test in female patients.

    PubMed

    Simionescu, L; Aman, E; Muşeţeanu, P; Dinulescu, E; Giurcăneanu, M

    1985-01-01

    The radioimmunoassay (RIA) of insulin was performed in the serum and saliva of 27 female patients during the oral glucose tolerance test (OGTT). The patients were divided into two groups: 19 non-diabetic patients and 8 patients diagnosed as impaired glucose tolerance (IGT) disease. In one patient in each group, the OGTT was performed twice at intervals of 3-5 days. The results show that immunoreactive insulin (IRI) is present in saliva and its concentration increases during the glucose stimulation test from 6.48 +/- 1.13 microU/ml (means +/- SEM) in basal conditions at peak values of 45.46 +/- 10.14 microU/ml at 2 hrs after glucose intake. In patients with IGT salivary IRI increases from 5.18 +/- 1.39 microU/ml in basal conditions to peak values of 83.34 +/- 25.85 microU/ml at 3 hrs after glucose administration. Great response variations were observed either inter-individual or intraindividual in both groups of patients. Some patients had unusual high salivary IRI concentration especially in those with gastrointestinal troubles. Further, some hypotheses and experimental models, are advanced, considered useful for the explanation of the physiologic significance of the salivary IRI or of the IRI-like material. PMID:3901231

  1. Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status.

    PubMed

    Santos, J L; Yévenes, I; Cataldo, L R; Morales, M; Galgani, J; Arancibia, C; Vega, J; Olmos, P; Flores, M; Valderas, J P; Pollak, F

    2016-06-01

    Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation. PMID:26660757

  2. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  3. Depressive symptoms linked to 1-h plasma glucose concentrations during the oral glucose tolerance test in men and women with the metabolic syndrome

    PubMed Central

    Birnbaum-Weitzman, O.; Goldberg, R.; Hurwitz, B. E.; Llabre, M. M.; Gellman, M. D.; Gutt, M.; McCalla, J. R.; Mendez, A. J.; Schneiderman, N.

    2014-01-01

    Aims The addition of the 1-h plasma glucose concentration measure from an oral glucose tolerance test to prediction models of future Type 2 diabetes has shown to significantly strengthen their predictive power. The present study examined the relationship between severity of depressive symptoms and hyperglycaemia, focusing on the 1-h glucose concentration vs. fasting and 2-h oral glucose tolerance test glucose measures. Methods Participants included 140 adults with the metabolic syndrome and without diabetes who completed a baseline psychobiological assessment and a 2-h oral glucose tolerance test, with measurements taken every 30 min. Depressive symptoms were assessed using the Beck Depression Inventory. Results Multivariate linear regression revealed that higher levels of depressive symptoms were associated with higher levels of 1-h plasma glucose concentrations after adjusting for age, gender, ethnicity, BMI, antidepressant use and high-sensitivity C-reactive protein. Results were maintained after controlling for fasting glucose as well as for indices of insulin resistance and secretion. Neither fasting nor 2-h plasma glucose concentrations were significantly associated with depressive symptoms. Conclusions Elevated depressive symptoms in persons with the metabolic syndrome were associated with greater glycaemic excursion 1-h following a glucose load that was not accounted for by differences in insulin secretory function or insulin sensitivity. Consistent with previous findings, this study highlights the value of the 1-h oral glucose tolerance test plasma glucose measurement in the relation between depressive symptoms and glucose metabolism as an indicator of metabolic abnormalities not visible when focusing on fasting and 2-h post-oral glucose tolerance test measurements alone. PMID:24344735

  4. Heritability of metabolic response to the intravenous glucose tolerance test in German Holstein Friesian bulls.

    PubMed

    Pieper, Laura; Staufenbiel, Rudolf; Christ, Jana; Panicke, Lothar; Müller, Uwe; Brockmann, Gudrun A

    2016-09-01

    Selection for improved health and welfare in farm animals is of increasing interest worldwide. Peripartum energy balance is a key factor for pathogenesis of diseases in dairy cows. The intravenous glucose tolerance test (ivGTT) can be used to study the metabolic response to a glucose stimulus. The aim of this study was to estimate heritability of ivGTT traits in German Holstein bulls. A total of 541 Holstein bulls aged 7 to 17 mo from 2 breeding stations were subjected to the ivGTT. Serum glucose concentrations were measured at 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 min relative to glucose infusion. The maximum increase in blood glucose concentration, glucose area equivalent, and blood glucose half-life period were calculated. Heritabilities were estimated using a univariate animal model including station-year-season and age as fixed effects, and animal additive genetic and residual as random effects. The estimated heritabilities were 0.19 for fasting glucose concentration, 0.43 for glucose area equivalent, 0.40 for glucose half-life period, 0.14 for the peak glucose concentration, and 0.12 for the maximum increase of blood glucose concentration. Correlations between ivGTT traits and breeding values for milk yield and composition were not found. The results indicate that heritability for response to glucose is high, which warrants further investigation of this trait for genetic improvement of metabolic disorders. Research is necessary to determine the target levels of ivGTT traits and potential associations between ivGTT traits in breeding bulls and periparturient diseases in their offspring. PMID:27394937

  5. The Preventive Effects of 8 Weeks of Resistance Training on Glucose Tolerance and Muscle Fiber Type Composition in Zucker Rats

    PubMed Central

    Kim, Ji-yeon; Choi, Mi Jung; So, Byunghun; Kim, Hee-jae; Seong, Je Kyung

    2015-01-01

    Background We investigated the therapeutic effects of resistance training on Zucker rats before and after the onset of diabetes to understand the importance of the timing of exercise intervention. We assessed whether 8 weeks of resistance training ameliorated impaired glucose tolerance and altered muscle fiber type composition in Zucker rats. Methods Five-week-old male Zucker rats were divided into Zucker lean control (ZLC-Con), non-exercised Zucker diabetic fatty (ZDF-Con), and exercised Zucker diabetic fatty (ZDF-Ex) groups. The ZDF-Ex rats climbed a ladder three times a week for 8 weeks. Intraperitoneal glucose tolerance tests (IPGTT) were performed on the 1st and 8th weeks of training, and grip strength was measured during the last week. We also measured glucose transporter 4 (GLUT4) expression by Western blot and immunofluorescence. Moreover, immunohistochemistry was performed to assess muscle fiber type composition. Results Fasting glucose levels and area under the curve responses to IPGTTs gradually increased as diabetes progressed in the ZDF-Con rats but decreased in the ZDF-Ex rats. Grip strength decreased in the ZDF-Con rats. However, resistance training did not improve grip strength in the ZDF-Ex rats. GLUT4 expression in the ZLC-Con and the ZDF-Con rats did not differ, but it increased in the ZDF-Ex rats. The proportions of myosin heavy chain I and II were lower and higher, respectively, in the ZDF-Con rats compared to the ZLC-Con rats. Muscle fiber type composition did not change in the ZDF-Ex rats. Conclusion Our results suggest that regular resistance training initiated at the onset of diabetes can improve glucose tolerance and GLUT4 expression without changing muscle morphology in Zucker rats. PMID:26566500

  6. The Association between HbA1c, Fasting Glucose, 1-Hour Glucose and 2-Hour Glucose during an Oral Glucose Tolerance Test and Cardiovascular Disease in Individuals with Elevated Risk for Diabetes

    PubMed Central

    Lind, Marcus; Tuomilehto, Jaakko; Uusitupa, Matti; Nerman, Olle; Eriksson, Johan; Ilanne-Parikka, Pirjo; Keinänen-Kiukaanniemi, Sirkka; Peltonen, Markku; Pivodic, Aldina; Lindström, Jaana

    2014-01-01

    Objective To determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes. Design We studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study. Setting Follow-up of clinical trial. Participants 504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c. Main Outcome Measure Relative risk of CVD. Results Over a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD. Conclusions and Relevance Current 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes. PMID:25285769

  7. Comparison of the effects of fetal hypothyroidism on glucose tolerance in male and female rat offspring.

    PubMed

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Zahediasl, Saleh; Ghasemi, Asghar

    2015-03-01

    Thyroid hormones are vital for survival of mammalian species and play critical roles in growth, development, and metabolism. Both fetal hypothyroidism and sex can affect carbohydrate metabolism during adult life. This study aims to assess carbohydrate metabolism in male and female offspring born from mothers who were hypothyroid during pregnancy. Pregnant rats were divided into two groups; the controls consumed water and the hypothyroid group received water containing 0.025 % 6-propyl-2-thiouracial throughout gestation. The intravenous glucose tolerance test (0.5 g/kg glucose) was carried out in 3-month-old offspring. Findings showed that compared to controls, male fetal hypothyroid rats during adulthood had glucose intolerance (area under the curve: 446.4 ± 9.7 vs. 486.4 ± 8.8, p < 0.01 in control and fetal hypothyroid groups, respectively) whereas females had improved glucose tolerance (478.1 ± 7.0 vs. 455.9 ± 8.5, p < 0.01). In conclusion, sex could modulate the effects of fetal hypothyroidism on glucose tolerance in rats. PMID:25649149

  8. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus

    PubMed Central

    Morgan, Donald A.; McDaniel, Latisha N.; Yin, Terry; Khan, Michael; Jiang, Jingwei; Acevedo, Michael R.; Walsh, Susan A.; Ponto, Laura L. Boles; Norris, Andrew W.; Lutter, Michael; Rahmouni, Kamal

    2015-01-01

    Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4RLHA signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4RLHA mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4RLHA mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4RLHA signaling. These results identify a novel role for MC4RLHA signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance. PMID:25605803

  9. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  10. Okara ameliorates glucose tolerance in GK rats

    PubMed Central

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-01-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  11. Mutations in Mll2, an H3K4 Methyltransferase, Result in Insulin Resistance and Impaired Glucose Tolerance in Mice

    PubMed Central

    Schröter, David; Matthews, Helen C.; Bogani, Debora; Moir, Lee; Long, Anna; Church, Christopher; Hugill, Alison; Anstee, Quentin M.; Goldin, Rob; Thursz, Mark; Hollfelder, Florian; Cox, Roger D.

    2013-01-01

    We employed a random mutagenesis approach to identify novel monogenic determinants of type 2 diabetes. Here we show that haplo-insufficiency of the histone methyltransferase myeloid-lineage leukemia (Mll2/Wbp7) gene causes type 2 diabetes in the mouse. We have shown that mice heterozygous for two separate mutations in the SET domain of Mll2 or heterozygous Mll2 knockout mice were hyperglycaemic, hyperinsulinaemic and developed non-alcoholic fatty liver disease. Consistent with previous Mll2 knockout studies, mice homozygous for either ENU mutation (or compound heterozygotes) died during embryonic development at 9.5–14.5 days post coitum. Heterozygous deletion of Mll2 induced in the adult mouse results in a normal phenotype suggesting that changes in chromatin methylation during development result in the adult phenotype. Mll2 has been shown to regulate a small subset of genes, a number of which Neurod1, Enpp1, Slc27a2, and Plcxd1 are downregulated in adult mutant mice. Our results demonstrate that histone H3K4 methyltransferase Mll2 is a component of the genetic regulation necessary for glucose homeostasis, resulting in a specific disease pattern linking chromatin modification with causes and progression of type 2 diabetes, providing a basis for its further understanding at the molecular level. PMID:23826075

  12. Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

    PubMed Central

    Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

    2016-01-01

    G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

  13. The effect of the interaction between glucose tolerance and breakfasts varying in carbohydrate and fibre on mood and cognition.

    PubMed

    Nabb, Samantha L; Benton, David

    2006-01-01

    As a glucose containing drink has been reported to improve memory, and missing breakfast has been reported to adversely influence memory late in the morning, meals designed to differ in their ability to release glucose into the blood stream were contrasted. Using a factorial design, breakfasts containing 15, 30 or 50 g of carbohydrate and 1.5, 6 or 13 g of fibre were compared. The glucose tolerance of participants proved to be an important factor. Those with better tolerance reported better mood. Those eating breakfasts containing greater amounts of carbohydrate reported feeling tired rather than energetic. The amount of carbohydrate did not negatively affect memory in those with better glucose tolerance, however, the consumption of more carbohydrate resulted in more forgetting in those with poorer glucose tolerance. The effect with reactions times differed from memory in that a greater intake of carbohydrate resulted in faster responses later in the morning. PMID:17176639

  14. Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults.

    PubMed

    Wang, Bei; Kammer, Lynne M; Ding, Zhenping; Lassiter, David G; Hwang, Jungyun; Nelson, Jeffrey L; Ivy, John L

    2012-01-01

    Certain amino acids have been reported to influence carbohydrate metabolism and blood glucose clearance, as well as improve the glucose tolerance in animal models. We hypothesized that an amino acid mixture consisting of isoleucine and 4 additional amino acids would improve the glucose response of healthy overweight men and women to an oral glucose tolerance test (OGTT). Twenty-two overweight healthy subjects completed 2 OGTTs after consuming 2 different test beverages. The amino acid mixture beverage (CHO/AA) consisted of 0.088 g cystine 2HCl, 0.043 g methionine, 0.086 g valine, 12.094 g isoleucine, 0.084 g leucine, and 100 g dextrose. The control beverage (CHO) consisted of 100 g dextrose only. Venous blood samples were drawn 10 minutes before the start of ingesting the drinks and 15, 30, 60, 120, and 180 minutes after the completion of the drinks. During the OGTT, the plasma glucose response for the CHO/AA treatment was significantly lower than that of the CHO treatment (P < .01), as was the plasma glucose area under the curve (CHO/AA 806 ± 31 mmol/L·3 hours vs CHO 942 ± 40 mmol/L·3 hours). Differences in plasma glucose between treatments occurred at 30, 60, 120, and 180 minutes after supplement ingestion. Plasma glucagon during the CHO/AA treatment was significantly higher than during the CHO treatment. However, there were no significant differences in plasma insulin or C-peptide responses between treatments. These results suggest that the amino acid mixture lowers the glucose response to an OGTT in healthy overweight subjects in an insulin-independent manner. PMID:22260861

  15. The effect of ispaghula (Fybogel and Metamucil) and guar gum on glucose tolerance in man.

    PubMed

    Jarjis, H A; Blackburn, N A; Redfern, J S; Read, N W

    1984-05-01

    The effects of incorporating Fybogel (3.5 and 7 g doses), Metamucil (7 g) or guar gum (2.5 and 14.5 g doses) in a drink containing 50 g glucose on plasma glucose, plasma insulin and gastric emptying were studied in thirty-eight normal volunteers. In addition, the effects of Fybogel (7 g) on glucose tolerance, plasma insulin and gastric emptying were measured in fourteen non-insulin-dependent diabetics. Both doses of guar gum significantly lowered plasma glucose and plasma insulin responses to the oral glucose load in normal subjects, although 14.5 g guar gum did not delay the half-time for gastric emptying. Neither Fybogel nor Metamucil had significant effects on plasma glucose responses in normal subjects. In addition, Fybogel (at either dose) had no significant effects on plasma insulin levels, or on gastric emptying in normal subjects or on plasma glucose and insulin responses in diabetic patients. The viscosity of ispaghula solutions ( Fybogel ) was lower than that of guar gum solutions. PMID:6326798

  16. Lipid storage by adipose tissue macrophages regulates systemic glucose tolerance

    PubMed Central

    Aouadi, Myriam; Vangala, Pranitha; Yawe, Joseph C.; Tencerova, Michaela; Nicoloro, Sarah M.; Cohen, Jessica L.; Shen, Yuefei

    2014-01-01

    Proinflammatory pathways in adipose tissue macrophages (ATMs) can impair glucose tolerance in obesity, but ATMs may also be beneficial as repositories for excess lipid that adipocytes are unable to store. To test this hypothesis, we selectively targeted visceral ATMs in obese mice with siRNA against lipoprotein lipase (LPL), leaving macrophages within other organs unaffected. Selective silencing of ATM LPL decreased foam cell formation in visceral adipose tissue of obese mice, consistent with a reduced supply of fatty acids from VLDL hydrolysis. Unexpectedly, silencing LPL also decreased the expression of genes involved in fatty acid uptake (CD36) and esterification in ATMs. This deficit in fatty acid uptake capacity was associated with increased circulating serum free fatty acids. Importantly, ATM LPL silencing also caused a marked increase in circulating fatty acid-binding protein-4, an adipocyte-derived lipid chaperone previously reported to induce liver insulin resistance and glucose intolerance. Consistent with this concept, obese mice with LPL-depleted ATMs exhibited higher hepatic glucose production from pyruvate and glucose intolerance. Silencing CD36 in ATMs also promoted glucose intolerance. Taken together, the data indicate that LPL secreted by ATMs enhances their ability to sequester excess lipid in obese mice, promoting systemic glucose tolerance. PMID:24986598

  17. Diurnal Cortisol Patterns, Future Diabetes, and Impaired Glucose Metabolism in the Whitehall II Cohort Study

    PubMed Central

    Kivimäki, Mika; Kumari, Meena; Steptoe, Andrew

    2016-01-01

    Context: The hypothalamic pituitary-adrenal axis is thought to play a role in type 2 diabetes (T2D). However, evidence for an association between cortisol and future glucose disturbance is sparse. Objective: The aim was to examine the association of diurnal cortisol secretion with future T2D and impaired glucose metabolism in a community-dwelling population. Design: This is a prospective cohort study of salivary cortisol measured at the 2002–2004 clinical examination of the Whitehall II study, United Kingdom. We measured cortisol (nmol/l) from six saliva samples obtained over the course of a day: at waking, +30 minutes, +2.5 hours, +8 hours, +12 hours, and bedtime. Participants who were normoglycemic in 2002–2004 (phase 7) were reexamined in 2012–2013 (phase 11). Setting: The occupational cohort was originally recruited in 1985–1988. Participants: A total of 3270 men and women with an average age of 60.85 years at phase 7 (2002–2004). Outcome Measures: Incident T2D and impaired fasting glucose in 2012–2013 were measured. Results: Raised evening cortisol at phase 7 was predictive of new-onset T2D at phase 11 (odds ratio [OR], 1.18; 95% confidence interval [CI], 1.01–1.37) with a trend for a flatter slope in participants with incident T2D (odds ratio, 1.15; 95% CI, 0.99–1.33). When expanding this analysis to a broader category of glucose disturbance we found that a flattened diurnal cortisol slope at phase 7 was predictive of future impaired fasting glucose or T2D at phase 11 (OR, 1.12; 95% CI, 1.02–1.22), as was high bedtime cortisol (OR, 1.10; 95% CI, 1.01–1.20). Conclusions: In this nonclinical population, alterations in diurnal cortisol patterns were predictive of future glucose disturbance. PMID:26647151

  18. Effect of growth hormone treatment on glucose tolerance in a patient with cystinosis after kidney transplantation.

    PubMed

    Kohlhauser, C; Balzar, E; Schober, E; Frisch, H

    1995-01-01

    A 16 year-old boy with nephropathic cystinosis and kidney transplantation was successfully treated with rhGH because of growth retardation. After 15 months of rhGH therapy he developed impaired glucose tolerance. Various causes like cystinosis itself, the immunosuppressive therapy with cyclosporine A and cortisone, but rhGH too might have been the responsible factors for that. Treatment with rhGH was initiated again after 4 months of interruption of therapy because no relation between impaired glucose tolerance and GH could be established. PMID:7623425

  19. Monitoring changes in the scattering properties of mouse skin with optical coherence tomography during an in vivo glucose tolerance test

    NASA Astrophysics Data System (ADS)

    Kinnunen, M.; Tausta, S.; Myllylä, R.; Vainio, S.

    2007-05-01

    A non-invasive glucose monitoring technique would make evaluation of blood glucose values easier and more convenient. This would help diabetic patients to control their blood glucose values more regularly. A few years ago optical coherence tomography (OCT) was proposed as a non-invasive sensor for monitoring changes in blood glucose concentration. The method is based on monitoring glucose-induced changes in the scattering properties of the target. This article describes how OCT was used to monitor changes in the scattering properties of mouse skin during an in vivo glucose tolerance test. The results show that OCT has the potential to register glucose-induced changes in the optical properties of the sample. However, a commercial OCT device with a probe designed for imaging is not very suitable for non-invasive monitoring of glucose-induced changes in scattering. The problems confronted in this study, possibly originating from the small size of the animals, are discussed in the article.

  20. [Amylase in the mixed saliva of diabetics and nondiabetics on an empty stomach and during the glucose tolerance test].

    PubMed

    Fekete, Z; Gol'denberg, A; Lukach, I; Korets, R; Shval'b, O; Platilova, G; Bandura, A

    1989-01-01

    The catalytic activity of alpha-amylase is significantly elevated in salivary pool from 146 diabetics (2176 +/- 149.3 mu catal.l-1) vs. the salivary pool from 78 nondiabetics (1159 +/- 97.3 mu catal X l-1), the difference in the concentrations of the saliva condensation index (the chloride concentration) in the diabetics and nondiabetics being negligible. Glucose tolerance test has been carried out in 54 subjects. Glucose intake has increased the alpha-amylase catalytic activity and augmented glycosialia in 14 diabetics, in 13 subjects with abnormal glucose tolerance, and in 16 nondiabetics; a negligible rise of glycosialia and a reduction of alpha-amylase catalytic activity have been observed in 11 subjects with a flat glycemia curve. Basing on these data, the authors claim that oral glucose activates amylase and glucose secretion by the salivary glands. PMID:2481117

  1. Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance.

    PubMed

    Penno, Giuseppe; Pucci, Laura; Lucchesi, Daniela; Lencioni, Cristina; Iorio, Maria Carla; Vanacore, Renato; Storti, Eugenia; Resi, Veronica; Di Cianni, Graziano; Del Prato, Stefano

    2011-07-01

    Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and β-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34(+)KDR(+) and CD34(+)CD133( +)KDR(+) cells at 27±3.2 weeks' gestation compared with NGT (ANOVA p<0.02 for both). CD34(+)KDR(+) and CD34(+)CD133(+)KDR(+) cells were inversely correlated with the area-under-the-glucose-curve (p<0.005, for both) and positively to insulin secretion-sensitivity index (p<0.05, for both). Alterations of glucose tolerance during pregnancy are associated with a decrease in EPCs. Hyperglycaemia might exert a direct effect on depletion of EPCs. PMID:21653675

  2. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat.

    PubMed

    Lin, Yi; Wei, Jie; Li, Yuanyuan; Chen, Jun; Zhou, Zhao; Song, Liqiong; Wei, Zhengzheng; Lv, Ziquan; Chen, Xi; Xia, Wei; Xu, Shunqing

    2011-09-01

    -Di(2-ethylhexyl) phthalate (DEHP), a typical endocrine-disrupting chemical (EDC), is widely used as plasticizer. DEHP exposure in humans is virtually ubiquitous, and those undergoing certain medical procedures can be especially high. In this study, we investigated whether developmental DEHP exposure disrupted glucose homeostasis in the rat and whether this was associated with the early impairment in endocrine pancreas. Pregnant Wistar rats were administered DEHP (1.25 and 6.25 mg·kg(-1)·day(-1)) or corn oil throughout gestation and lactation by oral gavage. Body weight, glucose and insulin tolerance, and β-cell morphometry and function were examined in offspring during the growth. In this study, developmental DEHP exposure led to abnormal β-cell ultrastructure, reduced β-cell mass, and pancreatic insulin content as well as alterations in the expression of genes involved in pancreas development and β-cell function in offspring at weaning. At adulthood, female DEHP-exposed offspring exhibited elevated blood glucose, reduced serum insulin, impaired glucose tolerance, and insulin secretion. Male DEHP-exposed offspring had increased serum insulin, although there were no significant differences in blood glucose at fasting and during glucose tolerance test. In addition, both male and female DEHP-exposed offspring had significantly lower birth weight and maintained relatively lower body weight up to 27 wk of age. These results suggest that developmental exposure to DEHP gives rise to β-cell dysfunction and the whole body glucometabolic abnormalities in the rat. DEHP exposure in critical periods of development can be a potential risk factor, at least in part, for developing diabetes. PMID:21673306

  3. Association between Advanced Glycation End Products and Impaired Fasting Glucose: Results from the SALIA Study

    PubMed Central

    Teichert, Tom; Hellwig, Anne; Peßler, Annette; Hellwig, Michael; Vossoughi, Mohammad; Sugiri, Dorothea; Vierkötter, Andrea; Schulte, Thomas; Freund, Juliane; Roden, Michael; Hoffmann, Barbara; Schikowski, Tamara; Luckhaus, Christian; Krämer, Ursula; Henle, Thomas; Herder, Christian

    2015-01-01

    Advanced glycation end products (AGEs) may contribute to the development of type 2 diabetes and related complications, whereas their role in the early deterioration of glycaemia is unknown. While previous studies used antibody-based methods to quantify AGEs, data from tandem mass spectrometry coupled liquid chromatography (LC-MS/MS)-based measurements are limited to patients with known diabetes. Here, we used the LC-MS/MS method to test the hypothesis that plasma AGE levels are higher in individuals with impaired fasting glucose (IFG) than in those with normal fasting glucose (NFG). Secondary aims were to assess correlations of plasma AGEs with quantitative markers of glucose metabolism and biomarkers of subclinical inflammation. This study included on 60 women with NFG or IFG (n = 30 each, mean age 74 years) from the German SALIA cohort. Plasma levels of free metabolites (3-deoxyfructose, 3-deoxypentosone, 3-deoxypentulose), two hydroimidazolones, oxidised adducts (carboxymethyllysine, carboxyethyllysine, methionine sulfoxide) and Nε-fructosyllysine were measured using LC-MS/MS. Plasma concentrations of all tested AGEs did not differ between the NFG and IFG groups (all p>0.05). Associations between plasma levels of AGEs and fasting glucose, insulin and HOMA-IR as a measure of insulin resistance were weak (r between -0.2 and 0.2, all p>0.05). The association between 3-deoxyglucosone-derived hydroimidazolone with several proinflammatory biomarkers disappeared upon adjustment for multiple testing. In conclusion, plasma AGEs assessed by LC-MS/MS were neither increased in IFG nor associated with parameters of glucose metabolism and subclinical inflammation in our study. Thus, these data argue against strong effects of AGEs in the early stages of deterioration of glucose metabolism. PMID:26018950

  4. Statins impair glucose uptake in human cells

    PubMed Central

    Nowis, Dominika; Malenda, Agata; Furs, Karolina; Oleszczak, Bozenna; Sadowski, Radoslaw; Chlebowska, Justyna; Firczuk, Malgorzata; Bujnicki, Janusz M; Staruch, Adam D; Zagozdzon, Radoslaw; Glodkowska-Mrowka, Eliza; Szablewski, Leszek; Golab, Jakub

    2014-01-01

    Objective Considering the increasing number of clinical observations indicating hyperglycemic effects of statins, this study was designed to measure the influence of statins on the uptake of glucose analogs by human cells derived from liver, adipose tissue, and skeletal muscle. Design Flow cytometry and scintillation counting were used to measure the uptake of fluorescently labeled or tritiated glucose analogs by differentiated visceral preadipocytes, skeletal muscle cells, skeletal muscle myoblasts, and contact-inhibited human hepatocellular carcinoma cells. A bioinformatics approach was used to predict the structure of human glucose transporter 1 (GLUT1) and to identify the presence of putative cholesterol-binding (cholesterol recognition/interaction amino acid consensus (CRAC)) motifs within this transporter. Mutagenesis of CRAC motifs in SLC2A1 gene and limited proteolysis of membrane GLUT1 were used to determine the molecular effects of statins. Results Statins significantly inhibit the uptake of glucose analogs in all cell types. Similar effects are induced by methyl-β-cyclodextrin, which removes membrane cholesterol. Statin effects can be rescued by addition of mevalonic acid, or supplementation with exogenous cholesterol. Limited proteolysis of GLUT1 and mutagenesis of CRAC motifs revealed that statins induce conformational changes in GLUTs. Conclusions Statins impair glucose uptake by cells involved in regulation of glucose homeostasis by inducing cholesterol-dependent conformational changes in GLUTs. This molecular mechanism might explain hyperglycemic effects of statins observed in clinical trials. PMID:25452863

  5. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    SciTech Connect

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-03-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific /sup 125/I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific /sup 125/I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity.

  6. Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes.

    PubMed

    Baker, Nicki A; English, Victoria; Sunkara, Manjula; Morris, Andrew J; Pearson, Kevin J; Cassis, Lisa A

    2013-12-01

    Resveratrol (RSV) is a plant polyphenol that exhibits several favorable effects on glucose homeostasis in adipocytes. Recent studies from our laboratory demonstrated that coplanar polychlorinated biphenyls (PCBs) that are ligands of the aryl hydrocarbon receptor impair glucose homeostasis in mice. PCB-induced impairment of glucose homeostasis was associated with augmented expression of inflammatory cytokines in adipose tissue, a site for accumulation of lipophilic PCBs. This study determined if RSV protects against PCB-77 induced impairment of glucose disposal in vitro and in vivo and if these beneficial effects are associated with enhanced nuclear factor erythoid 2-related factor 2 (Nrf2) signaling in adipose tissue. PCB-77 increased oxidative stress and abolished insulin stimulated 2-deoxy-d-glucose uptake in 3 T3-L1 adipocytes. These effects were restored by RSV, which resulted in a concentration-dependent increase in NAD(P)H:quinone oxidoreductase 1 (NQO1), the downstream target of Nrf2 signaling. We quantified glucose and insulin tolerance and components of Nrf2 and insulin signaling cascades in adipose tissue of male C57BL/6 mice administered vehicle or PCB-77 (50 mg/kg) and fed a diet with or without resVida (0.1%, or 160 mg/kg per day). PCB-77 impaired glucose and insulin tolerance, and these effects were reversed by RSV. PCB-77 induced reductions in insulin signaling in adipose tissue were also abolished by RSV, which increased NQO1 expression. These results demonstrate that coplanar PCB-induced impairment of glucose homeostasis in mice can be prevented by RSV, potentially through stimulation of Nrf2 signaling and enhanced insulin stimulated glucose disposal in adipose tissue. PMID:24231106

  7. Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes

    PubMed Central

    Baker, Nicki A.; English, Victoria; Sunkara, Manjula; Morris, Andrew J.; Pearson, Kevin J.; Cassis, Lisa A.

    2014-01-01

    Resveratrol (RSV) is a plant polyphenol that exhibits several favorable effects on glucose homeostasis in adipocytes. Recent studies from our laboratory demonstrated that coplanar polychlorinated biphenyls (PCBs) that are ligands of the aryl hydrocarbon receptor (AhR) impair glucose homeostasis in mice. PCB-induced impairment of glucose homeostasis was associated with augmented expression of inflammatory cytokines in adipose tissue, a site for accumulation of lipophilic PCBs. This study determined if RSV protects against PCB-77 induced impairment of glucose disposal in vitro and in vivo, and if these beneficial effects are associated with enhanced nuclear factor erythoid 2-related factor 2 (Nrf2) signaling in adipose tissue. PCB-77 increased oxidative stress and abolished insulin stimulated 2-deoxy-D-glucose (2DG) uptake in 3T3-L1 adipocytes. These effects were restored by RSV, which resulted in a concentration-dependent increase in NAD(P)H:quinone oxidoreductase 1 (NQO1), the downstream target of Nrf2 signaling. We quantified glucose and insulin tolerance and components of Nrf2 and insulin signaling cascades in adipose tissue of male C57BL/6 mice administered vehicle or PCB-77 (50 mg/kg) and fed a diet with or without resVida® (0.1%, or 160 mg/kg/day). PCB-77 impaired glucose and insulin tolerance, and these effects were reversed by RSV. PCB-77 induced reductions in insulin signaling in adipose tissue were also abolished by RSV, which increased NQO1 expression. These results demonstrate that coplanar PCB-induced impairment of glucose homeostasis in mice can be prevented by RSV, potentially through stimulation of Nrf2 signaling and enhanced insulin stimulated glucose disposal in adipose tissue. PMID:24231106

  8. Impaired Fasting Glucose Is Associated With Renal Hyperfiltration in the General Population

    PubMed Central

    Melsom, Toralf; Mathisen, Ulla Dorte; Ingebretsen, Ole C.; Jenssen, Trond G.; Njølstad, Inger; Solbu, Marit D.; Toft, Ingrid; Eriksen, Bjørn O.

    2011-01-01

    OBJECTIVE Increased glomerular filtration rate (GFR), also called hyperfiltration, is a proposed mechanism for renal injury in diabetes. The causes of hyperfiltration in individuals without diabetes are largely unknown, including the possible role of borderline hyperglycemia. We assessed whether impaired fasting glucose (IFG; 5.6–6.9 mmol/L), elevated HbA1c, or hyperinsulinemia are associated with hyperfiltration in the general middle-aged population. RESEARCH DESIGN AND METHODS A total of 1,560 individuals, aged 50–62 years without diabetes, were included in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6). GFR was measured as single-sample plasma iohexol clearance. Hyperfiltration was defined as GFR >90th percentile, adjusted for sex, age, weight, height, and use of renin-angiotensin system inhibitors. RESULTS Participants with IFG had a multivariable-adjusted odds ratio of 1.56 (95% CI 1.07–2.25) for hyperfiltration compared with individuals with normal fasting glucose. Odds ratios (95% CI) of hyperfiltration calculated for a 1-unit increase in fasting plasma glucose (FPG) and HbA1c, after multivariable-adjustment, were 1.97 (1.36–2.85) and 2.23 (1.30–3.86). There was no association between fasting insulin levels and hyperfiltration. A nonlinear association between FPG and GFR was observed (df = 3, P < 0.0001). GFR increased with higher glucose levels, with a steeper slope beginning at FPG ≥5.4 mmol/L. CONCLUSIONS Borderline hyperglycemia was associated with hyperfiltration, whereas hyperinsulinemia was not. Longitudinal studies are needed to investigate whether the hyperfiltration associated with IFG is a risk factor for renal injury in the general population. PMID:21593291

  9. Impaired glucose metabolism and exercise capacity with muscle-specific glycogen synthase 1 (gys1) deletion in adult mice

    PubMed Central

    Xirouchaki, Chrysovalantou E.; Mangiafico, Salvatore P.; Bate, Katherine; Ruan, Zheng; Huang, Amy M.; Tedjosiswoyo, Bing Wilari; Lamont, Benjamin; Pong, Wynne; Favaloro, Jenny; Blair, Amy R.; Zajac, Jeffrey D.; Proietto, Joseph; Andrikopoulos, Sofianos

    2016-01-01

    Objective Muscle glucose storage and muscle glycogen synthase (gys1) defects have been associated with insulin resistance. As there are multiple mechanisms for insulin resistance, the specific role of glucose storage defects is not clear. The aim of this study was to examine the effects of muscle-specific gys1 deletion on glucose metabolism and exercise capacity. Methods Tamoxifen inducible and muscle specific gys-1 KO mice were generated using the Cre/loxP system. Mice were subjected to glucose tolerance tests, euglycemic/hyperinsulinemic clamps and exercise tests. Results gys1-KO mice showed ≥85% reduction in muscle gys1 mRNA and protein concentrations, 70% reduction in muscle glycogen levels, postprandial hyperglycaemia and hyperinsulinaemia and impaired glucose tolerance. Under insulin-stimulated conditions, gys1-KO mice displayed reduced glucose turnover and muscle glucose uptake, indicative of peripheral insulin resistance, as well as increased plasma and muscle lactate levels and reductions in muscle hexokinase II levels. gys1-KO mice also exhibited markedly reduced exercise and endurance capacity. Conclusions Thus, muscle-specific gys1 deletion in adult mice results in glucose intolerance due to insulin resistance and reduced muscle glucose uptake as well as impaired exercise and endurance capacity. In brief This study demonstrates why the body prioritises muscle glycogen storage over liver glycogen storage despite the critical role of the liver in supplying glucose to the brain in the fasting state and shows that glycogen deficiency results in impaired glucose metabolism and reduced exercise capacity. PMID:26977394

  10. Urinary N-acetyl-β-d-Glucosaminidase Levels are Positively Correlated With 2-Hr Plasma Glucose Levels During Oral Glucose Tolerance Testing in Prediabetes

    PubMed Central

    Ouchi, Motoshi; Suzuki, Tatsuya; Hashimoto, Masao; Motoyama, Masayuki; Ohara, Makoto; Suzuki, Kazunari; Igari, Yoshimasa; Watanabe, Kentaro; Nakano, Hiroshi; Oba, Kenzo

    2012-01-01

    Background Urinary N-acetyl-β-D-glucosaminidase (NAG) excretion is increased in patients with impaired glucose tolerance (IGT). This study investigated when during the oral glucose tolerance test (OGTT) the plasma glucose, urine glucose, and insulin levels correlate most strongly with urinary N-acetyl-β-d-glucosaminidase (NAG) levels in prediabetic subjects. Methods The OGTT was administered to 80 subjects who had not yet received a diagnosis of diabetes mellitus (DM) and in whom HbA1c levels were ≤6.8% and fasting plasma glucose levels were <7.0 mmol/l. Forty-two subjects had normal glucose tolerance (NGT), 31 had impaired glucose tolerance (IGT), and 7 had DM according to World Health Organization criteria. Serum levels of cystatin C, the estimated glomerular filtration rate, the urinary albumin-to-creatinine (Cr) ratio, urinary and serum β2-microglobulin, and urinary NAG were measured as markers of renal function. Results NAG levels were significantly higher in subjects with DM and in subjects with IGT than in subjects with NGT. No significant associations were observed between glycemic status and other markers of renal function. Multiple linear regression analysis showed that the NAG level was positively correlated with plasma glucose levels at 120 min of the OGTT and was associated with the glycemic status of prediabetic patients. Conclusion These results suggest that postprandial hyperglycemia is an independent factor that causes renal tubular damage in prediabetes patients. PMID:23143631

  11. Progressive Hyperglycemia across the Glucose Tolerance Continuum in Older Obese Adults Is Related to Skeletal Muscle Capillarization and Nitric Oxide Bioavailability

    PubMed Central

    Solomon, Thomas P. J.; Haus, Jacob M.; Li, Yanjun

    2011-01-01

    Context: Reduced tissue nutrient exposure may aid in the progression of glucose intolerance. Objective: The aim of the study was to examine peripheral tissue glucose disposal in relation to muscle capillarization and plasma nitric oxide bioavailability. Design: Participants were carefully matched for age, adiposity, and lipid status and stratified into normal (n = 20), impaired (n = 20), and type 2 diabetic (n = 20) glucose-tolerant groups. Setting: The study was conducted in an outpatient setting at a Clinical Research Unit. Participants: Older, obese men and women (n = 60; age, 65 ± 1 yr; body mass index, 32.7 ± 0.5 kg/m2) participated in the study. Intervention: We performed a cross-sectional study. Main Outcome Measures: Body composition, energy metabolism, aerobic fitness (maximum oxygen consumption), insulin sensitivity (glucose clamp), vastus lateralis muscle morphology, and plasma nitric oxide were assessed. Results: Although subjects were identical with respect to age, body composition, energy expenditure, and lipid status, insulin-stimulated glucose disposal and maximum oxygen consumption showed progressive decline with increasing glucose intolerance. Muscle fiber type composition and mitochondrial density were not different between groups. However, capillary density markedly declined with advancing glucose intolerance (1.86 ± 0.31, 1.70 ± 0.28, 1.42 ± 0.24 capillary/fiber; P < 0.05), a trend that was mirrored by fasting plasma nitric oxide concentrations (26.3 ± 3.6, 19.8 ± 2.3, 15.2 ± 2.1 μmol/liter; P < 0.05). Furthermore, skeletal muscle capillary density correlated with insulin sensitivity (r = 0.65; P < 0.001). Conclusions: Impaired muscle capillarization and reduced nutrient exposure to the metabolizing tissue may play a major role in the progression of insulin resistance across the glucose tolerance continuum, independent of age, adiposity, lipid status, and resting energy metabolism. These data also highlight plasma nitric oxide as a

  12. Frequency of diabetes, impaired fasting glucose, and glucose intolerance in high-risk groups identified by a FINDRISC survey in Puebla City, Mexico

    PubMed Central

    García-Alcalá, Hector; Genestier-Tamborero, Christelle Nathalie; Hirales-Tamez, Omara; Salinas-Palma, Jorge; Soto-Vega, Elena

    2012-01-01

    Background As a first step in the prevention of diabetes, the International Diabetes Federation recommends identification of persons at risk using the Finnish type 2 Diabetes Risk Assessment (FINDRISC) survey. The frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in high-risk groups identified by FINDRISC is unknown in our country. The aim of this study was to determine the frequency of diabetes mellitus, impaired fasting glucose, and glucose intolerance in higher-risk groups using a FINDRISC survey in an urban population. Methods We used a television program to invite interested adults to fill out a survey at a television station. An oral glucose tolerance test was performed in all persons with a FINDRISC score ≥ 15 points (high-risk and very high-risk groups). Patients were classified as normal (fasting glucose < 100 mg/dL and 2-hour glucose < 140 mg/dL), or having impaired fasting glucose (fasting glucose 100–125 mg/dL and 2-hour glucose < 140 mg/dL), glucose intolerance (fasting glucose < 126 mg/dL and 2-hour glucose 140–199 mg/dL), and diabetes mellitus (fasting glucose ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL). We describe the frequency of each diagnostic category in this selected population according to gender and age. Results A total of 186 patients had a score ≥ 15. The frequencies of diabetes mellitus, impaired fasting glucose, glucose intolerance, and normal glucose levels were 28.6%, 25.9%, 29.2%, and 16.2%, respectively. We found a higher frequency of diabetes mellitus and impaired fasting glucose in men than in women (33% versus 27% and 40% versus 21%, respectively) and more glucose intolerance in women than in men (34% versus 16%, P < 0.05). Patients with diabetes mellitus (52.55 ± 9.2 years) were older than those with impaired fasting glucose (46.19 ± 8.89 years), glucose intolerance (46.15 ± 10.9 years), and normal levels (41.9 ± 10.45 years, P < 0.05). We found a higher frequency of diabetes

  13. High Glucose Impairs Insulin Signaling in the Glomerulus: An In Vitro and Ex Vivo Approach

    PubMed Central

    Katsoulieris, Elias N.; Drossopoulou, Garyfalia I.; Kotsopoulou, Eleni S.; Vlahakos, Dimitrios V.; Lianos, Elias A.; Tsilibary, Effie C.

    2016-01-01

    Objective Chronic hyperglycaemia, as seen in type II diabetes, results in both morphological and functional impairments of podocytes in the kidney. We investigated the effects of high glucose (HG) on the insulin signaling pathway, focusing on cell survival and apoptotic markers, in immortalized human glomerular cells (HGEC; podocytes) and isolated glomeruli from healthy rats. Methods and Findings HGEC and isolated glomeruli were cultured for various time intervals under HG concentrations in the presence or absence of insulin. Our findings indicated that exposure of HGEC to HG led to downregulation of all insulin signaling markers tested (IR, p-IR, IRS-1, p-Akt, p-Fox01,03), as well as to increased sensitivity to apoptosis (as seen by increased PARP cleavage, Casp3 activation and DNA fragmentation). Short insulin pulse caused upregulation of insulin signaling markers (IR, p-IR, p-Akt, p-Fox01,03) in a greater extent in normoglycaemic cells compared to hyperglycaemic cells and for the case of p-Akt, in a PI3K-dependent manner. IRS-1 phosphorylation of HG-treated podocytes was negatively regulated, favoring serine versus tyrosine residues. Prolonged insulin treatment caused a significant decrease of IR levels, while alterations in glucose concentrations for various time intervals demonstrated changes of IR, p-IR and p-Akt levels, suggesting that the IR signaling pathway is regulated by glucose levels. Finally, HG exerted similar effects in isolated glomeruli. Conclusions These results suggest that HG compromises the insulin signaling pathway in the glomerulus, promoting a proapoptotic environment, with a possible critical step for this malfunction lying at the level of IRS-1 phosphorylation; thus we herein demonstrate glomerular insulin signaling as another target for investigation for the prevention and/ or treatment of diabetic nephropathy. PMID:27434075

  14. Application of the Oral Minimal Model to Korean Subjects with Normal Glucose Tolerance and Type 2 Diabetes Mellitus

    PubMed Central

    Lim, Min Hyuk; Oh, Tae Jung; Choi, Karam; Lee, Jung Chan

    2016-01-01

    Background The oral minimal model is a simple, useful tool for the assessment of β-cell function and insulin sensitivity across the spectrum of glucose tolerance, including normal glucose tolerance (NGT), prediabetes, and type 2 diabetes mellitus (T2DM) in humans. Methods Plasma glucose, insulin, and C-peptide levels were measured during a 180-minute, 75-g oral glucose tolerance test in 24 Korean subjects with NGT (n=10) and T2DM (n=14). The parameters in the computational model were estimated, and the indexes for insulin sensitivity and β-cell function were compared between the NGT and T2DM groups. Results The insulin sensitivity index was lower in the T2DM group than the NGT group. The basal index of β-cell responsivity, basal hepatic insulin extraction ratio, and post-glucose challenge hepatic insulin extraction ratio were not different between the NGT and T2DM groups. The dynamic, static, and total β-cell responsivity indexes were significantly lower in the T2DM group than the NGT group. The dynamic, static, and total disposition indexes were also significantly lower in the T2DM group than the NGT group. Conclusion The oral minimal model can be reproducibly applied to evaluate β-cell function and insulin sensitivity in Koreans. PMID:27273909

  15. Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly

    PubMed Central

    Convit, Antonio; Wolf, Oliver T.; Tarshish, Chaim; de Leon, Mony J.

    2003-01-01

    Poor glucose tolerance and memory deficits, short of dementia, often accompanies aging. The purpose of this study was to ascertain whether, among nondiabetic, nondemented middle-aged and elderly individuals, poorer glucose tolerance is associated with reductions in memory performance and smaller hippocampal volumes. We studied 30 subjects who were evaluated consecutively in an outpatient research setting. The composition of the participant group was 57% female and 68.6 ± 7.5 years of age; the participants had an average education of 16.2 ± 2.3 years, a score on the Mini Mental State Examination of 28.6 ± 1.5, a glycosylated hemoglobin (HbA1C) of 5.88 ± 0.74%, and a body mass index of 24.9 ± 4.1 kg/m2. Glucose tolerance was measured by an i.v. glucose tolerance test. Memory was tested by using the Wechsler Paragraphs recall tests at the time of administering the i.v. glucose tolerance test. The hippocampus and other brain volumes were measured by using validated methods on standardized MRIs. Decreased peripheral glucose regulation was associated with decreased general cognitive performance, memory impairments, and atrophy of the hippocampus, a brain area that is key for learning and memory. These associations were independent of age and Mini Mental State Examination scores. Therefore, these data suggest that metabolic substrate delivery may influence hippocampal structure and function. This observation may bring to light a mechanism for aging brain injury that may have substantial medical impact, given the large number of elderly individuals with impaired glucose metabolism. PMID:12571363

  16. 25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

  17. [Study on prevention of untoward reaction of glucose tolerance test].

    PubMed

    Fan, L F; Li, H Y; Wang, G H

    1996-03-01

    The prevention methods of the side effects of 75g glucose tolerance test were studied. The results showed that the speed of taking glucose water was 3-5 minutes; the water temperature was 20-30 degrees C; water volume of dissolving glucose was 300ml; 0.25g citric acid was added, the side effects will be avoided or reduced. PMID:8826187

  18. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series.

    PubMed

    Tonoike, Mie; Kishimoto, Miyako; Yamamoto, Mayumi; Yano, Tetsu; Noda, Mitsuhiko

    2016-01-01

    Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM) in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases). Furthermore, the standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women. PMID:26949348

  19. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series

    PubMed Central

    Tonoike, Mie; Kishimoto, Miyako; Yamamoto, Mayumi; Yano, Tetsu; Noda, Mitsuhiko

    2016-01-01

    Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM) in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases). Furthermore, the standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women. PMID:26949348

  20. Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.

    PubMed

    Capiotti, Katiucia Marques; Antonioli, Régis; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2014-05-01

    Diabetes mellitus (DM) affects over 10% of the world's population. Hyperglycemia is the main feature for the diagnosis of this disease. The zebrafish (Danio rerio) is an established model organism for the study of various metabolic diseases. In this paper, hyperglycemic zebrafish, when immersed in a 111 mM glucose solution for 14 days, developed increased glycation of proteins from the eyes, decreased mRNA levels of insulin receptors in the muscle, and a reversion of high blood glucose level after treatment with anti-diabetic drugs (glimepiride and metformin) even after 7 days of glucose withdrawal. Additionally, hyperglycemic zebrafish developed an impaired response to exogenous insulin, which was recovered after 7 days of glucose withdrawal. These data suggest that the exposure of adult zebrafish to high glucose concentration is able to induce persistent metabolic changes probably underlined by a hyperinsulinemic state and impaired peripheral glucose metabolism. PMID:24704522

  1. Direct costs in impaired glucose regulation: results from the population-based Heinz Nixdorf Recall study

    PubMed Central

    Bächle, C; Claessen, H; Andrich, S; Brüne, M; Dintsios, C M; Slomiany, U; Roggenbuck, U; Jöckel, K H; Moebus, S; Icks, A

    2016-01-01

    Objective For the first time, this population-based study sought to analyze healthcare utilization and associated costs in people with normal fasting glycemia (NFG), impaired fasting glycemia (IFG), as well as previously undetected diabetes and previously diagnosed diabetes linking data from the prospective German Heinz Nixdorf Recall (HNR) study with individual claims data from German statutory health insurances. Research design and methods A total of 1709 participants of the HNR 5-year follow-up (mean age (SD) 64.9 (7.5) years, 44.5% men) were included in the study. Age-standardized and sex-standardized healthcare utilization and associated costs (reported as € for the year 2008, perspective of the statutory health insurance) were stratified by diabetes stage defined by the participants' self-report and fasting plasma glucose values. Cost ratios (CRs) were estimated using two-part regression models, adjusting for age, sex, sociodemographic variables and comorbidity. Results The mean total direct healthcare costs for previously diagnosed diabetes, previously undetected diabetes, IFG, and NFG were €2761 (95% CI 2378 to 3268), €2210 (1483 to 4279), €2035 (1732 to 2486) and €1810 (1634 to 2035), respectively. Corresponding age-adjusted and sex-adjusted CRs were 1.53 (1.30 to 1.80), 1.16 (0.91 to 1.47), and 1.09 (0.95 to 1.25) (reference: NFG). Inpatient, outpatient and medication costs varied in order between people with IFG and those with previously undetected diabetes. Conclusions The study provides claims-based detailed cost data in well-defined glucose metabolism subgroups. CRs of individuals with IFG and previously undetected diabetes were surprisingly low. Data are important for the model-based evaluation of screening programs and interventions that are aimed either to prevent diabetes onset or to improve diabetes therapy as well. PMID:27252871

  2. [Study of causes of untoward reactions of the glucose tolerance test].

    PubMed

    Fan, L F

    1994-07-01

    The observation of the Side-effects and influent factores after 75g OGTT indioated that the aotal rate of side-effects was 52.43%. After OGTT the commonest side-effect was vomiting. Others were dizzy and palpitation. The side-effects were also related to age, sex, starvation, speed of taking glucose water, water volum of dissolving glucose, gastrointestinal diseases, blood glucose level, etc. It was recommended in this paper that the speed of taking glucose water should be 3-5 minutes, the water temperature below 40 degrees C and starvation about 14 hours. PMID:7614609

  3. The characteristics of impaired fasting glucose associated with obesity and dyslipidaemia in a Chinese population

    PubMed Central

    2010-01-01

    Background Different populations have diverse patterns of relationships between Impaired Fasting Glucose (IFG) and obesity and lipid markers, it is important to investigate the characteristics of associations between IFG and other related risk factors including body mass index (BMI), waist circumstance (WC), serum lipids and blood pressure (BP) in a Chinese population. Methods This was a case-control study of 648 IFG subjects and 1,296 controls derived from a large-scale, community-based, cross-sectional survey of 10,867 participants. Each subject received a face-to-face interview, physical examination, and blood tests, including fasting blood glucose and lipids. Student's t-test, Chi-square test, Spearman correlation and multiple logistic regressions were used for the statistical analyses. Results Fasting plasma glucose (FPG) was positively correlated with BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), triglyceride (TG), and total cholesterol (TC), and was negatively correlated with high density lipoprotein-cholesterol (HDL-C) (all p < 0.05). BMI was more strongly correlated with IFG than with WC. The correlation coefficient of FPG was remarkably higher with TG (0.244) than with TC (0.134) and HDL-C (-0.192). TG was an important predictor of IFG, with odds ratios of 1.76 (95%CI: 1.31-2.36) for subjects with borderline high TG level (1.70 mmol/l ≤ TG < 2.26 mmol/l) and 3.13 (95% CI: 2.50-3.91) for those with higher TG level (TG ≥ 2.26 mmol/l), when comparing to subjects with TG < 1.70 mmol/l. There was a significant dose-response relationship between the number of abnormal variables and increased risk of IFG. Conclusions In this Chinese population, both BMI and WC were important predictors of IFG. Abnormal TG as a lipid marker was more strongly associated with IFG than were TC and HDL-C. These factors should be taken into consideration simultaneously for prevention of IFG. PMID:20233452

  4. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    PubMed Central

    Aekplakorn, Wichai; Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  5. Impaired cerebral development in fetuses with congenital cardiovascular malformations: Is it the result of inadequate glucose supply?

    PubMed

    Rudolph, Abraham M

    2016-08-01

    Cerebral development may be impaired in fetuses with congenital cardiovascular malformations, particularly hypoplastic left heart syndrome (HLHS) and aortopulmonary transposition (APT). The decreased cerebral arterial pusatility index observed in some of these fetuses led to the belief that cerebral vascular resistance was reduced as a result of arterial hypoxemia and cerebral hypoxia is thought to be responsible for impaired cerebral growth. However, other hemodynamic factors could affect pulsatility index. I propose that cerebral blood flow is reduced in fetuses with HLHS and that reduced glucose, rather than oxygen, delivery interferes with cerebral development. This is based on the fact that most of these fetuses do not have lactate accumulation in the brain.In fetuses with APT, umbilical venous blood, containing oxygen and glucose derived across the placenta, is distributed to the lungs and lower body; venous blood, with low oxygen and glucose content, is delivered to the ascending aorta and brain. Oxygen and glucose delivery may further be reduced by decreased cerebral blood flow resulting from run-off of aortic blood through the ductus arteriosus to the pulmonary circulation during diastole. In APT fetuses, lack of lactate in the brain also supports my proposal that glucose deficiency interferes with cerebral development. PMID:27055190

  6. The relationship between glycated hemoglobin and blood glucose levels of 75 and 100 gram oral glucose tolerance test during gestational diabetes diagnosis

    PubMed Central

    Mert, Meral; Purcu, Serhat; Soyluk, Ozlem; Okuturlar, Yildiz; Karakaya, Pinar; Tamer, Gonca; Adas, Mine; Ekin, Murat; Hatipoglu, Sami; Ure, Oznur Sari; Harmankaya, Ozlem; Kumbasar, Abdulbaki

    2015-01-01

    Objective: The diagnosis of gestational diabetes mellitus (GDM) is an important issue in terms of prevention of maternal and fetal complications. In our study we aimed to evaluate the relation of HbA1c and blood glucose levels of 75 and 50-100 gram oral glucose tolerance test (OGTT) in pregnant patients who were screened for GDM. Materials and methods: The parameters of 913 pregnant women screened for GDM are evaluated retrospectively. The two steps screening with 50-100 gram OGTT were used in 576 patients. The remaining 337 patients were screened with 75 gram OGTT. Results: The HbA1c levels of patients having high blood glucose (≥153 mg/dl) levels at 2nd hour in 75 gram OGTT were significantly higher than patients having normal blood glucose levels at 2nd hour of 75 gram OGTT (P=0.038). Correlation analyses showed no significant relation between any blood glucose level of 100 gram OGTT and HbA1c level. Whereas in 75 gram OGTT 1st and 2nd hour blood glucose levels were found to have a significant relation with A1c levels (P=0.001, P=0.001 respectively). Conclusion: HbA1c may be used as an important tool in the diagnosis of GDM. But due to the variation of HbA1c in pregnant women and there is not an absolute cut-off level for A1c, it may be more reliable to evaluate HbA1c level together with the blood glucose levels in OGTT. PMID:26550262

  7. GDF15 Is a Novel Biomarker for Impaired Fasting Glucose

    PubMed Central

    Hong, Jun Hwa; Chung, Hyo Kyun; Park, Hye Yoon; Joung, Kyong-Hye; Lee, Ju Hee; Jung, Jin Gyu; Kim, Koon Soon; Kim, Hyun Jin

    2014-01-01

    Background Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG. Methods The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level. Results Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females. Conclusion GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients. PMID:25541611

  8. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance

    PubMed Central

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    Background It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). Material/Methods We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. Results During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. Conclusions Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  9. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance.

    PubMed

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    BACKGROUND It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). MATERIAL AND METHODS We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. RESULTS During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. CONCLUSIONS Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  10. Mandatory oral glucose tolerance tests identify more diabetics in stable patients with chronic heart failure: a prospective observational study

    PubMed Central

    2014-01-01

    Background Many patients with chronic heart failure (CHF) are believed to have unrecognized diabetes, which is associated with a worse prognosis. This study aimed to describe glucose tolerance in a general stable CHF population and to identify determinants of glucose tolerance focusing on body composition and skeletal muscle strength. Methods A prospective observational study was set up. Inclusion criteria were diagnosis of CHF, stable condition and absence of glucose-lowering medication. Patients underwent a 2 h oral glucose tolerance test (OGTT), isometric strength testing of the upper leg and dual energy x-ray absorptiometry. Health-related quality of life and physical activity level were assessed by questionnaire. Results Data of 56 participants were analyzed. Despite near-normal fasting glucose values, 55% was classified as prediabetic, 14% as diabetic, and 20% as normal glucose tolerant. Of all newly diagnosed diabetic patients, 79% were diagnosed because of 2 h glucose values only and none because of HbA1c. Univariate mixed model analysis revealed ischaemic aetiology, daily physical activity, E/E’, fat trunk/fat limbs and extension strength as possible explanatory variables for the glucose curve during the glucose tolerance test. When combined in one model, only fat trunk/fat limbs and E/E’ remained significant predictors. Furthermore, fasting insulin was correlated with fat mass/height2 (r = 0.51, p < 0.0001), extension strength (r = -0.33, p < 0.01) and triglycerides (r = 0.39, p < 0.01). Conclusions Our data confirm that a large majority of CHF patients have impaired glucose tolerance. This glucose intolerance is related to fat distribution and left ventricular end-diastolic pressure. PMID:24673860

  11. Impaired glucose metabolism treatment and carcinogenesis

    PubMed Central

    MATYSZEWSKI, ARTUR; CZARNECKA, ANNA; KAWECKI, MACIEJ; KORZEŃ, PIOTR; SAFIR, ILAN J.; KUKWA, WOJCIECH; SZCZYLIK, CEZARY

    2015-01-01

    Carbohydrate metabolism disorders increase the risk of carcinogenesis. Diabetes mellitus alters numerous physiological processes that may encourage cancer growth. However, treating impaired glucose homeostasis may actually promote neoplasia; maintaining proper glucose plasma concentrations reduces metabolic stresses, however, certain medications may themselves result in oncogenic effects. A number of previous studies have demonstrated that metformin reduces the cancer risk. However, the use of sulfonylurea derivatives correlates with an increased risk of developing a malignancy. Another form of treatment, insulin therapy, involves using various forms of insulin that differ in pharmacodynamics, pharmacokinetics and efficacy. Previous studies have indicated that certain insulin variants also affect the cancer risk. The results from analyses that address the safety of long-lasting insulin types raise the most concern regarding the increased risk of malignancy. Rapid development of novel diabetic medications and their widespread use carries the risk of potentially increased rates of cancer, unnoticeable in limited, randomized, controlled trials. In the present review, the results of clinical and epidemiological studies are evaluated to assess the safety of anti-hyperglycemic medications and their effect on cancer risk and outcomes. PMID:26622538

  12. Abnormal oral glucose tolerance and glucose malabsorption after vagotomy and pyloroplasty. A tracer method for measuring glucose absorption rates

    SciTech Connect

    Radziuk, J.; Bondy, D.C.

    1982-11-01

    The mechanisms underlying the abnormal glucose tolerance in patients who had undergone vagotomy and pyloroplasty were investigated by measuring the rates of absorption of ingested glucose and the clearance rate of glucose using tracer methods. These methods are based on labeling a 100-g oral glucose load with (1-/sup 14/C)glucose and measuring glucose clearance using plasma levels of infused (3-/sup 3/H)glucose. The rate of appearance of both ingested and total glucose is then calculated continuously using a two-compartment model of glucose kinetics. It was found that about 30% of the ingested glucose (100 g) failed to appear in the systemic circulation. That this was due to malabsorption was confirmed using breath-hydrogen analysis. The absorption period is short (101 +/- 11 min) compared with normal values but the clearance of glucose is identical to that in control subjects, and it peaks 132 +/- 7 min after glucose loading. The peak plasma insulin values were more than four times higher in patients than in normal subjects, and this may afford an explanation of rates of glucose clearance that are inappropriate for the short absorption period. The combination of glucose malabsorption and this clearance pattern could yield the hypoglycemia that may be observed in patients after gastric surgery.

  13. Association between Markers of Fatty Liver Disease and Impaired Glucose Regulation in Men and Women from the General Population: The KORA-F4-Study

    PubMed Central

    Rückert, Ina-Maria; Heier, Margit; Rathmann, Wolfgang; Baumeister, Sebastian E.; Döring, Angela; Meisinger, Christa

    2011-01-01

    Objective To investigate whether the elevated liver enzymes gamma-glutamyltransferase (GGT), glutamate-pyruvate transaminase (GPT), glutamate-oxalacetate transaminase (GOT) and alkaline phosphatase (AP) and non-alcoholic fatty liver disease (NAFLD) respectively are independently associated with pre-diabetic states, namely impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) or known and newly diagnosed diabetes (NDD), in men and women from the general German population. Methods The study was based on 3009 subjects (1556 females, 1453 males) aged 32 to 81 years who participated in the KORA-F4-Study in 2006/2008 in Augsburg, Southern Germany. All non-diabetic participants underwent an oral glucose tolerance test to assess disturbances in glucose metabolism. NAFLD was estimated by liver enzyme concentrations and the Bedogni Fatty Liver Index (FLI). Results 229 participants (7.6%) reported known diabetes, 106 had NDD (3.5%), 107 (3.6%) had IFG, 309 (10.3%) had IGT, 69 (2.3%) were affected with both metabolic disorders (IFG/IGT) and 74 (2.5%) could not be classified. GGT and GPT were significantly elevated in persons with pre-diabetes and diabetes (GGT in diabetic persons OR = 1.76, [1.47–2.09], in IFG OR = 1.79 [1.50–2.13], GPT in diabetic persons OR = 1.51, [1.30–1.74], in NDD OR = 1.77 [1.52–2.06]), GOT and AP only inconsistently in some pre-diabetes groups. The effects were sharpened in models using an increase of two or three out of three enzymes as an estimate of fatty liver and especially in models using the FLI. Overall frequency of NAFLD applying the index was 39.8% (women: 27.3% and men: 53.2%). In participants with fatty liver disease, the OR for NDD adjusted for sex and age was 8.48 [5.13–14.00], 6.70 [3.74–12.01] for combined IFG and IGT and 4.78 [3.47–6.59] for known diabetes respectively. Conclusions Elevated GGT and GPT–values as well as estimates of fatty liver disease are significantly associated with pre

  14. A randomised trial of salsalate for insulin resistance and cardiovascular risk factors in persons with abnormal glucose tolerance

    PubMed Central

    Goldfine, A. B.; Conlin, P. R.; Halperin, F.; Koska, J.; Permana, P.; Schwenke, D.; Shoelson, S. E.

    2016-01-01

    Aims/hypothesis Chronic sub-acute inflammation contributes to the pathogenesis of type 2 diabetes mellitus and cardiovascular disease. High doses of salicylate reduce inflammation, glucose and triacylglycerols, and may improve insulin sensitivity, suggesting therapeutic potential in impaired fasting glucose and/or impaired glucose tolerance. This trial aimed to evaluate the effect of salsalate vs placebo on insulin resistance and glycaemia in impaired fasting glucose and/or impaired glucose tolerance. Methods We conducted a 12 week, two-centre, randomised, placebo-controlled study to evaluate the effect of salsalate (up to 4 g/day) vs placebo on systemic glucose disposal. Secondary objectives included treatment effects on glycaemia, inflammation and cardiovascular risk factors. Seventy-eight participants with impaired fasting glucose and/or impaired glucose tolerance from two VA healthcare systems were enrolled. Randomisation assignment was provided by the coordinating center directly to site pharmacists, and participants and research staff were blinded to treatment assignment. Results Seventy-one individuals were randomised to placebo (n = 36) or salsalate (n = 35). Glucose disposal did not change in either group (salsalate 1% [95% CI −39%, 56%]; placebo 6% [95% CI −20%, 61%], p = 0.3 for placebo vs salsalate). Fasting glucose was reduced by 6% during the study by salsalate (p = 0.006) but did not change with placebo. Declines in glucose were accompanied by declines in fasting C-peptide with salsalate. Insulin clearance was reduced with salsalate. In the salsalate group, triacylglycerol levels were lower by 25% (p = 0.01) and adiponectin increased by 53% (p = 0.02) at the end of the study. Blood pressure, endothelial function and other inflammation markers did not differ between groups. Adipose tissue nuclear factor κB (NF-κB) activity declined in the salsalate group compared with placebo (−16% vs 42%, p = 0.005), but was not correlated with metabolic

  15. PPARα Agonist Fenofibrate Reduced the Secreting Load of β-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance

    PubMed Central

    Liu, Jia; Lu, Rui; Wang, Ying; Hu, Yanjin; Jia, Yumei; Yang, Ning; Fu, Jing

    2016-01-01

    Hypertriglyceridemia is an important risk factor associated with insulin resistance and β-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and β-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group, n = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-β levels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL-C, and HOMA-β: P < 0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load of β-cells in the hypertriglyceridemia patients with normal glucose tolerance. PMID:27034649

  16. Pancreatic Islet APJ Deletion Reduces Islet Density and Glucose Tolerance in Mice.

    PubMed

    Han, Song; Englander, Ella W; Gomez, Guillermo A; Rastellini, Cristiana; Quertermous, Thomas; Kundu, Ramendra K; Greeley, George H

    2015-07-01

    Protection and replenishment of a functional pancreatic β-cell mass (BCM) are key goals of all diabetes therapies. Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor. The apelin-APJ signaling system is expressed in rodent and human islet cells. Apelin exposure has been shown to inhibit and to stimulate insulin secretion. Our aim was to assess the influence of a selective APJ deletion in pancreatic islet cells on islet homeostasis and glucose tolerance in mice. Cre-LoxP strategy was utilized to mediate islet APJ deletion. APJ deletion in islet cells (APJ(Δislet)) resulted in a significantly reduced islet size, density and BCM. An ip glucose tolerance test showed significantly impaired glucose clearance in APJ(Δislet) mice. APJ(Δislet) mice were not insulin resistant and in vivo glucose-stimulated insulin secretion was reduced modestly. In vitro glucose-stimulated insulin secretion showed a significantly reduced insulin secretion by islets from APJ(Δislet) mice. Glucose clearance in response to ip glucose tolerance test in obese APJ(Δislet) mice fed a chronic high-fat (HF) diet, but not pregnant APJ(Δislet) mice, was impaired significantly. In addition, the obesity-induced adaptive elevations in mean islet size and fractional islet area were reduced significantly in obese APJ(Δislet) mice when compared with wild-type mice. Together, these findings demonstrate a stimulatory role for the islet cell apelin-APJ signaling axis in regulation of pancreatic islet homeostasis and in metabolic induced β-cell hyperplasia. The results indicate the apelin-APJ system can be exploited for replenishment of BCM. PMID:25965959

  17. A simple risk score for identifying individuals with impaired fasting glucose in the Southern Chinese population.

    PubMed

    Wang, Hui; Liu, Tao; Qiu, Quan; Ding, Peng; He, Yan-Hui; Chen, Wei-Qing

    2015-02-01

    This study aimed to develop and validate a simple risk score for detecting individuals with impaired fasting glucose (IFG) among the Southern Chinese population. A sample of participants aged ≥20 years and without known diabetes from the 2006-2007 Guangzhou diabetes cross-sectional survey was used to develop separate risk scores for men and women. The participants completed a self-administered structured questionnaire and underwent simple clinical measurements. The risk scores were developed by multiple logistic regression analysis. External validation was performed based on three other studies: the 2007 Zhuhai rural population-based study, the 2008-2010 Guangzhou diabetes cross-sectional study and the 2007 Tibet population-based study. Performance of the scores was measured with the Hosmer-Lemeshow goodness-of-fit test and ROC c-statistic. Age, waist circumference, body mass index and family history of diabetes were included in the risk score for both men and women, with the additional factor of hypertension for men. The ROC c-statistic was 0.70 for both men and women in the derivation samples. Risk scores of ≥28 for men and ≥18 for women showed respective sensitivity, specificity, positive predictive value and negative predictive value of 56.6%, 71.7%, 13.0% and 96.0% for men and 68.7%, 60.2%, 11% and 96.0% for women in the derivation population. The scores performed comparably with the Zhuhai rural sample and the 2008-2010 Guangzhou urban samples but poorly in the Tibet sample. The performance of pre-existing USA, Shanghai, and Chengdu risk scores was poorer in our population than in their original study populations. The results suggest that the developed simple IFG risk scores can be generalized in Guangzhou city and nearby rural regions and may help primary health care workers to identify individuals with IFG in their practice. PMID:25625405

  18. Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose Metabolism

    PubMed Central

    Tavecchio, Michele; Lisanti, Sofia; Bennett, Michael J.; Languino, Lucia R.; Altieri, Dario C.

    2015-01-01

    Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo. PMID:26515038

  19. Restoration of early rise in plasma insulin levels improves the glucose tolerance of type 2 diabetic patients.

    PubMed

    Bruttomesso, D; Pianta, A; Mari, A; Valerio, A; Marescotti, M C; Avogaro, A; Tiengo, A; Del Prato, S

    1999-01-01

    production was suppressed in a prompter and more profound manner when lispro was administered (1.39 +/- 0.10 vs. 5.00 +/- 1.22 micromol x kg(-1) x min(-1); P < 0.05), while there was no difference in the late prandial phase. These results show that an early rise in plasma insulin levels after the ingestion of a glucose load is associated with a significant improvement in glucose tolerance due to a prompter, though short-lived, suppression of endogenous glucose production. This amelioration in plasma glucose profile prevents late hyperglycemia and hyperinsulinemia. Therefore, restoration of a more physiologic profile of prandial plasma insulin profile represents a rational approach for treatment of type 2 diabetic patients. PMID:9892228

  20. The Influence of Maternal Weight and Glucose Tolerance on Infant Birthweight in Latino Mother–Infant Pairs

    PubMed Central

    Kieffer, Edith C.; Tabaei, Bahman P.; Carman, Wendy J.; Nolan, George H.; Guzman, J. Ricardo; Herman, William H.

    2006-01-01

    Objectives. We assessed the influence of maternal anthropometric and metabolic variables, including glucose tolerance, on infant birthweight. Methods. In our prospective, population-based cohort study of 1041 Latino mother–infant pairs, we used standardized interviews, anthropometry, metabolic assays, and medical record reviews. We assessed relationships among maternal sociodemographic, prenatal care, anthropometric, and metabolic characteristics and birthweight with analysis of variance and bivariate and multivariate linear regression analyses. Results. Forty-two percent of women in this study entered pregnancy overweight or obese; at least 36% exceeded weight-gain recommendations. Twenty-seven percent of the women had at least some degree of glucose abnormality, including 6.8% who had gestational diabetes. Maternal multiparity, height, weight, weight gain, and 1-hour screening glucose levels were significant independent predictors of infant birthweight after adjustment for gestational age. Conclusion. Studies of birthweight should account for maternal glucose level. Given the increased risk of adverse maternal and infant outcomes associated with excessive maternal weight, weight gain, and glucose intolerance, and the high prevalence of these conditions and type 2 diabetes among Latinas, public health professionals have unique opportunities for prevention through prenatal and postpartum interventions. PMID:17077395

  1. Effect of glucose on Listeria monocytogenes biofilm formation, and assessment of the biofilm's sanitation tolerance.

    PubMed

    Kyoui, Daisuke; Hirokawa, Eri; Takahashi, Hajime; Kuda, Takashi; Kimura, Bon

    2016-08-01

    Listeria monocytogenes is an important cause of human foodborne infections and its ability to form biofilms is a serious concern to the food industry. To reveal the effect of glucose conditions on biofilm formation of L. monocytogenes, 20 strains were investigated under three glucose conditions (0.1, 1.0, and 2.0% w v(-1)) by quantifying the number of cells in the biofilm and observing the biofilm structure after incubation for 24, 72, and 168 h. In addition, the biofilms were examined for their sensitivity to sodium hypochlorite. It was found that high concentrations of glucose reduced the number of viable cells in the biofilms and increased extracellular polymeric substance production. Moreover, biofilms formed at a glucose concentration of 1.0 or 2.0% were more resistant to sodium hypochlorite than those formed at a glucose concentration of 0.1%. This knowledge can be used to help design the most appropriate sanitation strategy. PMID:27353113

  2. Intake of St John's wort improves the glucose tolerance in healthy subjects who ingest metformin compared with metformin alone

    PubMed Central

    Stage, Tore Bjerregaard; Pedersen, Rasmus Steen; Damkier, Per; Christensen, Mette Marie Hougaard; Feddersen, Søren; Larsen, John Teilmann; Højlund, Kurt; Brøsen, Kim

    2015-01-01

    Aims Our objective was to investigate the steady-state pharmacokinetic and pharmacodynamic interaction between the antidepressive herbal medicine St John's wort and the antidiabetic drug metformin. Methods We performed an open cross-over study in 20 healthy male subjects, who received 1 g of metformin twice daily for 1 week with and without 21 days of preceding and concomitant treatment with St John's wort. The pharmacokinetics of metformin was determined, and a 2 h oral glucose tolerance test was performed. Results St John's wort decreased the renal clearance of metformin but did not affect any other metformin pharmacokinetic parameter. The addition of St John's wort decreased the area under the glucose concentration–time curve [702 (95% confidence interval, 643–761) vs. 629 min*mmol/L (95% confidence interval, 568–690), P = 0.003], and this effect was caused by a statistically significant increase in the acute insulin response. Conclusions St John's wort improves glucose tolerance by enhancing insulin secretion independently of insulin sensitivity in healthy male subjects taking metformin. PMID:25223504

  3. Effect of pure zinc deficiency on glucose tolerance and insulin and glucagon levels

    SciTech Connect

    Park, J.H.Y.; Grandjean, C.J.; Hart, M.H.; Erdman, S.H.; Pour, P.; Vanderhoof, J.A.

    1986-03-05

    The effect of zinc deficiency on glucose tolerance was investigated using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Three groups of weanling male Sprague-Dawley rats were fed a purified powdered zinc-deficient diet: zinc-deficient ad libitum fed animals (ZDA); zinc-replete gavage force-fed controls (ZRF) fed the zinc-deficient diet in water with zinc (25 ppm); zinc-deficient gavage force-fed animals (ZDF) fed the zinc-deficient diet in distilled water. A fourth group of zinc-supplemented rats fed the diet ad libitum was included to determine caloric intake for ZDF and ZRF gavage fed groups. After 8 days of feeding, the zinc concentration in the serum and pancreas were lower in both zinc-deficient groups, but the difference was much greater in the ZDF rats than in the ZDA. The ZDF group had impaired glucose tolerance curves, yet blood insulin and glucagon levels were normal. The ZDA group had normal glucose tolerance with low insulin levels compared to the ZRF group. The islet cell morphology among the three dietary groups were similar. These results suggest that the glucose intolerance observed in ZDF rats is not due to altered blood insulin and glucagon levels but rather to peripheral resistance to insulin action.

  4. GLP-2 receptor deficiency in the mouse brain impairs glucose homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In response to food intake, glucagon-like peptide-2 (GLP-2) with GLP-1 is co-secreted from enteroendocrine L cells in the gut. GLP-2 receptor (GLP-2R) is expressed in the hypothalamus, a key tissue to integrate energy signals to regulate energy balance and glucose homeostasis. However, the physiolog...

  5. Impaired peripheral glucose sensing in F1 offspring of diabetic pregnancy.

    PubMed

    Kamel, Maher A; Helmy, Madiha H; Hanafi, Mervat Y; Mahmoud, Shimaa A; Abo Elfetooh, Hanan

    2014-09-01

    Maternal diabetes can induce permanent changes in glucose homeostasis that can occur pre- and post-natal and leads to type 2 diabetes in adulthood. This study aimed to investigate the effect of maternal diabetes on the F1 offspring peripheral glucose sensing and mitochondrial biogenesis in an attempt to clarify the mechanism of diabetogenic programming. Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. After the pregnancy and delivery, the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks, OGTT was constructed, and serum and tissues were obtained for the assessment of mTFA, mtDNA, UCP2, insulin receptor (IR), phospho-insulin receptor (phospho-IR), and GLUT4. The result indicated impaired glucose tolerance (IGT) and insulin resistance in the offspring under control diet at the 15th week of age and thereafter while those offspring under HCD showed IGT at 10th week, and diabetes was evidenced at the 25th week of age. This defect in glucose metabolism was preceded by impairment in the phosphorylation of IR and decreased IR and Glut4 that cause impaired glucose sensing together with inhibited mitochondrial biogenesis in muscle and adipose tissues. This study indicated that maternal diabetes caused impaired glucose sensing and insulin resistance in the peripheral tissues and caused change in the expression of genes involved in mitochondrial biogenesis and function. Post-natal feeding with HCD may accelerate these changes. Male F1 offspring appears to be more sensitive than females for fetal programming of T2D. PMID:24895245

  6. Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

    PubMed Central

    Martínez-Montes, Eduardo

    2013-01-01

    This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

  7. Need for testing glucose tolerance in the early weeks of pregnancy

    PubMed Central

    Veeraswamy, Seshiah; Divakar, Hema; Gupte, Sanjay; Datta, Manjula; Kapur, Anil; Vijayam, Balaji

    2016-01-01

    Aims: This observational study aims to determine the frequency of occurrence of glucose intolerance in the early weeks of pregnancy. Materials and Methods: New World Health Organization 2013 guidelines recommends “A Single Step Procedure” (SSP) as an option for diagnosing gestational diabetes mellitus (GDM). Pregnant women attending 131 prenatal clinics across India for the first time underwent SSP consisting of administration of 75 goral glucose irrespective of the last meal timing and to diagnose GDM with 2 h plasma glucose (PG) value ≥7.8 mmol/L (7.8 mmol/L). Results: In a cohort of n = 11,785, the number of pregnant women who underwent the test in first, second, and third trimesters were 4300, 4632, and 2853, respectively. Documented blood glucose values were available for 9282 pregnant women and in them, diagnosis of GDM was made in 740 (8%). Among them, 233 (31.5%), 320 (43.2%), and 187 (25.3%) were in the first, second and third trimesters, respectively. Positive family history of diabetes (43%) and history of fetal loss in previous pregnancy (27%) was more common in women diagnosed with GDM in the first trimester compared to GDM diagnosed in the second or third trimester. Conclusion: Manifestation of GDM in the early weeks of gestation is quite common. PMID:26904467

  8. The effect of a low-calorie diet with and without fenfluramine on the glucose tolerance and insulin secretion of obese maturity-onset diabetics

    PubMed Central

    Dykes, J. Ranald W.

    1973-01-01

    Glucose tolerance and insulin secretion have been measured in twenty-three obese maturity-onset diabetics (twelve high-insulin secretors and eleven lowor normal-insulin secretors) on first presentation and after 10 weeks on a low-calorie diet. There was a significant improvement in glucose tolerance alone, when the results were compared with those from diabetics not on any form of treatment. Thereafter nine of these subjects (five high-insulin secretors and four low- or normal-insulin secretors) continued on the dietary therapy alone, and eleven of the remaining fourteen subjects (six high-insulin secretors and five low- or normal-insulin secretors) continued on the low-calorie diet with the addition of fenfluramine, and their glucose tolerance and insulin secretion were measured again after a further 10 weeks. The remaining three subjects were no longer studied. The nine subjects continuing on the diet alone showed maintenance of the improvement in glucose tolerance achieved during the first 10-week period with no significant change in insulin secretion. The eleven subjects placed on fenfluramine in addition to the diet also showed maintenance of the improvement in glucose tolerance achieved during the first 10-week period with a significant decrease in insulin secretion in the six high-insulin secreting subjects and no significant change in insulin secretion in the five lowor normal-secretors. PMID:4804456

  9. [Amelioration of glucose tolerance and correction of reactive hypoglycemias induced by intravenous calcium infusion cannot be explained by modifications in blood glucagon levels].

    PubMed

    Vexiau, P; Cathelineau, G; Luyckx, A; Lefebvre, P

    1986-08-01

    Glucagon is not involved in intravenous calcium-induced improvement in glucose tolerance nor in correction of reactive hypoglycemia. Recent investigations have shown that intravenous (IV) calcium infusion improved blood glucose values in patients with moderately impaired glucose tolerance, and suppressed hypoglycemia in patients with isolated reactive hypoglycemia. The aim of this study was to investigate the possibility that these changes were secondary to calcium induced alterations in glucagon (IRG) secretion. Four groups of subjects were studied: group 1: normal controls (n = 7); group 2: patients with isolated hypoglycemia (n = 9); group 3: patients with impaired glucose tolerance without reactive hypoglycemia (n = 9) and group 4: patients with impaired glucose tolerance and reactive hypoglycemia (n = 10). All patients were submitted in randomized order to two 5 hour oral glucose tolerance tests (OGTT, 75 g glucose), during a simultaneous infusion, either of saline or of calcium (calcium gluconate 36.3 mEq/5 h.), starting 30 minutes before the OGTT. In none of the groups did calcium infusion influence basal plasma IRG. In group 1 and 3, oral glucose significantly suppressed IRG, and during IV calcium infusion this suppression disappeared. In group 2, glucose ingestion resulted in a paradoxical increase in IRG both during saline and during calcium infusion. In group 4, oral glucose induced a significant drop in plasma IRG and a rebound rise during hypoglycemia, results which were unaffected by IV calcium infusion. These data suggest that glucagon is not involved in the alterations of blood glucose profiles during OGTT observed during intravenous calcium infusion. PMID:3770273

  10. Rapamycin impairs HPD-induced beneficial effects on glucose homeostasis

    PubMed Central

    Chang, Geng-Ruei; Chiu, Yi-Shin; Wu, Ying-Ying; Lin, Yu-Chi; Hou, Po-Hsun; Mao, Frank Chiahung

    2015-01-01

    Background and Purpose Rapamycin, which is used clinically to treat graft rejection, has also been proposed to have an effect on metabolic syndrome; however, very little information is available on its effects in lean animals/humans. The purpose of this study was to characterize further the effects of the continuous use of rapamycin on glucose homeostasis in lean C57BL6/J mice. Experimental Approach Mice were fed a high-protein diet (HPD) for 12 weeks to develop a lean model and then were treated daily with rapamycin for 5 weeks while remaining on a HPD. Metabolic parameters, endocrine profiles, glucose tolerance tests, insulin sensitivity index, the expression of the glucose transporter GLUT4 and chromium distribution were measured in vivo. Key Results Lower body weight gain as well as a decreased caloric intake, fat pads, fatty liver scores, adipocyte size and glucose tolerance test values were observed in HPD-fed mice compared with mice fed a high-fat or standard diet. Despite these beneficial effects, rapamycin-treated lean mice showed greater glucose intolerance, reduced insulin sensitivity, lower muscle GLUT4 expression and changes in chromium levels in tissues even with high insulin levels. Conclusion and Implications Our findings demonstrate that continuous rapamycin administration may lead to the development of diabetes syndrome, as it was found to induce hyperglycaemia and glucose intolerance in a lean animal model. PMID:25884889

  11. Acute Inactivity Impairs Glycemic Control but Not Blood Flow to Glucose Ingestion

    PubMed Central

    Reynolds, Leryn J; Credeur, Daniel P; Holwerda, Seth W; Leidy, Heather J; Fadel, Paul J; Thyfault, John P

    2014-01-01

    Purpose Insulin-stimulated increases in skeletal muscle blood flow play a role in glucose disposal. Indeed, 7 days of aerobic exercise in type 2 diabetes patients increased blood flow responses to an oral glucose tolerance test (OGTT) and improved glucose tolerance. More recent work suggests that reduced daily physical activity impairs glycemic control (GC) in healthy individuals. Herein, we sought to determine if an acute reduction in daily activity (from >10,000 to <5,000 steps/day) for 5 days (RA5) in healthy individuals reduced insulin-stimulated blood flow and GC in parallel and if a 1 day return to activity (RTA1) improved these outcomes. Methods OGTTs were performed as a stimulus to increase insulin in 14 healthy, recreationally active men (24±1.1 yrs) at baseline, RA5, and RTA1. Measures of insulin sensitivity (Matsuda index) and femoral and brachial artery blood flow were made during the OGTT. Free living measures of GC including peak postprandial glucose (peak PPG) were also made via continuous glucose monitoring. Results Femoral and brachial artery blood flow increased during the OGTT but neither was significantly impacted by changes in physical activity (p>0.05). However, insulin sensitivity was decreased by RA5 (11.3±1.5 to 8.0±1.0; p<0.05). Likewise, free living GC measures of peak post prandial blood glucose (113±3 to 123±5 mg/dL; p<0.05) was significantly increased at RA5. Interestingly, insulin sensitivity and GC as assessed by peak PPG were not restored after RTA1 (p>0.05). Conclusions Thus, acute reductions in physical activity impaired GC and insulin sensitivity; however blood flow responses to an OGTT were not affected. Further, a 1 day return to activity was not sufficient to normalize GC following 5 days of reduced daily physical activity. PMID:25207931

  12. Chronic sleep disturbance impairs glucose homeostasis in rats.

    PubMed

    Barf, R Paulien; Meerlo, Peter; Scheurink, Anton J W

    2010-01-01

    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control. PMID:20339560

  13. Effect of insulin immunization on glucose tolerance in normal rats.

    PubMed

    Froguel, P; Reach, G

    1987-01-01

    Normal rats were immunized with insulin and Freund's adjuvant and submitted to an intravenous glucose tolerance test. Plasma glucose and free and total IRI levels were determined and compared to those observed in untreated rats, and in animals injected with the Freund's adjuvant used for the immunization procedure. In six of the 15 insulin injected animals, a significant amount of IRI (more than 100 mU/l) was found to circulate in bound form. In these animals, the fasting plasma glucose concentrations, and glucose disappearance rates were not different from those observed in all the other groups. However, the rise in their free IRI level was delayed, as was the return to basal level: 45 min after glucose injection, the free IRI concentration was still 98 +/- 29 mU/l in the six immunized rats vs 14 +/- 6 mU/l in those treated with Freund's adjuvant (p less than 0.01). Furthermore, the secondary nadir in the plasma glucose concentration observed at 60 min after glucose injection, was lower in the immunized rats (5.4 +/- 0.5 vs 6.8 +/- 0.3 mmol/l, p less than 0.05). It is concluded that in normal animals, IRI binding in proportions similar to those commonly observed in insulin-treated diabetic patients does not alter glucose tolerance but might lead to abnormal insulin kinetics and secondary hypoglycemia. These results might have implications for the use of closed-loop insulin delivery systems in type 1 (insulin-dependent) diabetic patients with insulin antibodies. PMID:3123287

  14. Low expression of insulin signaling molecules impairs glucose uptake in adipocytes after early overnutrition.

    PubMed

    Rodrigues, Ananda L; De Souza, Erica P G; Da Silva, Simone V; Rodrigues, Dayane S B; Nascimento, Aline B; Barja-Fidalgo, Christina; De Freitas, Marta S

    2007-12-01

    Experimental and clinical studies have demonstrated that early postnatal overnutrition represents a risk factor for later obesity and associated metabolic and cardiovascular disturbance. In the present study, we assessed the levels of glucose transporter 4 (GLUT-4), GLUT-1, insulin receptor (IR), IR substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt expression, as well as insulin-stimulated glucose transport and Akt activity in adipocytes from adult rats previously raised in small litters (SL). The normal litter (NL) served as control group. We also investigated glycemia, insulinemia, plasma lipid levels, and glucose tolerance. Our data demonstrated that early postnatal overfeeding induced a persistent hyperphagia accompanied by a significant increase in body weight until 90 days of age. The SL group also presented a significant increase ( approximately 42%) in epidydimal fat weight. Blood glucose, plasma insulin, and lipid levels were similar among the animals from the SL and NL groups. While insulin-stimulated glucose uptake was approximately twofold higher in adipocytes from the NL group, no stimulatory effect was observed in the SL group. The impaired insulin-stimulated glucose transport in adipose cells from the SL rats was associated with a significant decrease in GLUT-4, IRS-1 and PI3K expression, and Akt activity. In contrast, IR and Akt expression in adipocytes was not different between the SL and NL groups. Despite these alterations, our results showed no differences in glucose tolerance test in rats raised under different feeding conditions. Our findings reinforce a potent and long-term effect of neonatal overfeeding, which can program major changes in the metabolic regulatory mechanisms. PMID:18000310

  15. Glucose Homeostatic Law: Insulin Clearance Predicts the Progression of Glucose Intolerance in Humans

    PubMed Central

    Uda, Shinsuke; Kubota, Hiroyuki; Iwaki, Toshinao; Fukuzawa, Hiroki; Komori, Yasunori; Fujii, Masashi; Toyoshima, Yu; Sakaguchi, Kazuhiko; Ogawa, Wataru; Kuroda, Shinya

    2015-01-01

    Homeostatic control of blood glucose is regulated by a complex feedback loop between glucose and insulin, of which failure leads to diabetes mellitus. However, physiological and pathological nature of the feedback loop is not fully understood. We made a mathematical model of the feedback loop between glucose and insulin using time course of blood glucose and insulin during consecutive hyperglycemic and hyperinsulinemic-euglycemic clamps in 113 subjects with variety of glucose tolerance including normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). We analyzed the correlation of the parameters in the model with the progression of glucose intolerance and the conserved relationship between parameters. The model parameters of insulin sensitivity and insulin secretion significantly declined from NGT to IGT, and from IGT to T2DM, respectively, consistent with previous clinical observations. Importantly, insulin clearance, an insulin degradation rate, significantly declined from NGT, IGT to T2DM along the progression of glucose intolerance in the mathematical model. Insulin clearance was positively correlated with a product of insulin sensitivity and secretion assessed by the clamp analysis or determined with the mathematical model. Insulin clearance was correlated negatively with postprandial glucose at 2h after oral glucose tolerance test. We also inferred a square-law between the rate constant of insulin clearance and a product of rate constants of insulin sensitivity and secretion in the model, which is also conserved among NGT, IGT and T2DM subjects. Insulin clearance shows a conserved relationship with the capacity of glucose disposal among the NGT, IGT and T2DM subjects. The decrease of insulin clearance predicts the progression of glucose intolerance. PMID:26623647

  16. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  17. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    PubMed

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin

  18. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

    PubMed Central

    Ferroni, Patrizia; Riondino, Silvia; Buonomo, Oreste; Palmirotta, Raffaele; Guadagni, Fiorella; Roselli, Mario

    2015-01-01

    Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols. PMID:26171112

  19. Impaired fasting glucose is associated with increased regional cerebral amyloid.

    PubMed

    Morris, Jill K; Vidoni, Eric D; Wilkins, Heather M; Archer, Ashley E; Burns, Nicole C; Karcher, Rainer T; Graves, Rasinio S; Swerdlow, Russell H; Thyfault, John P; Burns, Jeffrey M

    2016-08-01

    The Alzheimer's disease risk gene apolipoprotein E epsilon 4 (APOE ε4) is associated with increased cerebral amyloid. Although impaired glucose metabolism is linked to Alzheimer's disease risk, the relationship between impaired glycemia and cerebral amyloid is unclear. To investigate the independent effects of APOE ε4 and impaired glycemia on cerebral amyloid, we stratified nondemented subjects (n = 73) into 4 groups: normal glucose, APOE ε4 noncarrier (control [CNT]; n = 31), normal glucose, APOE ε4 carrier (E4 only; n = 14) impaired glycemia, APOE ε4 noncarrier (IG only; n = 18), and impaired glycemia, APOE ε4 carrier (IG+E4; n = 10). Cerebral amyloid differed both globally (p = 0.023) and regionally; precuneus (p = 0.007), posterior cingulate (PCC; p = 0.020), superior parietal cortex (SPC; p = 0.029), anterior cingulate (p = 0.027), and frontal cortex (p = 0.018). Post hoc analyses revealed that E4 only subjects had increased cerebral amyloid versus CNT globally and regionally in the precuneus, PCC, SPC, anterior cingulate, and frontal cortex. In IG only subjects, increased cerebral amyloid compared with CNT was restricted to precuneus, PCC, and SPC. IG+E4 subjects exhibited higher cerebral amyloid only in the precuneus relative to CNT. These results indicate that impaired glycemia and APOE ε4 genotype are independent risk factors for regional cerebral amyloid deposition. However, APOE ε4 and impaired glycemia did not have an additive effect on cerebral amyloid. PMID:27318141

  20. The performance of hemoglobin A1c against fasting plasma glucose and oral glucose tolerance test in detecting prediabetes and diabetes

    PubMed Central

    Karakaya, Jale; Akin, Safak; Karagaoglu, Ergun; Gurlek, Alper

    2014-01-01

    Background: In recent years, hemoglobin A1c (HbA1c) is accepted among the algorithms used for making diagnosis for diabetes and prediabetes since it does not require subjects to be prepared for giving a blood sample. The aim of this study is to assess the performance of HbA1c against fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in detecting prediabetes and diabetes. Materials and Methods: A total of 315 subjects were included in this study. The success of HbA1c in distinguishing the three diagnostic classes was examined by three-way receiver operating characteristic (ROC) analysis. The best cut-off points for HbA1c were found for discriminating the three disease status. Results: The performance of HbA1c, measured by the volume under the ROC surface (VUS), is found to be statistically significant (VUS = 0.535, P < 0.001). The best cut-off points for discriminating between normal and prediabetes groups and between prediabetes and diabetes groups are c1 = 5.2% and c2 = 6.4% respectively. Conclusion: The performance of HbA1c in distinguishing between the prediabetes and diabetes groups was higher than its ability in distinguishing between healthy and prediabetes groups. This study provides enough information to understand what proportion of diabetes patients were skipped with the HbA1c especially when the test result is healthy or prediabetes. If a subject was diagnosed as healthy or prediabetes by HbA1c, it would be beneficial to verify the status of that subject by the gold standard test (OGTT and FPG). PMID:25657750

  1. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice

    PubMed Central

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E.; Bornfeldt, Karin E.; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  2. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

    PubMed

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E; Bornfeldt, Karin E; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  3. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  4. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time

    PubMed Central

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  5. Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time.

    PubMed

    Ottosson-Laakso, Emilia; Tuomi, Tiinamaija; Forsén, Björn; Gullström, Monika; Groop, Per-Henrik; Groop, Leif; Vikman, Petter

    2016-01-01

    Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time. PMID:26735923

  6. High levels of dietary fat impair glucose homeostasis in rainbow trout.

    PubMed

    Figueiredo-Silva, A Cláudia; Panserat, Stéphane; Kaushik, Sadasivam; Geurden, Inge; Polakof, Sergio

    2012-01-01

    This study was designed to assess the effects of dietary fat levels on glucose homeostasis in rainbow trout under prolonged hyperglycaemia induced by high carbohydrate intake. Trout were fed identical amounts of one of two iso-energetic diets containing either a low (LFD, 3%) or a high fat level (HFD, 20%) and similar amounts of digestible carbohydrates (26-30%) for 14 days. While a single high fat meal reduced glycaemia compared with a low fat meal, the consumption of a high fat diet for 14 days resulted in prolonged hypergylcaemia and reduced plasma glucose clearance in response to an exogenous glucose or insulin challenge. The hyperglycaemic phenotype in trout was characterised by a reduction of the activities of lipogenic and glucose phosphorylating enzymes with a concomitant stimulation of enzymes involved in glucose production in the liver and reduced glycogen levels in the white muscle. Impaired glucose tolerance (IGT) was further associated with a significant reduction of insulin receptor substrate 1 (IRS1) protein content in muscle, and with a poor response of HFD fed fish to an exogenous insulin load, suggestive of impaired insulin signalling in trout fed with a HFD. To our knowledge, this is the first study showing that a teleost can also develop a high fat-induced IGT, characterised by persistent hyperglycaemia and reduced insulin sensitivity, established symptoms of IGT and the prediabetic insulin-resistant state in mammals. Our results also provide evidence that persistent hyperglycaemia after a high carbohydrate meal stems from a metabolic interaction between dietary macronutrients rather than from high carbohydrate intake alone. PMID:22162865

  7. DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose

    PubMed Central

    Liu, Zhi; Chen, Tian; Sun, Wenhua; Yuan, Zongyi; Yu, Mei; Chen, Guoqing; Guo, Weihua; Xiao, Jingang; Tian, Weidong

    2016-01-01

    Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2′-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway. PMID:27273319

  8. DNA Demethylation Rescues the Impaired Osteogenic Differentiation Ability of Human Periodontal Ligament Stem Cells in High Glucose.

    PubMed

    Liu, Zhi; Chen, Tian; Sun, Wenhua; Yuan, Zongyi; Yu, Mei; Chen, Guoqing; Guo, Weihua; Xiao, Jingang; Tian, Weidong

    2016-01-01

    Diabetes mellitus, characterized by abnormally high blood glucose levels, gives rise to impaired bone remodeling. In response to high glucose (HG), the attenuated osteogenic differentiation capacity of human periodontal ligament stem cells (hPDLSCs) is associated with the loss of alveolar bone. Recently, DNA methylation was reported to affect osteogenic differentiation of stem cells in pathological states. However, the intrinsic mechanism linking DNA methylation to osteogenic differentiation ability in the presence of HG is still unclear. In this study, we found that diabetic rats with increased DNA methylation levels in periodontal ligaments exhibited reduced bone mass and density. In vitro application of 5-aza-2'-deoxycytidine (5-aza-dC), a DNA methyltransferase inhibitor, to decrease DNA methylation levels in hPDLSCs, rescued the osteogenic differentiation capacity of hPDLSCs under HG conditions. Moreover, we demonstrated that the canonical Wnt signaling pathway was activated during this process and, under HG circumstances, the 5-aza-dC-rescued osteogenic differentiation capacity was blocked by Dickkopf-1, an effective antagonist of the canonical Wnt signaling pathway. Taken together, these results demonstrate for the first time that suppression of DNA methylation is able to facilitate the osteogenic differentiation capacity of hPDLSCs exposed to HG, through activation of the canonical Wnt signaling pathway. PMID:27273319

  9. Effect of Stevia rebaudiana on glucose tolerance in normal adult humans.

    PubMed

    Curi, R; Alvarez, M; Bazotte, R B; Botion, L M; Godoy, J L; Bracht, A

    1986-01-01

    The effect of aqueous extracts of Stevia rebaudiana leaves on a glucose tolerance test was investigated in 16 normal volunteers. Aqueous extracts of 5 grams of leaves were administered to volunteers at regular 6-h intervals for 3 days. Glucose tolerance tests were performed before and after extract administration. A second group of 6 normal volunteers who ingested an aqueous arabinose solution was also studied to eliminate possible stress effects. The extract of Stevia rebaudiana increased glucose tolerance. The extract significantly decreased plasma glucose levels during the test and after overnight fasting in all volunteers. PMID:3651629

  10. Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats.

    PubMed

    Oritani, Yukihiro; Okitsu, Teru; Nishimura, Eisaku; Sai, Masahiko; Ito, Tatsuhiko; Takeuchi, Shoji

    2016-02-12

    Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that piceatannol increased the insulinogenic index during glucose tolerance tests and that piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that piceatannol orally intaken may enhance glucose tolerance by the effect of intact piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects. PMID:26773506

  11. Yuzu extract prevents cognitive decline and impaired glucose homeostasis in β-amyloid-infused rats.

    PubMed

    Yang, Hye Jeong; Hwang, Jin Taek; Kwon, Dae Young; Kim, Min Jung; Kang, Suna; Moon, Na Rang; Park, Sunmin

    2013-07-01

    Our preliminary study revealed that dementia induced by β-amyloid accumulation impairs peripheral glucose homeostasis (unpublished). We therefore evaluated whether long-term oral consumption of yuzu (Citrus junos Tanaka) extract improves cognitive dysfunction and glucose homeostasis in β-amyloid-induced rats. Male rats received hippocampal CA1 infusions of β-amyloid (25-35) [plaque forming β-amyloid; Alzheimer disease (AD)] or β-amyloid (35-25) [non-plaque forming β-amyloid; C (non-Alzheimer disease control)] at a rate of 3.6 nmol/d for 14 d. AD rats were divided into 2 dietary groups that received either 3% lyophilized 70% ethanol extracts of yuzu (AD-Y) or 3% dextrin (AD-C) in high-fat diets (43% energy as fat). The AD-C group exhibited greater hippocampal β-amyloid deposition, which was not detected in the C group, and attenuated hippocampal insulin signaling. Yuzu treatment prevented β-amyloid accumulation, increased tau phosphorylation, and attenuated hippocampal insulin signaling observed in AD-C rats. Consistent with β-amyloid accumulation, the AD-C rats experienced cognitive dysfunction, which was prevented by yuzu. AD-C rats gained less weight than did C rats due to decreased feed consumption, and yuzu treatment prevented the decrease in feed consumption. Serum glucose concentrations were higher in AD-C than in C rats at 40-120 min after glucose loading during an oral-glucose-tolerance test, but not at 0-40 min. Serum insulin concentrations were highly elevated in AD-C rats but not enough to lower serum glucose to normal concentrations, indicating that rats in the AD-C group had insulin resistance and a borderline diabetic state. Although AD-C rats were profoundly insulin resistant, AD-Y rats exhibited normal first and second phases of glucose tolerance and insulin sensitivity and secretion. In conclusion, yuzu treatment prevented the cognitive dysfunction and impaired energy and glucose homeostasis induced by β-amyloid infusion. PMID:23719224

  12. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    PubMed

    Moore, Rebecca; Adler, Hugh; Jackson, Valerie; Lawless, Mairead; Byrne, Maria; Eogan, Maeve; Lambert, John S

    2016-06-01

    Metabolic complications, including diabetes mellitus, have been increasingly recognised in HIV-infected individuals since the introduction of antiretroviral therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor for impaired glucose metabolism, and previous studies have given conflicting results regarding the contribution of PIs to impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) in pregnant HIV-infected women. We conducted a retrospective review of all HIV-infected women attending a combined infectious disease and antenatal clinic between 2007 and 2013 who underwent a 100 g oral glucose tolerance test (OGTT) at 24-28 weeks. We grouped the patients based on whether their OGTT result was normal or abnormal, and compared the groups using standard parametric tests (t-test and Fisher's exact test). Of 263 women with HIV who attended the clinic, 142 (53.9%) attended for OGTT and were eligible for inclusion. The mean age was 31 years (SD 5.37), all women were of European or African origin and 33.7% had a body mass index ≥30 kg/m(2) About 93.7% were on PI-based regimens. At delivery, the mean CD4 count was 526 cells/µL, and 13% of patients had a detectable viraemia. The prevalence of IGT was 2.8%, while the prevalence of GDM was 2.1%. Also, 71.4% (n = 5) of women with abnormal glucose metabolism were taking PIs versus 94.8% (n = 128) of normoglycaemic women (p = 0.06). We did not confirm an increased rate of GDM in HIV-infected women in our patient population and found no association between PI use and GDM. PMID:25999164

  13. Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study

    PubMed Central

    Wang, Liang; Cui, Liufu; Wang, Yanxue; Vaidya, Anand; Chen, Shuohua; Zhang, Caifeng; Zhu, Ying; Li, Dongqing; Hu, Frank B; Wu, Shouling; Gao, Xiang

    2015-01-01

    Background: To investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes. Methods: The prospective analysis included 73 357 participants of the Kailuan cohort (57 719 men and 15 638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models. Results: During 4 years of follow-up, 17 463 incident IFG cases and 4 649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8). Conclusion: Faster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes. PMID:26002923

  14. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    PubMed Central

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  15. Gut microbiota and diet in patients with different glucose tolerance

    PubMed Central

    Egshatyan, Lilit; Kashtanova, Daria; Popenko, Anna; Tkacheva, Olga; Tyakht, Alexander; Alexeev, Dmitry; Karamnova, Natalia; Kostryukova, Elena; Babenko, Vladislav; Vakhitova, Maria; Boytsov, Sergey

    2015-01-01

    Type 2 diabetes (T2D) is a serious disease. The gut microbiota (GM) has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. To investigate the GM composition in association with the dietary patterns in patients with different glucose tolerance, we analyzed 92 patients: with normal glucose tolerance (n=48), prediabetes (preD, n=24), and T2D (n=20). Metagenomic analysis was performed using 16S rRNA sequencing. The diet has been studied by a frequency method with a quantitative evaluation of food intake using a computer program. Microbiota in the samples was predominantly represented by Firmicutes, in a less degree by Bacteroidetes. Blautia was a dominant genus in all samples. The representation of Blautia, Serratia was lower in preD than in T2D patients, and even lower in those with normal glucose tolerance. After the clustering of the samples into groups according to the percentage of protein, fat, carbohydrates in the diet, the representation of the Bacteroides turned to be lower and Prevotella abundance turned to be higher in carbohydrate cluster. There were more patients with insulin resistance, T2D in the fat–protein cluster. Using the Calinski–Harabasz index identified the samples with more similar diets. It was discovered that half of the patients with a high-fat diet had normal tolerance, the others had T2D. The regression analysis showed that these T2D patients also had a higher representation of Blautia. Our study provides the further evidence concerning the structural modulation of the GM in the T2DM pathogenesis depending on the dietary patterns. PMID:26555712

  16. Blueberries improve glucose tolerance and lipid handling without altering body composition in obese postmenopausal mice

    PubMed Central

    Elks, Carrie M.; Terrebonne, Jennifer D.; Ingram, Donald K.; Stephens, Jacqueline M.

    2014-01-01

    Objective Metabolic syndrome (MetS) risk increases significantly during menopause and remains elevated post-menopause. Several botanicals, including blueberries (BB), have been shown to delay MetS progression, but few studies have been conducted in postmenopausal animal models. Here, we examined the effects of BB supplementation on obese postmenopausal mice using a chemically-induced menopause model. Design and Methods After induction of menopause, mice were fed a high-fat diet or the same diet supplemented with 4% BB powder for 12 weeks. Body weight and body composition were measured, and mice were subjected to glucose and insulin tolerance tests. Serum triglycerides and adiponectin were measured, and liver histology and hepatic gene expression were assessed. Results: Menopausal and BB-supplemented mice had significantly higher body weights and fat mass than control mice, while menopausal mice had impaired glucose tolerance and higher serum triglycerides when compared with control and BB-supplemented mice. Menopausal mice also had hepatic steatosis that was prevented by BB supplementation and correlated with expression of genes involved in hepatic fatty acid oxidation. Conclusions We conclude that BB supplementation prevents the glucose intolerance and hepatic steatosis that occur in obese postmenopausal mice, and that these effects are independent of body weight. PMID:25611327

  17. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  18. Chronic overeating impairs hepatic glucose uptake and disposition.

    PubMed

    Coate, Katie C; Kraft, Guillaume; Shiota, Masakazu; Smith, Marta S; Farmer, Ben; Neal, Doss W; Williams, Phil; Cherrington, Alan D; Moore, Mary Courtney

    2015-05-15

    Dogs consuming a hypercaloric high-fat and -fructose diet (52 and 17% of total energy, respectively) or a diet high in either fructose or fat for 4 wk exhibited blunted net hepatic glucose uptake (NHGU) and glycogen deposition in response to hyperinsulinemia, hyperglycemia, and portal glucose delivery. The effect of a hypercaloric diet containing neither fructose nor excessive fat has not been examined. Dogs with an initial weight of ≈25 kg consumed a chow and meat diet (31% protein, 44% carbohydrate, and 26% fat) in weight-maintaining (CTR; n = 6) or excessive (Hkcal; n = 7) amounts for 4 wk (cumulative weight gain 0.0 ± 0.3 and 1.5 ± 0.5 kg, respectively, P < 0.05). They then underwent clamp studies with infusions of somatostatin and intraportal insulin (4× basal) and glucagon (basal). The hepatic glucose load was doubled with peripheral (Pe) glucose infusion for 90 min (P1) and intraportal glucose at 4 mg·kg(-1)·min(-1) plus Pe glucose for the final 90 min (P2). NHGU was blunted (P < 0.05) in Hkcal during both periods (mg·kg(-1)·min(-1); P1: 1.7 ± 0.2 vs. 0.3 ± 0.4; P2: 3.6 ± 0.3 vs. 2.3 ± 0.4, CTR vs. Hkcal, respectively). Terminal hepatic glucokinase catalytic activity was reduced nearly 50% in Hkcal vs. CTR (P < 0.05), although glucokinase protein did not differ between groups. In Hkcal vs. CTR, liver glycogen was reduced 27% (P < 0.05), with a 91% increase in glycogen phosphorylase activity (P < 0.05) but no significant difference in glycogen synthase activity. Thus, Hkcal impaired NHGU and glycogen synthesis compared with CTR, indicating that excessive energy intake, even if the diet is balanced and nutritious, negatively impacts hepatic glucose metabolism. PMID:25783892

  19. Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance

    PubMed Central

    Mitchell, Ryan K.; Hu, Ming; Chabosseau, Pauline L.; Cane, Matthew C.; Meur, Gargi; Bellomo, Elisa A.; Carzaniga, Raffaella; Collinson, Lucy M.; Li, Wen-Hong

    2016-01-01

    Zinc transporter 8 (ZnT8), encoded by SLC30A8, is chiefly expressed within pancreatic islet cells, where it mediates zinc (Zn2+) uptake into secretory granules. Although a common nonsynonymous polymorphism (R325W), which lowers activity, is associated with increased type 2 diabetes (T2D) risk, rare inactivating mutations in SLC30A8 have been reported to protect against T2D. Here, we generate and characterize new mouse models to explore the impact on glucose homeostasis of graded changes in ZnT8 activity in the β-cell. Firstly, Slc30a8 was deleted highly selectively in these cells using the novel deleter strain, Ins1Cre. The resultant Ins1CreZnT8KO mice displayed significant (P < .05) impairments in glucose tolerance at 10 weeks of age vs littermate controls, and glucose-induced increases in circulating insulin were inhibited in vivo. Although insulin release from Ins1CreZnT8KO islets was normal, Zn2+ release was severely impaired. Conversely, transgenic ZnT8Tg mice, overexpressing the transporter inducibly in the adult β-cell using an insulin promoter-dependent Tet-On system, showed significant (P < .01) improvements in glucose tolerance compared with control animals. Glucose-induced insulin secretion from ZnT8Tg islets was severely impaired, whereas Zn2+ release was significantly enhanced. Our findings demonstrate that glucose homeostasis in the mouse improves as β-cell ZnT8 activity increases, and remarkably, these changes track Zn2+ rather than insulin release in vitro. Activation of ZnT8 in β-cells might therefore provide the basis of a novel approach to treating T2D. PMID:26584158

  20. Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance.

    PubMed

    Mitchell, Ryan K; Hu, Ming; Chabosseau, Pauline L; Cane, Matthew C; Meur, Gargi; Bellomo, Elisa A; Carzaniga, Raffaella; Collinson, Lucy M; Li, Wen-Hong; Hodson, David J; Rutter, Guy A

    2016-01-01

    Zinc transporter 8 (ZnT8), encoded by SLC30A8, is chiefly expressed within pancreatic islet cells, where it mediates zinc (Zn(2+)) uptake into secretory granules. Although a common nonsynonymous polymorphism (R325W), which lowers activity, is associated with increased type 2 diabetes (T2D) risk, rare inactivating mutations in SLC30A8 have been reported to protect against T2D. Here, we generate and characterize new mouse models to explore the impact on glucose homeostasis of graded changes in ZnT8 activity in the β-cell. Firstly, Slc30a8 was deleted highly selectively in these cells using the novel deleter strain, Ins1Cre. The resultant Ins1CreZnT8KO mice displayed significant (P < .05) impairments in glucose tolerance at 10 weeks of age vs littermate controls, and glucose-induced increases in circulating insulin were inhibited in vivo. Although insulin release from Ins1CreZnT8KO islets was normal, Zn(2+) release was severely impaired. Conversely, transgenic ZnT8Tg mice, overexpressing the transporter inducibly in the adult β-cell using an insulin promoter-dependent Tet-On system, showed significant (P < .01) improvements in glucose tolerance compared with control animals. Glucose-induced insulin secretion from ZnT8Tg islets was severely impaired, whereas Zn(2+) release was significantly enhanced. Our findings demonstrate that glucose homeostasis in the mouse improves as β-cell ZnT8 activity increases, and remarkably, these changes track Zn(2+) rather than insulin release in vitro. Activation of ZnT8 in β-cells might therefore provide the basis of a novel approach to treating T2D. PMID:26584158

  1. Strength training improves muscle aerobic capacity and glucose tolerance in elderly.

    PubMed

    Frank, P; Andersson, E; Pontén, M; Ekblom, B; Ekblom, M; Sahlin, K

    2016-07-01

    The primary aim of this study was to investigate the effect of short-term resistance training (RET) on mitochondrial protein content and glucose tolerance in elderly. Elderly women and men (age 71 ± 1, mean ± SEM) were assigned to a group performing 8 weeks of resistance training (RET, n = 12) or no training (CON, n = 9). The RET group increased in (i) knee extensor strength (concentric +11 ± 3%, eccentric +8 ± 3% and static +12 ± 3%), (ii) initial (0-30 ms) rate of force development (+52 ± 26%) and (iii) contents of proteins related to signaling of muscle protein synthesis (Akt +69 ± 20 and mammalian target of rapamycin +69 ± 32%). Muscle fiber type composition changed to a more oxidative profile in RET with increased amount of type IIa fibers (+26.9 ± 6.8%) and a trend for decreased amount of type IIx fibers (-16.4 ± 18.2%, P = 0.068). Mitochondrial proteins (OXPHOS complex II, IV, and citrate synthase) increased in RET by +30 ± 11%, +99 ± 31% and +29 ± 8%, respectively. RET resulted in improved oral glucose tolerance measured as reduced area under curve for glucose (-21 ± 26%) and reduced plasma glucose 2 h post-glucose intake (-14 ± 5%). In CON parameters were unchanged or impaired. In conclusion, short-term resistance training in elderly not only improves muscular strength, but results in robust increases in several parameters related to muscle aerobic capacity. PMID:26271931

  2. Experimental type II diabetes and related models of impaired glucose metabolism differentially regulate glucose transporters at the proximal tubule brush border membrane.

    PubMed

    Chichger, Havovi; Cleasby, Mark E; Srai, Surjit K; Unwin, Robert J; Debnam, Edward S; Marks, Joanne

    2016-06-01

    What is the central question of this study? Although SGLT2 inhibitors represent a promising treatment for patients suffering from diabetic nephropathy, the influence of metabolic disruption on the expression and function of glucose transporters is largely unknown. What is the main finding and its importance? In vivo models of metabolic disruption (Goto-Kakizaki type II diabetic rat and junk-food diet) demonstrate increased expression of SGLT1, SGLT2 and GLUT2 in the proximal tubule brush border. In the type II diabetic model, this is accompanied by increased SGLT- and GLUT-mediated glucose uptake. A fasted model of metabolic disruption (high-fat diet) demonstrated increased GLUT2 expression only. The differential alterations of glucose transporters in response to varying metabolic stress offer insight into the therapeutic value of inhibitors. SGLT2 inhibitors are now in clinical use to reduce hyperglycaemia in type II diabetes. However, renal glucose reabsorption across the brush border membrane (BBM) is not completely understood in diabetes. Increased consumption of a Western diet is strongly linked to type II diabetes. This study aimed to investigate the adaptations that occur in renal glucose transporters in response to experimental models of diet-induced insulin resistance. The study used Goto-Kakizaki type II diabetic rats and normal rats rendered insulin resistant using junk-food or high-fat diets. Levels of protein kinase C-βI (PKC-βI), GLUT2, SGLT1 and SGLT2 were determined by Western blotting of purified renal BBM. GLUT- and SGLT-mediated d-[(3) H]glucose uptake by BBM vesicles was measured in the presence and absence of the SGLT inhibitor phlorizin. GLUT- and SGLT-mediated glucose transport was elevated in type II diabetic rats, accompanied by increased expression of GLUT2, its upstream regulator PKC-βI and SGLT1 protein. Junk-food and high-fat diet feeding also caused higher membrane expression of GLUT2 and its upstream regulator PKC

  3. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans.

    PubMed

    Morris, Christopher J; Yang, Jessica N; Garcia, Joanna I; Myers, Samantha; Bozzi, Isadora; Wang, Wei; Buxton, Orfeu M; Shea, Steven A; Scheer, Frank A J L

    2015-04-28

    Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers. PMID:25870289

  4. Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

    PubMed

    Kuk, Jennifer L; Brown, Ruth E

    2016-07-01

    This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance. PMID:27216413

  5. Acute effects of guar gum on glucose tolerance and intestinal absorption of nutrients in rats.

    PubMed

    Daumerie, C; Henquin, J C

    1982-03-01

    The mechanism by which non-digestible fibres improve oral glucose tolerance is still unclear. We have studied the effects of guar gum on oral carbohydrate tolerance and intestinal absorption of nutrients in anaesthetized rats. Addition of guar to an intragastric glucose load (1 g/kg) markedly delayed the rise in plasma glucose levels when the concentration of the gum was adequate (10 mg/ml). The insulin response was somewhat less marked, but the differences were not significant. When glucose was introduced directly into the duodenum, the gum only slightly reduced the rise in glucose levels, during the first 15 min. If sucrose (1 g/kg) was infused in the duodenum, acarboseR, an alpha-glucosidase inhibitor, but not guar, slowed the rise in plasma glucose and insulin levels. Intestinal absorption was measured in a tied duodenojejunal loop. Guar decreased active transport of glucose (4 mmol/l) by approximately 20%, but had no significant effect on the passive transport of glucose (100 mmol/l), nor on the absorption of sucrose (40 mmol/l) or leucine (4 mmol/l). At the concentration which improved glucose tolerance (10 mg/ml), but not at lower concentrations, guar gum markedly slowed gastric emptying. These results suggest that guar gum improves tolerance to oral carbohydrates mainly by decreasing the rate of gastric emptying, but inhibition of intestinal absorption may also be involved in the presence of low concentrations of the sugars. PMID:6284563

  6. Central acylated ghrelin improves memory function and hippocampal AMPK activation and partly reverses the impairment of energy and glucose metabolism in rats infused with β-amyloid.

    PubMed

    Kang, Suna; Moon, Na Rang; Kim, Da Sol; Kim, Sung Hoon; Park, Sunmin

    2015-09-01

    Ghrelin is a gastric hormone released during the fasting state that targets the hypothalamus where it induces hunger; however, emerging evidence suggests it may also affect memory function. We examined the effect of central acylated-ghrelin and DES-acetylated ghrelin (native ghrelin) on memory function and glucose metabolism in an experimentally induced Alzheimer's disease (AD) rat model. AD rats were divided into 3 groups and Non-AD rats were used as a normal-control group. Each rat in the AD groups had intracerebroventricular (ICV) infusion of β-amyloid (25-35; 16.8nmol/day) into the lateral ventricle for 3 days, and then the pumps were changed to infuse either acylated-ghrelin (0.2nmol/h; AD-G), DES-acylated ghrelin (0.2nmol/h; AD-DES-G), or saline (control; AD-C) for 3 weeks. The Non-AD group had ICV infusion of β-amyloid (35-25) which does not deposit in the hippocampus. During the next 3 weeks memory function, food intake, body weight gain, body fat composition, and glucose metabolism were measured. AD-C exhibited greater β-amyloid deposition compared to Non-AD-C, and AD-G suppressed the increased β-amyloid deposition and potentiated the phosphorylation AMPK. In addition, AD-G increased the phosphorylation GSK and decreased the phosphorylation of Tau in comparison to AD-C and AD-DES-G. Cognitive function, measured by passive avoidance and water maze tests, was much lower in AD-C than Non-AD-C whereas AD-G but not AD-DES-G prevented the decrease (p<0.021). Body weight gain was lower in AD-C group than Non-AD-C group without changing epididymal fat mass. AD-G reversed the decrease in body weight which was due to increased energy intake and decreased energy expenditure. The AD-G group exhibited a decrease in the second part of serum glucose levels during an oral glucose tolerance test (OGTT) compared to the AD-C and AD-DES-G group (p<0.009). However, area under the curve of insulin during the first part of OGTT was higher in AD-DES-G than other groups

  7. Pre-Type 1 Diabetes Dysmetabolism: Maximal sensitivity achieved with Both Oral and Intravenous Glucose Tolerance Testing

    PubMed Central

    Barker, Jennifer M.; McFann, Kim; Harrison, Leonard C.; Fourlanos, Spiros; Krischer, Jeffrey; Cuthbertson, David; Chase, H. Peter; Eisenbarth, George S.; Group, the DPT-1 Study

    2007-01-01

    Objective To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes. Study design Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%). Conclusions Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. PMID:17188609

  8. Effect of the consumption of β-lactoglobulin and epigallocatechin-3-gallate with or without calcium on glucose tolerance in C57BL/6 mice.

    PubMed

    Carnovale, Valérie; Pilon, Geneviève; Britten, Michel; Bazinet, Laurent; Couillard, Charles

    2016-05-01

    Interactions between β-lactoglobulin (β-lg) and epigallocatechin-3-gallate (EGCG) may modulate their health benefits. The objective of this study was therefore to investigate the synergistic effect of consuming β-lg and EGCG complexes on glucose tolerance of C57BL/6 male mice given an oral glucose tolerance test (OGTT) and randomized to one of the following treatments administered prior to the OGTT: 1) simulated milk ultrafiltrate (SMUF(-)), 2) SMUF(-) + EGCG, 3) SMUF(-) + β-lg, 4) SMUF(-) + EGCG + β-lg, 5) SMUF + calcium (SMUF(+)) and 6) SMUF(+) + EGCG + β-lg. We found no significant between-group difference in postprandial glucose response. However, when mice were separated in those who received β-lg from those who did not, we found that the latter displayed significantly higher postprandial glucose concentrations. Our results support the beneficial impact of β-lg on glycemic control and suggest that concomitant EGCG or calcium consumption does not improve this effect. PMID:26960683

  9. Overexpression of SIRT1 in Mouse Forebrain Impairs Lipid/Glucose Metabolism and Motor Function

    PubMed Central

    Wu, Dongmei; Qiu, Yifu; Gao, Xiang; Yuan, Xiao-Bing; Zhai, Qiwei

    2011-01-01

    SIRT1 plays crucial roles in glucose and lipid metabolism, and has various functions in different tissues including brain. The brain-specific SIRT1 knockout mice display defects in somatotropic signaling, memory and synaptic plasticity. And the female mice without SIRT1 in POMC neuron are more sensitive to diet-induced obesity. Here we created transgenic mice overexpressing SIRT1 in striatum and hippocampus under the control of CaMKIIα promoter. These mice, especially females, exhibited increased fat accumulation accompanied by significant upregulation of adipogenic genes in white adipose tissue. Glucose tolerance of the mice was also impaired with decreased Glut4 mRNA levels in muscle. Moreover, the SIRT1 overexpressing mice showed decreased energy expenditure, and concomitantly mitochondria-related genes were decreased in muscle. In addition, these mice showed unusual spontaneous physical activity pattern, decreased activity in open field and rotarod performance. Further studies demonstrated that SIRT1 deacetylated IRS-2, and upregulated phosphorylation level of IRS-2 and ERK1/2 in striatum. Meanwhile, the neurotransmitter signaling in striatum and the expression of endocrine hormones in hypothalamus and serum T3, T4 levels were altered. Taken together, our findings demonstrate that SIRT1 in forebrain regulates lipid/glucose metabolism and motor function. PMID:21738790

  10. CMKLR1 deficiency influences glucose tolerance and thermogenesis in mice on high fat diet.

    PubMed

    Huang, Chen; Wang, Miaomiao; Ren, Lirong; Xiang, Liang; Chen, Jie; Li, Mengxia; Xiao, Tianxia; Ren, Peigen; Xiong, Likuan; Zhang, Jian V

    2016-04-29

    Obesity has become a global epidemic disease, contributing to increases in the prevalence of type 2 diabetes. CMKLR1, one of the receptors for chemerin, has a wide range of functions in physiological and pathological activity, including innate and adaptive immunity, inflammation, metabolism and reproduction. In our study, CMKLR1 deficiency did not influence the gain of body weight but did exacerbate glucose intolerance, increase serum insulin level, and promote insulin resistance in mice on high fat diets. The expression of thermogenesis related genes was examined and indicated to decrease in CMKLR1 knockout (KO) mice in both normal and cold environments, which indicated CMKLR1 influence the thermogenesis process. Cold exposure induced significant body mass decrease and improved glucose tolerance and insulin resistance in wild type HFD mice but had no obvious effect on CMKLR1 KO HFD mice. In vitro, loss of CMKLR1 did not significantly influence the differentiation of stromal vascular fibroblasts (SVFs) derived from adipose tissue, but did suppress the expression of thermogenesis related genes. Collectively, these data demonstrate that CMKLR1 deficiency induces inbalance of glucose metabolism and impairs the cold induced-thermogenesis process in high diet models. PMID:26972253

  11. Glucose-6-phosphate dehydrogenase regulation in the hepatopancreas of the anoxia-tolerant marine mollusc, Littorina littorea.

    PubMed

    Lama, Judeh L; Bell, Ryan A V; Storey, Kenneth B

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH) gates flux through the pentose phosphate pathway and is key to cellular antioxidant defense due to its role in producing NADPH. Good antioxidant defenses are crucial for anoxia-tolerant organisms that experience wide variations in oxygen availability. The marine mollusc, Littorina littorea, is an intertidal snail that experiences daily bouts of anoxia/hypoxia with the tide cycle and shows multiple metabolic and enzymatic adaptations that support anaerobiosis. This study investigated the kinetic, physical and regulatory properties of G6PDH from hepatopancreas of L. littorea to determine if the enzyme is differentially regulated in response to anoxia, thereby providing altered pentose phosphate pathway functionality under oxygen stress conditions. Several kinetic properties of G6PDH differed significantly between aerobic and 24 h anoxic conditions; compared with the aerobic state, anoxic G6PDH (assayed at pH 8) showed a 38% decrease in K m G6P and enhanced inhibition by urea, whereas in pH 6 assays K m NADP and maximal activity changed significantly between the two states. The mechanism underlying anoxia-responsive changes in enzyme properties proved to be a change in the phosphorylation state of G6PDH. This was documented with immunoblotting using an anti-phosphoserine antibody, in vitro incubations that stimulated endogenous protein kinases versus protein phosphatases and significantly changed K m G6P, and phosphorylation of the enzyme with (32)P-ATP. All these data indicated that the aerobic and anoxic forms of G6PDH were the high and low phosphate forms, respectively, and that phosphorylation state was modulated in response to selected endogenous protein kinases (PKA or PKG) and protein phosphatases (PP1 or PP2C). Anoxia-induced changes in the phosphorylation state of G6PDH may facilitate sustained or increased production of NADPH to enhance antioxidant defense during long term anaerobiosis and/or during the transition

  12. Adaptive Blood Glucose Monitoring and Insulin Measurement Devices for Visually Impaired Persons.

    ERIC Educational Resources Information Center

    Petzinger, R. A.

    1993-01-01

    This article describes devices that people with visual impairments and diabetes can use to monitor blood glucose levels and measure insulin. A table lists devices, their manufacturers (including address and telephone number), and comments about the devices. (DB)

  13. Role of Galectin-3 in Obesity and Impaired Glucose Homeostasis

    PubMed Central

    Menini, Stefano; Iacobini, Carla; Blasetti Fantauzzi, Claudia; Pesce, Carlo M.; Pugliese, Giuseppe

    2016-01-01

    Galectin-3 is an important modulator of several biological functions. It has been implicated in numerous disease conditions, particularly in the long-term complications of diabetes because of its ability to bind the advanced glycation/lipoxidation end products that accumulate in target organs and exert their toxic effects by triggering proinflammatory and prooxidant pathways. Recent evidence suggests that galectin-3 may also participate in the development of obesity and type 2 diabetes. It has been shown that galectin-3 levels are higher in obese and diabetic individuals and parallel deterioration of glucose homeostasis. Two studies in galectin-3 knockout mice fed a high-fat diet (HFD) have shown increased adiposity and adipose tissue and systemic inflammation associated with altered glucose homeostasis, suggesting that galectin-3 negatively modulates the responsiveness of innate and adaptive immunity to overnutrition. However, these studies have also shown that impaired glucose homeostasis occurs in galectin-3 knockout animals independently of obesity. Moreover, another study reported decreased weight and fat mass in HFD-fed galectin-3 knockout mice. In vitro, galectin-3 was found to stimulate differentiation of preadipocytes into mature adipocytes. Altogether, these data indicate that galectin-3 deserves further attention in order to clarify its role as a potential player and therapeutic target in obesity and type 2 diabetes. PMID:26770660

  14. Fructose impairs glucose-induced hepatic triglyceride synthesis

    PubMed Central

    2011-01-01

    Obesity, type 2 diabetes and hyperlipidemia frequently coexist and are associated with significantly increased morbidity and mortality. Consumption of refined carbohydrate and particularly fructose has increased significantly in recent years and has paralled the increased incidence of obesity and diabetes. Human and animal studies have demonstrated that high dietary fructose intake positively correlates with increased dyslipidemia, insulin resistance, and hypertension. Metabolism of fructose occurs primarily in the liver and high fructose flux leads to enhanced hepatic triglyceride accumulation (hepatic steatosis). This results in impaired glucose and lipid metabolism and increased proinflammatory cytokine expression. Here we demonstrate that fructose alters glucose-stimulated expression of activated acetyl CoA carboxylase (ACC), pSer hormone sensitive lipase (pSerHSL) and adipose triglyceride lipase (ATGL) in hepatic HepG2 or primary hepatic cell cultures in vitro. This was associated with increased de novo triglyceride synthesis in vitro and hepatic steatosis in vivo in fructose- versus glucose-fed and standard-diet fed mice. These studies provide novel insight into the mechanisms involved in fructose-mediated hepatic hypertriglyceridemia and identify fructose-uptake as a new potential therapeutic target for lipid-associated diseases. PMID:21261970

  15. How well are pregnant women in Croatia informed about the oral glucose tolerance test?

    PubMed Central

    Kocijancic, Marija

    2015-01-01

    Introduction Preanalytical errors still constitute the largest source of errors in laboratory work. Proper patient preparation and patient’s knowledge about a particular procedure affects its accuracy and reliability. We hypothesized that most of pregnant women are not well enough informed about the proper procedure for the OGTT. The aims of this study were to investigate: (i) how well pregnant women are informed about the OGTT; (ii) the most common way to inform pregnant women about OGTT and (iii) whether pregnant women’s level of knowledge about the OGTT differ regarding source of information. Materials and methods The anonymous questionnaire was conducted across the country in 23 Croatian primary and secondary healthcare centres. The questionnaire contained 9 questions on certain demographic data and familiarity with OGTT procedure. All 343 participants filled the questionnaire before the first blood draw. Results 42% of the participants demonstrated high and 38% adequate level of knowledge about the OGTT procedure. Majority of participants were informed about the procedure by gynaecologist (56%). The level of knowledge differed among participants with different sources of information (P = 0.030). Further analysis showed that the level of knowledge was lower in pregnant women having received information from their gynaecologist compared to pregnant women who received information from the laboratory staff. Conclusions In general, pregnant women are familiar with OGTT procedure, main source of information about the OGTT procedure is their gynaecologist, but the level of knowledge was higher in women who received information about the OGTT procedure from the laboratory staff. PMID:26110035

  16. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats

    PubMed Central

    Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I.; Cruzblanca, Humberto; Mancilla, Evelyn

    2016-01-01

    Objective Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Materials and Methods Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Results Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable

  17. Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans.

    PubMed

    Ciubotaru, Irina; Green, Stefan J; Kukreja, Subhash; Barengolts, Elena

    2015-11-01

    The importance of gut microbiota in pathogenesis of diabetes remains unknown. This study investigated the relationship between microbiota and metabolic markers in African American men (AAM) with prediabetes and hypovitaminosis D. The study was ancillary to a randomized trial of vitamin D supplementation with weekly ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based on changes in oral glucose tolerance between baseline and exit. Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2. Microbiota composition was analyzed in stool collected at the exit (n = 115) and compared between Gr-1 and Gr-2, as well as between the lowest and highest quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25-hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister. Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D (eg, Ruminococcus, Roseburia, Blautia, Dorea) were clearly distinct from those of dietary intake (eg, Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium, Catenibacterium, Streptococcus). These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development. Although results suggest that specific taxa are associated with glycemic stability over time, a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated. PMID:26209747

  18. Electroacupuncture improves glucose tolerance through cholinergic nerve and nitric oxide synthase effects in rats.

    PubMed

    Lin, Rong-Tsung; Chen, Ching-Yuan; Tzeng, Chung-Yuh; Lee, Yu-Chen; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Cheng, Juei-Tang; Lin, Jaung-Geng; Chang, Shih-Liang

    2011-04-25

    The purpose of this investigation was to evaluate the effect and mechanisms of electroacupuncture (EA) at the bilateral Zusanli acupoints (ST-36) on glucose tolerance in normal rats. Intravenous glucose tolerance test (IVGTT) was performed to examine the effects of electroacupuncture (EA) on glucose tolerance in rats. The EA group underwent EA at the ST-36, with settings of 15 Hz, 10 mA, and 60 min; the control group underwent the same treatments, but without EA. Atropine, hemicholinium-3 (HC-3) or NG-nitro-L-arginine methyl ester (L-NAME) were injected into the rats alone or simultaneously and EA was performed to investigate differences in plasma glucose levels compared to the control group. Plasma samples were obtained for assaying plasma glucose and free fatty acid (FFA) levels. Western blot was done to determine the insulin signal protein and nNOS to exam the correlation between EA and improvement in glucose tolerance. The EA group had significantly lower plasma glucose levels compared to the control group. Plasma glucose levels differed significantly between the EA and control groups after the administration of L-NAME, atropine, or HC-3 treatments alone, but there were no significant differences in plasma glucose with combined treatment of L-NAME and atropine or L-NAME and HC-3. EA decreased FFA levels and enhanced insulin signal protein (IRS1) and nNOS activities in skeletal muscle during IVGTT. In summary, EA stimulated cholinergic nerves and nitric oxide synthase for lowering plasma FFA levels to improve glucose tolerance. PMID:21376780

  19. Ywhaz/14-3-3ζ Deletion Improves Glucose Tolerance Through a GLP-1-Dependent Mechanism.

    PubMed

    Lim, Gareth E; Piske, Micah; Lulo, James E; Ramshaw, Hayley S; Lopez, Angel F; Johnson, James D

    2016-07-01

    Multiple signaling pathways mediate the actions of metabolic hormones to control glucose homeostasis, but the proteins that coordinate such networks are poorly understood. We previously identified the molecular scaffold protein, 14-3-3ζ, as a critical regulator of in vitro β-cell survival and adipogenesis, but its metabolic roles in glucose homeostasis have not been studied in depth. Herein, we report that Ywhaz gene knockout mice (14-3-3ζKO) exhibited elevated fasting insulin levels while maintaining normal β-cell responsiveness to glucose when compared with wild-type littermate controls. In contrast with our observations after an ip glucose bolus, glucose tolerance was significantly improved in 14-3-3ζKO mice after an oral glucose gavage. This improvement in glucose tolerance was associated with significantly elevated fasting glucagon-like peptide-1 (GLP-1) levels. 14-3-3ζ knockdown in GLUTag L cells elevated GLP-1 synthesis and increased GLP-1 release. Systemic inhibition of the GLP-1 receptor attenuated the improvement in oral glucose tolerance that was seen in 14-3-3ζKO mice. When taken together these findings demonstrate novel roles of 14-3-3ζ in the regulation of glucose homeostasis and suggest that modulating 14-3-3ζ levels in intestinal L cells may have beneficial metabolic effects through GLP-1-dependent mechanisms. PMID:27167773

  20. Long-term effects of high-fat or high-carbohydrate diets on glucose tolerance in mice with heterozygous carnitine palmitoyltransferase-1a deficiency

    PubMed Central

    Nyman, L R; Tian, L; Hamm, D A; Schoeb, T R; Gower, B A; Nagy, T R; Wood, P A

    2011-01-01

    Background: Abnormal fatty acid metabolism is an important feature in the mechanisms of insulin resistance and β-cell dysfunction. Carnitine palmitoyltransferase-1a (CPT-1a, liver isoform) has a pivotal role in the regulation of mitochondrial fatty acid oxidation. We investigated the role of CPT-1a in the development of impaired glucose tolerance using a mouse model for CPT-1a deficiency when challenged by either a high-carbohydrate (HCD) or a high-fat diet (HFD) for a total duration of up to 46 weeks. Methods: Insulin sensitivity and glucose tolerance were assessed in heterozygous CPT-1a-deficient (CPT-1a+/−) male mice after being fed either a HCD or a HFD for durations of 28 weeks and 46 weeks. Both glucose and insulin tolerance tests were used to investigate β-cell function and insulin sensitivity. Differences in islet insulin content and hepatic steatosis were evaluated by morphological analysis. Results: CPT-1a+/− mice were more insulin-sensitive than CPT-1a+/+ mice when fed either HCD or HFD. The increased insulin sensitivity was associated with an increased expression of Cpt-1b (muscle isoform) in liver, as well as increased microvesicular hepatic steatosis compared with CPT-1a+/+ mice. CPT-1a+/− mice were more glucose tolerant than CPT-1a+/+ mice when fed the HCD, but there was no significant difference when fed HFD. Moreover, CPT-1a+/− mice fed HFD or HCD had fewer and smaller pancreatic islets than CPT-1a+/+ mice. Conclusions: CPT-1a deficiency preserved insulin sensitivity when challenged by long-term feeding of either diet. Furthermore, CPT-1a-deficient mice had distinct phenotypes dependent on the diet fed demonstrating that both diet and genetics collectively have a role in the development of impaired glucose tolerance. PMID:22229081

  1. Association of the ACTN3 R557X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle

    PubMed Central

    Riedl, Isabelle; Osler, Megan E; Benziane, Boubacar; Chibalin, Alexander V; Zierath, Juleen R

    2015-01-01

    A common polymorphism (R577X) in the α-actinin (ACTN) 3 gene, which leads to complete deficiency of a functional protein in skeletal muscle, could directly influence metabolism in the context of health and disease. Therefore, we tested the hypothesis that states of glucose tolerance are associated with the ACTN3 R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured muscle-specific α-actinin 2 and 3 mRNA and protein abundance in skeletal muscle biopsies. Furthermore, we investigated the protein abundance of the myosin heavy chain isoforms and the components of the mitochondrial electron transport chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX genotype was higher in T2D patients, genotype distribution was unrelated to metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein abundance was unchanged between NGT and T2D participants. Protein abundance of mitochondrial complexes II and IV was related to genotype and glucose tolerance status. Gene expression of sarcomeric z-disk proteins was increased in skeletal muscle from NGT participants with the ACTN3 577XX genotype. While genetic variation in ACTN3 does not influence metabolic control, genotype does appear to influence gene expression of other sarcomeric proteins, which could contribute to the functional properties of skeletal muscle and the fatigue-resistant phenotype associated with the R577X polymorphism. PMID:25780092

  2. Association of the ACTN3 R577X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle.

    PubMed

    Riedl, Isabelle; Osler, Megan E; Benziane, Boubacar; Chibalin, Alexander V; Zierath, Juleen R

    2015-03-01

    A common polymorphism (R577X) in the α-actinin (ACTN) 3 gene, which leads to complete deficiency of a functional protein in skeletal muscle, could directly influence metabolism in the context of health and disease. Therefore, we tested the hypothesis that states of glucose tolerance are associated with the ACTN3 R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured muscle-specific α-actinin 2 and 3 mRNA and protein abundance in skeletal muscle biopsies. Furthermore, we investigated the protein abundance of the myosin heavy chain isoforms and the components of the mitochondrial electron transport chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX genotype was higher in T2D patients, genotype distribution was unrelated to metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein abundance was unchanged between NGT and T2D participants. Protein abundance of mitochondrial complexes II and IV was related to genotype and glucose tolerance status. Gene expression of sarcomeric z-disk proteins was increased in skeletal muscle from NGT participants with the ACTN3 577XX genotype. While genetic variation in ACTN3 does not influence metabolic control, genotype does appear to influence gene expression of other sarcomeric proteins, which could contribute to the functional properties of skeletal muscle and the fatigue-resistant phenotype associated with the R577X polymorphism. PMID:25780092

  3. Impaired stimulation of glucose transport in cardiac myocytes exposed to very low-density lipoproteins.

    PubMed

    Papageorgiou, I; Viglino, C; Brulhart-Meynet, M-C; James, R W; Lerch, R; Montessuit, C

    2016-07-01

    We recently observed that free fatty acids impair the stimulation of glucose transport into cardiomyocytes in response to either insulin or metabolic stress. In vivo, fatty acids for the myocardium are mostly obtained from triglyceride-rich lipoproteins (chylomicrons and Very Low-Density Lipoproteins). We therefore determined whether exposure of cardiac myocytes to VLDL resulted in impaired basal and stimulated glucose transport. Primary adult rat cardiac myocytes were chronically exposed to VLDL before glucose uptake was measured in response to insulin or metabolic stress, provoked by the mitochondrial ATP synthase inhibitor oligomycin. Exposure of cardiac myocytes to VLDL reduced both insulin-and oligomycin-stimulated glucose uptake. The reduction of glucose uptake was associated with a moderately reduced tyrosine phosphorylation of the insulin receptor. No reduction of the phosphorylation of the downstream effectors of insulin signaling Akt and AS160 was however observed. Similarly only a modest reduction of the activating phosphorylation of the AMP-activated kinase (AMPK) was observed in response to oligomycin. Similar to our previous observations with free fatty acids, inhibition of fatty acid oxidation restored oligomycin-stimulated glucose uptake. In conclusions, VLDL-derived fatty acids impair stimulated glucose transport in cardiac myocytes by a mechanism that seems to be mediated by a fatty acid oxidation intermediate. Thus, in the clinical context of the metabolic syndrome high VLDL may contribute to enhancement of ischemic injury by reduction of metabolic stress-stimulated glucose uptake. PMID:27052924

  4. Maternal dietary protein supplement confers long-term sex-specific beneficial consequences of obesity resistance and glucose tolerance to the offspring in Brandt's voles.

    PubMed

    Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Zhang, Xue-Ying; Wang, De-Hua

    2015-04-01

    Maternal under- or over-nutrition not only alters neonatal body mass but also increases the risk of metabolic disorders in adulthood. Little is known about how maternal dietary protein affects offspring fitness in wild rodents. The present study was conducted to test the hypothesis that maternal dietary protein supplement has a long-term beneficial effect on offspring fitness in Brandt's vole (Lasiopodomys brandtii), a herbivorous rodent model. The vole dams were fed either a control (18% protein) or high-protein (36% protein) diet throughout pregnancy and lactation. After weaning, all offspring received a control diet till 14 weeks old. Energetic parameters, serum leptin concentration and glucose tolerance were measured. The adult offspring were fed high-fat diet for 8 weeks, and body weight and food intake were measured. No difference was observed in litter size, litter mass or pup mass before weaning. Maternal protein supplement increased body mass and the mass of reproductive organ but decreased digestibility and fat deposition and alleviated HFD-induced obesity especially in the males. Glucose tolerance was elevated in the offspring from maternal protein supplement, especially in the females. The accelerated growth may be associated with high serum leptin concentration at weaning, a state of leptin resistance, and the low digestibility may predispose obesity resistance especially in male offspring from maternal high-protein diet. These data demonstrate that maternal protein supplement confers the long-term sex-specific beneficial consequences of accelerated growth and improved obesity resistance and glucose tolerance of their offspring. PMID:25499237

  5. Diabetic Hyperglycemia: Link to Impaired Glucose Transport in Pancreatic β Cells

    NASA Astrophysics Data System (ADS)

    Unger, Roger H.

    1991-03-01

    Glucose uptake into pancreatic β cells by means of the glucose transporter GLUT-2, which has a high Michaelis constant, is essential for the normal insulin secretory response to hyperglycemia. In both autoimmune and nonautoimmune diabetes, this glucose transport is reduced as a consequence of down-regulation of the normal β-cell transporter. In autoimmune diabetes, circulating immunoglobulins can further impair this glucose transport by inhibiting functionally intact transporters. Insights into mechanisms of the unresponsiveness of β cells to hyperglycemia may improve the management and prevention of diabetes.

  6. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    PubMed

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases. PMID:26126077

  7. A mechanism of glucose tolerance and stimulation of GH1 β-glucosidases

    PubMed Central

    Yang, Yang; Zhang, Xinxin; Yin, Qiang; Fang, Wei; Fang, Zemin; Wang, Xiaotang; Zhang, Xuecheng; Xiao, Yazhong

    2015-01-01

    β-Glucosidases are enzymes that hydrolyze β-glycosidic bonds to release non-reducing terminal glucosyl residues from glycosides and oligosaccharides, and thus have significant application potential in industries. However, most β-glucosidases are feedback inhibited by the glucose product, which restricts their application. Remarkably, some β-glucosidases of the glycoside hydrolase (GH) 1 family are tolerant to or even stimulated by glucose. Elucidation of the mechanisms of glucose tolerance and stimulation of the GH1 β-glucosidases will be crucial to improve their application through enzyme engineering. In this study, by comparing the primary and tertiary structures of two GH1 β-glucosidases with distinct glucose dependence, some putative glucose-dependence relevant sites were mutated to investigate their exact roles. Both biochemical and structural characterization of the mutants suggested that some sites at the entrance and middle of the substrate channel regulate the effects of glucose, and the relative binding affinity/preference of these sites to glucose modulates the glucose dependence. A mechanism was therefore proposed to interpret the glucose dependence of GH1 β-glucosidases. This research provides fresh insight into our current understanding of the properties and mechanisms of GH1 β-glycosidases and related enzymes that modulate their activity via feedback control mechanism. PMID:26603650

  8. A mechanism of glucose tolerance and stimulation of GH1 β-glucosidases.

    PubMed

    Yang, Yang; Zhang, Xinxin; Yin, Qiang; Fang, Wei; Fang, Zemin; Wang, Xiaotang; Zhang, Xuecheng; Xiao, Yazhong

    2015-01-01

    β-Glucosidases are enzymes that hydrolyze β-glycosidic bonds to release non-reducing terminal glucosyl residues from glycosides and oligosaccharides, and thus have significant application potential in industries. However, most β-glucosidases are feedback inhibited by the glucose product, which restricts their application. Remarkably, some β-glucosidases of the glycoside hydrolase (GH) 1 family are tolerant to or even stimulated by glucose. Elucidation of the mechanisms of glucose tolerance and stimulation of the GH1 β-glucosidases will be crucial to improve their application through enzyme engineering. In this study, by comparing the primary and tertiary structures of two GH1 β-glucosidases with distinct glucose dependence, some putative glucose-dependence relevant sites were mutated to investigate their exact roles. Both biochemical and structural characterization of the mutants suggested that some sites at the entrance and middle of the substrate channel regulate the effects of glucose, and the relative binding affinity/preference of these sites to glucose modulates the glucose dependence. A mechanism was therefore proposed to interpret the glucose dependence of GH1 β-glucosidases. This research provides fresh insight into our current understanding of the properties and mechanisms of GH1 β-glycosidases and related enzymes that modulate their activity via feedback control mechanism. PMID:26603650

  9. A novel EPO receptor agonist improves glucose tolerance via glucose uptake in skeletal muscle in a mouse model of diabetes.

    PubMed

    Scully, Michael S; Ort, Tatiana A; James, Ian E; Bugelski, Peter J; Makropoulos, Dorie A; Deutsch, Heather A; Pieterman, Elsbet J; van den Hoek, Anita M; Havekes, Louis M; Dubell, William H; Wertheimer, Joshua D; Picha, Kristen M

    2011-01-01

    Patients treated with recombinant human Epo demonstrate an improvement in insulin sensitivity. We aimed to investigate whether CNTO 530, a novel Epo receptor agonist, could affect glucose tolerance and insulin sensitivity. A single administration of CNTO 530 significantly and dose-dependently reduced the area under the curve in a glucose tolerance test in diet-induced obese and diabetic mice after 14, 21, and 28 days. HOMA analysis suggested an improvement in insulin sensitivity, and this effect was confirmed by a hyperinsulinemic-euglycemic clamp. Uptake of (14)C-2-deoxy-D-glucose indicated that animals dosed with CNTO 530 transported more glucose into skeletal muscle and heart relative to control animals. In conclusion, CNTO530 has a profound effect on glucose tolerance in insulin-resistant rodents likely because of improving peripheral insulin sensitivity. This effect was observed with epoetin-α and darbepoetin-α, suggesting this is a class effect, but the effect with these compounds relative to CNTO530 was decreased in duration and magnitude. PMID:21754921

  10. The vitamin D receptor polymorphism in the translation initiation codon is a risk factor for insulin resistance in glucose tolerant Caucasians

    PubMed Central

    Chiu, Ken C; Chuang, Lee-Ming; Yoon, Carol

    2001-01-01

    Background Although vitamin D receptor (VDR) polymorphisms have been shown to be associated with abnormal glucose metabolism, the reported polymorphisms are unlikely to have any biological consequences. The VDR gene has two potential translation initiation sites. A T-to-C polymorphism has been noted in the first ATG (f allele), abolishing the first translation initiation site and resulting in a peptide lacking the first three amino acids (F allele). We examined the role of this polymorphism in insulin sensitivity and beta cell function. This study included 49 healthy Caucasian subjects (28 females, age 28 ± 1 years old, body mass index 24.57 ± 0.57 kg/m2, waist-hip ratio 0.81 ± 0.01 cm/cm). They were all normotensive (less than 140/90 mmHg) and glucose tolerant, which was determined by a standard 75-gm oral glucose tolerance test. Their beta cell function (%B) and insulin sensitivity (%S) were calculated based on the Homeostasis Model Assessment (HOMA). Their genotypes were determined by a polymerase chain reaction-restriction fragment length polymorphism analysis. Phenotypes were compared between genotypic groups. Results There were 18 FF, 21 Ff, and 10 ff subjects. Since only 10 ff subjects were identified, they were pooled with the Ff subjects during analyses. The FF and Ff/ff groups had similar glucose levels at each time point before and after a glucose challenge. The Ff/ff group had higher insulin levels than the FF group at fasting (P=0.006), 30 minutes (P=0.009), 60 minutes (P=0.049), and 90 minutes (P=0.042). Furthermore, the Ff/ff group also had a larger insulin area under the curve than the FF group (P=0.009). While no difference was noted in %B, the Ff/ff group had a lower %S than the FF group (0.53 vs. 0.78, P=0.006). A stepwise regression analysis confirmed that the Fok I polymorphism was an independent determinant for %S, accounting for 29.3% of variation in %S when combined with waist-hip ratio. Conclusions We report that the Fok I polymorphism

  11. The mirage of impairing drug concentration thresholds: a rationale for zero tolerance per se driving under the influence of drugs laws.

    PubMed

    Reisfield, Gary M; Goldberger, Bruce A; Gold, Mark S; DuPont, Robert L

    2012-06-01

    Motor vehicle crashes are a leading cause of morbidity and mortality in the United States. Drivers with measurable quantities of potentially impairing illicit or prescription drugs in their body fluids are multiple times more likely to be involved in motor vehicle crashes than those without such drugs in their bodies. Drug-related impairment, however, cannot be inferred solely on the basis of the presence of drugs in biological fluids. Thus, for more than a quarter century, there has been a search for drug blood concentrations that are the equivalent of the 0.08 g/dL threshold for alcohol-impaired driving in the United States. We suggest that such equivalents are a mirage, and cannot be determined due to variable drug tolerance, lack of consistent relationships between drug blood concentrations and impairment, innumerable drug combinations and multiple other factors. Thus, while the idea of determining impairing drug concentrations is attractive, it is ultimately unattainable, and withholding drugged driving legislation pending the acquisition of such data is tantamount to a plan for inaction with regard to an important and growing public health and safety problem. We propose specific legislation to address alcohol- and drug-impaired driving in the United States. PMID:22582272

  12. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation.

    PubMed

    Mark, R J; Pang, Z; Geddes, J W; Uchida, K; Mattson, M P

    1997-02-01

    A deficit in glucose uptake and a deposition of amyloid beta-peptide (A beta) each occur in vulnerable brain regions in Alzheimer's disease (AD). It is not known whether mechanistic links exist between A beta deposition and impaired glucose transport. We now report that A beta impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation. A beta impaired 3H-deoxy-glucose transport in a concentration-dependent manner and with a time course preceding neurodegeneration. The decrease in glucose transport was followed by a decrease in cellular ATP levels. Impairment of glucose transport, ATP depletion, and cell death were each prevented in cultures pretreated with antioxidants. Exposure to FeSO4, an established inducer of lipid peroxidation, also impaired glucose transport. Immunoprecipitation and Western blot analyses showed that exposure of cultures to A beta induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced a concentration-dependent impairment of glucose transport and subsequent ATP depletion. Impaired glucose transport was not caused by a decreased energy demand in the neurons, because ouabain, which inhibits Na+/K(+)-ATPase activity and thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose transport. Collectively, the data demonstrate that lipid peroxidation mediates A beta-induced impairment of glucose transport in neurons and suggest that this action of A beta may contribute to decreased glucose uptake and neuronal degeneration in AD. PMID:8994059

  13. Association between the Melatonin Receptor 1B Gene Polymorphism on the Risk of Type 2 Diabetes, Impaired Glucose Regulation: A Meta-Analysis

    PubMed Central

    Wang, Yi-Chao; Ma, Yu-Shui; Zhang, Feng; Che, Wu; Fu, Da; Wang, Xiao-Feng

    2012-01-01

    Background Melatonin receptor 1B (MTNR1B) belongs to the seven-transmembrane G protein-coupled receptor superfamily involved in insulin secretion, which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) since it was first identified as a loci associated with fasting plasma glucose level through genome wide association approach. The relationship between MTNR1B and T2D has been reported in various ethnic groups. The aim of this study was to consolidate and summarize published data on the potential of MTNR1B polymorphisms in T2D risk prediction. Methods PubMed, EMBASE, ISI web of science and the CNKI databases were systematically searched to identify relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Heterogeneity and publication bias were also tested. Results A total of 23 studies involving 172,963 subjects for two common polymorphisms (rs10830963, rs1387153) on MTNR1B were included. An overall random effects per-allele OR of 1.05 (95% CI: 1.02–1.08; P<10−4) and 1.04 (95% CI: 0.98–1.10; P = 0.20) were found for the two variants respectively. Similar results were also observed using dominant or recessive genetic model. There was strong evidence of heterogeneity, which largely disappeared after stratification by ethnicity. Significant results were found in Caucasians when stratified by ethnicity; while no significant associations were observed in East Asians and South Asians. Besides, we found that the rs10830963 polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Conclusions This meta-analysis demonstrated that the rs10830963 polymorphism is a risk factor for developing impaired glucose regulation and T2D. PMID:23226241

  14. Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.

    PubMed

    Svane, Maria S; Bojsen-Møller, Kirstine N; Nielsen, Signe; Jørgensen, Nils B; Dirksen, Carsten; Bendtsen, Flemming; Kristiansen, Viggo B; Hartmann, Bolette; Holst, Jens J; Madsbad, Sten

    2016-04-01

    Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB. PMID:26786780

  15. Previously Associated Type 2 Diabetes Variants May Interact With Physical Activity to Modify the Risk of Impaired Glucose Regulation and Type 2 Diabetes

    PubMed Central

    Brito, Ema C.; Lyssenko, Valeriya; Renström, Frida; Berglund, Göran; Nilsson, Peter M.; Groop, Leif; Franks, Paul W.

    2009-01-01

    OBJECTIVE Recent advances in type 2 diabetes genetics have culminated in the discovery and confirmation of multiple risk variants. Two important and largely unanswered questions are whether this information can be used to identify individuals most susceptible to the adverse consequences of sedentary behavior and to predict their response to lifestyle intervention; such evidence would be mechanistically informative and provide a rationale for targeting genetically susceptible subgroups of the population. RESEARCH DESIGN AND METHODS Gene × physical activity interactions were assessed for 17 polymorphisms in a prospective population-based cohort of initially nondiabetic middle-aged adults. Outcomes were 1) impaired glucose regulation (IGR) versus normal glucose regulation determined with either fasting or 2-h plasma glucose concentrations (n = 16,003), 2) glucose intolerance (in mmol/l, n = 8,860), or 3) incident type 2 diabetes (n = 2,063 events). RESULTS Tests of gene × physical activity interactions on IGR risk for 3 of the 17 polymorphisms were nominally statistically significant:CDKN2A/B rs10811661 (Pinteraction = 0.015), HNF1B rs4430796 (Pinteraction = 0.026), and PPARG rs1801282 (Pinteraction = 0.04). Consistent interactions were observed for the CDKN2A/B (Pinteraction = 0.013) and HNF1B (Pinteraction = 0.0009) variants on 2-h glucose concentrations. Where type 2 diabetes was the outcome, only one statistically significant interaction effect was observed, and this was for the HNF1B rs4430796 variant (Pinteraction = 0.0004). The interaction effects for HNF1B on IGR risk and incident diabetes remained significant after correction for multiple testing (Pinteraction = 0.015 and 0.0068, respectively). CONCLUSIONS Our observations suggest that the genetic predisposition to hyperglycemia is partially dependent on a person's lifestyle. PMID:19324937

  16. Selective FFA2 Agonism Appears to Act via Intestinal PYY to Reduce Transit and Food Intake but Does Not Improve Glucose Tolerance in Mouse Models.

    PubMed

    Forbes, Sarah; Stafford, Stuart; Coope, Gareth; Heffron, Helen; Real, Katia; Newman, Robert; Davenport, Richard; Barnes, Matt; Grosse, Johannes; Cox, Helen

    2015-11-01

    Free fatty acid receptor 2 (FFA2) is expressed on enteroendocrine L cells that release glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) when activated by short-chain fatty acids (SCFAs). Functionally GLP-1 and PYY inhibit gut transit, increase glucose tolerance, and suppress appetite; thus, FFA2 has therapeutic potential for type 2 diabetes and obesity. However, FFA2-selective agonists have not been characterized in vivo. Compound 1 (Cpd 1), a potent FFA2 agonist, was tested for its activity on the following: GLP-1 release, modulation of intestinal mucosal ion transport and transit in wild-type (WT) and FFA2(-/-) tissue, and food intake and glucose tolerance in lean and diet-induced obese (DIO) mice. Cpd 1 stimulated GLP-1 secretion in vivo, but this effect was only detected with dipeptidyl peptidase IV inhibition, while mucosal responses were PYY, not GLP-1, mediated. Gut transit was faster in FFA2(-/-) mice, while Cpd 1 slowed WT transit and reduced food intake and body weight in DIO mice. Cpd 1 decreased glucose tolerance and suppressed plasma insulin in lean and DIO mice, despite FFA2(-/-) mice displaying impaired glucose tolerance. These results suggest that FFA2 inhibits intestinal functions and suppresses food intake via PYY pathways, with limited GLP-1 contribution. Thus, FFA2 may be an effective therapeutic target for obesity but not for type 2 diabetes. PMID:26239054

  17. Diminishing impairments in glucose uptake, mitochondrial content, and ADP-stimulated oxygen flux by mesenchymal stem cell therapy in the infarcted heart.

    PubMed

    Hughey, Curtis C; James, Freyja D; Ma, Lianli; Bracy, Deanna P; Wang, Zhizhang; Wasserman, David H; Rottman, Jeffrey N; Shearer, Jane

    2014-01-01

    A constant provision of ATP is of necessity for cardiac contraction. As the heart progresses toward failure following a myocardial infarction (MI), it undergoes metabolic alterations that have the potential to compromise the ability to meet energetic demands. This study evaluated the efficacy of mesenchymal stem cell (MSC) transplantation into the infarcted heart to minimize impairments in the metabolic processes that contribute to energy provision. Seven and twenty-eight days following the MI and MSC transplantation, MSC administration minimized cardiac systolic dysfunction. Hyperinsulinemic-euglycemic clamps, coupled with 2-[(14)C]deoxyglucose administration, were employed to assess systemic insulin sensitivity and tissue-specific, insulin-mediated glucose uptake 36 days following the MI in the conscious, unrestrained, C57BL/6 mouse. The improved systolic performance in MSC-treated mice was associated with a preservation of in vivo insulin-stimulated cardiac glucose uptake. Conserved glucose uptake in the heart was linked to the ability of the MSC treatment to diminish the decline in insulin signaling as assessed by Akt phosphorylation. The MSC treatment also sustained mitochondrial content, ADP-stimulated oxygen flux, and mitochondrial oxidative phosphorylation efficiency in the heart. Maintenance of mitochondrial function and density was accompanied by preserved peroxisome proliferator-activated receptor-γ coactivator-1α, a master regulator of mitochondrial biogenesis. These studies provide insight into mechanisms of action that lead to an enhanced energetic state in the infarcted heart following MSC transplantation that may assist in energy provision and dampen cardiac dysfunction. PMID:24196528

  18. Diminishing impairments in glucose uptake, mitochondrial content, and ADP-stimulated oxygen flux by mesenchymal stem cell therapy in the infarcted heart

    PubMed Central

    James, Freyja D.; Ma, Lianli; Bracy, Deanna P.; Wang, Zhizhang; Wasserman, David H.; Rottman, Jeffrey N.; Shearer, Jane

    2013-01-01

    A constant provision of ATP is of necessity for cardiac contraction. As the heart progresses toward failure following a myocardial infarction (MI), it undergoes metabolic alterations that have the potential to compromise the ability to meet energetic demands. This study evaluated the efficacy of mesenchymal stem cell (MSC) transplantation into the infarcted heart to minimize impairments in the metabolic processes that contribute to energy provision. Seven and twenty-eight days following the MI and MSC transplantation, MSC administration minimized cardiac systolic dysfunction. Hyperinsulinemic-euglycemic clamps, coupled with 2-[14C]deoxyglucose administration, were employed to assess systemic insulin sensitivity and tissue-specific, insulin-mediated glucose uptake 36 days following the MI in the conscious, unrestrained, C57BL/6 mouse. The improved systolic performance in MSC-treated mice was associated with a preservation of in vivo insulin-stimulated cardiac glucose uptake. Conserved glucose uptake in the heart was linked to the ability of the MSC treatment to diminish the decline in insulin signaling as assessed by Akt phosphorylation. The MSC treatment also sustained mitochondrial content, ADP-stimulated oxygen flux, and mitochondrial oxidative phosphorylation efficiency in the heart. Maintenance of mitochondrial function and density was accompanied by preserved peroxisome proliferator-activated receptor-γ coactivator-1α, a master regulator of mitochondrial biogenesis. These studies provide insight into mechanisms of action that lead to an enhanced energetic state in the infarcted heart following MSC transplantation that may assist in energy provision and dampen cardiac dysfunction. PMID:24196528

  19. The Uptake of Screening for Type 2 Diabetes and Prediabetes by Means of Glycated Hemoglobin versus the Oral Glucose Tolerance Test among 18 to 60-Year-Old People of South Asian Origin: A Comparative Study

    PubMed Central

    van Valkengoed, Irene G. M.; Vlaar, Everlina M. A.; Nierkens, Vera; Middelkoop, Barend J. C.; Stronks, Karien

    2015-01-01

    Background Direct comparisons of the effect of a glycated haemoglobin measurement or an oral glucose tolerance test on the uptake and yield of screening in people of South Asian origin have not been made. We evaluated this in 18 to 60-year-old South Asian Surinamese. Materials and Methods We invited 3173 South Asian Surinamese for an oral glucose tolerance test between June 18th 2009- December 31st 2009 and 2012 for a glycated hemoglobin measurement between April 19th 2010-November 11th, 2010. Participants were selected from 48 general practices in The Hague, The Netherlands. We used mixed models regression to analyse differences in response and participation between the groups. We described differences in characteristics of participants and calculated the yield as the percentage of all cases identified, if all invitees had been offered screening with the specified method. Results The response and participation in the glycated hemoglobin group was higher than in the group offered an oral glucose tolerance test (participation 23.9 vs. 19.3; OR: 1.30, 95%-confidence interval1.01–1.69). After adjustment for age and sex, characteristics of participants were similar for both groups. Overall, glycated hemoglobin identified a similar percentage of type 2 diabetes cases but a higher percentage of prediabetes cases, in the population than the oral glucose tolerance test. Conclusion We found that glycated hemoglobin and the oral glucose tolerance test may be equally efficient for identification of type 2 diabetes in populations of South Asian origin. However, for programs aimed at identifying people at high risk of type 2 diabetes (i.e. with prediabetes), the oral glucose tolerance test may be a less efficient choice than glycated hemoglobin. PMID:26317417

  20. Black Adzuki Bean (Vigna angularis) Extract Protects Pancreatic β Cells and Improves Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet.

    PubMed

    Kim, Mina; Kim, Dae Keun; Cha, Youn-Soo

    2016-05-01

    Adzuki beans have long been cultivated as a food and folk medicine in East Asia. In this study, we investigated the effect of black adzuki bean (BAB) extract on pancreatic cells and determined their mechanism of action in impaired glucose tolerance in an animal model of type 2 diabetes. In addition, we performed functional gene annotation analysis to identify genes related to the regulation of glucose metabolism and insulin response. Treatment of pancreatic β cells with BAB extract (0.2 mg/mL) led to tolerance of the high glucose-induced glucotoxicity, resulting in a similar viability as cells maintained in normal glucose media. In addition, dietary supplementation with BAB extract significantly (P < .05) improved hyperglycemia and homeostasis model assessment of insulin resistance index (HOMA-IR) in high-fat diet-induced glucose-intolerant obese C57BL/6J mice. Our results suggest that BAB extract ameliorates hyperglycemia and glucose intolerance, and lowers HOMA-IR by regulating insulin secretion and response, and by maintaining the integrity of pancreatic β cells exposed to hyperglycemic conditions. PMID:27070495

  1. Chromium Supplementation Improves Glucose Tolerance in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Abdourahman, Aicha; Edwards, John G.

    2016-01-01

    Summary Chromium supplementation (Cr) may be useful in the management of diabetes and appears to improve some aspects of glucose handling. However, several studies have used either high doses of Cr supplementation or have placed control animals on a Cr-deficient diet. We therefore wanted to test whether Cr dosages in the ranges that more closely approximate recommended levels of supplementation in humans are efficacious in glycemic control under normal dietary conditions. Euglycemic Wistar or diabetic Goto-Kakizaki (GK) rats (a model of nonobese NIDDM) were assigned to water (control) or chromium picolinate (Cr-P) supplementation (1 or 10 mg/kg/day) groups for up to 32 weeks. Glucose tolerance was tested following an overnight fast by injecting sterile glucose (1.0 g/kg, i.p.) and then measuring blood glucose at select times to determine the sensitivity to glucose by calculation of the area under the curve. Cr-P did not significantly alter the growth of the animals. In the euglycemic Wistar rats, Cr-P supplementation did not alter the response to a glucose tolerance test. In the GK rats, Cr-P supplementation significantly improved glucose tolerance at both levels of Cr-P supplementation (1 mg/kg/day: H20; 100 ± 11%; Cr-P 70 6 8%; 10 mg/kg/day: H20; 100 ± 10%; Cr-P 66 ± 9 %). Cr-P supplementation produced a small improvement in some indices of glycemic control. There were no differences observed for the two levels of Cr-P supplementation suggested that we did not identify a threshold for Cr-P effects, and future studies may use lower doses to find a threshold effect for improving glucose tolerance in diabetics. PMID:18629917

  2. Cacao liquor procyanidin extract improves glucose tolerance by enhancing GLUT4 translocation and glucose uptake in skeletal muscle.

    PubMed

    Yamashita, Yoko; Okabe, Masaaki; Natsume, Midori; Ashida, Hitoshi

    2012-01-01

    Hyperglycaemia and insulin resistance are associated with the increased risk of the metabolic syndrome and other severe health problems. The insulin-sensitive GLUT4 regulates glucose homoeostasis in skeletal muscle and adipose tissue. In this study, we investigated whether cacao liquor procyanidin (CLPr) extract, which contains epicatechin, catechin and other procyanidins, improves glucose tolerance by promoting GLUT4 translocation and enhances glucose uptake in muscle cells. Our results demonstrated that CLPr increased glucose uptake in a dose-dependent manner and promoted GLUT4 translocation to the plasma membrane of L6 myotubes. Oral administration of a single dose of CLPr suppressed the hyperglycaemic response after carbohydrate ingestion, which was accompanied by enhanced GLUT4 translocation in ICR mice. These effects of CLPr were independent of α-glucosidase inhibition in the small intestine. CLPr also promoted GLUT4 translocation in skeletal muscle of C57BL/6 mice fed a CLPr-supplemented diet for 7 d. These results indicate that CLPr is a beneficial food material for improvement of glucose tolerance by promoting GLUT4 translocation to the plasma membrane of skeletal muscle. PMID:25191549

  3. Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range.

    PubMed

    Lorenzo, Carlos; Hanley, Anthony J; Rewers, Marian J; Haffner, Steven M

    2014-08-01

    We aimed to evaluate disproportional proinsulinemia in the pre-diabetic state by analyzing the cross-sectional differences between proinsulin (PI) ratios across the entire range of fasting and 2-h plasma glucose. The study sample was 1,016 participants in the insulin resistance atherosclerosis study, who had no previous diagnosis of diabetes. Insulin sensitivity index (SI) and acute insulin response (AIR) were measured by the frequently sampled intravenous glucose tolerance test. Fasting intact and split PI-to-insulin ratios (PI/I, SPI/I), intact and split PI-to-C-peptide ratios (PI/C-pep, SPI/C-pep), and SI-adjusted AIR were assessed as a function of fasting and 2-h glucose levels. SI-adjusted AIR was decreased (fasting glucose 96-98 mg/dl; 2-h glucose 120-131 mg/dl) and SPI/C-pep increased at modestly elevated fasting glucose and 2-h glucose within the normal glucose tolerance range (fasting glucose 96-98 mg/dl; 2-h glucose 132-142 mg/dl). PI/I was not increased until plasma glucose values were in the diabetic range of fasting glucose (>126 mg/dl) or the impaired glucose tolerance range of 2-h glucose (143-156 mg/dl). SPI/I and PI/C-pep as a function of fasting and 2-h glucose were situated between the curves for SPI/C-pep and PI/I. In conclusion, inappropriate amounts of PI and conversion intermediaries are demonstrated at modestly elevated glucose levels within the normoglycemic range. Ratios that use SPI in the numerator or C-pep in the denominator (and especially SPI/C-pep) are more sensitive to early glycemic excursions than PI/I. Disordered processing of PI may accompany derangements in early insulin secretory response. PMID:24532116

  4. Impaired glucose utilization in man during acute exposure to environmental heat.

    PubMed

    Tatár, P; Vigas, M; Jurcovicová, J; Jezová, D; Strec, V; Palát, M

    1985-12-01

    In 6 healthy males the oral glucose tolerance test (OGTT) was performed after the administration of 100 g glucose during the hyperthermic Finnish sauna bath (85 degrees C) of 30 min duration. The lowered insulin response (P less than 0.001) to glucose challenge during heating and the subsequent prolonged hyperglycemia (P less than 0.001) after heating were observed, when compared to OGTT under thermoneutral conditions (23 degrees C). It is suggested that the heat-induced decrease in visceral blood flow and stimulation of sympathoadrenomedullary and pituitary activity may be responsible for this effect. PMID:3910408

  5. Association of Depressive Symptoms With Impaired Glucose Regulation, Screen-Detected, and Previously Known Type 2 Diabetes

    PubMed Central

    Mäntyselkä, Pekka; Korniloff, Katariina; Saaristo, Timo; Koponen, Hannu; Eriksson, Johan; Puolijoki, Hannu; Timonen, Markku; Sundvall, Jouko; Kautiainen, Hannu; Vanhala, Mauno

    2011-01-01

    OBJECTIVE To study the association between impaired glucose regulation (IGR), screen-detected type 2 diabetes, and previously known diabetes and depressive symptoms. RESEARCH DESIGN AND METHODS Altogether, 2,712 participants from three hospital districts in Finland attended a health examination. Cutoff scores ≥10 and ≥16 in the 21-item Beck Depression Inventory (BDI-21) were used for depressive symptoms. The participants were defined as having known diabetes if they reported diabetes. An oral glucose tolerance test was used to detect normal glucose regulation (NGR), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and screen-detected diabetes. The participants were defined as having IGR if they had IFG or IGT. RESULTS Prevalence of depressive symptoms, defined as a BDI-21 cutoff score ≥10, was 14.4% for those with NGR, 13.7% for those with IGR, 14.8% for those with screen-detected diabetes, and 26.4% for those with previously known diabetes. The corresponding prevalences for a cutoff score ≥16 were 3.4, 3.4, 4.2, and 7.5%, respectively. Compared with NGR and adjusted for demographic, lifestyle, and biological factors, the odds ratios for IGR, screen-detected diabetes, and previously known diabetes were 0.91 (95% CI 0.69–1.20), 0.70 (0.45–1.08), and 1.35 (0.84–2.15), respectively, for a cutoff score ≥10. For a cutoff score ≥16, the corresponding odds ratios were 1.05 (0.62–1.76), 0.87 (0.40–1.90), and 1.56 (0.69–3.50), respectively. CONCLUSIONS Participants with diagnosed diabetes had a higher prevalence of depressive symptoms than participants with NGR, IGR, and previously unknown diabetes. When potential confounding factors were included in the analysis, previously known diabetes was not significantly associated with depressive symptoms. PMID:20929992

  6. Strategies Associated with Higher Postpartum Glucose Tolerance Screening Rates for Gestational Diabetes Mellitus Patients

    PubMed Central

    Ko, Jean Y.; Dietz, Patricia M.; Conrey, Elizabeth J.; Rodgers, Loren E.; Shellhaas, Cynthia; Farr, Sherry L.; Robbins, Cheryl L.

    2016-01-01

    Background Most women with histories of gestational diabetes mellitus do not receive a postpartum screening test for type 2 diabetes, even though they are at increased risk. The objective of this study was to identify factors associated with high rates of postpartum glucose screening. Methods This cross-sectional analysis assessed characteristics associated with postpartum diabetes screening for patients with gestational diabetes mellitus (GDM)-affected pregnancies self-reported by randomly sampled licensed obstetricians/gynecologists (OBs/GYNs) in Ohio in 2010. Results Responses were received from 306 OBs/GYNs (56.5% response rate), among whom 69.9% reported frequently (always/most of the time) screening women with GDM-affected pregnancies for abnormal glucose tolerance at the postpartum visit. Compared to infrequent screeners, OBs/GYNs who frequently screen for postpartum glucose tolerance were statistically (p < 0.05) more likely to have a clinical protocol addressing postpartum testing (67.2% vs. 26.7%), an electronic reminder system for providers (10.8% vs. 2.2%) and provide reminders to patients (16.4% vs. 4.4%). Frequent screeners were more likely to use recommended fasting blood glucose or 2-hour oral glucose tolerance test (61.8% vs. 34.6%, p < 0.001) than infrequent screeners. Conclusions Strategies associated with higher postpartum glucose screening for GDM patients included clinical protocols for postpartum testing, electronic medical records to alert providers of the need for testing, and reminders to patients. PMID:23789581

  7. Development of diagnotors based on time-average values of plasma glucose and immunoreactive insulin levels during intravenous glucose tolerance testing

    NASA Astrophysics Data System (ADS)

    Denisova, Tatyana P.; Malinov, Igor A.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The diagnostic algorithm of glucose-insulinic violations for the patients with a clinically obvious atherosclerosis of coronary arteries, non-insulin dependent diabetes mellitus and persons with the heritable predisposition to these forms of pathology was designed. The realization of intravenous glucose tolerance test in specially fitted groups of patients served as basis of the algorithm.

  8. Genetic Polymorphism of Glucokinase on the Risk of Type 2 Diabetes and Impaired Glucose Regulation: Evidence Based on 298, 468 Subjects

    PubMed Central

    Ma, Yushui; Cai, Haidong; Cai, Mingxiang; Li, Dan; Lv, Mingli; Yuan, Xueyu; Huang, Yinghui; Lv, Zhongwei

    2013-01-01

    Background Glucokinase (GCK) is the key glucose phosphorylation enzyme which has attracted considerable attention as a candidate gene for type 2 diabetes (T2D) based on its enzyme function as the first rate-limiting step in the glycolysis pathway and regulates glucose-stimulated insulin secretion. In the past decade, the relationship between GCK and T2D has been reported in various ethnic groups. To derive a more precise estimation of the relationship and the effect of factors that might modify the risk, we performed this meta-analysis. Methods Databases including Pubmed, EMBASE, Web of Science and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. Results A total of 24 articles involving 88, 229 cases and 210, 239 controls were included. An overall random-effects per-allele OR of 1.06 (95% CI: 1.03–1.09; P<10−4) was found for the GCK −30G>A polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians; whereas no significant associations were found among Asians. In addition, we found that the −30G>A polymorphism is a risk factor associated with increased impaired glucose regulation susceptibility. Besides, −30G>A homozygous was found to be significantly associated with increased fasting plasma glucose level with weighted mean difference (WMD) of 0.15 (95%: 0.05–0.24, P = 0.001) compared with G/G genotype. Conclusions This meta-analysis demonstrated that the −30G>A polymorphism of GCK is a risk factor associated with increased T2D susceptibility, but these associations vary in different ethnic populations. PMID:23441155

  9. Plant Oils Were Associated with Low Prevalence of Impaired Glucose Metabolism in Japanese Workers

    PubMed Central

    Kurotani, Kayo; Kochi, Takeshi; Nanri, Akiko; Tsuruoka, Hiroko; Kuwahara, Keisuke; Pham, Ngoc Minh; Kabe, Isamu; Mizoue, Tetsuya

    2013-01-01

    Fatty acid has been suggested to be involved in development of diabetes. However, its association is unclear among Japanese populations, which consume large amounts of fish rich in n-3 polyunsaturated fatty acids. The present cross-sectional study examined the association of individual dietary fatty acids and dietary fatty acid patterns with abnormal glucose metabolism among 1065 Japanese employees, aged 18–69 years. Impaired glucose metabolism is defined if a person has a history of diabetes, current use of anti-diabetic drug, fasting plasma glucose of 110 mg/dl (≥6.1 mmol/L) or greater, or hemoglobin A1C of 6.0% (≥42 mmol/mol) or greater. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary fatty acid patterns were extracted by principal component analysis. Odds ratios of impaired glucose metabolism according to tertile categories of each fatty acids and dietary fatty acid patterns were estimated using logistic regression with adjustment for potential confounding variables. A higher intake of polyunsaturated fatty acid, n-6 fatty acid, linoleic acid, and oleic acid were significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03, 0.01, 0.02, and 0.04, respectively). Alpha-linolenic acid was marginally significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.12). Of three fatty acid patterns identified, a higher plant oil pattern score, which characterized by high intake of alpha-linolenic acid, linoleic acid, and oleic acid, was associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03). No association was observed for other patterns. In conclusion, plant source fatty acids might be protectively associated with development of diabetes in Japanese adults. PMID:23741386

  10. Plant oils were associated with low prevalence of impaired glucose metabolism in Japanese workers.

    PubMed

    Kurotani, Kayo; Kochi, Takeshi; Nanri, Akiko; Tsuruoka, Hiroko; Kuwahara, Keisuke; Pham, Ngoc Minh; Kabe, Isamu; Mizoue, Tetsuya

    2013-01-01

    Fatty acid has been suggested to be involved in development of diabetes. However, its association is unclear among Japanese populations, which consume large amounts of fish rich in n-3 polyunsaturated fatty acids. The present cross-sectional study examined the association of individual dietary fatty acids and dietary fatty acid patterns with abnormal glucose metabolism among 1065 Japanese employees, aged 18-69 years. Impaired glucose metabolism is defined if a person has a history of diabetes, current use of anti-diabetic drug, fasting plasma glucose of 110 mg/dl (≥6.1 mmol/L) or greater, or hemoglobin A1C of 6.0% (≥42 mmol/mol) or greater. Dietary intake was assessed with a self-administered diet history questionnaire. Dietary fatty acid patterns were extracted by principal component analysis. Odds ratios of impaired glucose metabolism according to tertile categories of each fatty acids and dietary fatty acid patterns were estimated using logistic regression with adjustment for potential confounding variables. A higher intake of polyunsaturated fatty acid, n-6 fatty acid, linoleic acid, and oleic acid were significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03, 0.01, 0.02, and 0.04, respectively). Alpha-linolenic acid was marginally significantly associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.12). Of three fatty acid patterns identified, a higher plant oil pattern score, which characterized by high intake of alpha-linolenic acid, linoleic acid, and oleic acid, was associated with a decreased prevalence of impaired glucose metabolism (P for trend = 0.03). No association was observed for other patterns. In conclusion, plant source fatty acids might be protectively associated with development of diabetes in Japanese adults. PMID:23741386