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Sample records for osteoporosis impaired glucose

  1. Epidemiology of Osteoporosis in Women with Cognitive Impairment

    ERIC Educational Resources Information Center

    Schrager, Sarina

    2006-01-01

    Osteoporosis is increasing due to the aging of the population. Women with cognitive impairment from childhood are at disproportionally high risk for osteoporosis and fractures. Suggested explanations for this increased risk include high use of anticonvulsant medications, lower peak bone densities, and higher rates of nonambulation. Down syndrome…

  2. Osteoporosis

    MedlinePlus

    Osteoporosis makes your bones weak and more likely to break. Anyone can develop osteoporosis, but it is common in older women. As ... than 50 will break a bone due to osteoporosis. Risk factors include Getting older Being small and ...

  3. Osteoporosis

    MedlinePlus

    ... Home > ePublications > Our ePublications > Osteoporosis fact sheet ePublications Osteoporosis fact sheet This information in Spanish (en español) Print this fact sheet Osteoporosis fact sheet (PDF, 412 KB) Related information Menopause ...

  4. Osteoporosis

    SciTech Connect

    Riggs, B.L. Melton III, L.J. )

    1988-01-01

    This book contains 20 chapters. Some of the titles are: Radiology of asteoporosis; Quantitative computed tomography in assessment of osteoporosis; Nuclear medicine and densitometry; Assessment of bone turnover by histormorphometry in osteoporosis; and The biochemistry of bone.

  5. Osteoporosis

    MedlinePlus

    ... IT? HIV AND OSTEOPOROSIS ANTACIDS AND BONE MINERAL DENSITY HOW DO I KNOW IF I HAVE OSTEOPOROSIS? ... have unusually high rates of low bone mineral density and broken bones. This may be because of ...

  6. Osteoporosis

    MedlinePlus Videos and Cool Tools

    Osteoporosis is a condition that leads to loss of bone mass. From the outside, osteoporotic bone is shaped like normal bone. However, the inside of ... aware of the presence of the disease. Prevention is the best measure for treating osteoporosis by eating ...

  7. Osteoporosis

    MedlinePlus

    ... Having a family history of osteoporosis Taking certain medicines Being a white or Asian woman Having osteopenia, which is low bone density Osteoporosis is a silent disease. You might not know you have it until you break a ... medicines can also help. NIH: National Institute of Arthritis ...

  8. Osteoporosis

    MedlinePlus Videos and Cool Tools

    Osteoporosis is a condition that leads to loss of bone mass. From the outside, osteoporotic bone is shaped like normal bone. ... routine activities, like walking, standing, or bathing. Often, a person will sustain a fracture before becoming aware ...

  9. 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

  10. [Osteoporosis].

    PubMed

    Uebelhart, Brigitte; Rizzoli, René

    2015-01-14

    Bone events related to bariatric surgery remain controversial. Denosumab, used in osteoporosis treatment, is safe and efficient. Romosozumab, an antibody raised against sclerostin, is a promising bone anabolic agent. Odanacatib, a cathepsin-K inhibitor, decreases bone resorption and reduces osteoporotic fracture risk. Denosumab, as bone resorption inhibitor, and Teriparatide, as anabolic agent, have been tested together in patients with osteoporosis. Calcium supplements and cardiovascular risk are still debated. Drug holiday, after long-term treatment with bisphosphonates, is not associated with an increased fracture rate in patients with moderate risk. PMID:25799662

  11. Blood biomarkers of osteoporosis in mild cognitive impairment and Alzheimer's disease.

    PubMed

    Luckhaus, Christian; Mahabadi, Bijan; Grass-Kapanke, Brigitte; Jänner, Michaela; Willenberg, Holger; Jäger, Marcus; Supprian, Tillmann; Fehsel, Karin

    2009-07-01

    Previous studies revealed some comorbidity of Alzheimer's disease and osteoporosis not only for advanced disease, but also for the incipient conditions cognitive decline and decline of bone mineral density. To detect comorbidity with osteoporosis at a subclinical level, we studied concentrations of biochemical osteoporosis markers in blood plasma of subjects with mild cognitive impairment and mild Alzheimer's disease compared to subjects with primary osteoporosis and age-matched cognitively normal controls in an explorative approach. Regarding disease-spanning molecular pathology we also studied osteoprotegerin, a decoy receptor of RANKL and TRAIL. Equally increased C-terminal collagen fragments, marking bone catabolism, were seen in osteoporosis and Alzheimer's disease (+68%) versus controls. Osteocalcin, marking bone remodelling and anabolism, was concomitantly increased in osteoporosis (+63%), as a trend, and significantly in Alzheimer's disease (+76%). Osteoprotegerin was unchanged between patient groups and controls. 25 (OH) vitamin D plasma levels were low normal and of equal amount in all groups except for the osteoporosis group. These results point to increased bone catabolism and concomitant remodelling/anabolism unrelated to vitamin D state in mild Alzheimer's disease, but not in mild cognitive impairment. This corroborates previous findings of comorbidity of Alzheimer's disease with osteoporosis in the early disease course at the level of biochemical blood markers. Regarding osteoprotegerin, previously reported plasma level increases in Alzheimer's disease were not observed in this study, which does not rule out subtle changes to be detected in larger samples or the possibility that other components of osteoprotegerin pathways are affected in Alzheimer's disease. PMID:19468818

  12. [Osteoporosis].

    PubMed

    Hintze, Gerhard; Graf, Dieter

    2016-06-01

    Osteoporosis is among the main causes for bone fractures. In this overview we report on the prevalence of the disease, the diagnostic procedures, and the therapeutic options. The prevalence increases with age and women are more often affected than men. The diagnosis usually is made on the basis of dual X-ray absorptiometry. Prophylactic measures include a sufficient intake of calcium and vitamin D. Bisphosphonates play a central role in the pharmacotherapy of this disease. PMID:27439255

  13. [Osteoporosis].

    PubMed

    Al-Khawajah, F F

    2002-01-01

    It is well known that people, especially white people, are getting osteoporosis more often than previously thought. Until now, no direct causative factor has been determined, but genetic factors are very likely to be involved. Usually, affected individuals are initially asymptomatic while the disease process is going on, and they come to the attention of the medical profession only late when their bones are fractured as a result of a simple trauma. Also it is vital to let people know that heavy sports, at times, can be harmful. PMID:15339135

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. Dysglycaemia and Other Predictors for Progression or Regression from Impaired Fasting Glucose to Diabetes or Normoglycaemia

    PubMed Central

    de Abreu, L.; Holloway, Kara L.; Kotowicz, Mark A.; Pasco, Julie A.

    2015-01-01

    Aims. Diabetes mellitus is a growing health problem worldwide. This study aimed to describe dysglycaemia and determine the impact of body composition and clinical and lifestyle factors on the risk of progression or regression from impaired fasting glucose (IFG) to diabetes or normoglycaemia in Australian women. Methods. This study included 1167 women, aged 20–94 years, enrolled in the Geelong Osteoporosis Study. Multivariable logistic regression was used to identify predictors for progression to diabetes or regression to normoglycaemia (from IFG), over 10 years of follow-up. Results. At baseline the proportion of women with IFG was 33.8% and 6.5% had diabetes. Those with fasting dysglycaemia had higher obesity-related factors, lower serum HDL cholesterol, and lower physical activity. Over a decade, the incidence of progression from IFG to diabetes was 18.1 per 1,000 person-years (95% CI, 10.7–28.2). Fasting plasma glucose and serum triglycerides were important factors in both progression to diabetes and regression to normoglycaemia. Conclusions. Our results show a transitional process; those with IFG had risk factors intermediate to normoglycaemics and those with diabetes. This investigation may help target interventions to those with IFG at high risk of progression to diabetes and thereby prevent cases of diabetes. PMID:26273669

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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)

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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.

  20. Statins Impair Glucose Uptake in Tumor Cells1

    PubMed Central

    Malenda, Agata; Skrobanska, Anna; Issat, Tadeusz; Winiarska, Magdalena; Bil, Jacek; Oleszczak, Bozenna; Sinski, Maciej; Firczuk, Małgorzata; Bujnicki, Janusz M; Chlebowska, Justyna; Staruch, Adam D; Glodkowska-Mrowka, Eliza; Kunikowska, Jolanta; Krolicki, Leszek; Szablewski, Leszek; Gaciong, Zbigniew; Koziak, Katarzyna; Jakobisiak, Marek; Golab, Jakub; Nowis, Dominika A

    2012-01-01

    Statins, HMG-CoA reductase inhibitors, are used in the prevention and treatment of cardiovascular diseases owing to their lipid-lowering effects. Previous studies revealed that, by modulating membrane cholesterol content, statins could induce conformational changes in cluster of differentiation 20 (CD20) tetraspanin. The aim of the presented study was to investigate the influence of statins on glucose transporter 1 (GLUT1)-mediated glucose uptake in tumor cells. We observed a significant concentration- and time-dependent decrease in glucose analogs' uptake in several tumor cell lines incubated with statins. This effect was reversible with restitution of cholesterol synthesis pathway with mevalonic acid as well as with supplementation of plasma membrane with exogenous cholesterol. Statins did not change overall GLUT1 expression at either transcriptional or protein levels. An exploratory clinical trial revealed that statin treatment decreased glucose uptake in peripheral blood leukocytes and lowered 18F-fluorodeoxyglucose (18F-FDG) uptake by tumor masses in a mantle cell lymphoma patient. A bioinformatics analysis was used to predict the structure of human GLUT1 and to identify putative cholesterol-binding motifs in its juxtamembrane fragment. Altogether, the influence of statins on glucose uptake seems to be of clinical significance. By inhibiting 18F-FDG uptake, statins can negatively affect the sensitivity of positron emission tomography, a diagnostic procedure frequently used in oncology. PMID:22577346

  1. 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

  2. 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

  3. Enhanced Glucose Transport, but not Phosphorylation Capacity, Ameliorates Lipopolysaccharide-Induced Impairments in Insulin-Stimulated Muscle Glucose Uptake.

    PubMed

    Otero, Yolanda F; Mulligan, Kimberly X; Barnes, Tammy M; Ford, Eric A; Malabanan, Carlo M; Zong, Haihong; Pessin, Jeffrey E; Wasserman, David H; McGuinness, Owen P

    2016-06-01

    Lipopolysaccharide (LPS) is known to impair insulin-stimulated muscle glucose uptake (MGU). We determined if increased glucose transport (GLUT4) or phosphorylation capacity (hexokinase II; HKII) could overcome the impairment in MGU. We used mice that overexpressed GLUT4 (GLUT4) or HKII (HK) in skeletal muscle. Studies were performed in conscious, chronically catheterized (carotid artery and jugular vein) mice. Mice received an intravenous bolus of either LPS (10 μg/g body weight) or vehicle (VEH). After 5 h, a hyperinsulinemic-euglycemic clamp was performed. As MGU is also dependent on cardiovascular function that is negatively affected by LPS, cardiac function was assessed using echocardiography. LPS decreased whole body glucose disposal and MGU in wild-type (WT) and HK mice. In contrast, the decrease was attenuated in GLUT4 mice. Although membrane-associated GLUT4 was increased in VEH-treated GLUT4 mice, LPS impaired membrane-associated GLUT4 in GLUT4 mice to the same level as LPS-treated WT mice. This suggested that overexpression of GLUT4 had further benefits beyond preserving transport activity. In fact, GLUT4 overexpression attenuated the LPS-induced decrease in cardiac function. The maintenance of MGU in GLUT4 mice following LPS was accompanied by sustained anaerobic glycolytic flux as suggested by increased muscle Pdk4 expression, and elevated lactate availability. Thus, enhanced glucose transport, but not phosphorylation capacity, ameliorates LPS-induced impairments in MGU. This benefit is mediated by long-term adaptations to the overexpression of GLUT4 that sustain muscle anaerobic glycolytic flux and cardiac function in response to LPS. PMID:26682946

  4. 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

  5. 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

  6. 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

  7. 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

  8. Assessment risk of osteoporosis in Chinese people: relationship among body mass index, serum lipid profiles, blood glucose, and bone mineral density

    PubMed Central

    Cui, Rongtao; Zhou, Lin; Li, Zuohong; Li, Qing; Qi, Zhiming; Zhang, Junyong

    2016-01-01

    Objective The aim of our study was to investigate the relationship among age, sex, body mass index (BMI), serum lipid profiles, blood glucose (BG), and bone mineral density (BMD), making an assessment of the risk of osteoporosis. Materials and methods A total of 1,035 male and 3,953 female healthy volunteers (aged 41–95 years) were recruited by an open invitation. The basic information, including age, sex, height, weight, waistline, hipline, menstrual cycle, and medical history, were collected by a questionnaire survey and physical examination. Serum lipid profiles, BG, postprandial blood glucose, and glycosylated hemoglobin were obtained after 12 hours fasting. BMD in lumbar spine was measured by dual-energy X-ray absorptiometry scanning. Results The age-adjusted BMD in females was significantly lower than in males. With aging, greater differences of BMD distribution exist in elderly females than in males (P<0.001), and the fastigium of bone mass loss was in the age range from 51 to 55 in females and from 61 to 65 years in males. After adjustment for sex, there were significant differences in BMD among BMI-stratified groups in both males and females. The subjects with a BMI of <18.5 had a higher incidence of osteoporosis than BMI ≥18.5 in both sexes. BMD in type 2 diabetes mellitus with a BG of >7.0 mmol/L was lower than in people with BG of ≤7.0 mmol/L (P<0.001). People with serum high-density lipoprotein cholesterol levels of ≥1.56 mmol/L had a greater prevalence of osteoporosis compared with high-density lipoprotein cholesterol ≤1.55 mmol/L. Logistic regression with odds ratios showed that no association was found among total cholesterol, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin, postprandial blood glucose and BMD. Conclusion The present study further confirmed that factors such as age, sex, weight, BMI, high-density lipoprotein cholesterol, and diabetes are significant predictors of osteoporosis in the Chinese people

  9. Thiamin deficiency impairs endotoxin-induced increases in hepatic glucose output.

    PubMed

    Molina, P E; Yousef, K A; Smith, R M; Tepper, P G; Lang, C H; Abumrad, N N

    1994-05-01

    We addressed the role of thiamin, a cofactor for several enzymes involved in glucose metabolism, in the glucose metabolic response to endotoxin. Characterized by hyperglycemia, increased hepatic glucose production exceeding elevated rates of whole-body glucose utilization, this response is mediated by hormones and cytokines and is dependent on the immune and nutritional status of the host. We hypothesized that a thiamin-deficient state would impair the metabolic response to endotoxin. Rats were fed a thiamin-deficient or control diet for 6 wk before in vivo assessment of glucose kinetics. In control rats, Escherichia coli endotoxin increased the rate of glucose appearance (+76%), disappearance (+70%), and metabolic clearance (+50%). Thiamin deficiency resulted in increased plasma glucose (18%) and lactate (3- to 4-fold) as well as in a 30% decrease in insulin and an increase in glucagon (2.6-fold) and corticosterone (3.6-fold). Thiamin deficiency inhibited the endotoxin-induced hyperglycemia and the rise in hepatic glucose production, glucose utilization, and metabolic clearance rate. PMID:8172089

  10. 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

  11. 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

  12. BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid

    PubMed Central

    Findlay, John A.; Hamilton, David L.; Ashford, Michael L. J.

    2015-01-01

    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD. PMID:26483636

  13. Subjects with Impaired Fasting Glucose: Evolution in a Period of 6 Years

    PubMed Central

    Leiva, E.; Mujica, V.; Orrego, R.; Wehinger, S.; Soto, A.; Icaza, G.; Vásquez, M.; Díaz, L.; Andrews, M.; Arredondo, M.

    2014-01-01

    Aim. To study the evolution of impaired fasting glucose (IFG), considering glucose and HbA1c levels and risk factors associated, in a period of 6 years. Methods. We studied 94 subjects with impaired fasting glucose (IFG) that were diagnosed in 2005 and followed up to 2012. Glucose and HbA1c levels were determined. A descriptive analysis of contingence charts was performed in order to study the evolution in the development of type-2 diabetes mellitus (T2DM). Results. Twenty-eight of ninety-four subjects became T2DM; 51/94 remained with IFG; and 20/94 presented normal fasting glucose. From the 28 diabetic subjects, 9 had already developed diabetes and were under treatment with oral hypoglycemic agents; 5 were diagnosed with plasma glucose < 126 mg/dL, but with HbA1c over 6.5%. In those who developed diabetes, 15/28 had a family history of T2DM in first relative degree. Also, diabetic subjects had a BMI significantly higher than nodiabetics (t test: P < 0.01). The individuals that in 2005 had the highest BMI are those who currently have diabetes. Conclusion. The IFG constitutes a condition of high risk of developing T2DM in a few years, especially over 110 mg/dL and in obesity patients. PMID:25215305

  14. 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

  15. 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

  16. 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

  17. 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

  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. Osteoporosis in Men

    PubMed Central

    Khosla, Sundeep; Amin, Shreyasee; Orwoll, Eric

    2008-01-01

    With the aging of the population, there is a growing recognition that osteoporosis and fractures in men are a significant public health problem, and both hip and vertebral fractures are associated with increased morbidity and mortality in men. Osteoporosis in men is a heterogeneous clinical entity: whereas most men experience bone loss with aging, some men develop osteoporosis at a relatively young age, often for unexplained reasons (idiopathic osteoporosis). Declining sex steroid levels and other hormonal changes likely contribute to age-related bone loss, as do impairments in osteoblast number and/or activity. Secondary causes of osteoporosis also play a significant role in pathogenesis. Although there is ongoing controversy regarding whether osteoporosis in men should be diagnosed based on female- or male-specific reference ranges (because some evidence indicates that the risk of fracture is similar in women and men for a given level of bone mineral density), a diagnosis of osteoporosis in men is generally made based on male-specific reference ranges. Treatment consists both of nonpharmacological (lifestyle factors, calcium and vitamin D supplementation) and pharmacological (most commonly bisphosphonates or PTH) approaches, with efficacy similar to that seen in women. Increasing awareness of osteoporosis in men among physicians and the lay public is critical for the prevention of fractures in our aging male population. PMID:18451258

  20. 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

  1. 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

  2. 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

  3. 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

  4. [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

  5. Myeloid-Cell-Derived VEGF Maintains Brain Glucose Uptake and Limits Cognitive Impairment in Obesity.

    PubMed

    Jais, Alexander; Solas, Maite; Backes, Heiko; Chaurasia, Bhagirath; Kleinridders, André; Theurich, Sebastian; Mauer, Jan; Steculorum, Sophie M; Hampel, Brigitte; Goldau, Julia; Alber, Jens; Förster, Carola Y; Eming, Sabine A; Schwaninger, Markus; Ferrara, Napoleone; Karsenty, Gerard; Brüning, Jens C

    2016-05-01

    High-fat diet (HFD) feeding induces rapid reprogramming of systemic metabolism. Here, we demonstrate that HFD feeding of mice downregulates glucose transporter (GLUT)-1 expression in blood-brain barrier (BBB) vascular endothelial cells (BECs) and reduces brain glucose uptake. Upon prolonged HFD feeding, GLUT1 expression is restored, which is paralleled by increased expression of vascular endothelial growth factor (VEGF) in macrophages at the BBB. In turn, inducible reduction of GLUT1 expression specifically in BECs reduces brain glucose uptake and increases VEGF serum concentrations in lean mice. Conversely, myeloid-cell-specific deletion of VEGF in VEGF(Δmyel) mice impairs BBB-GLUT1 expression, brain glucose uptake, and memory formation in obese, but not in lean mice. Moreover, obese VEGF(Δmyel) mice exhibit exaggerated progression of cognitive decline and neuroinflammation on an Alzheimer's disease background. These experiments reveal that transient, HFD-elicited reduction of brain glucose uptake initiates a compensatory increase of VEGF production and assign obesity-associated macrophage activation a homeostatic role to restore cerebral glucose metabolism, preserve cognitive function, and limit neurodegeneration in obesity. PMID:27133169

  6. Haemostatic effects of metformin in simvastatin-treated volunteers with impaired fasting glucose.

    PubMed

    Krysiak, Robert; Okopien, Boguslaw

    2012-12-01

    Our study investigated whether metformin has an impact on haemostasis in patients with pre-diabetes receiving statin therapy. The study included 41 simvastatin-treated patients with impaired fasting glucose who were randomized to either metformin (3 g daily) or placebo. The international normalized ratio, the partial thromboplastin time, fibrinogen, factor VII coagulant activity, plasminogen activator inhibitor-1 and von Willebrand factor were assessed on the day of randomization and after 90 days of treatment. Metformin treatment reduced plasma levels/activity of the assessed haemostatic risk factors, and this effect correlated with the improvement in insulin sensitivity. The obtained results indicate that high-dose metformin produces a multi-directional beneficial effect on coagulation and fibrinolysis in patients with impaired fasting glucose already receiving statin therapy. The effect of metformin on haemostasis may play a role in the prevention of atherosclerosis-related disorders and acute vascular events in this pre-diabetic state. PMID:22716204

  7. 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

  8. 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

  9. 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

  10. Osteoporosis (image)

    MedlinePlus

    Osteoporosis is a condition characterized by progressive loss of bone density, thinning of bone tissue and increased vulnerability to fractures. Osteoporosis may result from disease, dietary or hormonal deficiency ...

  11. 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

  12. Ethanol induced impairment of glucose metabolism involves alterations of GABAergic signaling in pancreatic β-cells.

    PubMed

    Wang, Shuanglian; Luo, Yan; Feng, Allen; Li, Tao; Yang, Xupeng; Nofech-Mozes, Roy; Yu, Meng; Wang, Changhui; Li, Ziwei; Yi, Fan; Liu, Chuanyong; Lu, Wei-Yang

    2014-12-01

    Alcohol overindulgence is a risk factor of type 2 diabetes mellitus. However, the mechanisms by which alcohol overindulgence damages glucose metabolism remain unclear. Pancreatic islet β-cells are endowed with type-A γ-aminobutyric acid receptor (GABAAR) mediated autocrine signaling mechanism, which regulates insulin secretion and fine-tunes glucose metabolism. In neurons GABAAR is one of the major targets for alcohol. This study investigated whether ethanol alters glucose metabolism by affecting GABAAR signaling in pancreatic β-cells. Blood glucose level of test mice was measured using a blood glucose meter. Insulin secretion by the pancreatic β-cell line INS-1 cells was examined using a specific insulin ELISA kit. Whole-cell patch-clamp recording was used to evaluate GABA-elicited current in INS-1 cells. Western blot and immunostaining were used to measure the expression of GABAAR subunits in mouse pancreatic tissues or in INS-1 cells. Intraperitoneal (i.p.) administration of ethanol (3.0g/kg body weight) to mice altered glucose metabolism, which was associated with decreased expression of GABAAR α1- and δ- subunits on the surface of pancreatic β-cells. Acute treatment of cultured INS-1cells with ethanol (60mM) decreased the GABA-induced current and reduced insulin secretion. In contrast, treating INS-1 cells with GABA (100μM) largely prevented the ethanol-induced reduction of insulin release. Importantly, pre-treating mice with GABA (i.p., 1.5mg/kg body weight) partially reversed ethanol-induced impairment of glucose homeostasis in mice. Our data suggest a novel role of pancreatic GABA signaling in protecting pancreatic islet β-cells from ethanol-induced dysfunction. PMID:25456265

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. Gut microbe-derived extracellular vesicles induce insulin resistance, thereby impairing glucose metabolism in skeletal muscle

    PubMed Central

    Choi, Youngwoo; Kwon, Yonghoon; Kim, Dae-Kyum; Jeon, Jinseong; Jang, Su Chul; Wang, Taejun; Ban, Minjee; Kim, Min-Hye; Jeon, Seong Gyu; Kim, Min-Sun; Choi, Cheol Soo; Jee, Young-Koo; Gho, Yong Song; Ryu, Sung Ho; Kim, Yoon-Keun

    2015-01-01

    Gut microbes might influence host metabolic homeostasis and contribute to the pathogenesis of type 2 diabetes (T2D), which is characterized by insulin resistance. Bacteria-derived extracellular vesicles (EVs) have been suggested to be important in the pathogenesis of diseases once believed to be non-infectious. Here, we hypothesize that gut microbe-derived EVs are important in the pathogenesis of T2D. In vivo administration of stool EVs from high fat diet (HFD)-fed mice induced insulin resistance and glucose intolerance compared to regular diet (RD)-fed mice. Metagenomic profiling of stool EVs by 16S ribosomal DNA sequencing revealed an increased amount of EVs derived from Pseudomonas panacis (phylum Proteobacteria) in HFD mice compared to RD mice. Interestingly, P. panacis EVs blocked the insulin signaling pathway in both skeletal muscle and adipose tissue. Moreover, isolated P. panacis EVs induced typical diabetic phenotypes, such as glucose intolerance after glucose administration or systemic insulin injection. Thus, gut microbe-derived EVs might be key players in the development of insulin resistance and impairment of glucose metabolism promoted by HFD. PMID:26510393

  19. Impaired Fasting Glucose in Nondiabetic Range: Is It a Marker of Cardiovascular Risk Factor Clustering?

    PubMed Central

    Valentino, Giovanna; Kramer, Verónica; Orellana, Lorena; Bustamante, María José; Casasbellas, Cinthia; Adasme, Marcela; Salazar, Alejandra; Navarrete, Carlos; Acevedo, Mónica

    2015-01-01

    Background. Impaired fasting glucose (IFG) through the nondiabetic range (100–125 mg/dL) is not considered in the cardiovascular (CV) risk profile. Aim. To compare the clustering of CV risk factors (RFs) in nondiabetic subjects with normal fasting glucose (NFG) and IFG. Material and Methods. Cross-sectional study in 3739 nondiabetic subjects. Demographics, medical history, and CV risk factors were collected and lipid profile, fasting glucose levels (FBG), C-reactive protein (hsCRP), blood pressure (BP), anthropometric measurements, and aerobic capacity were determined. Results. 559 (15%) subjects had IFG: they had a higher mean age, BMI, waist circumference, non-HDL cholesterol, BP, and hsCRP (p < 0.0001) and lower HDL (p < 0.001) and aerobic capacity (p < 0.001). They also had a higher prevalence of hypertension (34% versus 25%; p < 0.001), dyslipidemia (79% versus 74%; p < 0.001), and obesity (29% versus 16%; p < 0.001) and a higher Framingham risk score (8% versus 6%; p < 0.001). The probability of presenting 3 or more CV RFs adjusted by age and gender was significantly higher in the top quintile of fasting glucose (≥98 mg/dL; OR = 2.02; 1.62–2.51). Conclusions. IFG in the nondiabetic range is associated with increased cardiovascular RF clustering. PMID:26504260

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. Bisphenol A Impairs Hepatic Glucose Sensing in C57BL/6 Male Mice

    PubMed Central

    Perreault, Leigh; McCurdy, Carrie; Kerege, Anna A.; Houck, Julie; Færch, Kristine; Bergman, Bryan C.

    2013-01-01

    Aims/Hypothesis Glucose sensing (eg. glucokinase activity) becomes impaired in the development of type 2 diabetes, the etiology of which is unclear. Estrogen can stimulate glucokinase activity, whereas the pervasive environmental pollutant bisphenol A (BPA) can inhibit estrogen action, hence we aimed to determine the effect of BPA on glucokinase activity directly. Methods To evaluate a potential acute effect on hepatic glucokinase activity, BPA in water (n = 5) vs. water alone (n = 5) was administered at the EPA’s purported “safe dose” (50 µg/kg) by gavage to lean 6-month old male C57BL/6 mice. Two hours later, animals were euthanized and hepatic glucokinase activity measured over glucose levels from 1–20 mmol/l in liver homogenate. To determine the effect of chronic BPA exposure on hepatic glucokinase activity, lean 6-month old male C57BL/6 mice were provided with water (n = 15) or water with 1.75 mM BPA (∼50 µg/kg/day; n = 14) for 2 weeks. Following the 2-week exposure, animals were euthanized and glucokinase activity measured as above. Results Hepatic glucokinase activity was signficantly suppressed after 2 hours in animals given an oral BPA bolus compared to those who received only water (p = 0.002–0.029 at glucose 5–20 mmol/l; overall treatment effect p<0.001). Exposure to BPA over 2 weeks also suppressed hepatic glucokinase activity in exposed vs. unexposed mice (overall treatment effect, p = 0.003). In both experiments, the Hill coefficient was higher and Vmax lower in mice treated with BPA. Conclusions/Interpretation Both acute and chronic exposure to BPA significantly impair hepatic glucokinase activity and function. These findings identify a potential mechanism for how BPA may increase risk for diabetes. PMID:23922885

  6. New Horizons in Osteoporosis

    PubMed Central

    Rachner, Tilman D.; Khosla, Sundeep; Hofbauer, Lorenz C.

    2013-01-01

    Summary Osteoporosis is a common disease characterised by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. With an ageing population, the medical and socioeconomic impact of osteoporosis in general and postmenopausal osteoporosis in particular, will increase further. A detailed knowledge of bone biology with molecular insights into the communication between bone-forming osteoblasts and bone-resorbing osteoclasts and the orchestrating signalling network has led to the identification of novel therapeutic targets. Based on this, therapeutic strategies have been developed aimed at (I) inhibiting excessive bone resorption and by (II) increasing bone formation. The most promising novel treatments include denosumab, a monoclonal antibody against receptor activator of NF-κB ligand, a key osteoclast cytokine, odanacatib, a specific inhibitor of the osteoclast protease cathepsin K, and antibodies against the proteins sclerostin and dickkopf-1, two endogenous inhibitors of bone formation. This review provides an overview on these novel therapies and explains their underlying physiology. PMID:21450337

  7. 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

  8. 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

  9. Secondary osteoporosis.

    PubMed

    Sheu, Angela; Diamond, Terry

    2016-06-01

    Secondary osteoporosis is less common than primary osteoporosis. It may be suspected in patients who present with a fragility fracture despite having no risk factors for osteoporosis. In addition, secondary osteoporosis should be considered if the bone density Z-score is -2.5 or less. Consider the fracture site and presence of other clinical clues to guide investigations for an underlying cause. The tests to use are those that are indicated for the suspected cause. Baseline investigations include tests for bone and mineral metabolism (calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone), liver and kidney function, full blood count and thyroid-stimulating hormone. More detailed testing may be required in patients with severe osteoporosis. PMID:27346916

  10. Secondary osteoporosis

    PubMed Central

    Sheu, Angela; Diamond, Terry

    2016-01-01

    SUMMARY Secondary osteoporosis is less common than primary osteoporosis. It may be suspected in patients who present with a fragility fracture despite having no risk factors for osteoporosis. In addition, secondary osteoporosis should be considered if the bone density Z-score is –2.5 or less. Consider the fracture site and presence of other clinical clues to guide investigations for an underlying cause. The tests to use are those that are indicated for the suspected cause. Baseline investigations include tests for bone and mineral metabolism (calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D, parathyroid hormone), liver and kidney function, full blood count and thyroid-stimulating hormone. More detailed testing may be required in patients with severe osteoporosis. PMID:27346916

  11. Treating osteoporosis

    PubMed Central

    Gupta, Akhil; March, Lyn

    2016-01-01

    summary Osteoporotic fractures are common resulting in increased morbidity and mortality. Exercise can help prevent osteoporosis. It can also benefit patients with osteoporosis, but the exercises must be tailored to the patient. Most Australians should be able to obtain adequate calcium in their diet and vitamin D from the sun. Supplements may be needed in some patients and they are recommended for use with other drugs for osteoporosis. Bisphosphonates, and in some patients denosumab, are first-line drugs for osteoporosis. Raloxifene and strontium ranelate can be considered in patients who cannot take bisphosphonates or denosumab. Teriparatide is reserved for patients with severe osteoporosis and the use of strontium ranelate is declining because of cardiovascular safety concerns. PMID:27340321

  12. Aldosterone impairs vascular reactivity by decreasing glucose-6-phosphate dehydrogenase activity

    PubMed Central

    Leopold, Jane A.; Dam, Aamir; Maron, Bradley A.; Scribner, Anne W.; Liao, Ronglih; Handy, Diane E.; Stanton, Robert C.; Pitt, Bertram; Loscalzo, Joseph

    2013-01-01

    Hyperaldosteronism is associated with impaired vascular reactivity; however, the mechanism by which aldosterone promotes endothelial dysfunction remains unknown. Glucose-6-phosphate dehydrogenase (G6pd), the principal source of Nadph, modulates vascular function by limiting oxidant stress to preserve bioavailable nitric oxide (NO•). In these studies, we show that aldosterone (10−9-10−7 mol/l) decreases endothelial G6pd expression and activity in vitro resulting in increased oxidant stress and decreased cGMP levels similar to what is observed in G6pd-deficient cells. Aldosterone decreases G6pd expression by protein kinase A activation to increase expression of Crem, which interferes with Creb binding to the G6pd promoter. In vivo, infusion of aldosterone decreases vascular G6pd expression and impairs vascular reactivity. These effects are abrogated by spironolactone or vascular gene transfer of G6pd. These studies demonstrate that aldosterone induces a G6pd-deficient phenotype to impair endothelial function; aldosterone antagonism or gene transfer of G6pd improves vascular reactivity by restoring G6pd activity. PMID:17273168

  13. 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

  14. 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

  15. Impaired Lipid and Glucose Homeostasis in Hexabromocyclododecane-Exposed Mice Fed a High-Fat Diet

    PubMed Central

    Koike, Eiko; Win-Shwe, Tin-Tin; Yamamoto, Megumi; Takano, Hirohisa

    2014-01-01

    Background: Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear. Objectives: We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue. Results: In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice. Conclusions: Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity. Citation: Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health

  16. Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report.

    PubMed

    Mansur, Rodrigo B; Rizzo, Lucas B; Santos, Camila M; Asevedo, Elson; Cunha, Graccielle R; Noto, Mariane N; Pedrini, Mariana; Zeni-Graiff, Maiara; Gouvea, Eduardo S; Cordeiro, Quirino; Reininghaus, Eva Z; McIntyre, Roger S; Brietzke, Elisa

    2016-09-01

    This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course. PMID:27281261

  17. 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

  18. 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

  19. 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

  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. 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

  2. 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

  3. 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

  4. MALE OSTEOPOROSIS

    PubMed Central

    Oliveira, Lindomar Guimarães; Guimarães, Mara Lucia Rassi

    2015-01-01

    ABSTRACT Population aging is a reality that is being faced worldwide, and Brazil is no different. Osteoporosis was considered to be a postmenopausal women's disease for many years. Men have many development and hormonal factors that differentiate their skeletal maturation, which affects the incidence of osteoporosis and fractures. An up-to-date review of the specific literature within the Medline system is presented. PMID:27022584

  5. 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

  6. 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

  7. Ciliary Neurotrophic Factor Stimulates Muscle Glucose Uptake by a PI3-Kinase–Dependent Pathway That Is Impaired With Obesity

    PubMed Central

    Steinberg, Gregory R.; Watt, Matthew J.; Ernst, Matthias; Birnbaum, Morris J.; Kemp, Bruce E.; Jørgensen, Sebastian Beck

    2009-01-01

    OBJECTIVE Ciliary neurotrophic factor (CNTF) reverses muscle insulin resistance by increasing fatty acid oxidation through gp130-LIF receptor signaling to the AMP-activated protein kinase (AMPK). CNTF also increases Akt signaling in neurons and adipocytes. Because both Akt and AMPK regulate glucose uptake, we investigated muscle glucose uptake in response to CNTF signaling in lean and obese mice. RESEARCH DESIGN AND METHODS Mice were injected intraperitoneally with saline or CNTF, and blood glucose was monitored. The effects of CNTF on skeletal muscle glucose uptake and AMPK/Akt signaling were investigated in incubated soleus and extensor digitorum longus (EDL) muscles from muscle-specific AMPKα2 kinase-dead, gp130ΔSTAT, and lean and obese ob/ob and high-fat–fed mice. The effect of C2-ceramide on glucose uptake and gp130 signaling was also examined. RESULTS CNTF reduced blood glucose and increased glucose uptake in isolated muscles in a time- and dose-dependent manner with maximal effects after 30 min with 100 ng/ml. CNTF increased Akt-S473 phosphorylation in soleus and EDL; however, AMPK-T172 phosphorylation was only increased in soleus. Incubation of muscles from AMPK kinase dead (KD) and wild-type littermates with the PI3-kinase inhibitor LY-294002 demonstrated that PI3-kinase, but not AMPK, was essential for CNTF-stimulated glucose uptake. CNTF-stimulated glucose uptake and Akt phosphorylation were substantially reduced in obesity (high-fat diet and ob/ob) despite normal induction of gp130/AMPK signaling—effects also observed when treating myotubes with C2-ceramide. CONCLUSIONS CNTF acutely increases muscle glucose uptake by a mechanism involving the PI3-kinase/Akt pathway that does not require AMPK. CNTF-stimulated glucose uptake is impaired in obesity-induced insulin resistance and by ceramide. PMID:19136654

  8. 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

  9. [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

  10. Shiftwork and impaired glucose metabolism: a 14-year cohort study on 7104 male workers.

    PubMed

    Suwazono, Yasushi; Dochi, Mirei; Oishi, Mitsuhiro; Tanaka, Kumihiko; Kobayashi, Etsuko; Sakata, Kouichi

    2009-07-01

    The aim of this study was to assess the effect of shiftwork on hemoglobin A1c (HbA1c) level, as an index of glucose metabolism. A 14 yr prospective cohort study was conducted on day (n = 4219) and alternating shiftworkers (n = 2885) who received annual health checkups between 1991 and 2005 at a Japanese steel company. The endpoints were either a 10%, 15%, 20%, 25%, or 30% increase in HbA1c during the period of observation, compared to HbA1c at entry to the study. The association between the type of job schedule and increase in HbA1c was investigated after adjusting for age, body mass index, mean arterial pressure, total serum cholesterol, creatinine, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, drinking habit, smoking habit, and habitual exercise using multivariate pooled logistic regression analyses. Shiftwork was significantly associated with the various HbA1c endpoints (> or =10% HbA1c increase, odds ratio 1.35 [95% confidence interval 1.26-1.44]; > or =15% HbA1c increase, odds ratio 1.29 [95% confidence interval, 1.19-1.40]; > or =20% HbA1c increase, odds ratio 1.23 [95% confidence interval 1.11-1.37]; and > or =25% HbA1c increase, odds ratio 1.19 [95% confidence interval 1.03-1.36]). Age, body mass index, alanine aminotransferase, and gamma-glutamyl transpeptidase were associated positively with all five HbA1c endpoints. Uric acid was associated negatively with all five HbA1c endpoints. Our study on male Japanese workers revealed alternating shiftwork (in addition to other established factors, such as age and body mass index) was a consistent risk factor for impaired glucose metabolism. PMID:19637051

  11. 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

  12. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Watanabe, Reiko; Inoue, Daisuke

    2016-01-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients. PMID:27622174

  13. Osteoporosis Associated with Chronic Obstructive Pulmonary Disease.

    PubMed

    Okazaki, Ryo; Watanabe, Reiko; Inoue, Daisuke

    2016-08-01

    Recent epidemiological studies have revealed that osteoporosis is closely associated with common chronic diseases including diabetes, hypertension, chronic kidney disorders, and chronic obstructive pulmonary disease (COPD). COPD is a chronic inflammatory airway disease but now well known to be associated with various systemic comorbidities including osteoporosis. Osteoporosis and osteoporotic fractures are extremely common in COPD patients, which have significant impacts on their quality of life (QOL), activities of daily life (ADL), respiratory function, and possibly their prognosis. COPD-associated osteoporosis is however extremely under-recognized, hence undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality compromise bone strength causing fractures in COPD. In COPD patients, various general clinical risk factors for osteoporosis are present including smoking, older age, low body weight, and physical inactivity. In addition, disease-related risk factors such as decreased pulmonary function, inflammation, glucocorticoid use and vitamin D deficiency/insufficiency have been linked to the development of osteoporosis in COPD. Increased awareness of osteoporosis in COPD, especially that of high prevalence of vertebral fractures is called upon among general physicians as well as pulmonologists. Routine screening for osteoporosis and risk assessment of fractures will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage. Timely prevention of developing osteoporosis together with appropriate treatment of established osteoporosis may improve QOL and ADL of the COPD patients, preserve their lung function and eventually result in better prognosis in these patients. PMID:27622174

  14. 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

  15. 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

  16. 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

  17. Humanin: a mitochondrial signaling peptide as a biomarker for impaired fasting glucose-related oxidative stress.

    PubMed

    Voigt, Annet; Jelinek, Herbert F

    2016-05-01

    Mitochondrial RNR-2 (mt-RNR2, humanin) has been shown to play a role in protecting several types of cells and tissues from the effects of oxidative stress. Humanin (HN) functions through extracellular and intracellular pathways adjusting mitochondrial oxidative phosphorylation and ATP production. Addition of HN improved insulin sensitivity in animal models of diabetes mellitus but no clinical studies have been carried out to measure HN levels in humans associated with hyperglycemia. The plasma levels of HN in participants attending a diabetes complications screening clinic were measured. Clinical history and anthropometric data were obtained from all participants. Plasma levels of HN were measured by a commercial ELISA kit. All data were analyzed applying nonparametric statistics and general linear modeling to correct for age and gender. A significant decrease (P = 0.0001) in HN was observed in the impaired fasting glucose (IFG) group (n = 23; 204.84 ± 92.87 pg mL(-1)) compared to control (n = 58; 124.3 ± 83.91 pg mL(-1)) consistent with an adaptive cellular response by HN to a slight increase in BGL. PMID:27173674

  18. Associations between Dietary Patterns and Impaired Fasting Glucose in Chinese Men: A Cross-Sectional Study

    PubMed Central

    Zhang, Meilin; Zhu, Yufeng; Li, Ping; Chang, Hong; Wang, Xuan; Liu, Weiqiao; Zhang, Yuwen; Huang, Guowei

    2015-01-01

    Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG) which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ), and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1) a vegetables-fruits pattern; (2) an animal offal-dessert pattern; and (3) a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR) of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI): 1.87–5.30). The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships. PMID:26402695

  19. Inhibition of GSK-3 induces differentiation and impaired glucose metabolism in renal cancer.

    PubMed

    Pal, Krishnendu; Cao, Ying; Gaisina, Irina N; Bhattacharya, Santanu; Dutta, Shamit K; Wang, Enfeng; Gunosewoyo, Hendra; Kozikowski, Alan P; Billadeau, Daniel D; Mukhopadhyay, Debabrata

    2014-02-01

    Glycogen synthase kinase-3 (GSK-3), a constitutively active serine/threonine kinase, is a key regulator of numerous cellular processes ranging from glycogen metabolism to cell-cycle regulation and proliferation. Consistent with its involvement in many pathways, it has also been implicated in the pathogenesis of various human diseases, including type II diabetes, Alzheimer disease, bipolar disorder, inflammation, and cancer. Consequently, it is recognized as an attractive target for the development of new drugs. In the present study, we investigated the effect of both pharmacologic and genetic inhibition of GSK-3 in two different renal cancer cell lines. We have shown potent antiproliferative activity of 9-ING-41, a maleimide-based GSK-3 inhibitor. The antiproliferative activity is most likely caused by G(0)-G(1) and G(2)-M phase arrest as evident from cell-cycle analysis. We have established that inhibition of GSK-3 imparted a differentiated phenotype in renal cancer cells. We have also shown that GSK-3 inhibition induced autophagy, likely as a result of imbalanced energy homeostasis caused by impaired glucose metabolism. In addition, we have demonstrated the antitumor activity of 9-ING-41 in two different subcutaneous xenograft renal cell carcinoma tumor models. To our knowledge, this is the first report describing autophagy induction due to GSK-3 inhibition in renal cancer cells. PMID:24327518

  20. Associations between Dietary Patterns and Impaired Fasting Glucose in Chinese Men: A Cross-Sectional Study.

    PubMed

    Zhang, Meilin; Zhu, Yufeng; Li, Ping; Chang, Hong; Wang, Xuan; Liu, Weiqiao; Zhang, Yuwen; Huang, Guowei

    2015-09-01

    Few studies have examined the association between Asian dietary pattern and prediabetes, in particular, the Chinese diet. We conducted a cross-sectional study to identify dietary patterns associated with impaired fasting glucose (IFG) which considered a state of prediabetes in Chinese men. The study included 1495 Chinese men aged 20 to 75 years. Information about diet was obtained using an 81-item food frequency questionnaire (FFQ), and 21 predefined food groups were considered in a factor analysis. Three dietary patterns were generated by factor analysis: (1) a vegetables-fruits pattern; (2) an animal offal-dessert pattern; and (3) a white rice-red meat pattern. The multivariate-adjusted odds ratio (OR) of IFG for the highest tertile of the animal offal-dessert pattern in comparison with the lowest tertile was 3.15 (95% confidence intervals (CI): 1.87-5.30). The vegetables-fruits dietary pattern was negatively associated with the risk of IFG, but a significant association was observed only in the third tertile. There was no significant association between IFG and the white rice-red meat pattern. Our findings indicated that the vegetables-fruits dietary pattern was inversely associated with IFG, whereas the animal offal-dessert pattern was associated with an increased risk of IFG in Chinese men. Further prospective studies are needed to elucidate the diet-prediabetes relationships. PMID:26402695

  1. Prefrontal asymmetric interictal glucose hypometabolism and cognitive impairment in patients with temporal lobe epilepsy.

    PubMed

    Jokeit, H; Seitz, R J; Markowitsch, H J; Neumann, N; Witte, O W; Ebner, A

    1997-12-01

    Depressions of regional cerebral metabolism beyond the epileptogenic zone have been demonstrated in patients with intractable temporal lobe epilepsy. However, their clinical relevance, and the causes of prefrontal metabolic asymmetries are less well understood. We investigated 96 temporal lobe epilepsy patients by FDG-PET and neuropsychological assessment who had a corresponding unilateral temporal hypometabolism, left hemisphere speech dominance, full scale IQ of > 70 and no extratemporal lesion in MRIs. The regional glucose metabolism was determined in each patient in homologous regions including prefrontal cortex, and normalized to whole brain metabolism. Regional differences of > 10% were regarded as asymmetrical. Prefrontal metabolic asymmetries were more frequent in patients with left temporal lobe epilepsy (21 left, six right) and a history of secondarily generalized seizures. A multivariate analysis of variance revealed a main effect for prefrontal metabolic asymmetry on neuropsychological 'frontal lobe measures', including verbal and performance intelligence measures. Prefrontal metabolic asymmetry was not related to 'measures of episodic memory', presence of psychiatric symptoms or frontal interictal epileptiform discharges. We conclude that prefrontal metabolic asymmetry is associated with cognitive impairment. Patients with temporal lobe epilepsy of the left speech dominant hemisphere and a history of secondarily generalized seizures are at considerable risk of developing prefrontal metabolic asymmetry. PMID:9448582

  2. Mammalian Tribbles homolog 3 impairs insulin action in skeletal muscle: role in glucose-induced insulin resistance

    PubMed Central

    Liu, Jiarong; Franklin, John L.; Messina, Joseph L.; Hill, Helliner S.; Moellering, Douglas R.; Walton, R. Grace; Martin, Mitchell; Garvey, W. Timothy

    2009-01-01

    Tribbles homolog 3 (TRIB3) was found to inhibit insulin-stimulated Akt phosphorylation and modulate gluconeogenesis in rodent liver. Currently, we examined a role for TRIB3 in skeletal muscle insulin resistance. Ten insulin-sensitive, ten insulin-resistant, and ten untreated type 2 diabetic (T2DM) patients were metabolically characterized by hyperinsulinemic euglycemic glucose clamps, and biopsies of vastus lateralis were obtained. Skeletal muscle samples were also collected from rodent models including streptozotocin (STZ)-induced diabetic rats, db/db mice, and Zucker fatty rats. Finally, L6 muscle cells were used to examine regulation of TRIB3 by glucose, and stable cell lines hyperexpressing TRIB3 were generated to identify mechanisms underlying TRIB3-induced insulin resistance. We found that 1) skeletal muscle TRIB3 protein levels are significantly elevated in T2DM patients; 2) muscle TRIB3 protein content is inversely correlated with glucose disposal rates and positively correlated with fasting glucose; 3) skeletal muscle TRIB3 protein levels are increased in STZ-diabetic rats, db/db mice, and Zucker fatty rats; 4) stable TRIB3 hyperexpression in muscle cells blocks insulin-stimulated glucose transport and glucose transporter 4 (GLUT4) translocation and impairs phosphorylation of Akt, ERK, and insulin receptor substrate-1 in insulin signal transduction; and 5) TRIB3 mRNA and protein levels are increased by high glucose concentrations, as well as by glucose deprivation in muscle cells. These data identify TRIB3 induction as a novel molecular mechanism in human insulin resistance and diabetes. TRIB3 acts as a nutrient sensor and could mediate the component of insulin resistance attributable to hyperglycemia (i.e., glucose toxicity) in diabetes. PMID:19996382

  3. 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

  4. Failure of Hyperglycemia and Hyperinsulinemia to Compensate for Impaired Metabolic Response to an Oral Glucose Load

    PubMed Central

    Hussain, M; Janghorbani, M; Schuette, S; Considine, RV; Chisholm, RL; Mather, KJ

    2014-01-01

    Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese Type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes. PMID:25511878

  5. Prevalence and risk factors of diabetes and impaired fasting glucose in Nauru

    PubMed Central

    2011-01-01

    Background No comprehensive assessment of diabetes prevalence in Nauru has been conducted since an extreme prevalence was documented more than two decades ago. This study aims to determine the prevalence and risk factors of diabetes and impaired fasting glucose. Methods A nationwide survey in 2004 of people aged 15- 64 years (n = 1592). Fasting plasma glucose levels were used to defined diabetes (≥7.0 mmol/l or 126 mg/dl) and prediabetes (6.1-6.9 mmol/l or 110-125 mg/dl). Results The sex-standardized prevalence of diabetes was 13.0% (95% CI: 10.6, 15.4) in men, 14.4% (11.9, 16.9) in women, and 13.7% (12.0, 15.4) combined. The sex-standardized prevalence of prediabetes was 6.4% (4.6, 8.2) for men, 5.5% (3.9, 7.2) for women, and 6.0% (4.8, 7.3) combined. The prevalence of diabetes for individuals 15-24, 25-34, 35-44, 45-54 and 55-64 years was 4.5%, 7.6%, 24.1%, 32.9%, and 42.7%, respectively. The prevalence of prediabetes for the same age categories was 4.2%, 8.8%, 5.9%, 6.6%, 7.1%, respectively. Multivariable, multinomial logit modeling found risk factors for prediabetes were high cholesterol levels (OR: 2.02, 95% CI: 1.66, 2.47) and elevated waist circumference (OR: 1.04, 95% CI: 1.00, 1.08), and for diabetes were age in years (OR: 1.06; 95% CI: 1.04, 1.07), cholesterol levels (OR: 1.84, 95% CI: 1.58, 2.14) and waist circumference (OR: 1.04, 95% CI: 1.02, 1.07). Conclusions Diabetes remains a major public health problem in Nauru, affecting one out of every ten people. While the prevalence of diabetes has declined, its burden has persisted among the old but also extended towards the younger age groups. PMID:21943388

  6. Heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion, but not insulin action, in high-fat-fed mice.

    PubMed

    Kang, Li; Dai, Chunhua; Lustig, Mary E; Bonner, Jeffrey S; Mayes, Wesley H; Mokshagundam, Shilpa; James, Freyja D; Thompson, Courtney S; Lin, Chien-Te; Perry, Christopher G R; Anderson, Ethan J; Neufer, P Darrell; Wasserman, David H; Powers, Alvin C

    2014-11-01

    Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action, wild-type (sod2(+/+)) and heterozygous knockout mice (sod2(+/-)) were fed a chow or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin action in vivo. GSIS during HG clamps was equal in chow-fed sod2(+/-) and sod2(+/+) but was markedly decreased in HF-fed sod2(+/-). Remarkably, this impairment was not paralleled by reduced HG glucose infusion rate (GIR). Decreased GSIS in HF-fed sod2(+/-) was associated with increased ROS, such as superoxide ion. Surprisingly, insulin action determined by HI clamps did not differ between sod2(+/-) and sod2(+/+) of either diet. Since insulin action was unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2(+/-) was due to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho-AMPK protein in muscle of HF-fed sod2(+/-) support this hypothesis. We conclude that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes observed in diabetic humans, impairs GSIS in HF-fed mice without affecting insulin action. PMID:24947366

  7. Heterozygous SOD2 Deletion Impairs Glucose-Stimulated Insulin Secretion, but Not Insulin Action, in High-Fat–Fed Mice

    PubMed Central

    Dai, Chunhua; Lustig, Mary E.; Bonner, Jeffrey S.; Mayes, Wesley H.; Mokshagundam, Shilpa; James, Freyja D.; Thompson, Courtney S.; Lin, Chien-Te; Perry, Christopher G.R.; Anderson, Ethan J.; Neufer, P. Darrell; Wasserman, David H.; Powers, Alvin C.

    2014-01-01

    Elevated reactive oxygen species (ROS) are linked to insulin resistance and islet dysfunction. Manganese superoxide dismutase (SOD2) is a primary defense against mitochondrial oxidative stress. To test the hypothesis that heterozygous SOD2 deletion impairs glucose-stimulated insulin secretion (GSIS) and insulin action, wild-type (sod2+/+) and heterozygous knockout mice (sod2+/−) were fed a chow or high-fat (HF) diet, which accelerates ROS production. Hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI) clamps were performed to assess GSIS and insulin action in vivo. GSIS during HG clamps was equal in chow-fed sod2+/− and sod2+/+ but was markedly decreased in HF-fed sod2+/−. Remarkably, this impairment was not paralleled by reduced HG glucose infusion rate (GIR). Decreased GSIS in HF-fed sod2+/− was associated with increased ROS, such as superoxide ion. Surprisingly, insulin action determined by HI clamps did not differ between sod2+/− and sod2+/+ of either diet. Since insulin action was unaffected, we hypothesized that the unchanged HG GIR in HF-fed sod2+/− was due to increased glucose effectiveness. Increased GLUT-1, hexokinase II, and phospho-AMPK protein in muscle of HF-fed sod2+/− support this hypothesis. We conclude that heterozygous SOD2 deletion in mice, a model that mimics SOD2 changes observed in diabetic humans, impairs GSIS in HF-fed mice without affecting insulin action. PMID:24947366

  8. 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

  9. Palmitate-induced impairment of glucose-stimulated insulin secretion precedes mitochondrial dysfunction in mouse pancreatic islets.

    PubMed

    Barlow, Jonathan; Jensen, Verena Hirschberg; Jastroch, Martin; Affourtit, Charles

    2016-02-15

    It has been well established that excessive levels of glucose and palmitate lower glucose-stimulated insulin secretion (GSIS) by pancreatic β-cells. This β-cell 'glucolipotoxicity' is possibly mediated by mitochondrial dysfunction, but involvement of bioenergetic failure in the pathological mechanism is the subject of ongoing debate. We show in the present study that increased palmitate levels impair GSIS before altering mitochondrial function. We demonstrate that GSIS defects arise from increased insulin release under basal conditions in addition to decreased insulin secretion under glucose-stimulatory conditions. Real-time respiratory analysis of intact mouse pancreatic islets reveals that mitochondrial ATP synthesis is not involved in the mechanism by which basal insulin is elevated. Equally, mitochondrial lipid oxidation and production of reactive oxygen species (ROS) do not contribute to increased basal insulin secretion. Palmitate does not affect KCl-induced insulin release at a basal or stimulatory glucose level, but elevated basal insulin release is attenuated by palmitoleate and associates with increased intracellular calcium. These findings deepen our understanding of β-cell glucolipotoxicity and reveal that palmitate-induced GSIS impairment is disconnected from mitochondrial dysfunction, a notion that is important when targeting β-cells for the treatment of diabetes and when assessing islet function in human transplants. PMID:26621874

  10. 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

  11. Resistin impairs glucose permeability in EA.hy926 cells by down-regulating GLUT1 expression.

    PubMed

    Li, Qiang; Cai, Yuxi; Huang, Jing; Yu, Xiaolan; Sun, Jun; Yang, Zaiqing; Zhou, Lei

    2016-10-15

    Type 2 diabetes mellitus (T2DM) is a chronic disease which is now affecting the health of more and more people in the world. Resistin, discovered in 2001, is considered to be closely related to metabolic dysfunction and obesity. Previous study showed that hyperglycemia is always accompanied by a high serum resistin concentration. We therefore investigated whether resistin can mediate glucose transfer across the blood-tissue barrier. Here, we employed a transwell system to analyze glucose permeability in EA.hy926 human endothelial cells treated without or with human resistin. In EA.hy926 cells treated with resistin, the permeability to glucose was heavily impaired. This was due to the down-regulation of GLUT1 expression as a result of the treatment, rather than regulation of tight junctions. In addition, overexpression of GLUT1 in EA.hy926 cells was able to recover the blocking effect of resistin on glucose permeability. We further found that resistin could inhibit the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and consequently impede the transcription of GLUT1. The results of the present study suggested that resistin could cause glucose retention in serum and thus result in hyperglycemia. This provides a novel explanation for hyperglycemia and a potential new way of treating type 2 diabetes mellitus. PMID:27353463

  12. Male Osteoporosis

    PubMed Central

    Drake, Matthew T.; Khosla, Sundeep

    2013-01-01

    Synopsis Osteoporosis is now recognized as a major threat to health in aging men. Morbidity and mortality, particularly following hip fracture, are substantial. Whereas trabecular bone loss starts in early adulthood, loss of cortical bone only appears to occur from mid-life onwards. Declining bioavailable estradiol levels play an integral role in male age-associated bone loss. Both pharmacologic and supportive care interventions are important for optimal care in men at increased fracture risk. PMID:22877433

  13. 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

  14. Identification of Risk Factors Affecting Impaired Fasting Glucose and Diabetes in Adult Patients from Northeast China

    PubMed Central

    Yin, Yutian; Han, Weiqing; Wang, Yuhan; Zhang, Yue; Wu, Shili; Zhang, Huiping; Jiang, Lingling; Wang, Rui; Zhang, Peng; Yu, Yaqin; Li, Bo

    2015-01-01

    Background: Besides genetic factors, the occurrence of diabetes is influenced by lifestyles and environmental factors as well as trace elements in diet materials. Subjects with impaired fasting glucose (IFG) have an increased risk of developing diabetes mellitus (DM). This study aimed to explore risk factors affecting IFG and diabetes in patients from Northeast China. Methods: A population-based, cross-sectional survey of chronic diseases and related risk factors was conducted in Jilin Province of Northeast China. All adult residents, aged 18–79, were invited to participate in this survey using the method of multistage stratified random cluster sampling. One hundred thirty-four patients with IFG or DM and 391 healthy control subjects were recruited. We compared demographic factors, body size measurements, healthy-related behaviors, and hair metallic element contents between IFG/diabetes patients and healthy individuals. Results: IFG/diabetes patients had a greater weight, waist, hip, and body mass index (BMI) than control subjects. Significant differences in the content of zinc (Zn), potassium (K), copper (Ca), and sodium (Na) as well as Cu/Zn ratios between IFG or DM patients and control subjects (p < 0.05) were also observed. Hair Cu, selenium (Se), and Na contents were positively correlated with blood glucose levels (Cu: rs = 0.135, p = 0.002; Se: rs = 0.110, p = 0.012; Na: rs = 0.091, p = 0.038). Polytomous logistic regression adjusting for age, sex, family history of diabetes and BMI, showed that subjects with high BMI were more likely to develop IFG and DM (IFG: OR = 1.15, OR 95% CI = 1.02–1.29; DM: OR = 1.15, OR 95% CI = 1.01–1.33). Moreover, rarely or never eating fruits was a risk factor for DM (OR = 5.46, OR 95% CI = 1.87–15.98) but not for IFG (OR = 1.70, OR 95% CI = 0.72–4.02). Subjects with abdominal obesity or DM history were more susceptible to DM (abdominal obesity: OR = 2.99, OR 95% CI = 1.07–8.37; DM history: OR = 2.69, OR 95% CI = 1

  15. Ethanol impairs glucose uptake by human astrocytes and neurons: protective effects of acetyl-L-carnitine

    PubMed Central

    Muneer, P M Abdul; Alikunju, Saleena; Szlachetka, Adam M; Mercer, Aaron J; Haorah, James

    2011-01-01

    Alcohol consumption causes neurocognitive deficits, neuronal injury, and neurodegeneration. At the cellular level, alcohol abuse causes oxidative damage to mitochondria and cellular proteins and interlink with the progression of neuroinflammation and neurological disorders. We previously reported that alcohol inhibits glucose transport across the blood-brain barrier (BBB), leading to BBB dysfunction and neurodegeneration. In this study, we hypothesized that ethanol (EtOH)-mediated disruption in glucose uptake would deprive energy for human astrocytes and neurons inducing neurotoxicity and neuronal degeneration. EtOH may also have a direct effect on glucose uptake in neurons and astrocytes, which has not been previously described. Our results indicate that ethanol exposure decreases the uptake of D-(2-3H)-glucose by human astrocytes and neurons. Inhibition of glucose uptake correlates with a reduction in glucose transporter protein expression (GLUT1 in astrocytes and GLUT3 in neurons). Acetyl-L-carnitine (ALC), a neuroprotective agent, suppresses the effects of alcohol on glucose uptake and GLUT levels, thus reducing neurotoxicity and neuronal degeneration. These findings suggest that deprivation of glucose in brain cells contributes to neurotoxicity in alcohol abusers, and highlights ALC as a potential therapeutic agent to prevent the deleterious health conditions caused by alcohol abuse. PMID:21258656

  16. Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

    PubMed

    Wang, Hongdong; Wang, Xiaping; Zhu, Yunxia; Chen, Fang; Sun, Yujie; Han, Xiao

    2015-11-01

    Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction. PMID:26348137

  17. 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

  18. Genetic Disruption of SOD1 Gene Causes Glucose Intolerance and Impairs β-Cell Function

    PubMed Central

    Muscogiuri, Giovanna; Salmon, Adam B.; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L.; Reyna, Sara M.; Weir, Gordon; DeFronzo, Ralph A.; Van Remmen, Holly; Musi, Nicolas

    2013-01-01

    Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow–fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction. PMID:24009256

  19. Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice

    PubMed Central

    Biljes, Daniel; Hammerschmidt-Kamper, Christiane; Kadow, Stephanie; Diel, Patrick; Weigt, Carmen; Burkart, Volker; Esser, Charlotte

    2015-01-01

    Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor (AHR) is a sensor of small molecules including dietary components. AHR has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic AHR ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the AHR in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) AHR-deficient (AHR KO) mice. Fasted young wildtype (WT) and AHR-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old AHR-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old AHR-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young AHR-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, AHR-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in AHR KO mice suggest that AHR expression is relevant for the maintenance of glucose and lipid homeostasis in old mice. PMID:26664351

  20. 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

  1. Free fatty acid-induced PP2A hyperactivity selectively impairs hepatic insulin action on glucose metabolism.

    PubMed

    Galbo, Thomas; Olsen, Grith Skytte; Quistorff, Bjørn; Nishimura, Erica

    2011-01-01

    In type 2 Diabetes (T2D) free fatty acids (FFAs) in plasma are increased and hepatic insulin resistance is "selective", in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF) rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG) accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs). The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. PMID:22087313

  2. 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

  3. Impaired insulin-stimulated glucose transport in ATM-deficient mouse skeletal muscle.

    PubMed

    Ching, James Kain; Spears, Larry D; Armon, Jennifer L; Renth, Allyson L; Andrisse, Stanley; Collins, Roy L; Fisher, Jonathan S

    2013-06-01

    There are reports that ataxia telangiectasia mutated (ATM) plays a role in insulin-stimulated Akt phosphorylation, although this is not the case in some cell types. Because Akt plays a key role in insulin signaling, which leads to glucose transport in skeletal muscle, the predominant tissue in insulin-stimulated glucose disposal, we examined whether insulin-stimulated Akt phosphorylation and (or) glucose transport would be decreased in skeletal muscle of mice lacking functional ATM, compared with muscle from wild-type mice. We found that in vitro insulin-stimulated Akt phosphorylation was normal in soleus muscle from mice with 1 nonfunctional allele of ATM (ATM+/-) and from mice with 2 nonfunctional alleles (ATM-/-). However, insulin did not stimulate glucose transport or the phosphorylation of AS160 in ATM-/- soleus. ATM protein level was markedly higher in wild-type extensor digitorum longus (EDL) than in wild-type soleus. In EDL from ATM-/- mice, insulin did not stimulate glucose transport. However, in contrast to findings for soleus, insulin-stimulated Akt phosphorylation was blunted in ATM-/- EDL, concomitant with a tendency for insulin-stimulated phosphatidylinositol 3-kinase activity to be decreased. Together, the findings suggest that ATM plays a role in insulin-stimulated glucose transport at the level of AS160 in muscle comprised of slow and fast oxidative-glycolytic fibers (soleus) and at the level of Akt in muscle containing fast glycolytic fibers (EDL). PMID:23724874

  4. Restraint Stress Impairs Glucose Homeostasis Through Altered Insulin Signalling in Sprague-Dawley Rat.

    PubMed

    Morakinyo, Ayodele O; Ajiboye, Kolawole I; Oludare, Gabriel O; Samuel, Titilola A

    2016-01-01

    The study investigated the potential alteration in the level of insulin and adiponectin, as well as the expression of insulin receptors (INSR) and glucose transporter 4 GLUT-4 in chronic restraint stress rats. Sprague-Dawley rats were randomly divided into two groups: the control group and stress group in which the rats were exposed to one of the four different restraint stressors; 1 h, twice daily for a period of 7 days (S7D), 14 days (S14D) and 28 days (S28D). Glucose tolerance and insulin sensitivity were evaluated following the final stress exposure. ELISA were performed to assess the level of insulin and adiponectin as well as expression of INSR and GLUT4 protein in skeletal muscle. Plasma corticosterone level was also determined as a marker of stress exposure. Restraint stress for 7 days caused transient glucose intolerance, while S14D rats demonstrated increased glucose intolerance and insulin insensitivity. However, restraint stress for 28 days had no effect on glucose tolerance, but did cause an increase in glucose response to insulin challenge. The serum level of adiponectin was significantly (p< 0.05) lower compared with the control value while insulin remained unchanged except at in S28D rats that had a significant (p<0.05) increase. The expression of INSR and GLUT4 receptors were significantly (p< 0.05) decreased in the skeletal muscle of restraint stress exposed rats. There was a significant (p< 0.05) increase in the plasma corticosterone level of the stress rats compared with their control counterparts. Restraint stress caused glucose intolerance and insulin insensitivity in male Sprague-Dawley rats, which becomes accommodated with prolonged exposure and was likely related to the blunted insulin signalling in skeletal muscle. PMID:27574760

  5. MCH receptor deletion does not impair glucose-conditioned flavor preferences in mice.

    PubMed

    Sclafani, Anthony; Adamantidis, Antoine; Ackroff, Karen

    2016-09-01

    The post-oral actions of glucose stimulate intake and condition flavor preferences in rodents. Hypothalamic melanin-concentrating hormone (MCH) neurons are implicated in sugar reward, and this study investigated their involvement in glucose preference conditioning in mice. In Exp. 1 MCH receptor 1 knockout (KO) and C57BL/6 wildtype (WT) mice learned to prefer 8% glucose over an initially more-preferred non-nutritive 0.1% sucralose+saccharin (S+S) solution. In contrast, the KO and WT mice preferred S+S to 8% fructose, which is consistent with this sugar's weak post-oral reinforcing action. In Exp. 2 KO and WT mice were trained to drink a flavored solution (CS+) paired with intragastric (IG) infusion of 16% glucose and a different flavored solution (CS-) paired with IG water. Both groups drank more CS+ than CS- in training and preferred the CS+ to CS- in a 2-bottle test. These results indicate that MCH receptor signaling is not required for flavor preferences conditioned by the post-oral actions of glucose. This contrasts with other findings implicating MCH signaling in other types of sugar reward processing. PMID:27195455

  6. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity

    PubMed Central

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-01-01

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut−/−) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut−/− mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut−/− mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut−/− mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis. PMID:25331291

  7. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.

    PubMed

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-01-01

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut(-/-) mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut(-/-) mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut(-/-) mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis. PMID:25331291

  8. Impairment of erythrocytes incubated in glucose medium: a wavelet-information theory analysis.

    PubMed

    Korol, A M; Rosso, O A; Martín, M T; D'Arrigo, M; Riquelme, B D

    2011-07-01

    This study investigates the effects produced by an increased concentration of glucose in a suspending medium on the erythrocytes Information Theory quantifiers. Erythrocytes, which were obtained from eight healthy volunteers, were washed and incubated in vitro with glucose solutions at different concentrations. The measured Wavelet-based Information Theory quantifiers include the Relative Wavelet Energy (RWE), the Normalized Total Wavelet Shannon Entropy (NTWS), MPR-Statistical Complexity Measure (SCM) and entropy-complexity plane. The results show that the increase in glucose concentration does not produce significant changes on the RWE, while significant ones on the NTSE, which combined with SCM values allow to identify different behaviour for all the different populations in the entropy-complexity plane. Modification in the hemorheological properties of cells could be clearly detected with these Wavelet-based Information Theory quantifiers. PMID:21301991

  9. Understanding osteoporosis.

    PubMed Central

    Marcus, R.

    1991-01-01

    Considerable progress has been achieved recently in our understanding of the normal process by which bone mass is regulated. Age-related trabecular bone loss is characterized not simply by a global loss of bone but also by cortical porosity and loss of trabecular connections. Because bone strength depends on architectural as well as material properties, bone quantity alone cannot define fracture risk with precision. Traditional therapies for osteoporosis increase bone mass, and estrogen therapy, in particular, profoundly decreases fracture risk. The pharmacologic restoration of bone quantity and quality, however, remains elusive. Modern biotechnology offers the hope that progress may come about through the development of growth factors and other osteotropic compounds for clinical use. Images PMID:1877231

  10. 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

  11. 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

  12. Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells.

    PubMed

    Blanc, E M; Toborek, M; Mark, R J; Hennig, B; Mattson, M P

    1997-05-01

    Amyloid beta-peptide (A beta) is deposited as insoluble fibrils in the brain parenchyma and cerebral blood vessels in Alzheimer's disease (AD). In addition to neuronal degeneration, cerebral vascular alterations indicative of damage to vascular endothelial cells and disruption of the blood-brain barrier occur in AD. Here we report that A beta25-35 can impair regulatory functions of endothelial cells (ECs) from porcine pulmonary artery and induce their death. Subtoxic exposures to A beta25-35 induced albumin transfer across EC monolayers and impaired glucose transport into ECs. Cell death induced by A beta25-35 was of an apoptotic form, characterized by DNA condensation and fragmentation, and prevented by inhibitors of macromolecular synthesis and endonucleases. The effects of A beta25-35 were specific because A beta1-40 also induced apoptosis in ECs with the apoptotic cells localized to the microenvironment of A beta1-40 aggregates and because astrocytes did not undergo similar changes after exposure to A beta25-35. Damage and death of ECs induced by A beta25-35 were attenuated by antioxidants, a calcium channel blocker, and a chelator of intracellular calcium, indicating the involvement of free radicals and dysregulation of calcium homeostasis. The data show that A beta induces increased permeability of EC monolayers to macromolecules, impairs glucose transport, and induces apoptosis. If similar mechanisms are operative in vivo, then A beta and other amyloidogenic peptides may be directly involved in vascular EC damage documented in AD and other disorders that involve vascular amyloid accumulation. PMID:9109512

  13. 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...

  14. Antioxidant effects of a cinnamon extract on overweight subjects with impaired fasting glucose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: To determine the effects of an aqueous extract of cinnamon on antioxidant status of obese subjects. Methods: Twenty-two obese subjects with elevated blood glucose were enrolled in a double-blind placebo-controlled trial. Subjects were given either a placebo or 250 mg of an aqueous extract...

  15. Postmenopausal osteoporosis: microradiographic aspects.

    PubMed

    Dhem, A; Nyssen-Behets, C; Coppens, J

    1998-01-01

    A comparative microradiographic and histologic analysis of undecalcified bone samples was performed in men and women aged 18-98 years. These morphological methods showed that besides usual lamellar bone remodelling, all the so-called inert surfaces, namely both haversian and vascular canals as well as trabecular surfaces, were involved in weathering alterations of the superficial lamellae, resulting in eroded outlines devoid of osteoclast. These aspects, recorded in all pieces of our material, were visible from the earliest adult age and were randomly distributed. Except the grade of osteoporosis at a given age, the microradiographic and histologic aspects were similar in both aged men and women and did not allow sex distinction. These observations were consistent with the hypothesis of a particular destructive process affecting all the quiescent lamellar bone surfaces without osteoclast or cell participation. This kind of erosion, termed delitescence, could be at least partially responsible for the age-related and postmenopausal bone loss. In order to explain the increasing osteoporosis after menopause, it has been suggested that the estrogen deficiency could increase the percentage of dead osteocytes. Thereby the reduced cellular control on the bone surface could impair the remodeling process and fail to adapt the bone structure by repairing the microscopic lesions. PMID:11315966

  16. Impaired fasting glucose is associated with increased severity of subclinical coronary artery disease compared to patients with diabetes and normal fasting glucose: evaluation by coronary computed tomographic angiography

    PubMed Central

    Gurudevan, Swaminatha; Garg, Pankaj; Malik, Shaista; Khattar, Ramni; Saremi, Farhood; Hecht, Harvey; DeMaria, Anthony; Narula, Jagat

    2016-01-01

    Objective This study was designed to evaluate the severity of subclinical atherosclerosis in patients with asymptomatic impaired fasting glucose (IFG) compared to those with diabetes mellitus (DM) and normal fasting glucose (NFG), as measured by coronary computed tomographic angiography (CCTA). Design Subjects were divided into three groups: NFG (<100 mg/dL), IFG (100–125 mg/dL) and DM. Coronary artery calcium on non-contrast CT and plaque analysis on CCTA were performed. Setting University hospital, single centre. Participants 216 asymptomatic participants prospectively underwent CCTA for the evaluation of coronary artery disease (CAD). Primary and secondary outcome measures Atherosclerotic plaque burden in IFG compared to NFG patients. Results 2664 segments were analysed in 120 NFG, 44 IFG and 52 DM participants. The mean calcium scores were 178±395, 259±510 and 414±836 for NFG, IFG and DM, respectively (p=0·037). The mean plaque burdens in the NFG, IFG and DM groups were 0.31±0.45, 0.50±0.69 and 0.68±0.69, respectively (p=0·0007). A greater proportion of patients with DM (19/52, 36.5%) and IFG (13/44, 29.5%) had obstructive CAD compared to those with NFG (16/120, 13.3%) (p=0.0015). The number of segments with severe disease was significantly higher in the DM (60/637, 9.4%) and IFG (42/539, 7.8%) groups compared to that in the NFG group (34/1488, 2.3%) (p=0.0001). Conclusions (1) IFG and DM have significantly higher, but comparable, calcium scores, plaque burden and obstructive CAD compared to NFG in asymptomatic individuals. (2) Pending corroboration by other reports, more intensive efforts may be devoted to the evaluation and treatment of patients with IFG. PMID:27531720

  17. Impaired glucose homeostasis after a transient intermittent hypoxic exposure in neonatal rats.

    PubMed

    Pae, Eung-Kwon; Ahuja, Bhoomika; Kim, Marieyerie; Kim, Gyuyoup

    2013-11-22

    This initial report presents a neonatal rat model with exposure to a transient intermittent hypoxia (IH), which results in a persisting diabetes-like condition in the young rats. Twenty-five male pups were treated at postnatal day 1 with IH exposure by alternating the level of oxygen between 10.3% and 20.8% for 5h. The treated animals were then maintained in normal ambient oxygen condition for 3 week and compared to age-matched controls. The IH treated animals exhibited a significantly higher fasting glucose level than the control animals (237.00 ± 19.66 mg/dL vs. 167.25 ± 2.95 mg/dL; P=0.003); and a significantly lower insulin level than the control (807.0 ± 72.5 pg/mL vs. 1839.8 ± 377.6 pg/mL; P=0.023). There was no difference in the mass or the number of insulin producing beta cells as well as no indicative of inflammatory changes; however, glucose tolerance tests showed a significantly disturbed glucose homeostasis. In addition, the amount of C-peptide secreted from the islets harvested from the IH animals were decreased significantly (from 914 pM in control to 809 pM in IH; P=0.0006) as well. These observations demonstrate that the neonatal exposure to the IH regimen initiates the development of deregulation in glucose homeostasis without infiltration of inflammatory cells. PMID:24183722

  18. Central Regulation of Glucose Production May Be Impaired in Type 2 Diabetes.

    PubMed

    Esterson, Yonah B; Carey, Michelle; Boucai, Laura; Goyal, Akankasha; Raghavan, Pooja; Zhang, Kehao; Mehta, Deeksha; Feng, Daorong; Wu, Licheng; Kehlenbrink, Sylvia; Koppaka, Sudha; Kishore, Preeti; Hawkins, Meredith

    2016-09-01

    The challenges of achieving optimal glycemic control in type 2 diabetes highlight the need for new therapies. Inappropriately elevated endogenous glucose production (EGP) is the main source of hyperglycemia in type 2 diabetes. Because activation of central ATP-sensitive potassium (KATP) channels suppresses EGP in nondiabetic rodents and humans, this study examined whether type 2 diabetic humans and rodents retain central regulation of EGP. The KATP channel activator diazoxide was administered in a randomized, placebo-controlled crossover design to eight type 2 diabetic subjects and seven age- and BMI-matched healthy control subjects. Comprehensive measures of glucose turnover and insulin sensitivity were performed during euglycemic pancreatic clamp studies following diazoxide and placebo administration. Complementary rodent clamp studies were performed in Zucker Diabetic Fatty rats. In type 2 diabetic subjects, extrapancreatic KATP channel activation with diazoxide under fixed hormonal conditions failed to suppress EGP, whereas matched control subjects demonstrated a 27% reduction in EGP (P = 0.002) with diazoxide. Diazoxide also failed to suppress EGP in diabetic rats. These results suggest that suppression of EGP by central KATP channel activation may be lost in type 2 diabetes. Restoration of central regulation of glucose metabolism could be a promising therapeutic target to reduce hyperglycemia in type 2 diabetes. PMID:27207526

  19. Acute ozone (O3) -induced impairment of glucose regulation: Age-related and temporal changes

    EPA Science Inventory

    O3 is associated with adverse cardiopulmonary health effects in humans and is thought to produce metabolic effects, such as insulin resistance. Recently, we showed that episodic O3 exposure increased insulin levels in aged rats. We hypothesized that O3 exposure could impair gluc...

  20. 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

  1. Impaired fasting glucose and diabetes as predictors for radial artery calcification in end stage renal disease patients.

    PubMed

    Janda, Katarzyna; Krzanowski, Marcin; Gajda, Mariusz; Dumnicka, Paulina; Fedak, Danuta; Lis, Grzegorz J; Jaśkowski, Piotr; Litwin, Jan A; Sułowicz, Władysław

    2013-01-01

    Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20-24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death. PMID:24454371

  2. Impaired Fasting Glucose and Diabetes as Predictors for Radial Artery Calcification in End Stage Renal Disease Patients

    PubMed Central

    Janda, Katarzyna; Krzanowski, Marcin; Gajda, Mariusz; Dumnicka, Paulina; Fedak, Danuta; Lis, Grzegorz J.; Jaśkowski, Piotr; Litwin, Jan A.; Sułowicz, Władysław

    2013-01-01

    Objective. The objective of the study was to assess the relationship between selected clinical and biochemical parameters of end stage renal disease (ESRD) patients and arterial calcification. Materials and Methods. The study comprised 59 stage 5 chronic kidney disease patients (36 hemodialyzed and 23 predialysis). The examined parameters included common carotid artery intima-media thickness (CCA-IMT), BMI, incidence of diabetes and impaired fasting glucose (IFG), dyslipidemia, hypertension, and 3-year mortality. Plasma levels asymmetric dimethylarginine (ADMA), osteopontin (OPN), osteoprotegerin (OPG), and osteocalcin (OC) were also measured. Fragments of radial artery obtained during creation of hemodialysis access were stained for calcifications using von Kossa method and alizarin red. Results. Calcification of radial artery was significantly associated with higher prevalence of IFG and diabetes (P = 0.0004) and older age (P = 0.003), as well as higher OPG (P = 0.014) and ADMA concentrations (P = 0.022). Fasting glucose >5.6 mmol/l (IFG and diabetes) significantly predicted vascular calcification in multiple logistic regression. The calcification was also associated with higher CCA-IMT (P = 0.006) and mortality (P = 0.004; OR for death 5.39 [1.20–24.1] after adjustment for dialysis status and age). Conclusion. Combination of renal insufficiency and hyperglycemic conditions exerts a synergistic effect on vascular calcification and increases the risk of death. PMID:24454371

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. Osteoporosis and Hispanic Women

    MedlinePlus

    ... for the elderly, visit: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... Pub. No. 15-7924 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  9. Exercise and Osteoporosis

    MedlinePlus

    ... My Go4Life Get Free Stuff Be a Partner Exercise and Osteoporosis Osteoporosis is a disease that weakens ... calcium and vitamin D. Include regular weight-bearing exercise in your lifestyle. Stop smoking. Limit how much ...

  10. FastStats: Osteoporosis

    MedlinePlus

    ... this? Submit What's this? Submit Button NCHS Home Osteoporosis Recommend on Facebook Tweet Share Compartir Data are ... men 50 years of age and over with osteoporosis of the femur neck or lumbar spine: 4% ...

  11. Osteoporosis: An Overview.

    ERIC Educational Resources Information Center

    Johnston, C. Conrad; Slemenda, Charles

    1987-01-01

    An overview of osteoporosis, its types, causes, diagnosis, and treatment is presented. Risk factors and bone mass measurement are also discussed. This article serves as an introduction to a symposium on osteoporosis containing five other articles in this issue. (MT)

  12. Osteoporosis: Preventing Falls

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Osteoporosis Preventing Falls Past Issues / Winter 2011 Table of ... next to your bed Free NIH Videos About Osteoporosis The NIHSeniorHealth Web site features five brief, informative ...

  13. International Osteoporosis Foundation

    MedlinePlus

    ... Websites IOF International IOF Latin America IOF Asia-Pacific IOF Microsites Capture the Fracture Osteoporosis Essentials course ... on FRAX CME accreditation confirmed for 6th Asia-Pacific Osteoporosis Meeting in Singapore Milk and other dairy ...

  14. Osteoporosis and Your Spine

    MedlinePlus

    ... Movement › Osteoporosis and Your Spine Osteoporosis and Your Spine Your spine is made up of small bones ... called kyphosis. Kyphosis and Bone Breaks in the Spine The bones in the spine are called vertebrae. ...

  15. Medicines for osteoporosis

    MedlinePlus

    ... Raloxifene (Evista); Teriparatide (Forteo); Denosumab (Prolia); Low bone density - medicines; Osteoporosis - medicines ... to fracture (break). With osteoporosis, the bones lose density. Bone density measures the amount of bone tissue ...

  16. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury

    PubMed Central

    2010-01-01

    Introduction The optimal blood glucose target following severe traumatic brain injury (TBI) must be defined. Cerebral microdialysis was used to investigate the influence of arterial blood and brain glucose on cerebral glucose, lactate, pyruvate, glutamate, and calculated indices of downstream metabolism. Methods In twenty TBI patients, microdialysis catheters inserted in the edematous frontal lobe were dialyzed at 1 μl/min, collecting samples at 60 minute intervals. Occult metabolic alterations were determined by calculating the lactate- pyruvate (L/P), lactate- glucose (L/Glc), and lactate- glutamate (L/Glu) ratios. Results Brain glucose was influenced by arterial blood glucose. Elevated L/P and L/Glc were significantly reduced at brain glucose above 1 mM, reaching lowest values at blood and brain glucose levels between 6-9 mM (P < 0.001). Lowest cerebral glutamate was measured at brain glucose 3-5 mM with a significant increase at brain glucose below 3 mM and above 6 mM. While L/Glu was significantly increased at low brain glucose levels, it was significantly decreased at brain glucose above 5 mM (P < 0.001). Insulin administration increased brain glutamate at low brain glucose, but prevented increase in L/Glu. Conclusions Arterial blood glucose levels appear to be optimal at 6-9 mM. While low brain glucose levels below 1 mM are detrimental, elevated brain glucose are to be targeted despite increased brain glutamate at brain glucose >5 mM. Pathogenity of elevated glutamate appears to be relativized by L/Glu and suggests to exclude insulin- induced brain injury. PMID:20141631

  17. 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

  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. Blood glucose concentration for predicting poor outcomes in patients with and without impaired glucose metabolism undergoing off-pump coronary artery bypass surgery – long-term observational study

    PubMed Central

    Majstrak, Franciszek; Opolski, Grzegorz; Filipiak, Krzysztof J.

    2016-01-01

    Introduction Strict glucose control is an everyday practice in the perioperative period. Elevated glucose level has a deleterious impact on clinical results, but a therapeutic target has not been stated yet. Aim To determine a glucose concentration range affecting long-term outcomes after coronary artery bypass surgery (CABG). Material and methods This study is a retrospective evaluation of consecutive patients treated in a university hospital in Poland from 2004 to 2008. Patients were divided into 2 groups: an impaired glucose metabolism group (IGM) if they had 1) known DM or 2) perioperative hyperglycaemia defined as ≥ 200 mg/dl; and a non-IGM group. The end point (EP) was all-cause mortality. Results One thousand two hundred and eleven patients were covered by the analysis. The observation time was from 01.01.2004 until 01.08.2012. Patients who had maximal glucose concentrations < 242 mg/dl had the lowest mortality risk (EP in 21.1%); a higher risk was noted in the group with glucose concentrations 242–324 mg/dl (EP in 30.8%); and a very high risk was found for the group where glucose concentration was > 324 mg/dl (EP in 44.2%) (p = 0.041). Patients with IGM had a shorter survival at the end of the study (p < 0.001). The longest survival was observed in patients whose maximal glucose level was ≤ 242 mg/dl (p < 0.001) and the minimal glucose concentration was in the range 61–110 mg/dl (p < 0.001). Conclusions Tight glucose concentration control should be performed irrespective of a diabetes diagnosis and proper treatment introduced when necessary. Maximal glucose concentration should be kept < 242 mg/dl, while the minimum should be in the range 60–110 mg/dl. PMID:27625687

  20. High Glucose-enhanced Acetylcholine Stimulated CGMP Masks Impaired Vascular Reactivity in Tail Arteries from Short-Term Hyperglycemic Rats

    PubMed Central

    Hamaty, Marwan; Guzmán, Cristina B.; Walsh , Mary F.; Bode, Ann M.; Levy, Joseph

    2000-01-01

    Impaired vascular endothelium-dependent relaxation and augmented contractile responses have been reported in several models of long-term hyperglycemia. However, the effects of short-term ambient hyperglycemia are poorly understood. Since oxidative stress has been implicated as a contributor to impaired vascular function, we investigated the following: Aims: (1) the effects of high glucose exposure in vitro (7 – 10 days) on vascular relaxation to acetylcholine (Ach) and contractility to norepinephrine (NE) and KCl; (2) if NO-dependent cGMP generation is affected under these conditions; and (3) aortic redox status. Methods: Non-diabetic rat tail artery rings were incubated in normal (5mM) (control NG) or high (20mM) glucose buffer (control HG). Vascular responses to Ach, NE and KCl were compared to those of streptozotocin (SZ) diabetic animals in the same buffers (diabetic NG, diabetic HG). Ach stimulated cGMP levels were quantitated as an indirect assessment of endothelial nitric oxide (NO) production and oxidative stress evaluated by measuring vascular glutathione and oxidized glutathione. Results: Rings from diabetic rats in NG showed impaired relaxation to Ach (P = 0.002) but relaxed normally, when maintained in HG. Similarly, contractile responses to NE were attenuated in diabetic rings in NG but similar to controls in HG. HG markedly augmented maximal contraction to KCl compared to control and diabetic vessels in NG (P < 0.0001). Diabetic vessels in a hyperosmolar, but normoglycemic, milieu respond like those in HG. in vitro, HG for 2 hours changed neither relaxation nor contractile responses to NE and KCl in control rings. Basal cGMP levels were lower in aortae from diabetic animals pre-incubated in NG than in HG/LG or in control rings in NG (P < 0.05). cGMP responses to Ach were exaggerated in diabetic vessels in HG (P = 0.035 vs. control NG, P = 0.043 vs. diabetic NG) but not different between control and diabetic rings in NG. Vessels from diabetic animals

  1. Glucocorticoid Paradoxically Recruits Adipose Progenitors and Impairs Lipid Homeostasis and Glucose Transport in Mature Adipocytes

    PubMed Central

    Ayala-Sumuano, Jorge-Tonatiuh; Velez-delValle, Cristina; Beltrán-Langarica, Alicia; Marsch-Moreno, Meytha; Hernandez-Mosqueira, Claudia; Kuri-Harcuch, Walid

    2013-01-01

    Chronic treatment with glucocorticoids increases the mass of adipose tissue and promotes metabolic syndrome. However little is known about the molecular effects of dexamethasone on adipose biology. Here, we demonstrated that dexamethasone induces progenitor cells to undergo adipogenesis. In the adipogenic pathway, at least two cell types are found: cells with the susceptibility to undergo staurosporine-induced adipose conversion and cells that require both staurosporine and dexamethasone to undergo adipogenesis. Dexamethasone increased and accelerated the expression of main adipogenic genes such as pparg2, cebpa and srebf1c. Also, dexamethasone altered the phosphorylation pattern of C/EBPβ, which is an important transcription factor during adipogenesis. Dexamethasone also had effect on mature adipocytes mature adipocytes causing the downregulation of some lipogenic genes, promoted a lipolysis state, and decreased the uptake of glucose. These paradoxical effects appear to explain the complexity of the action of glucocorticoids, which involves the hyperplasia of adipose cells and insulin resistance. PMID:23999235

  2. 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

  3. Liver Fat Content, Evaluated through Semi-Quantitative Ultrasound Measurement, Is Associated with Impaired Glucose Profiles: A Community-Based Study in Chinese

    PubMed Central

    Li, Xiaoming; Xia, Mingfeng; Ma, Hui; Hu, Yu; Yan, Hongmei; He, Wanyuan; Lin, Huandong; Zhao, Naiqing; Gao, Jian; Gao, Xin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus. We investigated whether the deposition of fat in the liver is associated with glycemic abnormalities and evaluated the contribution of the liver fat content (LFC) to the impaired glucose regulation. We conducted a community-based study among 2836 residents (1018 males and 1818 females) without prior known diabetes mellitus from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The standardised ultrasound hepatic-renal echo-intensity and hepatic echo-intensity attenuation rate were used to assess the LFC. The cohort was stratified according to the quintiles for LFC. Two-hour glucose and fasting blood glucose increased across the LFC quintiles after adjustment for age and gender. LFC increased continuously among glucose categories after adjustment for age and gender (NGT: 7.7±0.3%, IFG: 10.0±0.8%, IGT: 11.8±0.5%, IFG+IGT: 11.7±0.9%, new- DM: 12.4±0.6%, P<0.001). By logistic regression analysis, 1% LFC increment independently predicted prediabetes and diabetes (OR 1.032, 1.019–1.045, P<0.001; 1.021, 1.005–1.037, P = 0.012, respectively) after adjustment for all potential confounders. Furthermore, participants with LFC higher than 10% had higher odds ratios of impaired glucose regulation as compared with those with LFC below 10% in fully adjusted logistic models. These results suggest that the LFC is strongly associated with impaired glucose regulation in the Chinese population, and that an even slightly elevated LFC is associated with increased glucose dysregulation. PMID:23843938

  4. Liver fat content, evaluated through semi-quantitative ultrasound measurement, is associated with impaired glucose profiles: a community-based study in Chinese.

    PubMed

    Li, Xiaoming; Xia, Mingfeng; Ma, Hui; Hu, Yu; Yan, Hongmei; He, Wanyuan; Lin, Huandong; Zhao, Naiqing; Gao, Jian; Gao, Xin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is closely associated with type 2 diabetes mellitus. We investigated whether the deposition of fat in the liver is associated with glycemic abnormalities and evaluated the contribution of the liver fat content (LFC) to the impaired glucose regulation. We conducted a community-based study among 2836 residents (1018 males and 1818 females) without prior known diabetes mellitus from the Changfeng Study who were at least 45 years old. A standard interview, anthropometrics and laboratory parameters were performed for each participant. The standardised ultrasound hepatic-renal echo-intensity and hepatic echo-intensity attenuation rate were used to assess the LFC. The cohort was stratified according to the quintiles for LFC. Two-hour glucose and fasting blood glucose increased across the LFC quintiles after adjustment for age and gender. LFC increased continuously among glucose categories after adjustment for age and gender (NGT: 7.7±0.3%, IFG: 10.0±0.8%, IGT: 11.8±0.5%, IFG+IGT: 11.7±0.9%, new- DM: 12.4±0.6%, P<0.001). By logistic regression analysis, 1% LFC increment independently predicted prediabetes and diabetes (OR 1.032, 1.019-1.045, P<0.001; 1.021, 1.005-1.037, P = 0.012, respectively) after adjustment for all potential confounders. Furthermore, participants with LFC higher than 10% had higher odds ratios of impaired glucose regulation as compared with those with LFC below 10% in fully adjusted logistic models. These results suggest that the LFC is strongly associated with impaired glucose regulation in the Chinese population, and that an even slightly elevated LFC is associated with increased glucose dysregulation. PMID:23843938

  5. Cinnamaldehyde impairs high glucose-induced hypertrophy in renal interstitial fibroblasts

    SciTech Connect

    Chao, Louis Kuoping; Chang, W.-T.; Shih, Y.-W.; Huang, J.-S.

    2010-04-15

    Cinnamaldehyde is a major and a bioactive compound isolated from the leaves of Cinnamomum osmophloeum kaneh. To explore whether cinnamaldehyde was linked to altered high glucose (HG)-mediated renal tubulointerstitial fibrosis in diabetic nephropathy (DN), the molecular mechanisms of cinnamaldehyde responsible for inhibition of HG-induced hypertrophy in renal interstitial fibroblasts were examined. We found that cinnamaldehyde caused inhibition of HG-induced cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, cleaved poly(ADP-ribose) polymerase (PARP) protein expression, and mitochondrial cytochrome c release in HG or cinnamaldehyde treatments in these cells. HG-induced extracellular signal-regulated kinase (ERK)/c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) (but not the Janus kinase 2/signal transducers and activators of transcription) activation was markedly blocked by cinnamaldehyde. The ability of cinnamaldehyde to inhibit HG-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of collagen IV, fibronectin, and alpha-smooth muscle actin (alpha-SMA). The results obtained in this study suggest that cinnamaldehyde treatment of renal interstitial fibroblasts that have been stimulated by HG reduces their ability to proliferate and hypertrophy through mechanisms that may be dependent on inactivation of the ERK/JNK/p38 MAPK pathway.

  6. Impairment of language is related to left parieto-temporal glucose metabolism in aphasic stroke patients.

    PubMed

    Karbe, H; Szelies, B; Herholz, K; Heiss, W D

    1990-02-01

    Twenty-six aphasic patients who had an ischaemic infarct in the territory of the left middle cerebral artery (MCA) were investigated. Cranial computed tomography (CT) showed various lesion sites: infarcts restricted to cortical structures in 12 patients, combined cortical and subcortical infarcts in 7 and isolated subcortical infarcts sparing the left cortex in another 7 cases. 18F-2-fluoro-2-deoxyglucose positron emission tomography revealed remote hypometabolism of the left convexity cortex and of the left basal ganglia, which was extended further than the morphological infarct zone in all cases. Types and degrees of aphasia were classified using the Aachener Aphasie Test (AAT): 10 patients had global aphasia, 2 Broca's, 5 Wernicke's, and 5 amnesic aphasia. Four patients suffered from minimal or residual aphasic symptoms. The AAT results were compared with the regional cerebral metabolic rates of glucose of the left hemisphere. Irrespective of the infarct location all five AAT subtests (Token test, repetition, written language, confrontation naming, auditory and reading comprehension) were closely correlated among each other and with left parieto-temporal metabolic rates, whereas left frontal and left basal ganglia metabolism showed no significant correlation. The close relation between left temporo-parietal functional activity and all five AAT subtests suggests that the different aspects of aphasia tested by AAT can be related to a common disorder of language processing in those areas. PMID:2319264

  7. 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

  8. 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

  9. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    PubMed Central

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  10. 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

  11. Prevalence of diabetes and impaired fasting glucose in Peru: report from PERUDIAB, a national urban population-based longitudinal study

    PubMed Central

    Seclen, Segundo N; Rosas, Moises E; Arias, Arturo J; Huayta, Ernesto; Medina, Cecilia A

    2015-01-01

    Objectives We aimed to estimate the prevalences of diabetes and impaired fasting glucose (IFG) in a national sample in Peru and assess the relationships with selected sociodemographic variables. Methods We estimated prevalence in PERUDIAB study participants, a nationwide, stratified urban and suburban population selected by random cluster sampling. Between 2010 and 2012, questionnaires were completed and blood tests obtained from 1677 adults ≥25 years of age. Known diabetes was defined as participants having been told so by a doctor or nurse and/or receiving insulin or oral antidiabetic agents. Newly diagnosed diabetes was defined as fasting plasma glucose ≥126 mg/dL determined during the study and without a previous diabetes diagnosis. IFG was defined as fasting plasma glucose of 100–125 mg/dL. Results The estimated national prevalence of diabetes was 7.0% (95% CI 5.3% to 8.7%) and it was 8.4% (95% CI 5.6% to 11.3%) in metropolitan Lima. No gender differences were detected. Known and newly diagnosed diabetes prevalences were estimated as 4.2% and 2.8%, respectively. A logistic regression response surface model showed a complex trend for an increased prevalence of diabetes in middle-aged individuals and in those with no formal education. Diabetes prevalence was higher in coastal (8.2%) than in highlands (4.5%; p=0.03), and jungle (3.5%; p<0.02) regions. The estimated national prevalence of IFG was 22.4%, higher in males than in females (28.3% vs 19.1%; p<0.001), and higher in coastal (26.4%) than in highlands (17.4%; p=0.03), but not jungle regions (14.9%; p=0.07). Conclusions This study confirms diabetes as an important public health problem, especially for middle-aged individuals and those with no formal education. 40% of the affected individuals were undiagnosed. The elevated prevalence of IFG shows that nearly a quarter of the adult population of Peru has an increased risk of diabetes. PMID:26512325

  12. 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

  13. Selection of reference genes for expression analyses in liver of rats with impaired glucose metabolism

    PubMed Central

    Hernández, Alfonso H; Curi, Rui; Salazar, Luis A

    2015-01-01

    Hepatic gene expression studies are vital for identification of molecular factors involved in insulin resistance. However, the need of normalized gene expression data has led to the search of stable genes which are useful as a reference in specific experimental conditions. The aim of this study was to evaluate expression stability of potential reference genes for real-time PCR gene expression studies, in rats with insulin resistance, early programmed in intrauterine environment of maternal insulin resistance and triggered by exposure to a high sucrose and fat diet in adult life. Male rats coming from insulin resistant (F1IR) mothers or normal (F1N) mothers were fed a standard rodent diet from postnatal day 21 to day 56, and then divided in two groups each. One of each subgroups were fed a high sucrose and fat diet (groups F1IR + HSFD and F1N + HSFD respectively), the rest were fed a control diet (groups F1IR + CD and F1N + CD) for 14 days. Glucose metabolism related tests were later performed. After liver extraction, RNA was isolated and gene expression analyzes of seven potential reference genes (Actb, Gapdh, Gusb, Hprt1, Ldha, Rpl13a and Rplp1) were carried out. LinRegPCR software was used to analyze raw data and determinate baseline corrections, threshold lines, efficiency of PCR reactions and corrected Cq values. Evaluations of gene expression stabilities as well as the number of necessary genes for normalization were assessed with geNorm tool. All samples from all groups showed acceptable PCR amplification efficiencies. The most stable genes were Rplp1, Ldha, Hprt1 and Rpl13a and the less stable was Gapdh. For all groups, just 2 to 3 of the most stable genes were necessary for optimal gene expression data normalization in rat liver. Genes encoding ribosomal proteins are the most appropriated for normalization of expression data in the presented animal model. By contrast, Gapdh, one of the most used genes in normalization, is not recommendable due to its high

  14. Prevalence of Diabetes and Impaired Fasting Glucose in Hypertensive Adults in Rural China: Far from Leveling-Off.

    PubMed

    Yu, Shasha; Sun, Zhaoqing; Zheng, Liqiang; Guo, Xiaofan; Yang, Hongmei; Sun, Yingxian

    2015-11-01

    In recent years data from many investigations has shown a leveling-off trend in diabetes incidence. In order to explain the diabetes epidemic in rural China during the past ten years, we conducted a survey from July 2012 to August 2013. Data from comprehensive questionnaires, physical examinations, and blood tests were obtained from 5919 residents with hypertension, aged ≥ 35 years. Diabetes and impaired fasting glucose (IFG) were defined according to the American Diabetes Association (ADA) criteria. The overall prevalence of diabetes and IFG were 15.3% (13.6% in men, 16.8% in women) and 40.7% (44.1% in men, 34.7% in women) in the hypertensive rural Chinese population. The prevalence of previously diagnosed diabetes was 6.5% (4.6% in men, 8.4% in women). The prevalence of undiagnosed diabetes was 8.7% (9.0% in men, 8.5% in women). Multivariate logistic regression revealed that increasing age, drinking, overweight or obesity, systolic blood pressure, low HDL-C, high total cholesterol and triglycerides increased the risk of diabetes (p < 0.05). Diabetes is thus still prevalent in rural areas of China and is manifesting an accelerating trend. It remains an important public health problem in China, especially in rural areas and routine assessment for the early detection and treatment of diabetes should be emphasized. PMID:26610531

  15. 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

  16. Prevalence of Diabetes and Impaired Fasting Glucose in Hypertensive Adults in Rural China: Far from Leveling-Off

    PubMed Central

    Yu, Shasha; Sun, Zhaoqing; Zheng, Liqiang; Guo, Xiaofan; Yang, Hongmei; Sun, Yingxian

    2015-01-01

    In recent years data from many investigations has shown a leveling–off trend in diabetes incidence. In order to explain the diabetes epidemic in rural China during the past ten years, we conducted a survey from July 2012 to August 2013. Data from comprehensive questionnaires, physical examinations, and blood tests were obtained from 5919 residents with hypertension, aged ≥ 35 years. Diabetes and impaired fasting glucose (IFG) were defined according to the American Diabetes Association (ADA) criteria. The overall prevalence of diabetes and IFG were 15.3% (13.6% in men, 16.8% in women) and 40.7% (44.1% in men, 34.7% in women) in the hypertensive rural Chinese population. The prevalence of previously diagnosed diabetes was 6.5% (4.6% in men, 8.4% in women). The prevalence of undiagnosed diabetes was 8.7% (9.0% in men, 8.5% in women). Multivariate logistic regression revealed that increasing age, drinking, overweight or obesity, systolic blood pressure, low HDL-C, high total cholesterol and triglycerides increased the risk of diabetes (p < 0.05). Diabetes is thus still prevalent in rural areas of China and is manifesting an accelerating trend. It remains an important public health problem in China, especially in rural areas and routine assessment for the early detection and treatment of diabetes should be emphasized. PMID:26610531

  17. 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

  18. Oxidative Stress in Mouse Sperm Impairs Embryo Development, Fetal Growth and Alters Adiposity and Glucose Regulation in Female Offspring

    PubMed Central

    Lane, Michelle; McPherson, Nicole O.; Fullston, Tod; Spillane, Marni; Sandeman, Lauren; Kang, Wan Xian; Zander-Fox, Deirdre L.

    2014-01-01

    Paternal health cues are able to program the health of the next generation however the mechanism for this transmission is unknown. Reactive oxygen species (ROS) are increased in many paternal pathologies, some of which program offspring health, and are known to induce DNA damage and alter the methylation pattern of chromatin. We therefore investigated whether a chemically induced increase of ROS in sperm impairs embryo, pregnancy and offspring health. Mouse sperm was exposed to 1500 µM of hydrogen peroxide (H2O2), which induced oxidative damage, however did not affect sperm motility or the ability to bind and fertilize an oocyte. Sperm treated with H2O2 delayed on-time development of subsequent embryos, decreased the ratio of inner cell mass cells (ICM) in the resulting blastocyst and reduced implantation rates. Crown-rump length at day 18 of gestation was also reduced in offspring produced by H2O2 treated sperm. Female offspring from H2O2 treated sperm were smaller, became glucose intolerant and accumulated increased levels of adipose tissue compared to control female offspring. Interestingly male offspring phenotype was less severe with increases in fat depots only seen at 4 weeks of age, which was restored to that of control offspring later in life, demonstrating sex-specific impacts on offspring. This study implicates elevated sperm ROS concentrations, which are common to many paternal health pathologies, as a mediator of programming offspring for metabolic syndrome and obesity. PMID:25006800

  19. P2X7R-Panx1 Complex Impairs Bone Mechanosignaling under High Glucose Levels Associated with Type-1 Diabetes

    PubMed Central

    Maung, Stephanie; Schaffler, Mitchell B.; Spray, David C.; Suadicani, Sylvia O.; Thi, Mia M.

    2016-01-01

    Type 1 diabetes (T1D) causes a range of skeletal problems, including reduced bone density and increased risk for bone fractures. However, mechanisms underlying skeletal complications in diabetes are still not well understood. We hypothesize that high glucose levels in T1D alters expression and function of purinergic receptors (P2Rs) and pannexin 1 (Panx1) channels, and thereby impairs ATP signaling that is essential for proper bone response to mechanical loading and maintenance of skeletal integrity. We first established a key role for P2X7 receptor-Panx1 in osteocyte mechanosignaling by showing that these proteins are co-expressed to provide a major pathway for flow-induced ATP release. To simulate in vitro the glucose levels to which bone cells are exposed in healthy vs. diabetic bones, we cultured osteoblast and osteocyte cell lines for 10 days in medium containing 5.5 or 25 mM glucose. High glucose effects on expression and function of P2Rs and Panx1 channels were determined by Western Blot analysis, quantification of Ca2+ responses to P2R agonists and oscillatory fluid shear stress (± 10 dyne/cm2), and measurement of flow-induced ATP release. Diabetic C57BL/6J-Ins2Akita mice were used to evaluate in vivo effects of high glucose on P2R and Panx1. Western blotting indicated altered P2X7R, P2Y2R and P2Y4R expression in high glucose exposed bone cells, and in diabetic bone tissue. Moreover, high glucose blunted normal P2R- and flow-induced Ca2+ signaling and ATP release from osteocytes. These findings indicate that T1D impairs load-induced ATP signaling in osteocytes and affects osteoblast function, which are essential for maintaining bone health. PMID:27159053

  20. 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

  1. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression

    PubMed Central

    Li, Yuanyuan; Liu, Liang; Tollefsbol, Trygve O.

    2010-01-01

    Cancer cells metabolize glucose at elevated rates and have a higher sensitivity to glucose reduction. However, the precise molecular mechanisms leading to different responses to glucose restriction between normal and cancer cells are not fully understood. We analyzed normal WI-38 and immortalized WI-38/S fetal lung fibroblasts and found that glucose restriction resulted in growth inhibition and apoptosis in WI-38/S cells, whereas it induced lifespan extension in WI-38 cells. Moreover, in WI-38/S cells glucose restriction decreased expression of hTERT (human telomerase reverse transcriptase) and increased expression of p16INK4a. Opposite effects were found in the gene expression of hTERT and p16 in WI-38 cells in response to glucose restriction. The altered gene expression was partly due to glucose restriction-induced DNA methylation changes and chromatin remodeling of the hTERT and p16 promoters in normal and immortalized WI-38 cells. Furthermore, glucose restriction resulted in altered hTERT and p16 expression in response to epigenetic regulators in WI-38 rather than WI-38/S cells, suggesting that energy stress-induced differential epigenetic regulation may lead to different cellular fates in normal and precancerous cells. Collectively, these results provide new insights into the epigenetic mechanisms of a nutrient control strategy that may contribute to cancer therapy as well as antiaging approaches.—Li, Y., Liu, L., Tollefsbol, T. O. Glucose restriction can extend normal cell lifespan and impair precancerous cell growth through epigenetic control of hTERT and p16 expression. PMID:20019239

  2. Bone tissue engineering in osteoporosis.

    PubMed

    Jakob, Franz; Ebert, Regina; Ignatius, Anita; Matsushita, Takashi; Watanabe, Yoshinobu; Groll, Juergen; Walles, Heike

    2013-06-01

    Osteoporosis is a polygenetic, environmentally modifiable disease, which precipitates into fragility fractures of vertebrae, hip and radius and also confers a high risk of fractures in accidents and trauma. Aging and the genetic molecular background of osteoporosis cause delayed healing and impair regeneration. The worldwide burden of disease is huge and steadily increasing while the average life expectancy is also on the rise. The clinical need for bone regeneration applications, systemic or in situ guided bone regeneration and bone tissue engineering, will increase and become a challenge for health care systems. Apart from in situ guided tissue regeneration classical ex vivo tissue engineering of bone has not yet reached the level of routine clinical application although a wealth of scaffolds and growth factors has been developed. Engineering of complex bone constructs in vitro requires scaffolds, growth and differentiation factors, precursor cells for angiogenesis and osteogenesis and suitable bioreactors in various combinations. The development of applications for ex vivo tissue engineering of bone faces technical challenges concerning rapid vascularization for the survival of constructs in vivo. Recent new ideas and developments in the fields of bone biology, materials science and bioreactor technology will enable us to develop standard operating procedures for ex vivo tissue engineering of bone in the near future. Once prototyped such applications will rapidly be tailored for compromised conditions like vitamin D and sex hormone deficiencies, cellular deficits and high production of regeneration inhibitors, as they are prevalent in osteoporosis and in higher age. PMID:23562167

  3. Osteoporosis: Therapeutic Options.

    PubMed

    Ivanova, Stefka; Vasileva, Liliya; Ivanova, Stanislava; Peikova, Lily; Obreshkova, Danka

    2016-01-01

    The definition of osteoporosis was originally formulated at a conference of the World Health Organization (WHO) in 1993 as 'a systemic skeletal disease characterized by decreased bone mass and altered micro-architecture of bone tissue, leading to enhanced bone fragility and risk of fractures'. Osteoporosis is characterized by low bone mineral density (BMD) and loss of the structural and bio-mechanical properties that are required to maintain bone homeostasis. This review aims to address the currently available options in prevention and treatment of osteoporosis. Management of osteoporosis includes non-pharmacological treatment - diet rich of calcium and vitamin D, healthy lifestyle, proper exercise plan, and pharmacological therapy. Combination of non-pharmacological and pharmacological treatment options have to be considered for prevention of osteoporosis and minimization of the risk of fractures. Given the heterogeneity of osteoporosis syndrome and lack of significant number of comparative studies, the choice of a pharmacological agents should be individualized. PMID:27180344

  4. Comparing Osteoporosis Drugs: The Bisphosphonates

    MedlinePlus

    Drugs to Treat Low Bone Density Comparing Osteoporosis Drugs: The Bisphosphonates What is osteoporosis (low bone density)? Osteoporosis is a condition in which the body does not build enough new bone. ...

  5. Osteoporosis: Build Up Your Bones!

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Osteoporosis Build Up Your Bones! Past Issues / Winter 2011 ... special needs of people with osteoporosis. A Complete Osteoporosis Program Remember, exercise is only one part of ...

  6. 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

  7. 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

  8. Exercise, Eating, Estrogen, and Osteoporosis.

    ERIC Educational Resources Information Center

    Brown, Jim

    1986-01-01

    Osteoporosis affects millions of people, especially women. Three methods for preventing or managing osteoporosis are recommended: (1) exercise; (2) increased calcium intake; and (3) estrogen replacement therapy. (CB)

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Osteoporosis in Gastrointestinal Diseases.

    PubMed

    Krela-Kaźmierczak, Iwona; Szymczak, Aleksandra; Łykowska-Szuber, Liliana; Eder, Piotr; Linke, Krzysztof

    2016-01-01

    Secondary osteoporosis occurs as an isolated pathology or co-exists with types I and II osteoporosis. The gastroenterologist may come across osteoporosis or osteopenia in a patient with a gastrointestinal disease. This is often a young patient in whom investigations should be carried out and appropriate treatment initiated, aimed at preventing bone fractures and the formation of the best peak bone mass. Osteoporosis occurs in patients with the following conditions: Crohn's disease, ulcerative colitis, celiac disease, post gastrectomy patients, patients with short bowel syndrome, chronic hepatitis and cirrhosis, treated with steroids (steroid-induced osteoporosis) and patients using proton pump inhibitors chronically (state of achlorhydria). It is therefore necessary to approve a list of risk factors of secondary osteoporosis, the presence of which would be an indication for screening for osteoporosis, including a DXA study and the development of a separate algorithm for the therapeutic management of secondary osteoporosis accompanying gastrointestinal diseases, especially in premenopausal young women and young men, because there are currently no registered drugs with proven antifracture activity for this group of patients. PMID:26935513

  15. Pituitary Disorders and Osteoporosis

    PubMed Central

    Jawiarczyk-Przybyłowska, Aleksandra

    2015-01-01

    Various hormonal disorders can influence bone metabolism and cause secondary osteoporosis. The consequence of this is a significant increase of fracture risk. Among pituitary disorders such effects are observed in patients with Cushing's disease, hyperprolactinemia, acromegaly, and hypopituitarism. Severe osteoporosis is the result of the coexistence of some of these disorders and hypogonadism at the same time, which is quite often. PMID:25873948

  16. Osteoporosis in women.

    PubMed

    Bowman, M A; Spangler, J G

    1997-03-01

    Many preventive and treatment strategies are now available for osteoporosis, offering many women the opportunity to forego its many complications. Exercise with calcium and vitamin D supplements is recommended for most patients. Estrogens are a preferred treatment but not acceptable to many women. Alendronate, a bisphosphonate, recently became available to treat osteoporosis. Calcitonin, subcutaneous or intranasal, also can be useful. PMID:9016728

  17. [Epidemiology of osteoporosis].

    PubMed

    Scheidt-Nave, C; Ziegler, R; Raspe, H

    1998-03-15

    Epidemiological studies have identified osteoporosis as a disease of significant public health impact and have delineated numerous potential risk factors. Nevertheless, it has proven difficult to establish preventive strategies for several reasons. First, there has been no final agreement on the definition of osteoporosis, which has hampered efforts to characterize the magnitude of the problem as a whole. Secondly, as osteoporosis is a multifactorial chronic disorder, effective programs for risk assessment and intervention depend on the development of complex disease models. In summarizing the contributions of epidemiological studies to the current understanding of osteoporosis this review intends to outline the scientific background for the European Vertebral Osteoporosis Study (EVOS) and its successors. PMID:9564151

  18. [Osteoporosis: a clinical perspective].

    PubMed

    Matikainen, Niina

    2016-01-01

    Osteoporosis is defined by decreased bone density and microarchitectural deterioration that predispose to fragility fractures. The WHO diagnostic criteria of osteoporosis require bone densitometry but treatment is possible on the basis of high clinical fracture risk and can be assessed by the FRAX risk algorithm. All those subject to fracture risk should be advised about proper basic treatment of osteoporosis, including exercise, prevention of falls, smoking cessation, avoidance of alcohol intake, and dietary or supplemental abundance of calcium and vitamin D. Underlying diseases must be studied after diagnosis of osteoporosis even if treatment is initiated without densitometry. When indicated, specific osteoporosis therapy includes bisphosphonates, denosumab, teriparatide, strontium ranelate or SERMs. In hypogonadism, gonadal steroids may be indicated alone or in addition to a specific treatment. Treatment effect and continuation are assessed after 2 to 5 years. PMID:27400591

  19. Bisphosphonates for the prevention and treatment of osteoporosis.

    PubMed

    Maraka, Spyridoula; Kennel, Kurt A

    2015-01-01

    Osteoporosis is a systemic skeletal disorder characterized by bone loss, which leads to impaired bone strength and an increased risk of fractures. Two million fractures are attributed to osteoporosis annually in the United States and they are associated with serious morbidity and mortality. Bisphosphonates reduce the risk of fracture by suppressing bone resorption and increasing bone strength, and they have been widely used for the prevention and treatment of osteoporosis. However, the use of these drugs for the management of osteoporosis remains a clinical challenge. There are several important considerations including appropriate patient selection, pretreatment evaluation, potential adverse effects, patient preferences, and adherence. This review will discuss the evidence informing the clinical strategy for using bisphosphonates in patients with osteoporosis and those at high risk of fracture, focusing on the benefits and risks of treatment. We will also consider issues related to the monitoring and duration of treatment. PMID:26333528

  20. OSTEOPOROSIS DIAGNOSIS AND TREATMENT

    PubMed Central

    de Souza, Márcio Passini Gonçalves

    2015-01-01

    Articles that update the state of knowledge regarding osteoporosis run the risk of quickly becoming obsolete because research and studies on osteoporosis today are arousing great interest among researchers, the pharmaceutical and medical equipment industries, governments and even WHO. All orthopedists know about osteoporosis because of its most deleterious effect: osteoporotic fracture. Osteoporosis without fractures does not arouse suspicion because this is a pathological condition with a nonspecific clinical profile. Osteoporotic fractures have an economic cost (from treatment), a social cost (from its sequelae) and a medical cost (from deaths). Many fractures could be avoided through diagnosing osteoporosis prior to the first fracture and thus many temporary and permanent disabilities could be avoided and many lives saved. Awareness of the risk factors for osteoporosis raises suspicions and bone densitometry aids in diagnosis. Treatment should be based on the physiopathology of the disease. Hence, for prevention or treatment of osteoporosis, the activity of osteoclasts should be diminished or the activity of osteoblasts should be increased, or both. Treatment that reduces the incidence of fractures by improving the bone geometry and microarchitecture would be ideal. Newly formed bone tissue needs to have good cell and matrix quality, normal mineralization, a good ratio between mineralized (mechanically resistant) and non-mineralized (flexible) bone, and no accumulated damage. The ideal treatment should have a positive remodeling rate and fast and long-lasting therapeutic effects. Such effects need to be easily detectable. They need to be safe. PMID:27022545

  1. Rare causes of osteoporosis

    PubMed Central

    Marcucci, Gemma; Brandi, Maria Luisa

    2015-01-01

    Summary Osteoporosis is a metabolic bone disease characterized by loss of bone mass and strength, resulting in increased risk of fractures. It is classically divided into primary (post-menopausal or senile), secondary and idiopathic forms. There are many rare diseases, that cause directly or indirectly osteoporosis. The identification and classification of most of these rare causes of osteoporosis is crucial for the specialists in endocrinology and not, in order to prevent this bone complication and to provide for an early therapy. Several pathogenic mechanisms are involved, including various aspects of bone metabolism such as: decreased bone formation, increased bone resorption, altered calcium, phosphorus and/or vitamin D homeostasis, and abnormal collagen synthesis. In this review, less common forms of primary and secondary osteoporosis are described, specifying, if applicable: genetic causes, epidemiology, clinical features, and pathogenic mechanisms causing osteoporosis. A greater awareness of all rare causes of osteoporosis could reduce the number of cases classified as idiopathic osteoporosis and allow the introduction of appropriate and timely treatments. PMID:26604941

  2. [Endocrine disorders and osteoporosis].

    PubMed

    Kinoshita, Yuka

    2015-10-01

    Secondary osteoporosis is a bone disease characterized by decreased bone mass that predisposes fractures due to underlying disorders or medication. Disorders of the endocrine system, such as primary hyperparathyroidism, hyperthyroidism, hypogonadism, growth hormone deficiency, Cushing's syndrome, and anorexia nervosa frequently cause secondary osteoporosis. In those diseases, hormone excess or deficiency affects functions of osteoblasts, osteocyte, and osteoclasts, leading to aberrant bone remodeling. Bisphosphonates are the first-choice pharmacological agents for fracture prevention in most patients with secondary osteoporosis along with treatment of the underlying disease. PMID:26529938

  3. Medicines for osteoporosis

    MedlinePlus

    ... Evista); Teriparatide (Forteo); Denosumab (Prolia); Low bone density - medicines; Osteoporosis - medicines ... Your doctor may prescribe medicines to help lower your risk of fractures. These medicines make the bones in your hips, spine, and other areas denser. ...

  4. Osteoporosis in Men

    MedlinePlus

    ... formation. Because it requires daily injections and is expensive, doctors usually prescribe it only for men with ... wine, or a single measure of spirits) • Quit smoking. If you already have osteoporosis, you should take ...

  5. Osteoporosis in anorexia nervosa.

    PubMed

    Treasure, J; Serpell, L

    1999-07-01

    Anorexia nervosa is a disorder characterized by low body weight and amenorrhoea (in females). These features lead to a risk of osteoporosis, a condition in which bone loss leads to weakening of bone structure and increased fracture risk. PMID:10605537

  6. What Is Osteoporosis?

    MedlinePlus Videos and Cool Tools

    ... easily. LAWRENCE RAISZ, M.D.: Osteoporosis and bone health have become enormous problems in the United States ... attention to. People ignore the issue of bone health-- they don't concern themselves about it until ...

  7. International Osteoporosis Foundation

    MedlinePlus

    ... Bosnia and Herzegovina - Brazil - Bulgaria - Cameroon - Canada - Chile - China - Colombia - Costa Rica - Croatia - Cuba - Cyprus - Czech Republic - ... warn of osteoporosis threat to Asia’s growing elderly population New drugs may help increase muscle strength and ...

  8. Diagnosis of Osteoporosis.

    ERIC Educational Resources Information Center

    Wahner, H. W.

    1987-01-01

    Early recognition of osteoporosis is difficult because symptoms are lacking and there are no distinct, readily accessible diagnostic features. This article reviews the standard approach, radiographic and laboratory diagnosis, bone mass measurement techniques, and interpretation of bone mineral data. (MT)

  9. Estrogen and Osteoporosis.

    ERIC Educational Resources Information Center

    Lindsay, Robert

    1987-01-01

    This article reviews the use of estrogen in the prevention and treatment of osteoporosis. Dosage levels, interactions with other factors, side effects, and the mechanism of estrogen action are discussed. (Author/MT)

  10. Osteoporosis in Men

    MedlinePlus

    ... talk to their doctor about having a bone mineral density (BMD) test. Men should also be tested ... tests. The doctor may also order a bone mineral density test. This test can identify osteoporosis, determine ...

  11. Secondary osteoporosis: pathophysiology & diagnosis.

    PubMed

    Emkey, Gregory R; Epstein, Sol

    2014-12-01

    Osteoporosis is a skeletal disease characterized by decreased bone mass and microarchitectural changes in bone tissue that increase the susceptibility to fracture. Secondary osteoporosis is loosely defined as low bone mineral density or increased risk of fragility fracture caused by any factor other than aging or postmenopausal status. The purpose of this review is to discuss the current understanding of the pathophysiology and contribution to fracture risk of many of the more common causes of secondary osteoporosis, as well as diagnostic considerations, outlined by organ system. While not comprehensive, included are a wide array of diseases, conditions, and medications that have been associated with bone loss and susceptibility to fractures. The hope is to highlight the importance to the general clinician of screening for and treating the osteoporosis in these patients, so to limit the resultant increased morbidity associated with fractures. PMID:25432361

  12. Sarcopenia and Osteoporosis

    PubMed Central

    Ji, Hyung-Min; Han, Jun

    2015-01-01

    Public health strategies designed to accomodate the ever-increasing human lifespan are urgently required. A good clinical understanding of frailty, as well as knowledge regarding how to prevent it, will therefore be required in order to overcome this challenge. Sarcopenia is an important component of the frailty syndrome, and its association with osteoporosis can lead to fractures and incident disability. Therefore, this review examined the literatuire pertaining to the association of sarcopenia with osteoporosis in order to assess preventive strategies.

  13. Chronic glucolipotoxic conditions in pancreatic islets impair insulin secretion due to dysregulated calcium dynamics, glucose responsiveness and mitochondrial activity

    PubMed Central

    2013-01-01

    Background In the progression towards diabetes, glucolipotoxicity is one of the main causes of pancreatic beta cell pathology. The aim of this study was to examine the in vitro effects of chronic glucolipotoxic conditions on cellular responses in pancreatic islets, including glucose and fat metabolism, Calcium mobilization, insulin secretion and insulin content. Results Exposure of islets to chronic glucolipotoxic conditions decreased glucose stimulated insulin secretion in vitro. Reduced protein levels of Glut2/slc2a2, and decreased glucokinase and pyruvate carboxylase mRNA levels indicated a significant lowering in glucose sensing. Concomitantly, both fatty acid uptake and triglyceride accumulation increased significantly while fatty acid oxidation decreased. This general suppression in glucose metabolism correlated well with a decrease in mitochondrial number and activity, reduction in cellular ATP content and dampening of the TCA cycle. Further, we also observed a decrease in IP3 levels and lower Calcium mobilization in response to glucose. Importantly, chronic glucolipotoxic conditions in vitro decreased insulin gene expression, insulin content, insulin granule docking (to the plasma membrane) and insulin secretion. Conclusions Our results present an integrated view of the effects of chronic glucolipotoxic conditions on known and novel signaling events, in vitro, that results in reduced glucose responsiveness and insulin secretion. PMID:23815372

  14. Impaired neutrophil activity and increased susceptibility to bacterial infection in mice lacking glucose-6-phosphatase–β

    PubMed Central

    Cheung, Yuk Yin; Kim, So Youn; Yiu, Wai Han; Pan, Chi-Jiunn; Jun, Hyun-Sik; Ruef, Robert A.; Lee, Eric J.; Westphal, Heiner; Mansfield, Brian C.; Chou, Janice Y.

    2007-01-01

    Neutropenia and neutrophil dysfunction are common in many diseases, although their etiology is often unclear. Previous views held that there was a single ER enzyme, glucose-6-phosphatase–α (G6Pase-α), whose activity — limited to the liver, kidney, and intestine — was solely responsible for the final stages of gluconeogenesis and glycogenolysis, in which glucose-6-phosphate (G6P) is hydrolyzed to glucose for release to the blood. Recently, we characterized a second G6Pase activity, that of G6Pase-β (also known as G6PC), which is also capable of hydrolyzing G6P to glucose but is ubiquitously expressed and not implicated in interprandial blood glucose homeostasis. We now report that the absence of G6Pase-β led to neutropenia; defects in neutrophil respiratory burst, chemotaxis, and calcium flux; and increased susceptibility to bacterial infection. Consistent with this, G6Pase-β–deficient (G6pc3–/–) mice with experimental peritonitis exhibited increased expression of the glucose-regulated proteins upregulated during ER stress in their neutrophils and bone marrow, and the G6pc3–/– neutrophils exhibited an enhanced rate of apoptosis. Our results define a molecular pathway to neutropenia and neutrophil dysfunction of previously unknown etiology, providing a potential model for the treatment of these conditions. PMID:17318259

  15. 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

  16. 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

  17. Bisphosphonates for Osteoporosis: Benefits and Risks

    MedlinePlus

    ... o es sis : Benefits and Risks What is osteoporosis? Osteoporosis is a condition in which your bones become ... through menopause are especially at risk of developing osteoporosis. Osteoporosis is more common in women than in ...

  18. BT-11 improves stress-induced memory impairments through increment of glucose utilization and total neural cell adhesion molecule levels in rat brains.

    PubMed

    Shin, Ki Young; Won, Beom Young; Heo, Chaejeong; Kim, Hee Jin; Jang, Dong-Pyo; Park, Cheol Hyoung; Kim, Seonghan; Kim, Hye-Sun; Kim, Young-Bo; Lee, Hyung Gun; Lee, Sang Hyung; Cho, Zang-Hee; Suh, Yoo-Hun

    2009-01-01

    In Oriental medicine, roots of Polygala tenuifolia Willdenow have been known to be an important herb that exhibits sedative effects in insomnia, palpitation with anxiety, restlessness, and disorientation in humans. We previously reported that BT-11, extracted from those roots, improved scopolamine-induced amnesia in rats and inhibited acetylcholinesterase activities in vitro. Therefore, we proposed that BT-11 could remedy stress-induced memory deficits in rats. In this study, the stress-induced memory impairments in rats were significantly reversed almost to the control level by BT-11 treatment. To seek an active component of BT-11 that plays an important role in antipsychotic effects, we compared BT-11 with 3,4,5-trimethoxycinnamic acid (TMCA), which is a constituent of those root extracts. However, the effects of TMCA were less or were not consistent with those of BT-11 in some of tests. In particular, BT-11 reversed the stress-induced reduction of glucose utilization by [(18)fluorodeoxyglucose]FDG-PET and the levels of neural cell adhesion molecule (NCAM) in rat brains to the control levels, whereas TMCA did not. Therefore, BT-11 improved stress-induced memory impairments through increment of glucose utilization and total NCAM levels in rat brains. In conclusion, BT-11 may be strongly effective against stress-induced amnesia in rats, through the combined effects of TMCA and other active components of BT-11. PMID:18712849

  19. 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

  20. [Osteoporosis and stress].

    PubMed

    Kumano, Hiroaki

    2005-09-01

    There may be three ways of relationship between stress and osteoporosis. The first is that stress induces some physiological changes leading to osteoporosis. The second is that stress induces behavioral distortion of eating, drinking, exercise, and sleep habits, which leads to osteoporosis. The third is that osteoporosis, on the other hand, brings about anxiety, depression, loss of social roles, and social isolation, which leads to stress. The susceptible sex and age groups are postmenopausal women and young women. The abrupt decrease of estrogen in postmenopausal women promotes reabsorption of bone, and it was also reported that the increase of interleukin-6 (IL-6) that is downstream of estrogen was related to the production of osteoclast and to the development of disability of the aged. Regarding the association with stress, while it was reported that depression or depressive states directly increased inflammation-induced cytokines including IL-6, it was also pointed out that stress-induced easy infectious may produce chronic infection, which indirectly increases inflammation-induced cytokines. Anorexia Nervosa that is assumed to be associated with adolescent developmental stress is noteworthy in young women. Amenorrhea is always present in this disease, and in addition to bone reabsorption associated with estrogen deficiency, the decrease of bone formation associated with malnutrition may be related to the development of osteoporosis. PMID:16137956

  1. Glucocorticoid-induced osteoporosis

    PubMed Central

    Briot, Karine; Roux, Christian

    2015-01-01

    Corticosteroid-induced osteoporosis is the most common form of secondary osteoporosis and the first cause in young people. Bone loss and increased rate of fractures occur early after the initiation of corticosteroid therapy, and are then related to dosage and treatment duration. The increase in fracture risk is not fully assessed by bone mineral density measurements, as it is also related to alteration of bone quality and increased risk of falls. In patients with rheumatoid arthritis, a treat-to-target strategy focusing on low disease activity including through the use of low dose of prednisone, is a key determinant of bone loss prevention. Bone loss magnitude is variable and there is no clearly identified predictor of the individual risk of fracture. Prevention or treatment of osteoporosis should be considered in all patients who receive prednisone. Bisphosphonates and the anabolic agent parathyroid hormone (1–34) have shown their efficacy in the treatment of corticosteroid-induced osteoporosis. Recent international guidelines are available and should guide management of corticosteroid-induced osteoporosis, which remains under-diagnosed and under-treated. Duration of antiosteoporotic treatment should be discussed at the individual level, depending on the subject's characteristics and on the underlying inflammation evolution. PMID:26509049

  2. COPD and osteoporosis: links, risks, and treatment challenges.

    PubMed

    Inoue, Daisuke; Watanabe, Reiko; Okazaki, Ryo

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD. COPD-associated osteoporosis is however extremely undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described. It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks. Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. PMID:27099481

  3. COPD and osteoporosis: links, risks, and treatment challenges

    PubMed Central

    Inoue, Daisuke; Watanabe, Reiko; Okazaki, Ryo

    2016-01-01

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease associated with various systemic comorbidities including osteoporosis. Osteoporosis and its related fractures are common and have significant impacts on quality of life and even respiratory function in patients with COPD. COPD-associated osteoporosis is however extremely undertreated. Recent studies have suggested that both decreased bone mineral density (BMD) and impaired bone quality contribute to bone fragility, causing fractures in COPD patients. Various clinical risk factors of osteoporosis in COPD patients, including older age, emaciation, physical inactivity, and vitamin D deficiency, have also been described. It is critically important for pulmonologists to be aware of the high prevalence of osteoporosis in COPD patients and evaluate them for such fracture risks. Routine screening for osteoporosis will enable physicians to diagnose COPD patients with comorbid osteoporosis at an early stage and give them appropriate treatment to prevent fracture, which may lead to improved quality of life as well as better long-term prognosis. PMID:27099481

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. Osteoporosis and Asian American Women

    MedlinePlus

    ... ligand (RANKL) inhibitor. Resources NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... No. 15-7925-E NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  11. [Clinical characteristics of male osteoporosis].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2016-07-01

    As men are less likely than women to develop osteoporosis, male osteoporosis remains poorly understood. However, elderly men have a clearly reduced bone mineral density and increased risk for fractures. In Japan, one in four patients with osteoporosis is male. Male osteoporosis is associated with not only reduction in androgen, but also estrogen, and differs from postmenopausal osteoporosis in that decreased bone formation is involved and that age-related changes in cortical bone structure and perforation of the trabeculae of cancellous bone are unlikely to occur. The proportion of secondary osteoporosis is higher for men than women;therefore, differential diagnosis is important in the diagnosis of male osteoporosis. In addition, it is recommended that bone mineral density be measured at the femoral neck or total hip in men. Men have a worse prognosis following fractures than women, and management of male osteoporosis is highly important for extending healthy life expectancy. PMID:27346307

  12. Pathophysiology of immobilization osteoporosis

    NASA Technical Reports Server (NTRS)

    Doty, S. B.; DiCarlo, E. F.

    1995-01-01

    The reduction of gravity-related forces on the skeleton creates a type of osteoporosis that is unique because its severity is dependent on the mechanical stress bearing function of the skeleton as well as the length of time that the forces are absent or reduced. Bones that bear weight under normal conditions are more affected than bones that normally do not bear weight. The cytokine environment and the cells in the affected bones are altered in time so that stem cells produce fewer new cells and the differentiated cells tend to be less active. These alterations in the local environment of the affected parts appear to resemble those of age- and disease-associated systemic forms of osteoporosis. The osteoporosis produced as a result of the loss of normal activity however, appears to be at least partially reversible through remobilization, strenuous exercise, and--possibly in the future--cytokine therapy.

  13. Male osteoporosis: A review.

    PubMed

    Herrera, Antonio; Lobo-Escolar, Antonio; Mateo, Jesús; Gil, Jorge; Ibarz, Elena; Gracia, Luis

    2012-12-18

    Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. The etiology can be idiopathic or secondary to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic and every disease or drug use that alters bone metabolism.Risk factors such as a previous history of fragility fracture should be assessed for the diagnosis. However, risk factors in men are very heterogeneous. There are significant differences in the pharmacological treatment of osteoporosis between men and women fundamentally due to the level of evidence in published trials supporting each treatment. New treatments will offer new therapeutic prospects. The goal of this work is a revision of the present status knowledge about male osteoporosis. PMID:23362466

  14. Immunologic aspects of osteoporosis.

    PubMed

    Ershler, W B; Harman, S M; Keller, E T

    1997-01-01

    Osteoporosis is a major cause of morbidity in older people. There are a large number of risk factors for the development of osteoporosis. However, these risk factors eventually must mediate their effects through modulation of bone remodeling. A variety of compounds including hormones and nutrients modulate bone remodeling. In addition to these well-characterized substances, the immune system plays a role in bone remodeling through pro-inflammatory cytokines. Specifically, interleukin-1 (IL-1), IL-11, interferon-g are known to influence osteoclasts and osteoblasts. Recently, the cytokine IL-6 has joined ranks with these cytokines as a bone reactive agent. IL-6 has been shown to increase with age and menopause. Additionally, murine models suggest that IL-6 plays a central role in bone resorption. Finally, in vitro studies demonstrate that IL-6 induces osteoclast activity. In this review, we will discuss the pathogenesis of osteoporosis in the context of aging and IL-6. PMID:9463782

  15. Male osteoporosis: A review

    PubMed Central

    Herrera, Antonio; Lobo-Escolar, Antonio; Mateo, Jesús; Gil, Jorge; Ibarz, Elena; Gracia, Luis

    2012-01-01

    Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. The etiology can be idiopathic or secondary to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic and every disease or drug use that alters bone metabolism. Risk factors such as a previous history of fragility fracture should be assessed for the diagnosis. However, risk factors in men are very heterogeneous. There are significant differences in the pharmacological treatment of osteoporosis between men and women fundamentally due to the level of evidence in published trials supporting each treatment. New treatments will offer new therapeutic prospects. The goal of this work is a revision of the present status knowledge about male osteoporosis. PMID:23362466

  16. [Epidemiology of osteoporosis].

    PubMed

    Grazio, Simeon

    2006-01-01

    Osteoporosis represents a major and increasing public health problem with the aging of population. Major clinical consequences and economic burden of the disease are fractures. Many risk factors are associated with the fractures including low bone mass, hormonal disorders, personal and family history of fractures, low body weight, use of certain drugs (e.g. glucocorticoids), cigarette smoking, elevated intake of alchohol, low physical activity, insufficient level of vitamin D and low intake of calcium. This epidemiological review describes frequency, importance of risk factors and impact of osteoporosis and osteoporotic fractures. Objective measures of bone mineral density along with clinical assessment of risk factors can help identify patients who will benefit from prevention and intervention efforts and eventually reduce the morbidity and mortality associated with osteoporosis-related fractures. PMID:17580550

  17. Emerging therapies for osteoporosis.

    PubMed

    Minisola, G; Iuliano, A; Prevete, I

    2014-01-01

    Currently available drugs for the treatment of osteoporosis can still be improved in terms of pharmacokinetics, pharmacodynamics and management. New approaches for the development of innovative drugs are possible thanks to our increasing understanding of the bone tissue biology and the cellular and molecular processes that regulate it. One of the new anti-bone resorption agents, odanacatib, a selective cathepsin-K inhibitor, is in late phase III clinical research. Among new bone anabolic drugs, those that have an action on the Wnt signaling pathway appear to be particularly promising. The development of new compounds for the treatment of osteoporosis represents an excellent example of translational medicine efforts aimed to extend the range of treatment options for osteoporosis, a very common disease with a high social and economic impact, particularly when causing fractures. PMID:25069493

  18. Mice Abundant in Muricholic Bile Acids Show Resistance to Dietary Induced Steatosis, Weight Gain, and to Impaired Glucose Metabolism

    PubMed Central

    Bonde, Ylva; Eggertsen, Gösta; Rudling, Mats

    2016-01-01

    High endogenous production of, or treatment with muricholic bile acids, strongly reduces the absorption of cholesterol. Mice abundant in muricholic bile acids may therefore display an increased resistance against dietary induced weight gain, steatosis, and glucose intolerance due to an anticipated general reduction in lipid absorption. To test this hypothesis, mice deficient in steroid 12-alpha hydroxylase (Cyp8b1-/-) and therefore abundant in muricholic acids were monitored for 11 weeks while fed a high fat diet. Food intake and body and liver weights were determined, and lipids in liver, serum and feces were measured. Further, responses during oral glucose and intraperitoneal insulin tolerance tests were evaluated. On the high fat diet, Cyp8b1-/- mice displayed less weight gain compared to wildtype littermates (Cyp8b1+/+). In addition, liver enlargement with steatosis and increases in serum LDL-cholesterol were strongly attenuated in Cyp8b1-/- mice on high fat diet. Fecal excretion of cholesterol was increased and there was a strong trend for doubled fecal excretion of free fatty acids, while excretion of triglycerides was unaltered, indicating dampened lipid absorption. On high fat diet, Cyp8b1-/- mice also presented lower serum glucose levels in response to oral glucose gavage or to intraperitoneal insulin injection compared to Cyp8b1+/+. In conclusion, following exposure to a high fat diet, Cyp8b1-/- mice are more resistant against weight gain, steatosis, and to glucose intolerance than Cyp8b1+/+ mice. Reduced lipid absorption may in part explain these findings. Overall, the results suggest that muricholic bile acids may be beneficial against the metabolic syndrome. PMID:26824238

  19. Lifestyle and osteoporosis.

    PubMed

    Zhu, Kun; Prince, Richard L

    2015-02-01

    Osteoporosis is associated with a number of lifestyle factors, including nutritional factors such as intake of calcium, protein, dairy food, fruits and vegetables and vitamin D status, and behavioural factors such as physical activity, smoking and alcohol consumption. Ensuring adequate calcium intake and vitamin D status and having regular weight-bearing physical activity throughout life are important for bone health and the prevention of osteoporosis and related fractures. Studies have shown that smoking and excessive alcohol intake have adverse effects on bone health and increase the risk of fracture. There is evidence suggesting that adequate protein intake and higher intake of fruits and vegetables are beneficial to bone health. PMID:25416958

  20. 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

  1. Beneficial effects of calcitriol on hypertension, glucose intolerance, impairment of endothelium-dependent vascular relaxation, and visceral adiposity in fructose-fed hypertensive rats.

    PubMed

    Chou, Chu-Lin; Pang, Cheng-Yoong; Lee, Tony J F; Fang, Te-Chao

    2015-01-01

    Besides regulating calcium homeostasis, the effects of vitamin D on vascular tone and metabolic disturbances remain scarce in the literature despite an increase intake with high-fructose corn syrup worldwide. We investigated the effects of calcitriol, an active form of vitamin D, on vascular relaxation, glucose tolerance, and visceral fat pads in fructose-fed rats. Male Wistar-Kyoto rats were divided into 4 groups (n = 6 per group). Group Con: standard chow diet for 8 weeks; Group Fru: high-fructose diet (60% fructose) for 8 weeks; Group Fru-HVD: high-fructose diet as Group Fru, high-dose calcitriol treatment (20 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding; and Group Fru-LVD: high-fructose diet as Group Fru, low-dose calcitriol treatment (10 ng / 100 g body weight per day) 4 weeks after the beginning of fructose feeding. Systolic blood pressure was measured twice a week by the tail-cuff method. Blood was examined for serum ionized calcium, phosphate, creatinine, glucose, triglycerides, and total cholesterol. Intra-peritoneal glucose intolerance test, aortic vascular reactivity, the weight of visceral fat pads, adipose size, and adipose angiotensin II levels were analyzed at the end of the study. The results showed that the fructose-fed rats significantly developed hypertension, impaired glucose tolerance, heavier weight and larger adipose size of visceral fat pads, and raised adipose angiotensin II expressions compared with the control rats. High- and low-dose calcitriol reduced modestly systolic blood pressure, increased endothelium-dependent aortic relaxation, ameliorated glucose intolerance, reduced the weight and adipose size of visceral fat pads, and lowered adipose angiotensin II expressions in the fructose-fed rats. However, high-dose calcitriol treatment mildly increased serum ionized calcium levels (1.44 ± 0.05 mmol/L). These results suggest a protective role of calcitriol treatment on endothelial function, glucose

  2. Glucose uptake and lipid metabolism are impaired in epicardial adipose tissue from heart failure patients with or without diabetes.

    PubMed

    Burgeiro, Ana; Fuhrmann, Amelia; Cherian, Sam; Espinoza, Daniel; Jarak, Ivana; Carvalho, Rui A; Loureiro, Marisa; Patrício, Miguel; Antunes, Manuel; Carvalho, Eugénia

    2016-04-01

    Type 2 diabetes mellitus is a complex metabolic disease, and cardiovascular disease is a leading complication of diabetes. Epicardial adipose tissue surrounding the heart displays biochemical, thermogenic, and cardioprotective properties. However, the metabolic cross-talk between epicardial fat and the myocardium is largely unknown. This study sought to understand epicardial adipose tissue metabolism from heart failure patients with or without diabetes. We aimed to unravel possible differences in glucose and lipid metabolism between human epicardial and subcutaneous adipocytes and elucidate the potential underlying mechanisms involved in heart failure. Insulin-stimulated [(14)C]glucose uptake and isoproterenol-stimulated lipolysis were measured in isolated epicardial and subcutaneous adipocytes. The expression of genes involved in glucose and lipid metabolism was analyzed by reverse transcription-polymerase chain reaction in adipocytes. In addition, epicardial and subcutaneous fatty acid composition was analyzed by high-resolution proton nuclear magnetic resonance spectroscopy. The difference between basal and insulin conditions in glucose uptake was significantly decreased (P= 0.006) in epicardial compared with subcutaneous adipocytes. Moreover, a significant (P< 0.001) decrease in the isoproterenol-stimulated lipolysis was also observed when the two fat depots were compared, and it was strongly correlated with lipolysis, lipid storage, and inflammation-related gene expression. Moreover, the fatty acid composition of these tissues was significantly altered by diabetes. These results emphasize potential metabolic differences between both fat depots in the presence of heart failure and highlight epicardial fat as a possible therapeutic target in situ in the cardiac microenvironment. PMID:26814014

  3. SECONDARY OSTEOPOROSIS: PATHOPHYSIOLOGY AND MANAGEMENT

    PubMed Central

    Mirza, Faryal; Canalis, Ernesto

    2015-01-01

    Osteoporosis is a skeletal disorder characterized by decreased bone mineral density and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions. PMID:25971649

  4. Direct inhibition of hexokinase activity by metformin at least partially impairs glucose metabolism and tumor growth in experimental breast cancer

    PubMed Central

    Marini, Cecilia; Salani, Barbara; Massollo, Michela; Amaro, Adriana; Esposito, Alessia Isabella; Orengo, Anna Maria; Capitanio, Selene; Emionite, Laura; Riondato, Mattia; Bottoni, Gianluca; Massara, Cinzia; Boccardo, Simona; Fabbi, Marina; Campi, Cristina; Ravera, Silvia; Angelini, Giovanna; Morbelli, Silvia; Cilli, Michele; Cordera, Renzo; Truini, Mauro; Maggi, Davide; Pfeffer, Ulrich; Sambuceti, Gianmario

    2013-01-01

    Emerging evidence suggests that metformin, a widely used anti-diabetic drug, may be useful in the prevention and treatment of different cancers. In the present study, we demonstrate that metformin directly inhibits the enzymatic function of hexokinase (HK) I and II in a cell line of triple-negative breast cancer (MDA-MB-231). The inhibition is selective for these isoforms, as documented by experiments with purified HK I and II as well as with cell lysates. Measurements of 18F-fluoro-deoxyglycose uptake document that it is dose- and time-dependent and powerful enough to virtually abolish glucose consumption despite unchanged availability of membrane glucose transporters. The profound energetic imbalance activates phosphorylation and is subsequently followed by cell death. More importantly, the “in vivo” relevance of this effect is confirmed by studies of orthotopic xenografts of MDA-MB-231 cells in athymic (nu/nu) mice. Administration of high drug doses after tumor development caused an evident tumor necrosis in a time as short as 48 h. On the other hand, 1 mo metformin treatment markedly reduced cancer glucose consumption and growth. Taken together, our results strongly suggest that HK inhibition contributes to metformin therapeutic and preventive potential in breast cancer. PMID:24240433

  5. 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

  6. Genetics of osteoporosis

    SciTech Connect

    Urano, Tomohiko; Inoue, Satoshi

    2014-09-19

    Highlights: • Single-nucleotide polymorphisms (SNPs) associated with osteoporosis were identified. • SNPs mapped close to or within VDR and ESR1 are associated with bone mineral density. • WNT signaling pathway plays a pivotal role in regulating bone mineral density. • Genetic studies will be useful for identification of new therapeutic targets. - Abstract: Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which increases susceptibility to fractures. BMD is a complex quantitative trait with normal distribution and seems to be genetically controlled (in 50–90% of the cases), according to studies on twins and families. Over the last 20 years, candidate gene approach and genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with low BMD, osteoporosis, and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding nuclear receptors and WNT-β-catenin signaling proteins. Understanding the genetics of osteoporosis will help identify novel candidates for diagnostic and therapeutic targets.

  7. Osteoporosis and Women's Health

    MedlinePlus

    ... down by the body (a process called bone turnover). Your highest bone mass (size and thickness) is reached between ages 20 and 25, and it declines after that. After menopause, however, women begin to lose bone at an even faster rate. Osteoporosis develops when your body cannot replace bone ...

  8. Animal models for osteoporosis.

    PubMed

    Turner, R T; Maran, A; Lotinun, S; Hefferan, T; Evans, G L; Zhang, M; Sibonga, J D

    2001-01-01

    Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge. PMID:11704974

  9. Teriparatide for postmenopausal osteoporosis.

    PubMed

    2004-12-01

    Teriparatide (Forsteo - Eli Lilly) is the first parathyroid hormone derivative to be licensed for the treatment of women with postmenopausal osteoporosis. It is described as a "bone-formation agent", in contrast to established treatments, such as bisphosphonates, raloxifene, calcitriol and calcitonin, which reduce bone resorption. Here we consider whether teriparatide offers any worthwhile advantages over these other options. PMID:15587764

  10. Animal models for osteoporosis

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Maran, A.; Lotinun, S.; Hefferan, T.; Evans, G. L.; Zhang, M.; Sibonga, J. D.

    2001-01-01

    Animal models will continue to be important tools in the quest to understand the contribution of specific genes to establishment of peak bone mass and optimal bone architecture, as well as the genetic basis for a predisposition toward accelerated bone loss in the presence of co-morbidity factors such as estrogen deficiency. Existing animal models will continue to be useful for modeling changes in bone metabolism and architecture induced by well-defined local and systemic factors. However, there is a critical unfulfilled need to develop and validate better animal models to allow fruitful investigation of the interaction of the multitude of factors which precipitate senile osteoporosis. Well characterized and validated animal models that can be recommended for investigation of the etiology, prevention and treatment of several forms of osteoporosis have been listed in Table 1. Also listed are models which are provisionally recommended. These latter models have potential but are inadequately characterized, deviate significantly from the human response, require careful choice of strain or age, or are not practical for most investigators to adopt. It cannot be stressed strongly enough that the enormous potential of laboratory animals as models for osteoporosis can only be realized if great care is taken in the choice of an appropriate species, age, experimental design, and measurements. Poor choices will results in misinterpretation of results which ultimately can bring harm to patients who suffer from osteoporosis by delaying advancement of knowledge.

  11. Clinical Practice. Postmenopausal Osteoporosis.

    PubMed

    Black, Dennis M; Rosen, Clifford J

    2016-01-21

    Key Clinical Points Postmenopausal Osteoporosis Fractures and osteoporosis are common, particularly among older women, and hip fractures can be devastating. Treatment is generally recommended in postmenopausal women who have a bone mineral density T score of -2.5 or less, a history of spine or hip fracture, or a Fracture Risk Assessment Tool (FRAX) score indicating increased fracture risk. Bisphosphonates (generic) and denosumab reduce the risk of hip, nonvertebral, and vertebral fractures; bisphosphonates are commonly used as first-line treatment in women who do not have contraindications. Teriparatide reduces the risk of nonvertebral and vertebral fractures. Osteonecrosis of the jaw and atypical femur fractures have been reported with treatment but are rare. The benefit-to-risk ratio for osteoporosis treatment is strongly positive for most women with osteoporosis. Because benefits are retained after discontinuation of alendronate or zoledronic acid, drug holidays after 5 years of alendronate therapy or 3 years of zoledronic acid therapy may be considered for patients at lower risk for fracture. PMID:26789873

  12. Management of osteoporosis

    PubMed Central

    Lewiecki, E Michael

    2004-01-01

    Osteoporosis or osteopenia occurs in about 44 million Americans, resulting in 1.5 million fragility fractures per year. The consequences of these fractures include pain, disability, depression, loss of independence, and increased mortality. The burden to the healthcare system, in terms of cost and resources, is tremendous, with an estimated direct annual USA healthcare expenditure of about $17 billion. With longer life expectancy and the aging of the baby-boomer generation, the number of men and women with osteoporosis or low bone density is expected to rise to over 61 million by 2020. Osteoporosis is a silent disease that causes no symptoms until a fracture occurs. Any fragility fracture greatly increases the risk of future fractures. Most patients with osteoporosis are not being diagnosed or treated. Even those with previous fractures, who are at extremely high risk of future fractures, are often not being treated. It is preferable to diagnose osteoporosis by bone density testing of high risk individuals before the first fracture occurs. If osteoporosis or low bone density is identified, evaluation for contributing factors should be considered. Patients on long-term glucocorticoid therapy are at especially high risk for developing osteoporosis, and may sustain fractures at a lower bone density than those not taking glucocorticoids. All patients should be counseled on the importance of regular weight-bearing exercise and adequate daily intake of calcium and vitamin D. Exposure to medications that cause drowsiness or hypotension should be minimized. Non-pharmacologic therapy to reduce the non-skeletal risk factors for fracture should be considered. These include fall prevention through balance training and muscle strengthening, removal of fall hazards at home, and wearing hip protectors if the risk of falling remains high. Pharmacologic therapy can stabilize or increase bone density in most patients, and reduce fracture risk by about 50%. By selecting high risk

  13. 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

  14. Rodent models of osteoporosis

    PubMed Central

    Sophocleous, Antonia; Idris, Aymen I

    2014-01-01

    The aim of this protocol is to provide a detailed description of male and female rodent models of osteoporosis. In addition to indications on the methods of performing the surgical procedures, the choice of reliable and safe anaesthetics is also described. Post-operative care, including analgesia administration for pain management, is also discussed. Ovariectomy in rodents is a procedure where ovaries are surgically excised. Hormonal changes resulting from ovary removal lead to an oestrogen-deprived state, which enhances bone remodelling, causes bone loss and increases bone fracture risk. Therefore, ovariectomy has been considered as the most common preclinical model for understanding the pathophysiology of menopause-associated events and for developing new treatment strategies for tackling post-menopausal osteoporosis. This protocol also provides a detailed description of orchidectomy, a model for androgen-deficient osteoporosis in rodents. Endocrine changes following testes removal lead to hypogonadism, which results in accelerated bone loss, increasing osteoporosis risk. Orchidectomised rodent models have been proposed to mimic male osteoporosis and therefore remain a valuable tool for understanding androgen deficiency in aged men. Although it would have been particularly difficult to assemble an internationally acceptable description of surgical procedures, here we have attempted to provide a comprehensive guide for best practice in performing ovariectomy and orchidectomy in laboratory rodents. Research scientists are reminded that they should follow their own institution's interpretation of such guidelines. Ultimately, however, all animal procedures must be overseen by the local Animal Welfare and Ethical Review Body and conducted under licences approved by a regulatory ethics committee. PMID:25852854

  15. Xanthohumol impairs glucose uptake by a human first-trimester extravillous trophoblast cell line (HTR-8/SVneo cells) and impacts the process of placentation.

    PubMed

    Correia-Branco, Ana; Azevedo, Cláudia F; Araújo, João R; Guimarães, João T; Faria, Ana; Keating, Elisa; Martel, Fátima

    2015-10-01

    In this study, we aimed to investigate modulation of glucose uptake by the HTR-8/SVneo human first-trimester extravillous trophoblast cell line by a series of compounds and to study its consequences upon cell proliferation, viability and migration. We observed that uptake of (3)H-deoxy-d-glucose ((3)H-DG; 10 nM) was time-dependent, saturable, inhibited by cytochalasin B (50 and 100 µM), phloretin (0.5 mM) and phloridzin (1 mM), insulin-insensitive and sodium-independent. In the short term (30 min), neither 5-HT (100-1000 µM), melatonin (10 nM) nor the drugs of abuse ethanol (100 mM), nicotine (100 µM), cocaine (25 µM), amphetamine (10-25 µM) and 3,4-methylenedioxy-N-methamphetamine (10 µM) affected (3)H-DG uptake, while dexamethasone (100-1000 µM), fluoxetine (100-300 µM), quercetin, epigallocatechin-3-gallate (30-1000 µM), xanthohumol (XH) and resveratrol (1-500 µM) decreased it. XH was the most potent inhibitor [IC50 = 3.55 (1.37-9.20) µM] of (3)H-DG uptake, behaving as a non-competitive inhibitor of (3)H-DG uptake, both after short- and long-term (24 h) treatment. The effect of XH (5 µM; 24 h) upon (3)H-DG uptake involved mammalian target of rapamycin, tyrosine kinases and c-Jun N-terminal kinases intracellular pathways. Moreover, XH appeared to decrease cellular uptake of lactate due to inhibition of the monocarboxylate transporter 1. Additionally, XH (24 h; 5 µM) decreased cell viability, proliferation, culture growth and migration. The effects of XH upon cell viability and culture growth, but not the antimigratory effect, were mimicked by low extracellular glucose conditions and reversed by high extracellular glucose conditions. We thus suggest that XH, by inhibiting glucose cellular uptake and impairing HTR-8/SVneo cell viability and proliferation, may have a deleterious impact in the process of placentation. PMID:26194608

  16. Increase in gastric secretion induced by 2-deoxy-D-glucose is impaired in capsaicin pretreated rats.

    PubMed Central

    Evangelista, S.; Santicioli, P.; Maggi, C. A.; Meli, A.

    1989-01-01

    Gastric acid secretion was determined following intravenous administration of 2-deoxy-D-glucose (2-DG; 60 mg kg-1) or electrical stimulation of the vagus nerve in urethane-anaesthetized rats pretreated when newborn with either capsaicin or the vehicle. The secretory response to 2-DG was substantially reduced in the capsaicin pretreated rats, while that induced by electrical vagal stimulation (1 mA, 1 ms. 3 Hz) was unaffected. These results suggest that capsaicin-sensitive fibres are involved in the afferent branch of the reflex response activated by 2-DG to stimulate gastric acid secretion. PMID:2804552

  17. Postmenopausal osteoporosis - clinical, biological and histopathological aspects.

    PubMed

    Pavel, Oana Roxana; Popescu, Mihaela; Novac, Liliana; Mogoantă, LaurenŢiu; Pavel, LaurenŢiu Petrişor; Vicaş, Răzvan Marius; Trăistaru, Magdalena Rodica

    2016-01-01

    Osteoporosis is one of the most common disorders in postmenopausal women, affecting the quality of life and increasing the risk for fractures in minor traumas. Changes in the bone microarchitecture causes static changes in the body and affects motility. In this study, we analyzed two groups of women, one with physiological menopause and one with surgically induced menopause. The diagnosis of osteoporosis was suspected based on the clinical symptoms and confirmed by assessing bone mineral density by the dual-energy X-ray absorptiometry (DEXA). Comparing some clinical and biological aspects there was noted that a much higher percentage of women with surgically induced menopause exhibited increases in body mass index, changes in serum lipids, cholesterol, triglycerides, blood glucose, serum calcium, magnesemia and osteocalcin. In contrast, no significant differences were observed in the histopathological aspects of bone tissue examined from these two groups. In all patients, there was identified a significant reduction in the number of osteocytes and osteoblasts, the expansion of haversian channels, reducing the number of trabecular bone in the cancellous bone with wide areola cavities often full of adipose tissue, non-homogenous demineralization of both the compact bone and the cancellous bone, atrophy and even absence of the endosteal, and the presence of multiple microfractures. Our study showed that early surgically induced menopause more intensely alters the lipid, carbohydrate and mineral metabolism, thus favoring the onset of osteoporosis. PMID:27151697

  18. Polydatin Restores Endothelium-Dependent Relaxation in Rat Aorta Rings Impaired by High Glucose: A Novel Insight into the PPARβ-NO Signaling Pathway.

    PubMed

    Wu, Yang; Xue, Lai; Du, Weimin; Huang, Bo; Tang, Cuiping; Liu, Changqing; Qiu, Hongmei; Jiang, Qingsong

    2015-01-01

    Polydatin, a natural component from Polygonum Cuspidatum, has important therapeutic effects on metabolic syndrome. A novel therapeutic strategy using polydatin to improve vascular function has recently been proposed to treat diabetes-related cardiovascular complications. However, the biological role and molecular basis of polydatin's action on vascular endothelial cells (VECs)-mediated vasodilatation under diabetes-related hyperglycemia condition remain elusive. The present study aimed to assess the contribution of polydatin in restoring endothelium-dependent relaxation and to determine the details of its underlying mechanism. By measuring endothelium-dependent relaxation, we found that acetylcholine-induced vasodilation was impaired by elevated glucose (55 mmol/L); however, polydatin (1, 3, 10 μmol/L) could restore the relaxation in a dose-dependent manner. Polydatin could also improve the histological damage to endothelial cells in the thoracic aorta. Polydatin's effects were mediated via promoting the expression of endothelial NO synthase (eNOS), enhancing eNOS activity and decreasing the inducible NOS (iNOS) level, finally resulting in a beneficial increase in NO release, which probably, at least in part, through activation of the PPARβ signaling pathway. The results provided a novel insight into polydatin action, via PPARβ-NO signaling pathways, in restoring endothelial function in high glucose conditions. The results also indicated the potential utility of polydatin to treat diabetes related cardiovascular diseases. PMID:25941823

  19. Association between Sleep Duration and Impaired Fasting Glucose in Korean Adults: Results from the Korean National Health and Nutrition Examination Survey 2011–2012

    PubMed Central

    Kim, Cho-Rong; Shin, Jin-Young; Gim, Wook

    2016-01-01

    Background Impaired fasting glucose (IFG) is an established risk factor for type 2 diabetes and cardiovascular disease. This study evaluated the relationship between sleep duration and IFG. Methods This cross-sectional study included 14,925 Korean adults (5,868 men and 9,057 women) ≥19 years of age who participated in the Korean National Health and Nutrition Examination Survey between 2011 and 2012. Blood glucose levels were measured after at least eight hours of fasting. Study subjects were categorized into three groups based on self-reported sleep duration (<7, 7–8, or >8 h/d). IFG was diagnosed according to recommendations American Diabetes Association guidelines. Multiple logistic regression analysis was performed with adjustment for covariates. Results In men, short sleep duration (<7 hours) was associated with increased risk of IFG (odds ratio [OR], 1.46; 95% confidence interval [CI], 1.08 to 1.96) compared to adequate sleep duration (7–8 hours), whereas long sleep duration (>8 hours) was not associated with risk of IFG (OR, 0.90; 95% CI, 0.37 to 2.18). In women, sleep duration was not associated with risk of IFG. Conclusion The association between sleep duration and IFG differed by sex; sleep deprivation, was associated with increased risk of IFG, especially in men. PMID:26885323

  20. Heterozygous Hfe gene deletion leads to impaired glucose homeostasis, but not liver injury in mice fed a high-calorie diet.

    PubMed

    Britton, Laurence; Jaskowski, Lesley; Bridle, Kim; Santrampurwala, Nishreen; Reiling, Janske; Musgrave, Nick; Subramaniam, V Nathan; Crawford, Darrell

    2016-06-01

    Heterozygous mutations of the Hfe gene have been proposed as cofactors in the development and progression of nonalcoholic fatty liver disease (NAFLD). Homozygous Hfe deletion previously has been shown to lead to dysregulated hepatic lipid metabolism and accentuated liver injury in a dietary mouse model of NAFLD We sought to establish whether heterozygous deletion of Hfe is sufficient to promote liver injury when mice are exposed to a high-calorie diet (HCD). Eight-week-old wild-type and Hfe(+/-) mice received 8 weeks of a control diet or HCD Liver histology and pathways of lipid and iron metabolism were analyzed. Liver histology demonstrated that mice fed a HCD had increased NAFLD activity score (NAS), steatosis, and hepatocyte ballooning. However, liver injury was unaffected by Hfe genotype. Hepatic iron concentration (HIC) was increased in Hfe(+/-) mice of both dietary groups. HCD resulted in a hepcidin-independent reduction in HIC Hfe(+/-) mice demonstrated raised fasting serum glucose concentrations and HOMA-IR score, despite unaltered serum adiponectin concentrations. Downstream regulators of hepatic de novo lipogenesis (pAKT, SREBP-1, Fas, Scd1) and fatty acid oxidation (AdipoR2, Pparα, Cpt1) were largely unaffected by genotype. In summary, heterozygous Hfe gene deletion is associated with impaired iron and glucose metabolism. However, unlike homozygous Hfe deletion, heterozygous gene deletion did not affect lipid metabolism pathways or liver injury in this model. PMID:27354540

  1. 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

  2. Breastfeeding and postmenopausal osteoporosis.

    PubMed

    Grimes, Julia P; Wimalawansa, Sunil J

    2003-06-01

    Bone loss associated with osteoporosis occurs with high frequency among the elderly and often results in debilitating fractures. A combination of lifestyle behaviors, genetic predisposition, and disease processes contributes to bone metabolism. Therefore, any discussion regarding bone health must address these factors. The impact of menopause on bone turnover has been generally well studied and characterized. Breastfeeding places significant stress on calcium metabolism and, as a consequence, directly influences bone metabolism. The most significant factors affecting bone mineral density (BMD) and bone metabolism are the duration and frequency of lactation, the return of menses, and pre-pregnancy weight. Although transient, lactation is associated with bone loss. As clinical guidelines and public health policies are being formulated, there is a compelling need for further investigation into the relationship of lactation, BMD, and subsequent risk of osteoporosis. Better understanding of this relationship will provide new opportunities for early intervention and ultimately help in the prevention of bone loss in postmenopausal women. PMID:12734029

  3. Osteoporosis in anorexia nervosa.

    PubMed

    Mehler, Philip S; Cleary, Barbara S; Gaudiani, Jennifer L

    2011-01-01

    Osteoporosis is common in anorexia nervosa. It places these patients at increased lifetime risk for fractures. Bone loss may never recover completely even once weight is restored. The strongest predictors of osteoporosis include low body weight and amenorrhea. Loss of bone density can occur rapidly and very early in the course of anorexia nervosa. The etiology of bone loss in the patient with anorexia nervosa is multifactorial. In addition to reduced estrogen and progesterone, excess cortisol levels and low levels of insulin growth factor (IGF-1), a correlate for bone formation, are observed. Dual energy x-ray absorptiometry screening is important to assess bone density. However, successful treatments to reverse bone loss, in those with anorexia nervosa, are lacking. Early diagnosis and treatment of anorexia nervosa are paramount to prevent initial weight loss and subsequent loss of bone. PMID:21360368

  4. [Biological therapy for osteoporosis].

    PubMed

    Nakamura, Shinya; Tanaka, Sakae

    2014-06-01

    Osteoporosis is a disorder of bone formation and resorption balance. Advances in our knowledge of the molecular mechanisms of bone formation and resorption led to promising therapeutic targets for osteoporosis. In the novel biological drugs, denosumab, a monoclonal antibody against receptor activator of nuclear factor-κB ligand (RANKL) has been clinically applied by positive effect on bone mineral density, negative effect on bone resorption, preventive effect on fragility fractures and safety. Odanacatib, a cathepsin K inhibitor is drawing attention as an antiresorptive drug which has lower bone resorption potency than bisphosphoneate. On the other hand, BHQ-880, an anti-Dickkopf-1 (Dkk-1) antibody and romosozumab (AMG-785) , an anti-sclerostin antibody which activate Wnt/β-catenin signaling pathway are drawing attention as bone formation accelerators with no bone resorption acceleration. Clinical studies of these drugs are now ongoing and their clinical applications are expected. PMID:24870844

  5. [Osteoporosis in phlebology].

    PubMed

    van der Molen, H R; Overvelde, S

    1993-01-01

    Patient often think that the pains of their extremities (especially during the night) are caused by a plebo or an angiopathy whereas they are in fact due to a vertebral or lumbar discal affection. 84 patients with osteoporosis were treated by an intramuscular injection of deca-durabolin (25 mg/month) and calcium phosphate (tertiare). Results were satisfactory: six months later, 62 patients no longer suffered, 13 had felt improvement and 2 remained unchanged. PMID:8362009

  6. Sodium Orthovanadate and Trigonella Foenum Graecum Prevents Neuronal Parameters Decline and Impaired Glucose Homeostasis in Alloxan Diabetic Rats.

    PubMed

    Kumar, Pardeep; Taha, Asia; Kumar, Nitin; Kumar, Vinod; Baquer, Najma Zaheer

    2015-01-01

    Hyperglycemia is the most important contributor in the onset and progress of diabetic complications mainly by producing oxidative stress. The present study was carried out to observe, the antihyperglycemic effect of sodium orthovanadate (SOV) and Trigonella foenum graecum seed powder (TSP) administration on blood glucose and insulin levels, membrane linked enzymes (monoamine oxidase, acetylcholinesterase, Ca2+ATPase), intracellular calcium (Ca2+) levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in brain of the alloxan induced diabetic rats and to see whether the treatment with SOV and TSP was capable of reversing the diabetic effects. Diabetes was induced by administration of alloxan monohydrate (15 mg/100 g body weight) and rats were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP in the diet and a combination of 0.2 mg/ml SOV and 5% TSP separately for three weeks. Diabetic rats showed hyperglycemia with almost four fold high blood glucose levels. Activities of acetylcholinesterase and Ca2+ATPase decreased in diabetic rat brain. Diabetic rats exhibited an increased level of intracellular Ca2+ levels, lipid peroxidation, neurolipofuscin accumulations and monoamine oxidase activity. Treatment of diabetic rats with insulin, TSP, SOV and a combined therapy of lower dose of SOV with TSP revived normoglycemia and restored the altered level of membrane bound enzymes, lipid peroxidation and neurolipofuscin accumulation. Our results showed that lower doses of SOV (0.2 mg/ml) could be used in combination with TSP in normalization of altered metabolic parameters and membrane linked enzymes without any harmful side effect. PMID:26093667

  7. Osteoporosis and trace elements--an overview.

    PubMed

    Aaseth, Jan; Boivin, Georges; Andersen, Ole

    2012-06-01

    More than 200 million people are affected by osteoporosis worldwide, as estimated by 2 million annual hip fractures and other debilitating bone fractures (vertebrae compression and Colles' fractures). Osteoporosis is a multi-factorial disease with potential contributions from genetic, endocrine functional, exercise related and nutritional factors. Of particular considerations are calcium (Ca) status, vitamin D, fluoride, magnesium and other trace elements. Several trace elements such as zinc and copper are essential for normal development of the skeleton in humans and animals. Fluoride accumulates in new bone and results in a net gain in bone mass, but may be associated with a tissue of poor quality. Aluminum induces impairment of bone formation. Gallium and cadmium suppresses bone turnover. However, exact involvements of the trace elements in osteoporosis have not yet been fully clarified. Numerous investigators have evaluated the role of medications and supplementations with minerals and trace substances to reverse the progression of this disease. Although bisphosphonates are still the drugs of choice, low-dosed fluoride and strontium salts have shown promise for the future. PMID:22575536

  8. [Prevention of osteoporosis].

    PubMed

    Dambacher, M A; Kissling, R; Neff, M

    1998-11-01

    The European Parliament presented June 10th in Brussels the 'Osteoporosis Report in EU--Means for Prevention'. It was emphasized that in the EU more than 3500 million Ecu have to be spent for hospitalization and that more than 500,000 hospitals beds are being used by osteoporotic patients. According to some calculations this number will double within the next 50 years. The EU has set up eight steps to be considered, e.g. have densitometric measurements available for persons with high risk and have these measurement paid by the insurances to further finance and support research for the very important areas of prevention and treatment. One distinguishes between primary, secondary and tertiary prevention of osteoporosis. Primary prevention aims at reaching at adolescent age a peak bone mass as high as possible. Secondary prevention aims at reducing bone loss peri- and postmenopausal. The tertiary prevention with manifest osteoporosis aims at preventing fractures. Emphasis of the primary prevention is, besides a sufficient calcium intake, to omit risk factors; with secondary prevention the use of medical treatments such as estrogens/gestagens, bisphosphonates, and recently also SERMs is applied. The tertiary prevention tries mostly to reduce the femur fractures. In addition to drugs such as vitamin D/calcium, vitamin D metabolites and bisphosphonates it is very important to create 'a fall-proof home'. Also very useful are hip protectors. PMID:9865147

  9. Osteoporosis and fragility fractures.

    PubMed

    Sànchez-Riera, Lídia; Wilson, Nicholas; Kamalaraj, Narainraj; Nolla, Joan M; Kok, Cindy; Li, Yang; Macara, Monique; Norman, Rosana; Chen, Jian Sheng; Smith, Emma U R; Sambrook, Philip N; Hernández, Carmen Santos; Woolf, Anthony; March, Lyn

    2010-12-01

    The prevalence of osteoporosis is expected to increase with the ageing of the world's population. This article reviews the epidemiology, risk factors and health burden of osteoporosis. In the Global Burden of Disease (GBD) Study 2005, osteoporosis is studied as a risk factor for fracture by considering the bone-mineral-density (BMD) measurement as the continuous exposure variable. We have performed a systematic review seeking population-based studies with BMD data measured by dual-X-ray absorptiometry (DXA). The femoral neck was selected as the unique location and all values were converted into Hologic(®) to enable inclusion of worldwide data for analysis. Provisional results on mean BMD values for different world regions are shown in age breakdowns for males and females 50 years or over, as well as mean T-scores using the young, white, female reference of National Health and Nutrition Examination Survey (NHANES) III. Results show remarkable geographical differences and a time trend towards improvement of the BMD values in Asian and European populations. PMID:21665127

  10. The societal burden of osteoporosis.

    PubMed

    Becker, David J; Kilgore, Meredith L; Morrisey, Michael A

    2010-06-01

    Osteoporosis currently affects 10 million Americans and is responsible for more than 1.5 million fractures annually. The financial burden of osteoporosis is substantial, with annual direct medical costs estimated at 17 to 20 billion dollars. Most of these costs are related to the acute and rehabilitative care following osteoporotic fractures, particularly hip fractures. The societal burden of osteoporosis includes these direct medical costs and the monetary (eg, caregiver time) and nonmonetary costs of poor health. The aging of the US population is expected to increase the prevalence of osteoporosis and the number of osteoporotic fractures. Growth of the older adult population will pose significant challenges to Medicare and Medicaid, which bear most of the cost of osteoporosis. Efforts to address the looming financial burden must focus on reducing the prevalence of osteoporosis and the incidence of costly fragility fractures. PMID:20425518

  11. 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.

  12. Osteoporosis: Symptoms, Diagnosis, Treatment and Prevention

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Osteoporosis Osteoporosis: Symptoms, Diagnosis, Treatment and Prevention Past Issues / Winter 2011 Table of Contents Osteoporosis can strike at any age, although the risk ...

  13. 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

  14. 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

  15. 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

  16. Increased Levels of Circulating Advanced Glycation End-Products in Menopausal Women with Osteoporosis

    PubMed Central

    Yang, Deng-Ho; Chiang, Tsay-I; Chang, I-Chang; Lin, Fu-Huang; Wei, Cheng-Chung; Cheng, Ya-Wen

    2014-01-01

    Background: Advanced glycation end-products (AGEs) can accumulate in organs and tissues during ageing and diabetes. Increased levels of AGEs are found in the bone tissue of patients with osteoporosis. The purpose of this study was to evaluate circulating AGEs in patients with osteoporosis. Methods: We evaluated plasma AGEs, osteoporosis-related biomarkers, and bone mass in 82 menopausal women with osteoporosis or osteopenia, 16 young women with osteopenia, and 43 healthy women without osteoporosis or osteopenia. Results: Higher levels of serum AGEs were found in the osteoporosis or osteopenia group compared to healthy women (P < 0.0001). A negative correlation was observed between serum AGEs and lumbar spine bone density (BMD of lumbar spine, r = -0.249, P = 0.028; T-score of lumbar spine, r = -0.261, P = 0.021). Women with a increased level of serum AGEs (> 8.12 U/mL) had a 5.34-fold risk of osteopenia regarding lumbar spine T-score and a 3.31-fold risk of osteopenia regarding the hip T-score. Conclusion: Serum AGEs could be used to monitor the severity and progression of osteoporosis. An increased serum level of AGEs was associated with impaired bone formation and was a risk factor for the development of osteoporosis. Targeting AGEs may represent a novel therapeutic approach for primary or secondary osteoporosis. PMID:24688308

  17. 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

  18. Short-term effectiveness of an individual counseling program for impaired fasting glucose and mild type 2 diabetes in Japan: a multi-center randomized control trial.

    PubMed

    Watanabe, Makoto; Okayama, Akira; Shimamoto, Kazuaki; Ueshima, Hirotsugu

    2007-01-01

    The aim of this study is to evaluate the short-term effectiveness of our individual-based counseling program and tools among individuals in ordinary Japanese communities with impaired fasting glucose (IFG) and mild type 2 diabetes. A total of 233 eligible participants (age 30-69 years) in 14 local study centers were randomly assigned to an intervention group (INT, N=119) and a control group (CONT, N=114). During the 4-month intervention, the INT received 4 individual counseling sessions and one reminder on life style modification. The CONT received only an explanation of blood test results and general information on diabetes. Baseline characteristics did not differ significantly between groups. Percentages of participants with desirable changes in glycemic level and weight were significantly higher in INT than CONT: fasting plasma glucose reduction of more than 10 mg/dL (39% in INT vs. 26% in CONT, p=0.045), hemoglobinA1c reduction greater than 0.3% (14% vs. 4%, p=0.01), and weight reduction of more than 4 kg (13% vs. 4%, p=0.025). Decreases in total energy intake and percentage of heavy alcohol drinkers (more than 46 g/day) were significantly greater in INT than CONT. The increase in percentages of participants who engaged in leisure time physical activity more than 12 times per month was significantly greater in INT than CONT. Our program resulted in life style modification and glycemic level improvement in the short-term among individuals with IFG and mild type 2 diabetes. Results indicated that the program was sufficiently effective and feasible for implementation in ordinary communities. PMID:17704031

  19. 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

  20. 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

  1. 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

  2. Testosterone deficiency induced by progressive stages of diabetes mellitus impairs glucose metabolism and favors glycogenesis in mature rat Sertoli cells.

    PubMed

    Rato, Luís; Alves, Marco G; Duarte, Ana I; Santos, Maria S; Moreira, Paula I; Cavaco, José E; Oliveira, Pedro F

    2015-09-01

    The incidence of type 2 diabetes mellitus and its prodromal stage, pre-diabetes, is rapidly increasing among young men, leading to disturbances in testosterone synthesis. However, the impact of testosterone deficiency induced by these progressive stages of diabetes on the metabolic behavior of Sertoli cells remains unknown. We evaluated the effects of testosterone deficiency associated with pre-diabetes and type 2 diabetes on Sertoli cells metabolism, by measuring (1) the expression and/or activities of glycolysis and glycogen metabolism-related proteins and (2) the metabolite secretion/consumption in Sertoli cells obtained from rat models of different development stages of the disease, to unveil the mechanisms by which testosterone deregulation may affect spermatogenesis. Glucose and pyruvate uptake were decreased in cells exposed to the testosterone concentration found in pre-diabetic rats (600nM), whereas the decreased testosterone concentrations found in type 2 diabetic rats (7nM) reversed this profile. Lactate production was not altered, although the expression and/or activity of lactate dehydrogenase and monocarboxylate transporter 4 were affected by progressive testosterone-deficiency. Sertoli cells exposed to type 2 diabetic conditions exhibited intracellular glycogen accumulation. These results illustrate that gradually reduced levels of testosterone, induced by progressive stages of diabetes mellitus, favor a metabolic reprogramming toward glycogen synthesis. Our data highlights a pivotal role for testosterone in the regulation of spermatogenesis metabolic support by Sertoli cells, particularly in individuals suffering from metabolic diseases. Such alterations may be in the basis of male subfertility/infertility associated with the progression of diabetes mellitus. PMID:26148570

  3. Epidemiology of spinal osteoporosis.

    PubMed

    Melton, L J

    1997-12-15

    Approximately 30% of postmenopausal white women in the United States have osteoporosis, and 16% have osteoporosis of the lumbar spine in particular. Bone density of the spine is positively associated with greater height and weight, older age at menopause, a history of arthritis, more physical activity, moderate use of alcoholic beverages, diuretic treatment, and current estrogen replacement therapy, whereas later age at menarche and a maternal history of fracture are associated with lower levels of density. Low bone density leads to an increased risk of osteoporotic fractures. Fracture risk also increase with age. Vertebral fractures affect approximately 25% of postmenopausal women, although the exact figure depends on the definition used. Recent data show that vertebral fracture rates are as great in men as in women but, because women live longer, the lifetime risk of a vertebral fracture from age 50 onward is 16% in white women and only 5% in white men. Fracture rates are less in most nonwhite populations, but vertebral fractures are as common in Asian women as in those of European heritage. Other risk factors for vertebral fractures are less clear but include hypogonadism and secondary osteoporosis; obesity is protective of fractures as it is of bone loss. Compared with hip fractures, vertebral fractures are less disabling and less expensive, costing approximately $746 million in the United States in 1995. However, they have a substantial negative impact on the patient's function and quality of life. The adverse effects of osteoporotic fractures are likely to increase in the future with the growing number of elderly people. PMID:9431638

  4. Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal.

    PubMed

    Treesukosol, Yada; Spector, Alan C

    2012-07-15

    Evidence in the literature supports the hypothesis that the T1R2+3 heterodimer binds to compounds that humans describe as sweet. Here, we assessed the necessity of the T1R2 and T1R3 subunits in the maintenance of normal taste sensitivity to carbohydrate stimuli. We trained and tested water-restricted T1R2 knockout (KO), T1R3 KO and their wild-type (WT) same-sex littermate controls in a two-response operant procedure to sample a fluid and differentially respond on the basis of whether the stimulus was water or a tastant. Correct responses were reinforced with water and incorrect responses were punished with a time-out. Testing was conducted with a modified descending method of limits procedure across daily 25-min sessions. Both KO groups displayed severely impaired performance and markedly decreased sensitivity when required to discriminate water from sucrose, glucose, or maltose. In contrast, when Polycose was tested, KO mice had normal EC(50) values for their psychometric functions, with some slight, but significant, impairment in performance. Sensitivity to NaCl did not differ between these mice and their WT controls. Our findings support the view that the T1R2+3 heterodimer is the principal receptor that mediates taste detection of natural sweeteners, but not of all carbohydrate stimuli. The combined presence of T1R2 and T1R3 appears unnecessary for the maintenance of relatively normal sensitivity to Polycose, at least in this task. Some detectability of sugars at high concentrations might be mediated by the putative polysaccharide taste receptor, the remaining T1R subunit forming either a homodimer or heteromer with another protein(s), or nontaste orosensory cues. PMID:22621968

  5. [Osteoporosis in males].

    PubMed

    Audran, M; Legrand, E; Chappard, D; Bigorgne, J C; Basle, M F

    2000-09-01

    A shorter life expectancy, a higher peak bone mass and the absence of distinct menopause equivalent explain the lower incidence of osteoporotic fractures in men. In contrast to women, osteoporosis in younger men is in most cases secondary. Causes such as prolonged glucocorticoid therapy, ethanol abuse, hypogonadism and gastrointestinal disorders are now well recognized. The impact of cigarette smoking, low calcium intake, vitamin D deficiency, hypercalciuria and thyrotoxicosis is more controversial but seems to constitute real risk factors for bone loss. Furthermore increased propensity to fall also plays a major role in fracture risk, particularly in alcoholic patients and in elderly men with neurologic disorders. PMID:11033475

  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

    , whereas during the second part it was suppressed in AD-G as much as Non-AD. In conclusion, central acylated ghrelin in rats prevented the deterioration of memory function, and energy and glucose metabolisms were partially improved, possibly due to less β-amyloid accumulation. This research suggests that interventions such as intermittent fasting to facilitate sustained elevations of acyl-ghrelin should be investigated for cognitive and metabolic benefits, especially in person with early symptoms of memory impairment. PMID:26188171

  7. Male Osteoporosis in the Elderly

    PubMed Central

    D'Amelio, Patrizia; Isaia, Giovanni Carlo

    2015-01-01

    Osteoporosis is now recognized as an important public health problem in elderly men as fragility fractures are complicated by increased morbidity, mortality, and social costs. This review comprises an overview of recent findings in pathophysiology, diagnosis, and treatment of male osteoporosis, with particular regard to the old population. PMID:26457082

  8. mRNA GPR162 changes are associated with decreased food intake in rat, and its human genetic variants with impairments in glucose homeostasis in two Swedish cohorts.

    PubMed

    Caruso, Vanni; Sreedharan, Smitha; Carlini, Valeria P; Jacobsson, Josefin A; Haitina, Tatjana; Hammer, Joanna; Stephansson, Olga; Crona, Filip; Sommer, Wolfgang H; Risérus, Ulf; Lannfelt, Lars; Marcus, Claude; Heilig, Markus; de Barioglio, Susana R; Fredriksson, Robert; Schiöth, Helgi B

    2016-05-01

    G protein-coupled receptors (GPCRs) are a class of integral membrane proteins mediating intercellular interactions of fundamental physiological importance for survival including regulation of food intake, blood pressure, and hormonal sensing signaling, among other roles. Homeostatic alterations in the physiological status of GPCRs are often associated with underlying causes of disease, and to date, several orphan GPCRs are still uncharacterized. Findings from our previous study demonstrate that the Rhodopsin family protein GPR162 is widely expressed in GABAergic as well as other neurons within the mouse hippocampus, whereas extensive expression is observed in hypothalamus, amygdala, and ventral tegmental area, regions strictly interconnected and involved in the regulation of energy homeostasis and hedonic feeding. In this study, we provide a further anatomical characterization of GPR162 in mouse brain via in situ hybridization as well as detailed mRNA expression in a panel of rat tissues complementing a specie-specific mapping of the receptor. We also provide an attempt to demonstrate a functional implication of GPR162 in food intake-related behavior via antisense knockdown studies. Furthermore, we performed human genetic studies in which for the first time, variants of the GPR162 gene were associated with impairments in glucose homeostasis. PMID:26827797

  9. Osteoporosis, Fractures, and Diabetes

    PubMed Central

    2014-01-01

    It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. PMID:25050121

  10. Novel therapies for osteoporosis.

    PubMed

    Biskobing, Diane M

    2003-04-01

    Osteoporosis remains a significant clinical problem despite effective therapies. Many patients cannot or will not take currently available therapies. For this reason research continues in search of more effective and more tolerable agents. Anabolic agents offer a unique mechanism of action. The anabolic agents parathyroid hormone and strontium will be discussed. The investigational bisphosphonates ibandronate, minodronate and zoledronic acid may offer the advantage of less frequent dosing. Arzoxifene, bazedoxifene, lasofoxifene, MDL-103,323 and ospemifene are investigational selective oestrogen receptor modulators shown to be effective in animal studies and are now in clinical studies. Tibolone is a tissue-specific steroid that is currently used in Europe for prevention and treatment of osteoporosis. Multiple studies have shown efficacy in improving bone mineral density, but no fracture studies have been conducted to date. While studies of the effect of isoflavones on bone mineral density have been encouraging, a large, multi-centre study in Europe showed no effect of isoflavones on fractures. The newly described agent osteoprotegerin has been shown in early studies to inhibit bone turnover. Other agents with unique mechanisms of action in early development include cathepsin K inhibitors, integrin receptor inhibitors, nitrosylated non-steroidal anti-inflammatory agents and Src inhibitors. The efficacy of statins in bone continues to be debated with no prospective, randomised studies yet to confirm the suggestion of benefit seen in epidemiological studies. PMID:12665416

  11. Osteoporosis and Lifestyle.

    PubMed

    Ishimi, Yoshiko

    2015-01-01

    Skeletal tissue is formed during the first two decades of life; then a constant bone mass is maintained until 40 y of age. In the case of women, the bone mass is rapidly reduced at menopause at around 50 y of age. After that, bone mass slowly decreases in both men and women who have passed the 70-y-old mark. The National Institute of Health Consensus Conference adopted the definition of osteoporosis as a skeletal disorder that is characterized by compromised bone strength leading to a predisposition for and an increased risk of fracture. Since osteoporotic fractures are the third-highest cause for becoming bedridden, the maintenance of healthy bones is an important factor in extending a person's healthy lifespan. Bone mass is influenced by many factors, such as nutrition, physical activity, smoking and alcohol intake, as well as by genetic factors. Thus, a healthy diet providing balanced nutrients including calcium, vitamin D, vitamin K and protein, regular physical activity, and not smoking help maintain bone health and delay or prevent osteoporosis. Some functional foods containing soy isoflavones, milk basic protein and n-3 fatty acid may help promote bone health. PMID:26598829

  12. Novel therapies for osteoporosis.

    PubMed

    Makras, Polyzois; Delaroudis, Sideris; Anastasilakis, Athanasios D

    2015-10-01

    Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action. Denosumab, a monoclonal antibody against RANKL, approved for the treatment of postmenopausal and male osteoporosis, significantly and continuously increases bone mineral density (BMD) and maintains a low risk of vertebral, non-vertebral, and hip fractures for up to 8 years. Currently available combinations of estrogens with selective estrogen receptor modulators moderately increase BMD without causing the extra-skeletal adverse effects of each compound alone. The cathepsin K inhibitor odanacatib has recently been shown to decrease vertebral, non-vertebral, and hip fracture rates and is nearing approval. Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile. Several other agents are currently in earlier clinical and preclinical phases of development, including dickkopf-1 antagonists, activin A antagonists, β-arrestin analogs, calcilytics, and Src tyrosine kinase inhibitors. PMID:26277199

  13. Osteoporosis: Prevention and Management Strategies

    PubMed Central

    Evers, Susan; Myers, Anita

    1987-01-01

    Osteoporosis is a major cause of morbidity in post-menopausal women. Strategies to prevent or delay bone loss in normal post-menopausal women and to reduce the risk of fractures in women with osteoporosis are within the scope of family practice. Certain factors, such as inadequate calcium intake, estrogen deficiency, cigarette smoking and lack of physical activity can be modified in peri- and post-menopausal women. For patients with osteoporosis, there is potential for lowering the risk of fractures by means of calcium supplements or other therapies, physical training and rehabilitation, and modification of factors associated with risk of falling. PMID:21267348

  14. Pathogenesis of Osteoporosis

    PubMed Central

    Khosla, Sundeep

    2013-01-01

    As for most multifactorial disorders, the pathogenesis of osteoporosis is complex, and a different set of mechanisms may be operative in any given individual. However, there are certain common causes of bone loss and increased fracture risk with aging in most people. These include genetic factors contributing to the acquisition of peak bone mass, illnesses affecting skeletal growth and development, sex steroid deficiency following the menopause in women and with aging in men, and intrinsic, age-related changes in bone metabolism. Superimposed on these factors are specific secondary causes of bone loss, such as corticosteroid use or other illnesses affecting bone metabolism that may contribute to fracture risk in individuals exposed to these factors. The past decade has witnessed tremendous advances in our understanding of each of these various causes of bone loss, leading to the development of novel, mechanism-based therapeutic approaches to prevent and treat this important public health disorder. PMID:25243055

  15. [Osteoporosis in thyroid diseases].

    PubMed

    Kosińska, Agnieszka; Syrenicz, Anhelli; Kosiński, Bogusław; Garanty-Bogacka, Barbara; Syrenicz, Małgorzata; Gromniak, Elwira

    2005-01-01

    Thyroid hormones play the essential role in the regulation of metabolism and bone remodeling in physiological conditions and in the course of thyroid dysfunction. Introduction of densitometry to the diagnostics of osteoporosis has made possible the evaluation of influence of both hyperthyroidism and hypothyroidism and their treatment on bone mineral density. Moreover it became possible to estimate the influence of treatment with exogenous thyroid hormones on the skeletal system. Authors presented mechanisms of the thyroid hormones action on bone tissue and analysed current state of knowledge concerning the influence of the thyroxine treatment with replacement and suppressive doses on the bone mineral density. The influence of thyroid hormones on the skeletal system with respect to premenopausal and postmenopausal period was also discussed. Great discrepancies in literature data and its reasons were underlined. PMID:16335687

  16. New therapeutics for osteoporosis.

    PubMed

    Ng, Kong Wah; Martin, T John

    2014-06-01

    Two new approaches for the treatment of osteoporosis are summarized, each having arisen out of important new discoveries in bone biology. Odanacatib (ODN) inhibits the enzyme, cathepsin K, that is essential for the resorbing activity of osteoclasts. It is effective in preventing ovariectomy-induced bone loss in preclinical studies, and a phase II clinical study has shown inhibition of resorption sustained over five years. Outcome of a phase III study is awaited. The finding from mouse and human genetics that Wnt signaling is a powerful inducer of bone formation led to developments aimed at enhancing this pathway. Of the several approaches towards this, the most advanced is with a neutralizing antibody against sclerostin, the osteocyte-derived inhibitor of Wnt signaling. Preclinical studies show a powerful bone anabolic effect, and a clinical phase II study shows dose-dependent increases in bone formation and decreases in bone resorption markers. PMID:24699340

  17. TNFα Altered Inflammatory Responses, Impaired Health and Productivity, but Did Not Affect Glucose or Lipid Metabolism in Early-Lactation Dairy Cows

    PubMed Central

    Mamedova, Laman K.; Sordillo, Lorraine M.; Bradford, Barry J.

    2013-01-01

    Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-α (rbTNFα), affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous) were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control), 1.5, or 3.0 µg/kg body weight rbTNFα, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNFα administration. Plasma TNFα concentrations at 16 h post-administration tended to be increased (P<0.10) by rbTNFα administration, but no dose effect (P>0.10) was detected; rbTNFα treatments increased (P<0.01) concentrations of plasma haptoglobin. Most plasma eicosanoids were not affected (P>0.10) by rbTNFα administration, but 6 out of 16 measured eicosanoids changed (P<0.05) over the first week of lactation, reflecting elevated inflammatory mediators in the days immediately following parturition. Dry matter and water intake, milk yield, and milk fat and protein yields were all decreased (P<0.05) by rbTNFα treatments by 15 to 18%. Concentrations of plasma glucose, insulin, β-hydroxybutyrate, non-esterified fatty acids, triglyceride, 3-methylhistidine, and liver triglyceride were unaffected (P>0.10) by rbTNFα treatment. Glucose turnover rate was unaffected (P = 0.18) by rbTNFα administration. The higher dose of rbTNFα tended to increase the risk of cows developing one or more health disorders (P = 0.08). Taken together, these results indicate that administration of rbTNFα daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows. PMID:24260367

  18. Instrumental diagnosis of osteoporosis.

    PubMed

    Rossini, M; Viapiana, O; Adami, S

    1998-06-01

    Considerable progress in the development of methods for assessing the skeleton now makes it possible to detect osteoporosis non-invasively and early. There is a variety of techniques available at present: single-photon (SPA) and single X-ray absorptiometry (SXA), dual-photon (DPA) and dual X-ray absorptiometry (DXA), quantitative computed tomography (QCT), radiographic absorptiometry (RA), and quantitative ultrasound (QUS), and their development has certainly been driven by the need to overcome the inherent shortcomings of plain radiography for this purpose. Both SPA and SXA methods make a quantitative assessment of the bone mineral content (BMC) or density (BMD) at peripheral sites of the skeleton possible. Single energy measurements are not possible at sites with variable soft tissue thickness and composition, i.e., the axial skeleton. For these purposes, DPA and DXA techniques were introduced. The main advantages of an X-ray system over a radionuclide system are shortened examination time, greater accuracy and precision limited to higher resolution, and removal of errors due to source decay correction. Low radiation dose, availability, capacity to evaluate multiple sites, and ease of use have made DXA the most widely used technique for measuring bone mineral density. QCT can determine the true volumetric density of trabecular or cortical bone in three dimensions at any skeletal site. Recently developed new computer-assisted methods have improved RA precision, thus providing a simple and inexpensive technique for screening of bone mineral status of large populations. QUS was reported to provide information regarding the structural characteristics of bone, which may be relevant to the appearance of osteoporotic fractures; indeed, some studies suggest a relationship between QUS and bone strength beyond that which can be explained by BMD. Recent experimental studies suggested that magnetic resonance might also constitute a promising tool for assessing osteoporosis

  19. 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

  20. Managing osteoporosis in ulcerative colitis: Something new?

    PubMed Central

    Piodi, Luca Petruccio; Poloni, Alessandro; Ulivieri, Fabio Massimo

    2014-01-01

    The authors revise the latest evidence in the literature regarding managing of osteoporosis in ulcerative colitis (UC), paying particular attention to the latest tendency of the research concerning the management of bone damage in the patient affected by UC. It is wise to assess vitamin D status in ulcerative colitis patients to recognize who is predisposed to low levels of vitamin D, whose deficiency has to be treated with oral or parenteral vitamin D supplementation. An adequate dietary calcium intake or supplementation and physical activity, if possible, should be guaranteed. Osteoporotic risk factors, such as smoking and excessive alcohol intake, must be avoided. Steroid has to be prescribed at the lowest possible dosage and for the shortest possible time. Moreover, conditions favoring falling have to been minimized, like carpets, low illumination, sedatives assumption, vitamin D deficiency. It is advisable to assess the fracture risk in all UC patient by the fracture assessment risk tool (FRAX® tool), that calculates the ten years risk of fracture for the population aged from 40 to 90 years in many countries of the world. A high risk value could indicate the necessity of treatment, whereas a low risk value suggests a follow-up only. An intermediate risk supports the decision to prescribe bone mineral density (BMD) assessment and a subsequent patient revaluation for treatment. Dual energy X-ray absorptiometry bone densitometry can be used not only for BMD measurement, but also to collect data about bone quality by the means of trabecular bone score and hip structural analysis assessment. These two indices could represent a method of interesting perspectives in evaluating bone status in patients affected by diseases like UC, which may present an impairment of bone quality as well as of bone quantity. In literature there is no strong evidence for instituting pharmacological therapy of bone impairment in UC patients for clinical indications other than those that

  1. Hyponatremia Is Associated With Increased Osteoporosis and Bone Fractures in a Large US Health System Population

    PubMed Central

    Usala, Rachel L.; Fernandez, Stephen J.; Mete, Mihriye; Cowen, Laura; Shara, Nawar M.; Barsony, Julianna

    2015-01-01

    Context: The significance of studies suggesting an increased risk of bone fragility fractures with hyponatremia through mechanisms of induced bone loss and increased falls has not been demonstrated in large patient populations with different types of hyponatremia. Objective: This matched case-control study evaluated the effect of hyponatremia on osteoporosis and fragility fractures in a patient population of more than 2.9 million. Design, Setting, and Participants: Osteoporosis (n = 30 517) and fragility fracture (n = 46 256) cases from the MedStar Health database were matched on age, sex, race, and patient record length with controls without osteoporosis (n = 30 517) and without fragility fractures (n = 46 256), respectively. Cases without matched controls or serum sodium (Na+) data or with Na+ with a same-day blood glucose greater than 200 mg/dL were excluded. Main Outcome Measures: Incidence of diagnosis of osteoporosis and fragility fractures of the upper or lower extremity, pelvis, and vertebrae were the outcome measures. Results: Multivariate conditional logistic regression models demonstrated that hyponatremia was associated with osteoporosis and/or fragility fractures, including chronic [osteoporosis: odds ratio (OR) 3.97, 95% confidence interval (CI) 3.59–4.39; fracture: OR 4.61, 95% CI 4.15–5.11], recent (osteoporosis: OR 3.06, 95% CI 2.81–3.33; fracture: OR 3.05, 95% CI 2.83–3.29), and combined chronic and recent hyponatremia (osteoporosis: OR 12.09, 95% CI 9.34–15.66; fracture: OR 11.21, 95% CI 8.81–14.26). Odds of osteoporosis or fragility fracture increased incrementally with categorical decrease in median serum Na+. Conclusions: These analyses support the hypothesis that hyponatremia is a risk factor for osteoporosis and fracture. Additional studies are required to evaluate whether correction of hyponatremia will improve patient outcomes. PMID:26083821

  2. Osteoporosis treatment: a missed opportunity.

    PubMed

    Milat, Frances; Ebeling, Peter R

    2016-08-15

    Osteoporosis affects 1.2 million Australians and, in 2012, fractures due to osteoporosis and osteopenia in Australians aged over 50 years cost $2.75 billion. Even minor minimal trauma fractures are associated with increased morbidity and mortality. Despite increasing therapeutic options for managing osteoporosis, fewer than 20% of patients with a minimal trauma fracture are treated or investigated for osteoporosis, so under-treatment is extremely common. Fracture risk assessment is important for selecting patients who require specific anti-osteoporosis therapy. Post-menopausal osteoporosis is frequently due to an imbalance in bone remodelling, with bone resorption exceeding bone formation. Antiresorptive drugs reduce the number, activity and lifespan of osteoclasts, and include bisphosphonates, oestrogen, selective oestrogen receptor-modulating drugs, strontium ranelate, and the human monoclonal antibody denosumab. Teriparatide is the only anabolic agent currently available that stimulates osteoblast recruitment and activity; its antifracture efficacy for non-vertebral fractures increases with the duration of therapy for up to 2 years when it is associated with persisting increases in bone formation rate at the tissue level. Newer anabolic agents are imminent and include an analogue of parathyroid hormone-related protein, abaloparatide, and a humanised monoclonal antibody to an inhibitor of bone formation, romosozumab. Selection of anti-osteoporosis therapy should be individualised to patients, and the duration of bisphosphonate therapy has been covered in recent guidelines. The benefits of treatment far outweigh any risks associated with long term treatment. General practitioners need to take up the challenge imposed by osteoporosis and become champions of change to close the evidence-treatment gap. PMID:27510350

  3. The Role of Calcium in Osteoporosis

    NASA Technical Reports Server (NTRS)

    Arnaud, C. D.; Sanchez, S. D.

    1991-01-01

    Calcium requirements may vary throughout the lifespan. During the growth years and up to age 25 to 30, it is important to maximize dietary intake of calcium to maintain positive calcium balance and achieve peak bone mass, thereby possibly decreasing the risk of fracture when bone is subsequently lost. Calcium intake need not be greater than 800 mg/day during the relatively short period of time between the end of bone building and the onset of bone loss (30 to 40 years). Starting at age 40 to 50, both men and women lose bone slowly, but women lose bone more rapidly around the menopause and for about 10 years after. Intestinal calcium absorption and the ability to adapt to low calcium diets are impaired in many postmenopausal women and elderly persons owing to a suspected functional or absolute decrease in the ability of the kidney to produce 1,25(OH)2D2. The bones then become more and more a source of calcium to maintain critical extracellular fluid calcium levels. Excessive dietary intake of protein and fiber may induce significant negative calcium balance and thus increase dietary calcium requirements. Generally, the strongest risk factors for osteoporosis are uncontrollable (e.g., sex, age, and race) or less controllable (e.g., disease and medications). However, several factors such as diet, physical activity, cigarette smoking, and alcohol use are lifestyle related and can be modified to help reduce the risk of osteoporosis.

  4. 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

  5. Emerging Therapies for Osteoporosis.

    PubMed

    McClung, Michael R

    2015-12-01

    Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients. PMID:26354487

  6. Emerging Therapies for Osteoporosis

    PubMed Central

    2015-01-01

    Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients. PMID:26354487

  7. Social inequalities in prevalence of diagnosed and undiagnosed diabetes and impaired glucose regulation in participants in the Health Surveys for England series

    PubMed Central

    Moody, Alison; Cowley, Giovanna; Ng Fat, Linda; Mindell, Jennifer S

    2016-01-01

    Objectives To ascertain the extent of socioeconomic and health condition inequalities in people with diagnosed and undiagnosed diabetes and impaired glucose regulation (IGR) in random samples of the general population in England, as earlier diagnosis of diabetes and treatment of people with IGR can reduce adverse sequelae of diabetes. Various screening instruments were compared to identify IGR, in addition to undiagnosed diabetes. Design 5, annual cross-sectional health examination surveys; data adjusted for complex survey design. Setting Random selection of private homes across England, new sample annually 2009–2013. Participants 5, nationally representative random samples of the general, free-living population: ≥1 adult interviewed in 24 254 of 36 889 eligible addresses selected. 18 399 adults had a valid glycated haemoglobin (HbA1c) measurement and answered the diabetes questions. Main outcome measures Diagnosed diabetes, undiagnosed diabetes (HbA1c ≥48 mmol/mol), IGR (HbA1c 42–47 mmol/mol). Results Overall, 11% of the population had IGR, 2% undiagnosed and 6% diagnosed diabetes. Age-standardised prevalence was highest among Asian (19% (95% CI 16% to 23%), 3% (2% to 5%) and 12% (9% to 16%) respectively) and black participants (17% (13% to 21%), 2% (1% to 4%) and 14% (9% to 20%) respectively). These were also higher among people with lower income, less education, lower occupational class and greater deprivation. Education (OR 1.49 (95% CI 1.27 to 1.74) for no qualifications vs degree or higher) and income (1.35 (1.12 to 1.62) for lowest vs highest income quintile) remained significantly associated with IGR or undiagnosed diabetes on multivariate regression. The greatest odds of IGR or undiagnosed diabetes were with increasing age over 34 years (eg, OR 18.69 (11.53 to 30.28) aged 65–74 vs 16–24). Other significant associations were ethnic group (Asian (3.91 (3.02 to 5.05)), African-American (2.34 (1.62 to 3.38)) or ‘other’ (2.04 (1

  8. Elevated glucose levels impair the WNT/β-catenin pathway via the activation of the hexosamine biosynthesis pathway in endometrial cancer.

    PubMed

    Zhou, Fuxing; Huo, Junwei; Liu, Yu; Liu, Haixia; Liu, Gaowei; Chen, Ying; Chen, Biliang

    2016-05-01

    Endometrial cancer (EC) is one of the most common gynecological malignancies in the world. Associations between fasting glucose levels (greater than 5.6mmol/L) and the risk of cancer fatality have been reported. However, the underlying link between glucose metabolic disease and EC remains unclear. In the present study, we explored the influence of elevated glucose levels on the WNT/β-catenin pathway in EC. Previous studies have suggested that elevated concentrations of glucose can drive the hexosamine biosynthesis pathway (HBP) flux, thereby enhancing the O-GlcNAc modification of proteins. Here, we cultured EC cell lines, AN3CA and HEC-1-B, with various concentrations of glucose. Results showed that when treated with high levels of glucose, both lines showed increased expression of β-catenin and O-GlcNAcylation levels; however, these effects could be abolished by the HBP inhibitors, Azaserine and 6-Diazo-5-oxo-l-norleucine, and be restored by glucosamine. Moreover the AN3CA and HEC-1-B cells that were cultured with or without PUGNAc, an inhibitor of the O-GlcNAcase, showed that PUGNAc increased β-catenin levels. The results suggest that elevated glucose levels increase β-catenin expression via the activation of the HBP in EC cells. Subcellular fractionation experiments showed that AN3CA cells had a higher expression of intranuclear β-catenin in high glucose medium. Furthermore, TOP/FOP-Flash and RT-PCR results showed that glucose-induced increased expression of β-catenin triggered the transcription of target genes. In conclusion, elevated glucose levels, via HBP, increase the O-GlcNAcylation level, thereby inducing the over expression of β-catenin and subsequent transcription of the target genes in EC cells. PMID:26923859

  9. Managing Osteoporosis: A Survey of Knowledge, Attitudes and Practices among Primary Care Physicians in Israel

    PubMed Central

    Segal, Elena; Ish-Shalom, Sofia

    2016-01-01

    Background Osteoporosis is a systemic skeletal disorder characterized by impaired bone quality and microstructural deterioration leading to an increased propensity to fractures. This is a major health problem for older adults, which comprise an increasingly greater proportion of the general population. Due to a large number of patients and the insufficient availability of specialists in Israel and worldwide, osteoporosis is treated in large part by primary care physicians. We assessed the knowledge of primary care physicians on the diagnosis and treatment of osteoporosis. Methods Physician's knowledge, sources of knowledge acquisition and self-evaluation of knowledge were assessed using a multiple choice questionnaire. Professional and demographic characteristics were assessed as well. Results Of 490 physicians attending a conference, 363 filled the questionnaires (74% response rate). The physicians demonstrated better expertise in diagnosis than in medications (mechanism of action, side effects or contra-indications) but less than for other treatment related decisions. Overall, 50% demonstrated adequate knowledge of calcium and vitamin D supplementation, 51% were aware of the main therapeutic purpose of osteoporosis pharmacotherapy and 3% were aware that bisphosphonates should be avoided in patients with impaired renal function. Respondents stated frontal lectures at meetings as their main source of information on the subject. Conclusion The study indicates the need to intensify efforts to improve the knowledge of primary care physicians regarding osteoporosis, in general; and osteoporosis pharmacotherapy, in particular. PMID:27494284

  10. Osteoporosis: Cloris Leachman Leads by Example

    MedlinePlus

    ... please turn Javascript on. Feature: Osteoporosis Cloris Leachman Leads By Example Past Issues / Winter 2011 Table of ... age discrimination! Read More "Osteoporosis" Articles Cloris Leachman Leads By Example / Preventing and Treating Brittle Bones and ...

  11. Diagnosis and management of osteoporosis.

    PubMed

    Ralston, Stuart H; Fraser, Jamie

    2015-12-01

    Osteoporosis is a common condition characterised by low bone mineral density (BMD) and an increased risk of fragility fractures. It affects up to 30% of women and 12% of men at some point in their lives. Two of the most important risk factors are increasing age and female gender, although other common and potentially modifiable risk factors include long-term corticosteroid therapy, chronic inflammatory disease, malabsorption and untreated premature menopause. The diagnosis of osteoporosis can be confirmed by DEXA but this should only be performed in patients who have an increased risk of fracture on the basis of clinical risk factors. DEXA should be considered if the 10-year risk of major osteoporotic fracture is > 10%. If the BMD T-score values by DEXA at the lumbar spine, femoral neck or total hip are at or below -2.5 then the diagnosis of osteoporosis is confirmed. Vertebral fractures are generally taken as diagnostic of osteoporosis, even if spine BMD values are not in the osteoporotic range. Oral bisphosphonates are the first-line treatment. If they are contraindicated or not tolerated then parenteral therapy should be considered. There is evidence that fractures occur in glucocorticoid-induced osteoporosis at higher levels of BMD than in postmenopausal osteoporosis so therapy should be considered in patients with a BMD T-score of <-1.5. Although it is useful to have a DEXA scan before starting treatment to provide a baseline value to assess response, this investigation is not absolutely necessary to initiate bone protective therapy, especially in those aged above 65 since the vast majority of these patients will have a T-score of -1.5 or below. In younger individuals where BMD is likely to be higher DEXA is useful in determining if bone protective treatment is needed immediately or if it could be delayed until the T score falls below -1.5. PMID:26882774

  12. Osteoporosis in liver disease: pathogenesis and management

    PubMed Central

    Handzlik-Orlik, Gabriela; Holecki, Michał; Wilczyński, Krzysztof; Duława, Jan

    2016-01-01

    Osteoporosis affects a substantial proportion of patients with chronic liver disease. Pathologic fracture in osteoporosis significantly affects quality of life and life expectancy. By some estimates, 40% of patients with chronic liver disease may experience osteoporotic fracture. In this study we review the pathogenesis, diagnosis and treatment of specific liver disease entities and their relation to osteoporosis. PMID:27293541

  13. Older Men's Explanatory Model for Osteoporosis

    ERIC Educational Resources Information Center

    Solimeo, Samantha L.; Weber, Thomas J.; Gold, Deborah T.

    2011-01-01

    Purpose: To explore the nature of men's experiences of osteoporosis by developing an understanding of men's explanatory models. Design and Methods: This descriptive study invited community-residing male osteoporosis patients aged 50+ to participate in interviews about osteoporosis. Participants were recruited from a hospital-affiliated bone…

  14. Evaluation and Treatment of Osteoporosis.

    PubMed

    O'Connor, Kim M

    2016-07-01

    As the population ages, the rates of osteoporotic fractures will increase, with postmenopausal women incurring most of these fractures. Diagnosis and treatment of osteoporosis are extremely important. Dual-energy x-ray absorptiometry scan screening is recommended in all women more than 65 years of age or in women aged 50 to 64 years with certain risk factors. Treatment should be considered if osteoporosis is present, there is a history of fragility fracture, or in the setting of osteopenia plus high risk for fracture. PMID:27235616

  15. New horizons in osteoporosis therapies.

    PubMed

    Harsløf, Torben; Langdahl, Bente L

    2016-06-01

    Efficient therapies are available for the treatment of osteoporosis, however, there are still unmet needs. Anti-resorptive therapies only increase bone mineral density to a certain extent and reduce the risk of non-vertebral fractures by 20%, only one anabolic option is available-the effect of which levels off over time, and the evidence for combination therapy targeting both resorption and formation is limited. The current review will focus on emerging treatments of osteoporosis with the potential of enhanced anabolic effects (romosozumab and abaloparatide) or uncoupling of resorption and formation (odanacatib and romosozumab) as well as the effect of combination therapy. PMID:26989807

  16. 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

  17. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

    SciTech Connect

    Alquier, Thierry; Peyot, Marie-Line; Latour, M. G.; Kebede, Melkam; Sorensen, Christina M.; Gesta, Stephane; Kahn, C. R.; Smith, Richard D.; Jetton, Thomas L.; Metz, Thomas O.; Prentki, Marc; Poitout, Vincent J.

    2009-11-01

    The G protein-coupled receptor GPR40 mediates fatty-acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. We observed that glucose- and arginine-stimulated insulin secretion, assessed by hyperglycemic clamps, was decreased by approximately 60% in GPR40 knock-out (KO) fasted and fed mice, without changes in insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps. Glucose and palmitate metabolism were not affected by GPR40 deletion. Lipid profiling revealed a similar increase in triglyceride and decrease in lysophosphatidylethanolamine species in WT and KO islets in response to palmitate. These results demonstrate that GPR40 regulates insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism.

  18. Psychological stress impairs Na+-dependent glucose absorption and increases GLUT2 expression in the rat jejunal brush-border membrane.

    PubMed

    Boudry, Gaëlle; Cheeseman, Christopher I; Perdue, Mary H

    2007-02-01

    Chronic psychological stress impacts many functions of the gastrointestinal tract. However, the effect of stress on nutrient absorption is poorly documented. This study was designed to investigate glucose transporters in rats submitted to different periods of water-avoidance stress (WAS). Rats were subjected to WAS (1 h/day) for 1, 5, or 10 consecutive days. Four hours after the last WAS session, rats were killed and segments of jejunum were mounted in Ussing chambers to study electrophysiological properties of the jejunum and Na+-dependent glucose absorption kinetics. Mucosa was obtained to prepare brush-border membrane vesicles (BBMV) used to measure [14C]fructose uptake as well as sodium-glucose transporter 1 (SGLT-1) and GLUT2 expression by Western blot analysis. Exposure of animals to WAS induced a decrease in Na+-dependent glucose absorption Vmax after 1, 5, and 10 days without any change in SGLT-1 expression. Potential difference across the jejunum was decreased for all stressed groups. Furthermore, we observed an increase in phloretin-sensitive uptake of [14C]fructose by BBMV after 1, 5, or 10 days of WAS, which was not present in control animals. This suggested the abnormal appearance of GLUT2 in the brush border, which was confirmed by Western blot analysis. We concluded that psychological stress induces major changes in glucose transport with a decrease in Na+-dependent glucose absorption and an increase in GLUT2 expression at the brush-border membrane level. PMID:17053095

  19. Postmenopausal bone loss and the risk of osteoporosis.

    PubMed

    Christiansen, C

    1994-01-01

    The two most important risk factors for long-term skeletal health are the peak bone mass and the subsequent rate of bone loss. The rate of bone loss after skeletal maturity is determined by both genetic factors and environmental factors. Furthermore, all factors that impair estrogen production will increase bone loss. The present risk of developing osteoporosis and fractures may be assessed by bone mass measurements in the total skeleton, or in local parts of the skeleton such as the spine, hip and forearm, by single-photon/X-ray absorptiometry (SPA or SXA), dual-photon/energy X-ray absorptiometry (DPA or DXA), or quantitative computed tomography (QCT). Furthermore, the rate of bone loss in postmenopausal women may be assessed by means of a number of biochemical markers. The fútúre risk of developing osteoporosis may thus be determined by combining the values for bone mineral content and bone loss. PMID:8081059

  20. Osteoporosis in lysinuric protein intolerance.

    PubMed

    Parto, K; Penttinen, R; Paronen, I; Pelliniemi, L; Simell, O

    1993-01-01

    Lysinuric protein intolerance (LPI) is an autosomal recessive disease characterized by defective transport of cationic amino acids. Patients have an increased incidence of fractures and their skeletal radiographs show osteoporosis. The aim of the study was to characterize the osteopenia in LPI. Twenty-nine Finnish LPI patients (age range 3.7-44.4 years) were screened for parameters of bone metabolism. Morphometric analysis of bone was carried out in specimens of 9 patients. Collagen synthesis was studied with cultured skin fibroblasts (4 patients) and collagen fibril sizes (3 patients) were measured using electron microscopy. Most histological bone specimens (8/9) showed osteoporosis. Osteomalacia was excluded. Routine clinical laboratory tests were unrevealing. The concentrations of free hydroxyproline and type III procollagen N-propeptide in serum and the urinary excretion of hydroxyproline were increased in almost all patients during their growth and in about half of adult patients. Collagen synthesis in LPI fibroblast cultures was significantly decreased compared with that in age-matched controls at 5 (p < 0.01), 14 (p < 0.01) and still at 30 years (p < 0.01), whereas no difference was observed at the age of 44 years (p = N.S.). Osteoporosis in LPI might reflect defective matrix protein synthesis caused by protein deprivation and deficiency of cationic amino acids. Increased collagen turnover can also contribute to the osteoporosis. PMID:8412005

  1. [Osteoporosis secondary to various disorders].

    PubMed

    Yamaguchi, Toru

    2012-06-01

    Secondary osteoporosis is caused by various disorders, metabolic derangements, and drug administration. Among causative disorders, primary hyperparathyroidism, rheumatoid arthritis, type 2 diabetes mellitus, and chronic kidney disease are prevalent ones. Fractures in type 2 diabetes and chronic kidney disease tend to result from the reduction in bone quality rather than that in bone mass. PMID:22653018

  2. Research Advances: Onions Battle Osteoporosis

    ERIC Educational Resources Information Center

    King, Angela G.

    2005-01-01

    Researchers at the University of Bern in Switzerland have identified a compound in the popular vegetable that appears to decrease bone loss in laboratory studies using rat bone cells. It is suggested that eating onions might help prevent bone loss and osteoporosis, a disease, which predominantly affects older women.

  3. Osteoporosis across chronic liver disease.

    PubMed

    Guarino, M; Loperto, I; Camera, S; Cossiga, V; Di Somma, C; Colao, A; Caporaso, N; Morisco, F

    2016-06-01

    Osteoporosis is a complication of chronic liver disease, with impact on morbidity, quality of life, and survival. The progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with liver disease. So, it is fundamental to make better the quality of life and to prevent complications. Metabolic bone disorders are common complications of chronic liver disease (CLD). Patients with CLD have an increased risk of bone fractures, with significant impact on morbidity, quality of life, and even on survival. Bone diseases, including osteomalacia, osteoporosis, and osteopenia, are frequently observed in many types of liver disease. The pathogenesis of damage and the mechanisms of bone loss are different in relation to the specific liver disease. The relevance of these conditions induced many authors to create a new nosographic entity known as "hepatic osteodystrophy", although this term is rarely used anymore and it is now commonly referred to as osteopenia or osteoporosis associated with chronic liver disease. This review is based on the personal experiences of the authors and upon research done of the available literature on this subject matter. The authors searched the PubMed database for publications containing the term "liver disease" in combination with "bone disease", "hepatic osteodistrophy", "osteoporosis", "osteopenia", "osteomalacia", and "fractures". They selected publications from the past 10 years but did not exclude older seminal publications, especially for colestatic liver diseases. This review of literature shows that osteoporosis crosses all CLD. It is important to underline that the progress of medicine and the new therapies stretched the disease's natural history and improved the survival of patients with CLD. It is fundamental to make better the quality of life and it is mandatory to prevent complications and in particular the osteoporotic ones, especially fractures. PMID:26846777

  4. Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the {beta}-cell line INS-1E

    SciTech Connect

    Piaggi, Simona; Novelli, Michela; Martino, Luisa; Masini, Matilde; Raggi, Chiara; Orciuolo, Enrico; Masiello, Pellegrino; Casini, Alessandro; De Tata, Vincenzo . E-mail: v.detata@ipg.med.unipi.it

    2007-05-01

    The aim of this research was to characterize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxicity on the insulin-secreting {beta}-cell line INS-1E. A sharp decline of cell survival (below 20%) was observed after 1 h exposure to TCDD concentrations between 12.5 and 25 nM. Ultrastructurally, {beta}-cell death was characterized by extensive degranulation, appearance of autophagic vacuoles, and peripheral nuclear condensation. Cytotoxic concentrations of TCDD rapidly induced a dose-dependent increase in intracellular calcium concentration. Blocking calcium entry by EGTA significantly decreased TCDD cytotoxicity. TCDD was also able to rapidly induce mitochondrial depolarization. Interestingly, 1 h exposition of INS-1E cells to very low TCDD concentrations (0.05-1 nM) dramatically impaired glucose-stimulated but not KCl-stimulated insulin secretion. In conclusion, our results clearly show that TCDD exerts a direct {beta}-cell cytotoxic effect at concentrations of 15-25 nM, but also markedly impairs glucose-stimulated insulin secretion at concentrations 20 times lower than these. On the basis of this latter observation we suggest that pancreatic {beta}-cells could be considered a specific and sensitive target for dioxin toxicity.

  5. Changes in Plasma Levels of N-Arachidonoyl Ethanolamine and N-Palmitoylethanolamine following Bariatric Surgery in Morbidly Obese Females with Impaired Glucose Homeostasis

    PubMed Central

    Mallipedhi, Akhila; Prior, Sarah L.; Dunseath, Gareth; Bracken, Richard M.; Barry, Jonathan; Caplin, Scott; Eyre, Nia; Morgan, James; Baxter, John N.; O'Sullivan, Saoirse E.; Sarmad, Sarir; Barrett, David A.; Bain, Stephen C.; Luzio, Steve D.

    2015-01-01

    Aim. We examined endocannabinoids (ECs) in relation to bariatric surgery and the association between plasma ECs and markers of insulin resistance. Methods. A study of 20 participants undergoing bariatric surgery. Fasting and 2-hour plasma glucose, lipids, insulin, and C-peptide were recorded preoperatively and 6 months postoperatively with plasma ECs (AEA, 2-AG) and endocannabinoid-related lipids (PEA, OEA). Results. Gender-specific analysis showed differences in AEA, OEA, and PEA preoperatively with reductions in AEA and PEA in females postoperatively. Preoperatively, AEA was correlated with 2-hour glucose (r = 0.55, P = 0.01), HOMA-IR (r = 0.61, P = 0.009), and HOMA %S (r = −0.71, P = 0.002). OEA was correlated with weight (r = 0.49, P = 0.03), waist circumference (r = 0.52, P = 0.02), fasting insulin (r = 0.49, P = 0.04), and HOMA-IR (r = 0.48, P = 0.05). PEA was correlated with fasting insulin (r = 0.49, P = 0.04). 2-AG had a negative correlation with fasting glucose (r = −0.59, P = 0.04). Conclusion. Gender differences exist in circulating ECs in obese subjects. Females show changes in AEA and PEA after bariatric surgery. Specific correlations exist between different ECs and markers of obesity and insulin and glucose homeostasis. PMID:25874237

  6. Environmental risk factors for osteoporosis

    SciTech Connect

    Goyer, R.A.; Korach, K.S. ); Epstein, S. ); Bhattacharyya, M. ); Pounds, J. )

    1994-04-01

    Environmental risk factors for osteoporosis were reviewed at a conference held at the National Institute for Environmental Health Sciences 8-9 November 1993. The conference was co-sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Disease and the NIH Office of Research in Women's Health. The objective of the conference was to review what is known about risk factors for osteoporosis and to identify gaps in the present state of knowledge that might be addressed by future research. The conference was divided into two broad themes. The first session focused on current knowledge regarding etiology, risk factors, and approaches to clinical and laboratory diagnosis. This was followed by three sessions in which various environmental pollutants were discussed. Topics selected for review included environmental agents that interfere with bone and calcium metabolism, such as the toxic metals lead, cadmium, aluminum, and fluoride, natural and antiestrogens, calcium, and vitamin D.

  7. [Epidemiology of Osteoporosis in Men].

    PubMed

    Fujiwara, Saeko

    2016-07-01

    Estimated number of those with osteoporosis was about 12,800,000, and about 23%, 3,000,000 were male osteoporosis in Japan. Incidence of hip, vertebral, distal radius, and proximal humeral fracture in men was half of that in women. Lifetime risk of hip fracture was 5.6% in men. Risk factors for osteoporotic fracture in men were low bone mineral density(BMD), previous fracture, low body mass index, smoking, family history of fracture, glucocorticoid use and others. For osteoporotic fractures, the fracture risk in smokers was significantly higher in men than in women. There was no differences in fracture risks by BMD, previous fracture, glucocorticoid use, and family fracture history between men and women. PMID:27346311

  8. Hyperinsulinemia and metabolic syndrome at mean age of 10 years in black and white schoolgirls and development of impaired fasting glucose and type 2 diabetes mellitus by mean age of 24 years.

    PubMed

    Morrison, John A; Glueck, Charles J; Umar, Muhammad; Daniels, Stephen; Dolan, Lawrence M; Wang, Ping

    2011-01-01

    The objective of the study was to evaluate preteen insulin and metabolic syndrome (MS) as independent predictors of impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) in black and white females by mean age of 24 years. This was a prospective cohort study. There were 8 measures of fasting glucose and insulin from mean age of 10 years through mean age of 24 years, and insulin also at mean age of 25 years. Childhood MS was defined by at least 3 abnormal values among waist circumference, triglyceride, high-density lipoprotein cholesterol, blood pressure, and glucose. Hyperinsulinemia was defined by insulin greater than or equal to race-specific 75th percentile. Patients with type 1 diabetes mellitus were excluded. The study was held in schools and in an outpatient clinical center. Participants were schoolgirls (260 white, 296 black). There was no intervention. The outcome measures were IFG (fasting glucose of at least 100 to 125 mg/dL) and T2DM (fasting glucose of at least 126 mg/dL). By the age of 24 years, there were 11 cases of T2DM (2%) and 108 cases of IFG (19%). By the age of 24 years, IFG + T2DM was present in 18% of women (73/412) who had normal insulin-no MS at the age of 10 years vs 28% (34/122) of those with high insulin-no MS at the age of 10 years (P = .014) and 67% (10/15) of those with high insulin + MS at the age of 10 years (P < .0001). By stepwise logistic regression, significant, independent, positive predictors of IFG + T2DM were first insulin measure in childhood, age at last sampling, childhood MS, change in body mass index over 15 years, and, separately, initial glucose of at least 100 mg/dL and average of all insulin quartile ranks over 15 years. The correlation between childhood insulin z score and insulin z score 15 years later was r = .30, P < .0001. Insulin and MS at a mean age of 10 years plus change in body mass index over 15 years, and 15-year average insulin rank independently predict IFG + T2DM by mean age of 24 years

  9. The natural approach to osteoporosis.

    PubMed

    Bartolozzi, Emanuela

    2015-01-01

    Osteoporosis is normally the result of a wrong life-style (diet, physical inactivity, smoke, dental hygiene, intestinal dysbiosis,…) and environmental toxicity which stimulate the chronic expression of inflammatory genes and alter the immuno-endocrine balance. A natural approch should face all the factors involved, leading the patients to become aware of their own responsability, and helping them with natural therapies, healthy food and life-style which support their body in the process of self-healing. PMID:26604935

  10. Safety of drugs used in the treatment of osteoporosis.

    PubMed

    McGreevy, Cora; Williams, David

    2011-08-01

    A number of drug classes are licensed for the treatment of osteoporosis including bisphosphonates, recombinant human parathyroid hormone (PTH), strontium, hormone replacement therapy (HRT), selective oestrogen receptor modulators (SERMS) and denosumab. This review discusses the safety of osteoporosis treatments and their efficacies. Recent concerns about the safety of calcium and high-dose vitamin D are discussed. Bisphosphonates have substantial postmarketing experience and a clearer picture of safety issues is emerging. Along with the well recognized effects on the gastrointestinal tract and kidney function, recently described adverse effects such as osteonecrosis of the jaw, oesophageal cancer, atrial fibrillation, subtrochanteric femur fractures and ocular complications of bisphosphonate therapy are discussed. Therapy with PTH is limited to two years' duration because of the development of osteogenic sarcomas in animal studies, which appeared related to dose, duration and timing of therapy. Strontium should be used with caution in patients with renal impairment and its use has been associated with venous thromboembolism. The role of HRT and SERMs in the treatment of postmenopausal osteoporosis is restricted as a result of an increased risk of stroke, venous thromboembolism and breast cancer. Postmarketing experience with denusomab is limited but a number of potential safety concerns including osteonecrosis of the jaw are emerging. All of these drugs have been proven to reduce fractures. The decision to use a drug to reduce fracture risk should be based on risk-benefit analysis of the drug and its suitability for individual patients. PMID:25083210

  11. [Nutritional factors in preventing osteoporosis].

    PubMed

    Martín Jiménez, Juan Antonio; Consuegra Moya, Belkis; Martín Jiménez, María Teresa

    2015-01-01

    Osteoporosis, main risk factor for suffering fragility fractures, is an important public health problem which has undoubted social, health and economic impact; but mainly causes pain, functional limitation and severe alterations in the patient's quality of life. Its current prevalence is very high and a further increase is expected due to a higher life expectancy and the progressive ageing of the population. In the prevention of osteoporosis, the main goal is to prevent fragility fractures; for this reason, it is necessary to: 1) promote bone formation in youth, to get sufficient bone mass peak, 2) reduce bone loss in adulthood, especially after menopause, 3) maintain bone health throughout life, and 4) prevent falls. There is enough evidence that multifactorial strategies (assessment of risk factors, healthy lifestyle habits, smoking cessation, moderation in alcohol consumption, physical exercise, outdoor activity with prudent exposure to sunlight, and a varied and balanced diet), are effective in the population at risk. Regarding factors for the prevention of osteoporosis, current recommendations are: increased consumption of calcium, phosphorus, magnesium and fluoride; provide adequate vitamin D (even with fortified food if necessary); consumption of foods rich in omega-3 acids; reduction of salt and prepared ready meals; sufficient but moderate intake of protein and, in the absence of intolerance, promote the consumption of milk and dairy products, especially yogurt and fermented milk products. PMID:26267775

  12. Prevention and treatment of osteoporosis in women.

    PubMed

    Al-Azzawi, Farook; Barlow, David; Hillard, Tim; Studd, John; Williamson, Jenny; Rees, Margaret

    2007-12-01

    Osteoporosis affects one in three women. There has been some confusion among women and health professionals about the management of osteoporosis since the publication of the Women's Health Initiative and Million Women studies. This guidance regarding estrogen-based and non-estrogen-based treatments for osteoporosis responds to the controversies about the benefits and risks of individual agents. Treatment choice should be based on up-to-date evidence and targeted to individual women's needs. PMID:18088530

  13. The management of osteoporosis in children.

    PubMed

    Ward, L M; Konji, V N; Ma, J

    2016-07-01

    This article reviews the manifestations and risk factors associated with osteoporosis in childhood, the definition of osteoporosis and recommendations for monitoring and prevention. As well, this article discusses when a child should be considered a candidate for osteoporosis therapy, which agents should be prescribed, duration of therapy and side effects. There has been significant progress in our understanding of risk factors and the natural history of osteoporosis in children over the past number of years. This knowledge has fostered the development of logical approaches to the diagnosis, monitoring, and optimal timing of osteoporosis intervention in this setting. Current management strategies are predicated upon monitoring at-risk children to identify and then treat earlier rather than later signs of osteoporosis in those with limited potential for spontaneous recovery. On the other hand, trials addressing the prevention of the first-ever fracture are still needed for children who have both a high likelihood of developing fractures and less potential for recovery. This review focuses on the evidence that shapes the current approach to diagnosis, monitoring, and treatment of osteoporosis in childhood, with emphasis on the key pediatric-specific biological principles that are pivotal to the overall approach and on the main questions with which clinicians struggle on a daily basis. The scope of this article is to review the manifestations of and risk factors for primary and secondary osteoporosis in children, to discuss the definition of pediatric osteoporosis, and to summarize recommendations for monitoring and prevention of bone fragility. As well, this article reviews when a child is a candidate for osteoporosis therapy, which agents and doses should be prescribed, the duration of therapy, how the response to therapy is adjudicated, and the short- and long-term side effects. With this information, the bone health clinician will be poised to diagnose

  14. Health Beliefs about Osteoporosis and Osteoporosis Screening in Older Women and Men

    ERIC Educational Resources Information Center

    Nayak, Smita; Roberts, Mark S.; Chang, Chung-Chou H.; Greenspan, Susan L.

    2010-01-01

    Objective: To examine older adults' beliefs about osteoporosis and osteoporosis screening to identify barriers to screening. Design: Cross-sectional mailed survey. Setting: Western Pennsylvania. Methods: Surveys were mailed to 1,830 women and men aged 60 years and older. The survey assessed socio-demographic characteristics, osteoporosis and…

  15. 73 FR 56477 - Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2008-09-29

    ...The Food and Drug Administration (FDA) is amending its labeling regulation authorizing a health claim on the relationship between calcium and a reduced risk of osteoporosis to include vitamin D so that, in addition to the claim for calcium and osteoporosis, an additional claim can be made for calcium and vitamin D and osteoporosis; eliminate the requirement that the claim list sex, race, and......

  16. 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

  17. Laboratory testing for secondary osteoporosis evaluation.

    PubMed

    Adler, Robert A

    2012-08-01

    Osteoporosis has been classified into primary and secondary forms. All patients with osteoporosis should have measurements of 25-hydroxyvitamin D, serum and urine calcium, and some estimation of renal function. There are a wide variety of disorders that lead to secondary osteoporosis, and the tests that confirm these diagnoses are described herein. Making the specific diagnosis is important because treatment of the underlying condition may be sufficient to lessen fracture risk, although some patients may also need usual treatment for osteoporosis. Laboratory testing in addition to a careful history and physical examination will often lead to diagnoses of treatable conditions. PMID:22333732

  18. [An update on glucocorticoid-induced osteoporosis].

    PubMed

    Krasselt, Marco; Baerwald, Christoph

    2016-03-01

    Glucocorticoid-induced osteoporosis is the most common cause of secondary osteoporosis. Moreover, it is the most common reason for an osteoporosis among young adults. The clinical use of oral glucocorticoids increases the fracture incidence already within three months after starting the therapy. There does not seem to be a lower threshold: even doses as low as 2,5 mg of prednisone equivalent increase the risk of fractures. Adequate diagnostic and therapy are able to significantly reduce the resulting fracture risk. This article will discuss the pathophysiology of glucocorticoid-induced osteoporosis and give a summary of the current recommendations including the recently updated German guidelines. PMID:26939107

  19. What Prostate Cancer Survivors Need to Know about Osteoporosis

    MedlinePlus

    ... information on osteoporosis, visit: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... Pub. No. 16-7905 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  20. What People with Lupus Need to Know about Osteoporosis

    MedlinePlus

    ... information on osteoporosis, contact: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... No. 16-7902-E NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  1. What Breast Cancer Survivors Need to Know about Osteoporosis

    MedlinePlus

    ... browser. Home Osteoporosis Osteoporosis and Other Conditions What Breast Cancer Survivors Need to Know About Osteoporosis Publication available ... Print-Friendly Page April 2016 The Impact of Breast Cancer Other than skin cancer, breast cancer is the ...

  2. What People with Anorexia Nervosa Need to Know about Osteoporosis

    MedlinePlus

    ... Osteoporosis Osteoporosis and Other Conditions What People With Anorexia Nervosa Need to Know About Osteoporosis Publication available ... focus(); */ } //--> Print-Friendly Page April 2016 What Is Anorexia Nervosa? Anorexia nervosa is an eating disorder characterized ...

  3. What People with Rheumatoid Arthritis Need to Know about Osteoporosis

    MedlinePlus

    ... increased risk for osteoporosis, are two to three times more likely than men to have rheumatoid arthritis as well. Osteoporosis Management Strategies Strategies for preventing and treating osteoporosis in ...

  4. What People with Asthma Need to Know about Osteoporosis

    MedlinePlus

    ... Osteoporosis Osteoporosis and Other Conditions What People With Asthma Need to Know About Osteoporosis Publication available in: ... focus(); */ } //--> Print-Friendly Page April 2016 What Is Asthma? According to the National Heart, Lung, and Blood ...

  5. What People with Diabetes Need to Know about Osteoporosis

    MedlinePlus

    ... Osteoporosis Osteoporosis and Other Conditions What People With Diabetes Need to Know About Osteoporosis Publication available in: ... focus(); */ } //--> Print-Friendly Page April 2016 What Is Diabetes? Diabetes is a disorder of metabolism, a term ...

  6. [Locomotive syndrome and frailty. Osteoporosis as an underlying disorder in the locomotive syndrome].

    PubMed

    Hagino, Hiroshi

    2012-04-01

    Osteoporosis, a disorder related to locomotive syndrome, has been nicknamed "the silent disease" since it has no symptoms until fragility fracture occurs. However, a new fragility fracture cannot only reduce daily activity but can also increase fracture risk resulting in possible repetition of the fracture or other new fractures. As a result, daily living activities requiring mobility are often rapidly reduced and the quality of life can be considerably impaired. There are three strategies for preventing fragility fractures : prevention of falls, anti-osteoporosis treatment and hip protectors. A multidisciplinary approach including these strategies should be emphasized to impede the damaging process involved in fragility fracture. PMID:22460510

  7. Randomized, double-blind, placebo-controlled, clinical study on the effect of Diabetinol® on glycemic control of subjects with impaired fasting glucose

    PubMed Central

    Evans, Malkanthi; Judy, William V; Wilson, Dale; Rumberger, John A; Guthrie, Najla

    2015-01-01

    Background This study investigated the efficacy of Diabetinol® in people with diabetes on medication but not meeting the American Association of Clinical Endocrinologists and American Diabetes Association glycemic, blood pressure, and lipid targets. Subjects and methods Fifty subjects, aged 18–75 years, with fasting blood glucose ≤15.4 mmol/L, hemoglobin A1c levels ≤12%, and a body mass index between 25 and 40 kg/m2, were enrolled in a 24-week, randomized, double-blind, placebo-controlled, parallel study. Diabetinol® or placebo was administered as 2×525 mg capsules/day. Results In the Diabetinol® group, 14.3% versus 0% in the placebo group, 33.3% versus 15.4% in placebo, 20.0% versus 12.5% in placebo, and 83.3% versus 60% in placebo achieved the American Association of Clinical Endocrinologists and American Diabetes Association targets for hemoglobin A1c, low-density lipoprotein, total cholesterol, and systolic blood pressure, respectively. There was no difference in the maximum concentration (Cmax) of serum glucose or area under the curve (AUC)0–240 minutes. The time to Cmax was longer for participants on Diabetinol® than placebo group at week 12 (P=0.01). Fasting blood glucose increased from baseline to week 24 in both groups; however, this increase was 14.3 mg/dL lower in the Diabetinol® group versus placebo. The Diabetinol® group showed an increase of 5.53 mg/dL in fasting insulin at week 12 (P=0.09) and 3.2 mg/dL at week 24 (P=0.41) over and above the placebo group. A decrease of 1.5% in total cholesterol, 5.8% in low-density lipoprotein, and a 1.6% increase in high-density lipoprotein concentrations were seen in the Diabetinol® group. Diabetinol® improved 6-month oral glucose tolerance test and 2-hour postprandial glucose profiles in participants between 40 and 60 years of age. Conclusion The current study suggests a role for Diabetinol® as an adjunctive therapy for glycemic maintenance and for decreasing the risk of diabetes

  8. Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism

    NASA Astrophysics Data System (ADS)

    Lam, Tony K. T.; Gutierrez-Juarez, Roger; Pocai, Alessandro; Rossetti, Luciano

    2005-08-01

    The brain keenly depends on glucose for energy, and mammalians have redundant systems to control glucose production. An increase in circulating glucose inhibits glucose production in the liver, but this negative feedback is impaired in type 2 diabetes. Here we report that a primary increase in hypothalamic glucose levels lowers blood glucose through inhibition of glucose production in rats. The effect of glucose requires its conversion to lactate followed by stimulation of pyruvate metabolism, which leads to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Thus, interventions designed to enhance the hypothalamic sensing of glucose may improve glucose homeostasis in diabetes.

  9. Fish oil supplemented for 9 months does not improve glycaemic control or insulin sensitivity in subjects with impaired glucose regulation: a parallel randomised controlled trial.

    PubMed

    Clark, Louise F; Thivierge, M C; Kidd, Claire A; McGeoch, Susan C; Abraham, Prakash; Pearson, Donald W M; Horgan, Graham W; Holtrop, Grietje; Thies, Frank; Lobley, Gerald E

    2016-01-14

    The effects of fish oil (FO) supplementation on glycaemic control are unclear, and positive effects may occur only when the phospholipid content of tissue membranes exceeds 14% as n-3 PUFA. Subjects (n 36, thirty-three completed) were paired based on metabolic parameters and allocated into a parallel double-blind randomised trial with one of each pair offered daily either 6 g of FO (3·9 g n-3 PUFA) or 6 g of maize oil (MO) for 9 months. Hyperinsulinaemic-euglycaemic-euaminoacidaemic (HIEGEAA) clamps (with [6,6 2H2 glucose]) were performed at the start and end of the intervention. Endogenous glucose production (EGP) and whole-body protein turnover (WBPT) were each measured after an overnight fast. The primary outcome involved the effect of oil type on insulin sensitivity related to glycaemic control. The secondary outcome involved the effect of oil type on WBPT. Subjects on FO (n 16) had increased erythrocyte n-3 PUFA concentrations >14%, whereas subjects on MO (n 17) had unaltered n-3 PUFA concentrations at 9%. Type of oil had no effect on fasting EGP, insulin sensitivity or total glucose disposal during the HIEGEAA clamp. In contrast, under insulin-stimulated conditions, total protein disposal (P=0·007) and endogenous WBPT (P=0·001) were both increased with FO. In an associated pilot study (n 4, three completed), although n-3 PUFA in erythrocyte membranes increased to >14% with the FO supplement, the enrichment in muscle membranes remained lower (8%; P<0·001). In conclusion, long-term supplementation with FO, at amounts near the safety limits set by regulatory authorities in Europe and the USA, did not alter glycaemic control but did have an impact on WBPT. PMID:26537735

  10. Leucine supplementation does not affect protein turnover and impairs the beneficial effects of endurance training on glucose homeostasis in healthy mice.

    PubMed

    Costa Júnior, José M; Rosa, Morgana R; Protzek, André O; de Paula, Flávia M; Ferreira, Sandra M; Rezende, Luiz F; Vanzela, Emerielle C; Zoppi, Cláudio C; Silveira, Leonardo R; Kettelhut, Isis C; Boschero, Antonio C; de Oliveira, Camila A M; Carneiro, Everardo M

    2015-04-01

    Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis. PMID:25575490

  11. 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

  12. Medical treatment of vertebral osteoporosis.

    PubMed

    Lippuner, K

    2003-10-01

    Although osteoporosis is a systemic disease, vertebral fractures due to spinal bone loss are a frequent, sometimes early and often neglected complication of the disease, generally associated with considerable disability and pain. As osteoporotic vertebral fractures are an important predictor of future fracture risk, including at the hip, medical management is targeted at reducing fracture risk. A literature search for randomized, double-blind, prospective, controlled clinical studies addressing medical treatment possibilities of vertebral fractures in postmenopausal Caucasian women was performed on the leading medical databases. For each publication, the number of patients with at least one new vertebral fracture and the number of randomized patients by treatment arm was retrieved. The relative risk (RR) and the number needed to treat (NNT, i.e. the number of patients to be treated to avoid one radiological vertebral fracture over the duration of the study), together with the respective 95% confidence intervals (95%CI) were calculated for each study. Treatment of steroid-induced osteoporosis and treatment of osteoporosis in men were reviewed separately, based on the low number of publications available. Forty-five publications matched with the search criteria, allowing for analysis of 15 different substances tested regarding their anti-fracture efficacy at the vertebral level. Bisphosphonates, mainly alendronate and risedronate, were reported to have consistently reduced the risk of a vertebral fracture over up to 50 months of treatment in four (alendronate) and two (risedronate) publications. Raloxifene reduced vertebral fracture risk in one study over 36 months, which was confirmed by 48 months' follow-up data. Parathormone (PTH) showed a drastic reduction in vertebral fracture risk in early studies, while calcitonin may also be a treatment option to reduce fracture risk. For other substances published data are conflicting (calcitriol, fluoride) or insufficient

  13. Impaired CD4+ and T-helper 17 cell memory response to Streptococcus pneumoniae is associated with elevated glucose and percent glycated hemoglobin A1c in Mexican Americans with type 2 diabetes mellitus.

    PubMed

    Martinez, Perla J; Mathews, Christine; Actor, Jeffrey K; Hwang, Shen-An; Brown, Eric L; De Santiago, Heather K; Fisher Hoch, Susan P; McCormick, Joseph B; Mirza, Shaper

    2014-01-01

    Individuals with type 2 diabetes are significantly more susceptible to pneumococcal infections than healthy individuals of the same age. Increased susceptibility is the result of impairments in both innate and adaptive immune systems. Given the central role of T-helper 17 (Th17) and T-regulatory (Treg) cells in pneumococcal infection and their altered phenotype in diabetes, this study was designed to analyze the Th17 and Treg cell responses to a whole heat-killed capsular type 2 strain of Streptococcus pneumoniae. Patients with diabetes demonstrated a lower frequency of total CD+T-cells, which showed a significant inverse association with elevated fasting blood glucose. Measurement of specific subsets indicated that those with diabetes had, low intracellular levels of interleukin (IL)-17, and lower pathogen-specific memory CD4+ and IL-17+ cell numbers. No significant difference was observed in the frequency of CD4+ and Th17 cells between those with and without diabetes. However, stratification of data by obesity indicated a significant increase in frequency of CD4+ and Th17 cells in obese individuals with diabetes compared with nonobese individual with diabetes. The memory CD+T-cell response was associated inversely with both fasting blood glucose and percent glycated hemoglobin A1c. This study demonstrated that those with type 2 diabetes have a diminished pathogen-specific memory CD4+ and Th17 response, and low percentages of CD+T-cells in response to S. pneumoniae stimulation. PMID:23927943

  14. [Regulation of bone metabolism in osteoporosis : novel drugs for osteoporosis in development].

    PubMed

    Jakob, F; Genest, F; Baron, G; Stumpf, U; Rudert, M; Seefried, L

    2015-11-01

    Bone is continuously regenerated and remodeled as an adaptation to mechanical load. Bone mass and fracture resistance are maintained by a balanced equilibrium between bone formation and bone resorption. Regeneration and response to mechanical load are, however, impaired in osteoporosis and during aging. Bone resorption is enhanced by chronic inflammation while bone formation is altered by rising levels of inhibitors in the aging organism. Core molecular principles of the regulation of bone metabolism in health and disease have been characterized and developed as therapeutic targets. The receptor activator of nuclear factor kappaB ligand (RANKL) and osteoclast-derived protease cathepsin K are important regulators and effectors of osteoclast differentiation and bone resorption. Bone formation is stimulated by bone morphogenetic proteins (BMP) and via the parathyroid hormone receptor and the Wnt signaling pathway. The principles of osteoclast inhibition using bisphosphonates have now been known for almost three decades. Based on more recent knowledge RANKL and cathepsin K have been developed as new therapeutic targets to inhibit bone resorption. While denosumab, a RANKL antibody, has already been introduced into routine treatment strategies, the cathepsin K antagonist odanacatib is currently in the licensing process. Bone formation can also be stimulated by local administration of BMPs, by systemic treatment with the parathyroid hormone fragment teriparatide and by using antibodies targeting the Wnt inhibitor sclerostin. The latter are presently being tested in phase III clinical studies. In the near future a panel of traditional and novel treatment strategies will be available that will enable us to meet the individual clinical needs during aging and for the treatment of osteoporosis. PMID:26471379

  15. The natural approach to osteoporosis

    PubMed Central

    Bartolozzi, Emanuela

    2015-01-01

    Summary Osteoporosis is normally the result of a wrong life-style (diet, physical inactivity, smoke, dental hygiene, intestinal dysbiosis,…) and environmental toxicity which stimulate the chronic expression of inflammatory genes and alter the immuno-endocrine balance. A natural approch should face all the factors involved, leading the patients to become aware of their own responsability, and helping them with natural therapies, healthy food and life-style which support their body in the process of self-healing. PMID:26604935

  16. High glucose and hyperglycemic sera from type 2 diabetic patients impair DC differentiation by inducing ROS and activating Wnt/β-catenin and p38 MAPK.

    PubMed

    Gilardini Montani, Maria Saveria; Granato, Marisa; Cuomo, Laura; Valia, Sandro; Di Renzo, Livia; D'Orazi, Gabriella; Faggioni, Alberto; Cirone, Mara

    2016-04-01

    Type 2 is the type of diabetes with higher prevalence in contemporary time, representing about 90% of the global cases of diabetes. In the course of diabetes, several complications can occur, mostly due to hyperglycemia and increased reactive oxygen species (ROS) production. One of them is represented by an increased susceptibility to microbial infections and by a reduced capacity to clear them. Therefore, knowing the impact of hyperglycemia on immune system functionality is of utmost importance for the management of the disease. In this study, we show that medium containing high glucose reduced the in-vitro differentiation of monocytes into functional DCs and their activation mediated by PAMPs or DAMPs. Most importantly, the same effects were mediated by the hyperglycemic sera derived by type 2 diabetic patients, mimicking a more physiologic condition. DC dysfunction caused by hyperglycemia may be involved in the inefficient control of infections observed in diabetic patients, given the pivotal role of these cells in both the innate and adaptive immune response. Searching for the molecular mechanisms underlying DC dysfunction, we found that canonical Wnt/β-catenin and p38 MAPK pathways were activated in the DCs differentiated either in the presence of high glucose or of hyper-glycemic sera. Interestingly, the activation of these pathways and the DC immune dysfunction were partially counteracted by the anti-oxidant quercetin, a flavonoid already known to exert several beneficial effects in diabetes. PMID:26769359

  17. Osteoporosis in adults with cystic fibrosis.

    PubMed Central

    Haworth, C S; Selby, P L; Webb, A K; Adams, J E

    1998-01-01

    Osteoporosis is prevalent in adults with CF Longitudinal data have not been collected and so the natural history is unknown. The aetiology is not known. There are no published randomized controlled trials evaluating treatments for osteoporosis in CF patients. Images Figure 1 PMID:9709383

  18. Update on the epidemiology of osteoporosis.

    PubMed

    Wolf, R L; Zmuda, J M; Stone, K L; Cauley, J A

    2000-02-01

    Osteoporosis is a major public health problem that affects the entire aging population. This report provides an update on the epidemiology of osteoporosis and its associated fractures. Published studies from 1997 to the present are highlighted. The current US prevalence estimates for osteoporosis, trends in fracture incidence rates, and latest reports on the morbidity, mortality, and costs attributable to osteoporotic fractures are discussed. Recent advances in our understanding of risk factors associated with osteoporosis and related fractures are reviewed. Special attention is paid to the rapid progress being made in the field of genetics, the growing importance of nutrition, and the new questions being raised as to the influence of hormonal factors on bone mineral density and fracture risk. New studies linking osteoporosis to several other important diseases in women including breast cancer, osteoarthritis, and stroke are also reviewed. PMID:11123043

  19. The epidemiology and management of postmenopausal osteoporosis: a viewpoint from Brazil

    PubMed Central

    Baccaro, Luiz Francisco; Conde, Délio Marques; Costa-Paiva, Lúcia; Pinto-Neto, Aarão Mendes

    2015-01-01

    Brazil has an aging population, with an associated increase in the prevalence of chronic diseases. Postmenopausal osteoporosis is of particular concern because it leads to an increased risk of fractures, with subsequent negative impacts on health in older women. In recent years, efforts have been made to better understand the epidemiology of osteoporosis in Brazil, and to manage both direct and indirect costs to the Brazilian health care system. The reported prevalence of osteoporosis among postmenopausal women in Brazil varies from 15% to 33%, depending on the study methodology and the use of bone densitometry data or self-reporting by participants. A diagnosis of osteoporosis can be made on the basis of fractures occurring without significant trauma or on the basis of low bone mineral density measured by dual energy X-ray absorptiometry. To reduce the risk of osteoporosis, all postmenopausal women should be encouraged to maintain a healthy lifestyle, which includes physical activity and a balanced diet. Smoking and alcohol use should also be addressed. Special attention should be given to interventions to reduce the risk of falls, especially among older women. Calcium intake should be encouraged, preferably through diet. The decision to recommend calcium supplementation should be made individually because there is concern about a possible increased risk of cardiovascular disease associated with this treatment. Brazilian women obtain a minimal amount of vitamin D from their diet, and supplementation is warranted in women with little exposure to solar ultraviolet-B radiation. For women diagnosed with osteoporosis, some form of pharmacologic therapy should be initiated. Compliance with treatment should be monitored, and the treatment period should be individualized for each patient. The Brazilian government provides medication for osteoporosis through the public health system free of charge, but without proper epidemiological knowledge, the implementation of public

  20. Bisphosphonates for treatment of osteoporosis

    PubMed Central

    Brown, Jacques P.; Morin, Suzanne; Leslie, William; Papaioannou, Alexandra; Cheung, Angela M.; Davison, Kenneth S.; Goltzman, David; Hanley, David Arthur; Hodsman, Anthony; Josse, Robert; Jovaisas, Algis; Juby, Angela; Kaiser, Stephanie; Karaplis, Andrew; Kendler, David; Khan, Aliya; Ngui, Daniel; Olszynski, Wojciech; Ste-Marie, Louis-Georges; Adachi, Jonathan

    2014-01-01

    Abstract Objective To outline the efficacy and risks of bisphosphonate therapy for the management of osteoporosis and describe which patients might be eligible for bisphosphonate “drug holiday.” Quality of evidence MEDLINE (PubMed, through December 31, 2012) was used to identify relevant publications for inclusion. Most of the evidence cited is level II evidence (non-randomized, cohort, and other comparisons trials). Main message The antifracture efficacy of approved first-line bisphosphonates has been proven in randomized controlled clinical trials. However, with more extensive and prolonged clinical use of bisphosphonates, associations have been reported between their administration and the occurrence of rare, but serious, adverse events. Osteonecrosis of the jaw and atypical subtrochanteric and diaphyseal femur fractures might be related to the use of bisphosphonates in osteoporosis, but they are exceedingly rare and they often occur with other comorbidities or concomitant medication use. Drug holidays should only be considered in low-risk patients and in select patients at moderate risk of fracture after 3 to 5 years of therapy. Conclusion When bisphosphonates are prescribed to patients at high risk of fracture, their antifracture benefits considerably outweigh their potential for harm. For patients taking bisphosphonates for 3 to 5 years, reassess the need for ongoing therapy. PMID:24733321

  1. New anabolic therapies in osteoporosis.

    PubMed

    Rubin, Mishaela R; Bilezikian, John P

    2003-03-01

    Anabolic agents represent an important new advance in the therapy of osteoporosis. Their potential might be substantially greater than the anti-resorptives. Because the anti-resorptives and anabolic agents work by completely distinct mechanisms of action, it is possible that the combination of agents could be significantly more potent than either agent alone. Recent evidence suggests that a plateau in BMD might occur after prolonged exposure to PTH. Anti-resorptive therapy during or after anabolic therapy might prevent this skeletal adaptation. Protocols to consider anabolic agents as intermittent recycling therapy would be of interest. Of all the anabolics, PTH is the most promising. However, there are unanswered questions about PTH. More studies are needed to document an anabolic effect on cortical bone. More large-scale studies are needed to further determine the reduction in nonvertebral fractures with PTH, especially at the hip. In the future, PTH is likely to be modified for easier and more targeted delivery. Oral or transdermal delivery systems may become available. Recently, Gowen et al have described an oral calcilytic molecule that antagonizes the parathyroid cell calcium receptor, thus stimulating the endogenous release of PTH. This approach could represent a novel endogenous delivery system for intermittent PTH administration. Rising expectations that anabolic therapies for osteoporosis will soon play a major role in treating this disease are likely to fuel further studies and the development of even more novel approaches to therapy. PMID:12699304

  2. Nanohydroxyapatite Application to Osteoporosis Management

    PubMed Central

    Noor, Zairin

    2013-01-01

    Hydroxyapatite is chemically related to the inorganic component of bone matrix as a complex structure with the formula of Ca10(OH)2(PO4)6. Previous studies have reported the application of microsized hydroxyapatite to bone regeneration, but the result is not satisfied. The limitation comes from the size of hydroxyapatite. In addition, the duration of treatment is very long. The advantages of hydroxyapatite nanocrystal are the osteoconduction, bioresorption, and contact in close distance. Crystal in osteoporotic bone is calcium phosphate hydroxide with the chemical formula of Ca10(OH)2(PO4)6. Crystal of normal bone is sodium calcium hydrogen carbonate phosphate hydrate with the chemical formula of Ca8H2(PO4)6·H2O–NaHCO3–H2O. The recent development is applying nanobiology approach to hydroxyapatite. This is based on the concept that the mineral atoms arranged in a crystal structure of hydroxyapatite can be substituted or incorporated by the other mineral atoms. In conclusion, the basic elements of hydroxyapatite crystals, composed of atomic minerals in a certain geometric pattern, and their relationship to the bone cell biological activity have opened opportunities for hydroxyapatite crystals supplement application on osteoporosis. Understanding of the characteristics of bone hydroxyapatite crystals as well as the behavior of mineral atom in the substitution will have a better impact on the management of osteoporosis. PMID:24288653

  3. Osteoporosis

    MedlinePlus

    ... with weak bones in their spine gradually lose height and their posture becomes hunched over. Over time a bent spine can make it hard to walk or even sit up. Broken hips are a very serious problem as we age. ...

  4. Osteoporosis

    MedlinePlus

    ... foods and regular exercise, such as walking or running, to strengthen bones. A doctor may also recommend ... In other words, play a lot! Playing sports, running, jumping, dancing — whatever you like to do. Don' ...

  5. [Osteoporosis].

    PubMed

    Reza-Albarrán, Alfredo Adolfo

    2016-09-01

    Calcium intake has a role on the development of peak bone mass, and has a mild impact on the maintenance of bone mass during adulthood and the reduction of bone loss rate in postmenopausal women and the elderly in both genders. Calcium dietary intake should be privileged over supplementation. Dairy products are the main calcium dietary sources. Prospective studies have not clearly demonstrated an effect on the prevention of fractures, because of the practical difficulties of a long follow-up in order to get to solid conclusions; however the physiological rationale is that an adequate calcium intake and 25(OH) vitamin D levels exceeding 20 ng/ml is beneficial for bone health and may decrease to certain extent the risk of fractures. PMID:27603893

  6. Osteoporosis

    MedlinePlus

    ... or she may suggest you have a bone density scan. A common test that measures bone density is called a dual energy X-ray absorptiometry (DEXA). This test measures the density of the bones in your hips, spine and ...

  7. Bone regeneration associated with nontherapeutic and therapeutic surface coatings for dental implants in osteoporosis.

    PubMed

    Alghamdi, Hamdan S; Jansen, John A

    2013-06-01

    Oral implantology is considered as the treatment of choice for replacing missing teeth in elderly people. However, implant complications may occur in patients with osteoporosis. The pathogenesis underlying osteoporosis is due to an alteration in bone cell response to hormonal, nutritional, and aging factors. For such challenging situations, improved bone regeneration has been shown around dental implants for certain surface modifications. These modifications include coatings of titanium implants with calcium phosphate (CaP) ceramics. Surface coating developments also allow for the addition of organic biomolecules, like growth factors, into the inorganic coatings that increase the bone formation process at the bone-implant interface. The application of therapeutic-based coatings is becoming a rapidly growing research field of interest. CaP-coated implants have the ability to incorporate anti-osteoporotic drugs, which then can be locally released over time from an implant surface in a controlled manner. Thus, it can be anticipated that nontherapeutic and/or therapeutic coated implants can significantly increase low bone density as well as improve impaired bone regeneration in osteoporosis. This review aims to provide a thorough understanding of the underlying mechanisms for impaired bone regeneration around dental implants in osteoporosis. Secondly, the review will focus on biological interactions and beneficial role of the surface-coated (i.e., nontherapeutics and therapeutics) bone implants in osteoporotic bone tissue. PMID:23088597

  8. Intestinal Absorption and Metabolism of Epimedium Flavonoids in Osteoporosis Rats.

    PubMed

    Zhou, Jing; Ma, Yi Hua; Zhou, Zhong; Chen, Yan; Wang, Ying; Gao, Xia

    2015-10-01

    Herba Epimdii is a traditional Chinese medicine used to treat osteoporosis. Its main pharmacological ingredients are flavonoids. In previous studies conducted in healthy animals, we showed that epimedium flavonoids could be hydrolyzed into secondary glycosides or aglycon by intestinal flora or enzymes, thereby enhancing their absorption and antiosteoporosis activity. To study the medicine in the pathologic state, epimedium flavonoids were incubated with intestinal mucosa and feces in vitro and intestinal perfusion in situ to explore the differences in absorption and metabolism between sham and osteoporosis rats. For osteoporosis rats, the hydrolysis rates of icariin, epimedin A, epimedin B, and epimedin C incubated with intestinal flora for 1 hour were reduced by 0.19, 0.26, 0.19, and 0.14, respectively, compared with that in sham rats. Hydrolysis rates were reduced by 0.21, 0.24, 0.08, and 0.31 for icariin, epimedin A, epimedin B, and epimedin C incubated with duodenal enzymes for 1 hour and by 0.13, 0.09, 0.07, and 0.47 for icariin, epimedin A, epimedin B, and epimedin C incubated with jejunum enzymes, respectively, compared with the sham group. In addition, the apparent permeability coefficient and elimination percentage of the four epimedium flavonoids in the duodenum, jejunum, ileum, and colon decreased by 29%-44%, 32%-50%, 40%-56%, and 27%-53% compared with that in sham rats, respectively. The main metabolites of the four epimedium flavonoids were the same for the two groups after intestinal perfusion, or flora and enzyme incubation. In conclusion, the amount and activity of intestinal flora and enzymes changed in ovariectomized rats, which affected the intestinal absorption and hydrolysis of epimedium flavonoids whose structures contain 7-glucose. PMID:26135008

  9. Implant treatment in patients with osteoporosis.

    PubMed

    Mellado-Valero, Ana; Ferrer-García, Juan Carlos; Calvo-Catalá, Javier; Labaig-Rueda, Carlos

    2010-01-01

    Osteoporosis is very common, particularly in post-menopausal women and is characterized by a decrease in bone mass and strength. Osteoporosis also affects the jawbone and it is considered a potential contraindication to placement of dental implants. The present paper reviews the literature regarding the effect of osteoporosis on osseointegration of implants. Experimental models have shown that osteoporosis affects the process of osseointegration, which can be reversed by treatment. However, studies in subjects with osteoporosis have shown no differences in survival of the implants compared to healthy individuals. Therefore, osteoporosis cannot be considered a contraindication for implant placement. Oral bisphosphonates are the most commonly used pharmacological agents in the treatment of osteoporosis. Although there have been cases of osteonecrosis of the jaw in patients treated with bisphosphonates, they are very rare and it is more usually associated with intravenous bisphosphonates in patients with neoplasms or other serious diseases. Nevertheless, patients treated with bisphosphonates must be informed in writing about the possibility of this complication and must give informed consent. Ceasing to use bisphosphonates before implant placement does not seem to be necessary. PMID:19767691

  10. Secondary osteoporosis: differential diagnosis and workup.

    PubMed

    Diab, Dima L; Watts, Nelson B

    2013-12-01

    There are numerous causes of secondary osteoporosis including endocrine disorders, nutritional deficiencies, and other miscellaneous conditions and medications. It is essential to identify and address these factors to appropriately manage patients with osteoporosis. Failure to do so may result in further bone loss despite pharmacologic intervention for osteoporosis. The following diagnostic studies should be considered initially: complete blood count, complete metabolic panel, 25-hydroxyvitamin D level, testosterone level in men, and 24-hour urinary calcium, sodium, and creatinine. Further testing may be performed in selected patients depending on the clinical picture and results of the initial workup. PMID:24100597

  11. [Status and issues of medical treatment for osteoporosis].

    PubMed

    Yamauchi, Mika; Sugimoto, Toshitsugu

    2015-10-01

    Although various osteoporosis medications have become available with proven effects for protecting against bone fracture, such osteoporosis treatment is only given to 20 to 25% of those eligible in Japan. The most urgent task at present is to increase the treatment rate. The guidelines for prevention and treatment of osteoporosis were revised in 2015 and now include criteria for commencing medical treatment. However, guidelines for management of osteoporosis, including the duration of medical treatment for osteoporosis, are still under discussion. PMID:26529921

  12. 72 FR 497 - Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2007-01-05

    ...The Food and Drug Administration (FDA) is proposing to amend the regulation authorizing a health claim on the relationship between calcium and a reduced risk of osteoporosis to: Include vitamin D so that, in addition to claims for calcium and osteoporosis, additional claims can be made for calcium and vitamin D and osteoporosis; eliminate the requirement in Sec. 101.72(c)(2)(i)(A) (21 CFR......

  13. Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome.

    PubMed

    Jiang, Linlin; Huang, Jia; Chen, Yaxiao; Yang, Yabo; Li, Ruiqi; Li, Yu; Chen, Xiaoli; Yang, Dongzi

    2016-07-01

    This study aimed to detect serum microRNAs (miRNAs) differentially expressed between polycystic ovary syndrome (PCOS) patients with impaired glucose metabolism (IGM), PCOS patients with normal glucose tolerance (NGT), and healthy controls. A TaqMan miRNA array explored serum miRNA profiles as a pilot study, then selected miRNAs were analyzed in a validation cohort consisting of 65 PCOS women with IGM, 65 PCOS women with NGT, and 45 healthy women The relative expression of miR-122, miR-193b, and miR-194 was up-regulated in PCOS patients compared with controls, whereas that of miR-199b-5p was down-regulated. Furthermore, miR-122, miR-193b, and miR-194 were increased in the PCOS-IGM group compared with the PCOS-NGT group. Multiple linear regression analyses revealed that miR-193b and body mass index contributed independently to explain 43.7 % (P < 0.0001) of homeostasis model assessment-insulin resistance after adjustment for age. Investigation of diagnostic values confirmed the optimal combination of BMI and miR-193b to explore the possibility of IGM in PCOS women with area under the curve of 0.752 (95 % CI 0.667-0.837, P < 0.001). Bioinformatics analysis indicated that the predicted target functions of these miRNAs mainly involved glycometabolism and ovarian follicle development pathways, including the insulin signaling pathway, the neurotrophin signaling pathway, the PI3K-AKT signaling pathway, and regulation of actin cytoskeleton. This study expands our knowledge of the serum miRNA expression profiles of PCOS patients with IGM and the predicted target signal pathways involved in disease pathophysiology. PMID:26860517

  14. Uteroplacental insufficiency leads to hypertension, but not glucose intolerance or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats

    PubMed Central

    Tran, Melanie; Young, Margaret E; Jefferies, Andrew J; Hryciw, Deanne H; Ward, Michelle M; Fletcher, Erica L; Wlodek, Mary E; Wadley, Glenn D

    2015-01-01

    Growth restriction impacts on offspring development and increases their risk of disease in adulthood which is exacerbated with “second hits.” The aim of this study was to investigate if blood pressure, glucose tolerance, and skeletal muscle mitochondrial biogenesis were altered in 12-month-old male and female offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel ligation induced uteroplacental insufficiency and growth restriction in offspring (Restricted). A sham surgery was also performed during pregnancy (Control) and some litters from sham mothers had their litter size reduced (Reduced litter), which restricted postnatal growth. Growth-restricted females only developed hypertension at 12 months, which was not observed in males. In Restricted females only homeostasis model assessment for insulin resistance was decreased, indicating enhanced hepatic insulin sensitivity, which was not observed in males. Plasma leptin was increased only in the Reduced males at 12 months compared to Control and Restricted males, which was not observed in females. Compared to Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males and females, suggesting that at 12 months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1α levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12 months of age. In summary, sex strongly impacts the cardiometabolic effects of growth restriction in 12-month-old rats and it is females who are at particular risk of developing long-term hypertension following growth restriction. PMID:26416974

  15. The expression of dominant negative TCF7L2 in pancreatic beta cells during the embryonic stage causes impaired glucose homeostasis

    PubMed Central

    Shao, Weijuan; Xiong, Xiaoquan; Ip, Wilfred; Xu, Fenghao; Song, Zhuolun; Zeng, Kejing; Hernandez, Marcela; Liang, Tao; Weng, Jianping; Gaisano, Herbert; Nostro, M. Cristina; Jin, Tianru

    2015-01-01

    Objective Disruption of TCF7L2 in mouse pancreatic β-cells has generated different outcomes in several investigations. Here we aim to clarify role of β-cell TCF7L2 and Wnt signaling using a functional-knockdown approach. Methods Adenovirus-mediated dominant negative TCF7L2 (TCF7L2DN) expression was conducted in Ins-1 cells. The fusion gene in which TCF7L2DN expression is driven by PTRE3G was utilized to generate the transgenic mouse line TCF7L2DNTet. The double transgenic line was created by mating TCF7L2DNTet with Ins2-rtTA, designated as βTCFDN. β-cell specific TCF7L2DN expression was induced in βTCFDN by doxycycline feeding. Results TCF7L2DN expression in Ins-1 cells reduced GSIS, cell proliferation and expression of a battery of genes including incretin receptors and β-cell transcription factors. Inducing TCF7L2DN expression in βTCFDN during adulthood or immediately after weaning generated no or very modest metabolic defect, while its expression during embryonic development by doxycycline feeding in pregnant mothers resulted in significant glucose intolerance associated with altered β-cell gene expression and reduced β-cell mass. Conclusions Our observations support a cell autonomous role for TCF7L2 in pancreatic β-cells suggested by most, though not all, investigations. βTCFDN is a novel model for further exploring the role of TCF7L2 in β-cell genesis and metabolic homeostasis. PMID:25830097

  16. Uteroplacental insufficiency leads to hypertension, but not glucose intolerance or impaired skeletal muscle mitochondrial biogenesis, in 12-month-old rats.

    PubMed

    Tran, Melanie; Young, Margaret E; Jefferies, Andrew J; Hryciw, Deanne H; Ward, Michelle M; Fletcher, Erica L; Wlodek, Mary E; Wadley, Glenn D

    2015-09-01

    Growth restriction impacts on offspring development and increases their risk of disease in adulthood which is exacerbated with "second hits." The aim of this study was to investigate if blood pressure, glucose tolerance, and skeletal muscle mitochondrial biogenesis were altered in 12-month-old male and female offspring with prenatal or postnatal growth restriction. Bilateral uterine vessel ligation induced uteroplacental insufficiency and growth restriction in offspring (Restricted). A sham surgery was also performed during pregnancy (Control) and some litters from sham mothers had their litter size reduced (Reduced litter), which restricted postnatal growth. Growth-restricted females only developed hypertension at 12 months, which was not observed in males. In Restricted females only homeostasis model assessment for insulin resistance was decreased, indicating enhanced hepatic insulin sensitivity, which was not observed in males. Plasma leptin was increased only in the Reduced males at 12 months compared to Control and Restricted males, which was not observed in females. Compared to Controls, leptin, ghrelin, and adiponectin were unaltered in the Restricted males and females, suggesting that at 12 months of age the reduction in body weight in the Restricted offspring is not a consequence of circulating adipokines. Skeletal muscle PGC-1α levels were unaltered in 12-month-old male and female rats, which indicate improvements in lean muscle mass by 12 months of age. In summary, sex strongly impacts the cardiometabolic effects of growth restriction in 12-month-old rats and it is females who are at particular risk of developing long-term hypertension following growth restriction. PMID:26416974

  17. Osteoporosis - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Arthritis and Musculoskeletal and Skin Diseases Osteoporosis and Asian American Women English 骨質疏鬆症與亞裔美國婦女 - 繁體中文 (Chinese - Traditional) PDF National Institute ...

  18. Glucocorticoid-Induced Osteoporosis and Osteonecrosis

    PubMed Central

    Weinstein, Robert S.

    2012-01-01

    SYNOPSIS Glucocorticoid administration is the most common cause of secondary osteoporosis and the leading cause of nontraumatic osteonecrosis. In patients receiving long-term therapy, glucocorticoids induce fractures in 30 to 50% and osteonecrosis in 9 to 40%. This article reviews glucocorticoid-induced osteoporosis and osteonecrosis addressing the risk factors, pathogenesis, evaluation, treatment, and uncertainties in the clinical management of these disorders. PMID:22877431

  19. [Therapy of osteoporosis: towards personalized treatment?].

    PubMed

    Harbeck, Birgit; Lehnert, Hendrik

    2015-11-01

    Osteoporosis is the most common clinical disorder of bone metabolism. With regard to the growing spectrum of therapy options, treatment decisions should be made on an individual basis, taking into account the relative benefits and risks in different patient populations. Prioritization of drugs should be based on the form (primary / secondary) and severity of osteoporosis, sex, age, the specific contraindications and precautions of use of the various available medications and in particular, existing comorbidities. PMID:26536644

  20. Preventing osteoporosis in every day life.

    PubMed

    Lau, E M C

    2004-03-01

    Osteoporosis is a condition characterized by low bone mineral density, microarchitectural deterioration of bone tissue, and a consequent increase in fracture risk. The public health impact of osteoporosis stems from its association with fractures of the hip, spine and forearm. Between 10 and 20 percent of hip fracture patients die within a year of the event, and among those who survive, almost two-thirds remain disabled. The medical costs of osteoporosis and its attendant fractures have been placed at 5.2 billion dollars each year in the US and 615 million pound sterling each year in the UK. In Asia, osteoporosis is rapidly becoming a major public health problem with an increasing incidence of hip fracture and a rapidly aging population. By the year 2050, more than half of the hip fracture around the world would occur in Asia, with the total number approaching 3.2 million. Osteoporosis can be attributed to both genetic factors and environmental factors. While it is difficult to modify genes, much can be done to prevent osteoporosis in our every day life. These are discussed below. PMID:15577003

  1. Advanced Glycation End Products Impair Glucose-Stimulated Insulin Secretion of a Pancreatic β-Cell Line INS-1-3 by Disturbance of Microtubule Cytoskeleton via p38/MAPK Activation

    PubMed Central

    You, Jia; Xu, Shiqing; Zhang, Wenjian; Fang, Qing; Liu, Honglin; Peng, Liang; Deng, Tingting

    2016-01-01

    Advanced glycation end products (AGEs) are believed to be involved in diverse complications of diabetes mellitus. Overexposure to AGEs of pancreatic β-cells leads to decreased insulin secretion and cell apoptosis. Here, to understand the cytotoxicity of AGEs to pancreatic β-cells, we used INS-1-3 cells as a β-cell model to address this question, which was a subclone of INS-1 cells and exhibited high level of insulin expression and high sensitivity to glucose stimulation. Exposed to large dose of AGEs, even though more insulin was synthesized, its secretion was significantly reduced from INS-1-3 cells. Further, AGEs treatment led to a time-dependent increase of depolymerized microtubules, which was accompanied by an increase of activated p38/MAPK in INS-1-3 cells. Pharmacological inhibition of p38/MAPK by SB202190 reversed microtubule depolymerization to a stabilized polymerization status but could not rescue the reduction of insulin release caused by AGEs. Taken together, these results suggest a novel role of AGEs-induced impairment of insulin secretion, which is partially due to a disturbance of microtubule dynamics that resulted from an activation of the p38/MAPK pathway.

  2. Mechanisms of osteocyte stimulation in osteoporosis.

    PubMed

    Verbruggen, Stefaan W; Vaughan, Ted J; McNamara, Laoise M

    2016-09-01

    Experimental studies have shown that primary osteoporosis caused by oestrogen-deficiency results in localised alterations in bone tissue properties and mineral composition. Additionally, changes to the lacunar-canalicular architecture surrounding the mechanosensitive osteocyte have been observed in animal models of the disease. Recently, it has also been demonstrated that the mechanical stimulation sensed by osteocytes changes significantly during osteoporosis. Specifically, it was shown that osteoporotic bone cells experience higher maximum strains than healthy bone cells after short durations of oestrogen deficiency. However, in long-term oestrogen deficiency there was no significant difference between bone cells in healthy and normal bone. The mechanisms by which these changes arise are unknown. In this study, we test the hypothesis that complex changes in tissue composition and lacunar-canalicular architecture during osteoporosis alter the mechanical stimulation of the osteocyte. The objective of this research is to employ computational methods to investigate the relationship between changes in bone tissue composition and microstructure and the mechanical stimulation of osteocytes during osteoporosis. By simulating physiological loading, it was observed that an initial decrease in tissue stiffness (of 0.425GPa) and mineral content (of 0.66wt% Ca) relative to controls could explain the mechanical stimulation observed at the early stages of oestrogen deficiency (5 weeks post-OVX) during in situ bone cell loading in an oestrogen-deficient rat model of post-menopausal osteoporosis (Verbruggen et al., 2015). Moreover, it was found that a later increase in stiffness (of 1.175GPa) and mineral content (of 1.64wt% Ca) during long-term osteoporosis (34 weeks post-OVX), could explain the mechanical stimuli previously observed at a later time point due to the progression of osteoporosis. Furthermore, changes in canalicular tortuosity arising during osteoporosis were shown

  3. 73 FR 66754 - Food Labeling: Health Claims; Calcium and Osteoporosis, and Calcium, Vitamin D, and Osteoporosis

    Federal Register 2010, 2011, 2012, 2013, 2014

    2008-11-12

    ... Osteoporosis, and Calcium, Vitamin D, and Osteoporosis AGENCY: Food and Drug Administration, HHS. ACTION: Final... appeared in the Federal Register of Monday, September 29, 2008 (73 FR 56477). The final rule was published...-436-1450. SUPPLEMENTARY INFORMATION: In FR Doc. E8-22730, appearing on page 56477 in the...

  4. Osteoporosis in unstable adult scoliosis

    SciTech Connect

    Velis, K.P.; Healey, J.H.; Schneider, R.

    1988-12-01

    New noninvasive techniques as well as conventional methods were used to evaluate skeletal mass in the following three populations of adult white women as follows: (1) 79 subjects with preexisting idiopathic scoliosis designated as unstable (US) because of the associated presence in the lumbar spine of lateral spondylolisthesis with segmental instability; (2) 67 subjects with preexisting idiopathic scoliosis without lateral spondylolisthesis designated as stable (SS); and (3) 248 age-matched nonscoliotic controls. Ages in all three groups were categorized into premenopausal (25-44 years), perimenopausal (45-54 years), and postmenopausal (55-84 years). The results showed higher scoliosis morbidity in the US compared to the SS populations. The prevalence and severity of osteoporosis were markedly increased in US versus SS populations. Femoral neck density determined by dual-photon absorptiometry techniques averaged 26% to 48% lower in all age categories of US patients compared to controls. These changes were found in the youngest age groups, indicating reductions in bone mineral content earlier in the adult life of white women with a specific type of high-morbidity US characterized by the marker of lateral spondylolisthesis.

  5. Osteoporosis in survivors of early life starvation.

    PubMed

    Weisz, George M; Albury, William R

    2013-01-01

    The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The 'fetal programming' of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of 'fetal programming' but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors - those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life - not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient's risk of osteoporosis in later life. PMID:22951115

  6. 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

  7. Transcription Factor 7-Like 2 (TCF7L2) Polymorphism and Context-Specific Risk of Impaired Fasting Glucose in African American and Caucasian Adults: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Yan, Y.; North, K. E.; Heiss, G.; Klein, R.; Girman, C. J.; Lange, E. M.; Pankow, J. S.; Brancati, F. L.; Boerwinkle, E.

    2010-01-01

    Background Although variants in the transcription factor 7-like 2 (TCF7L2) gene are consistently associated with impaired fasting glucose (IFG) in Caucasians, data from large population-based studies of African Americans are lacking. Moreover, few studies have investigated the effects of TCF7L2 on IFG in the context of metabolic risk factors for diabetes. Methods We investigated the association between the TCF7L2 rs7903146 polymorphism and incident IFG defined as fasting serum glucose levels of 100–125 mg/dl (5.6–6.9 mmol/l) in 1,377 African American and 5,152 Caucasian participants without diabetes and IFG at intake who participated in the Atherosclerosis Risk in Communities (ARIC) Study in 1987–1989 and were followed for 9 years. Results Incident IFG was identified in 810 (58.8%) African American and 2,652 (51.5%) Caucasian participants. Compared to homozygous CC Caucasian individuals, heterozygous CT [hazard ratio (HR) = 1.09 (95% CI=1.03–1.15)] and homozygous TT [1.18 (1.05–1.33)] individuals had significantly higher risk of developing IFG over 9-year follow up. The association between rs7903146 and IFG risk was stronger in Caucasians with obesity [HRCT vs. CC=1.28 (1.12, 1.47); HRTT vs. CC=1.65 (1.25, 2.17)] or high triglycerides [HRCT vs. CC=1.31(1.10, 1.56); HRTT vs. CC=1.72 (1.21, 2.43)]. No association of the TCF7L2 rs7903146 polymorphism and incident IFG was noted in African Americans. Conclusions Our study replicates the association between rs7903146 and IFG risk in a population-based, longitudinal cohort of Caucasians but not in African Americans. For the first time, our study provides evidence for interactions between TCF7L2 and metabolic risk factors on the occurrence of IFG in Caucasians. PMID:20578204

  8. Osteoporosis in paediatric patients with spina bifida

    PubMed Central

    Marreiros, Humberto Filipe; Loff, Clara; Calado, Eulalia

    2012-01-01

    The prevalence and morbidity associated with osteoporosis and fractures in patients with spina bifida (SB) highlight the importance of osteoporosis prevention and treatment in early childhood; however, the issue has received little attention. The method for the selection of appropriate patients for drug treatment has not been clarified. Objective To review the literature concerning fracture risks and low bone density in paediatric patients with SB. We looked for studies describing state-of-the-art treatments and for prevention of secondary osteoporosis. Methods Articles were identified through a search in the electronic database (PUBMED) supplemented with reviews of the reference lists of selected papers. The main outcome measures were incidence of fractures and risk factors for fracture, an association between bone mineral density (BMD) and occurrence of fracture, risk factors of low BMD, and effects of pharmacological and non-pharmacological treatments on BMD and on the incidence of fractures. We considered as a secondary outcome the occurrence of fractures in relation to the mechanism of injury. Results Results indicated that patients with SB are at increased risk for fractures and low BMD. Risk factors that may predispose patients to fractures include higher levels of neurological involvement, non-ambulatory status, physical inactivity, hypercalciuria, higher body fat levels, contractures, and a previous spontaneous fracture. Limitations were observed in the number and quality of studies concerning osteoporosis prevention and treatment in paediatric patients with SB. The safety and efficiency of drugs to treat osteoporosis in adults have not been evaluated satisfactorily in children with SB. PMID:22330186

  9. Osteoporosis Prevention, Screening, and Treatment: A Review

    PubMed Central

    Kling, Juliana M.; Clarke, Bart L.

    2014-01-01

    Abstract Osteoporosis, defined as low bone mass leading to increased fracture risk, is a major health problem that affects approximately 10 million Americans. The aging U.S. population is predicted to contribute to as much as a 50% increase in prevalence by 2025. Although common, osteoporosis can be clinically silent, and without prevention and screening, the costs of osteoporotic fracture–related morbidity and mortality will burden the U.S. healthcare system. This is a particularly relevant concern in the context of diminishing health care resources. Dual-energy X-ray absorptiometry is the most widely used, validated technique for measuring bone mineral density (BMD) and diagnosing osteoporosis. Cost-effectiveness analyses support early detection and treatment of high-risk patients with antiresorptive medications such as bisphosphonates. Moreover, optimization of bone health throughout life can help prevent osteoporosis. Current guidelines recommend screening women by age 65 years, but because no guidelines for screening intervals exist, decisions are made on the basis of clinical judgment alone. Although the recent literature provides some guidance, this review further explores current recommendations in light of newer evidence to provide more clarity on prevention, screening, and management strategies for patients with osteoporosis in the primary care setting. PMID:24766381

  10. Management of osteoporosis in spine surgery.

    PubMed

    Lehman, Ronald A; Kang, Daniel Gene; Wagner, Scott Cameron

    2015-04-01

    Osteoporosis is a burgeoning clinical problem that is characterized by decreased bone strength and density. It predisposes patients to fragility fractures and debilitating spine deformities. Several complications are associated with spine surgery in patients with osteoporosis, and there is currently no treatment algorithm to guide the spine surgeon. A multidisciplinary approach to treatment of patients with osteoporosis and spine deformity or fracture is encouraged, and preoperative planning is crucial for successful surgical outcomes. Several surgical techniques have been developed to treat osteoporosis-related deformities, including posterior instrumentation with fusion. However, achieving fixation and fusion in these patients can be difficult secondary to poor bone stock. Augmentation methods to improve pedicle screw fixation have evolved, including instrumentation at multiple levels, bioactive cement augmentation, and fenestrated or expandable pedicle screws, but their impact on clinical outcomes remains unknown. Management of osteoporosis in patients undergoing spine surgery is challenging, but with appropriate patient selection, medical optimization, and surgical techniques, these patients can experience pain relief, deformity correction, and improved function. PMID:25808687

  11. Osteoporosis in the at-risk asthmatic.

    PubMed

    Aljubran, S A; Whelan, G J; Glaum, M C; Lockey, R F

    2014-11-01

    The effect of inhaled glucocorticosteroids (ICS) on bone metabolism and subsequent osteoporosis is controversial. Explanations for this controversy include various study designs, duration of use, outcome measures, and population demographics of research studies with intranasal or inhalational ICS. Patients with poorly controlled asthma are at greatest risk of osteoporosis because they are commonly treated with intermittent or continuous systemic corticosteroids (SCS) or high-dose ICS. A 45-year-old Caucasian woman presents with moderate-to-severe asthma with frequent albuterol use and nighttime awakenings at least once weekly. She is on fluticasone/salmeterol 500/50 μg one inhalation twice daily and montelukast 10 mg/day. She requires prednisone 15 mg three times per day for 5 days up to three times a year. Is this patient at greater risk of osteopenia, characterized by a T-score between -1.0 and -2.5, and subsequent osteoporosis and an increased risk of fractures? If she has osteopenia, should she be treated with a bisphosphonate? The risk of osteoporosis and fracture increases significantly with frequent administration of SCS, and patients on such medications should undergo preventative measures and treatment. This study discuses factors that contribute to an increased risk of osteoporosis/osteopenia in patients with asthma and suggests recommendations based on the current literature. PMID:25039444

  12. What Are Osteoporosis and Arthritis and How Are They Different?

    MedlinePlus

    ... and Other Related Conditions: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ... www.niams.nih.gov NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  13. For People with Osteoporosis: How to Find a Doctor

    MedlinePlus

    ... No. 15-7888-E NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ... another language, contact the NIH Osteoporosis and Related Bone Diseases ~ National Resource Center at NIHBoneInfo@mail.nih.gov . ...

  14. What People with Celiac Disease Need to Know about Osteoporosis

    MedlinePlus

    ... ligand (RANKL) inhibitor. Resources NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... Pub. No. 16-7897 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  15. A review of osteoporosis management in younger premenopausal women.

    PubMed

    McLendon, Amber N; Woodis, C Brock

    2014-01-01

    The purpose of this review is to describe the available evidence for osteoporosis treatments in young and premenopausal women. A review of articles evaluating the treatment or prevention of osteoporosis in young (age less than 50 years) or premenopausal women was conducted. Several trials evaluating the treatment of anorexia nervosa and use of hormone therapy in those women, the use of bisphosphonates in women undergoing chemotherapy for breast cancer and the use of bisphosphonates, teriparatide and vitamin D in women with glucocorticoid-induced osteoporosis are described. Limited data were found to support the treatment of osteoporosis in women with idiopathic osteoporosis or cystic fibrosis, or after kidney transplant. The evidence for treatment of osteoporosis in premenopausal women is not nearly as robust as that for postmenopausal osteoporosis. Although fracture risk in the premenopausal population is low, women with secondary osteoporosis may benefit from treatment with various agents, depending upon the condition. PMID:24328599

  16. Injected Drug May Help Fight Osteoporosis in Women

    MedlinePlus

    ... fullstory_160452.html Injected Drug May Help Fight Osteoporosis in Women Abaloparatide appears to reduce fractures better ... risk of bone fractures in postmenopausal women with osteoporosis better than a placebo and the currently available ...

  17. Acute Glucose Response Properties Beyond Feeding.

    PubMed

    Burnett, C Joseph; Krashes, Michael J

    2016-05-01

    Hypothalamic AgRP neurons potently coordinate feeding behavior to ensure an organism's viability. However, their acute role in glucose-regulatory function remains to be addressed. Steculorum et al. now report that activation of a specific set of AgRP neurons results in an impairment of insulin-stimulated glucose uptake in brown fat through a myogenic signature program. PMID:27052261

  18. 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 ...

  19. Osteoporosis in chronic obstructive pulmonary disease.

    PubMed

    Sarkar, Malay; Bhardwaj, Rajeev; Madabhavi, Irappa; Khatana, Jasmin

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a lifestyle-related chronic inflammatory pulmonary disease associated with significant morbidity and mortality worldwide. COPD is associated with various comorbidities found in all stages of COPD. The comorbidities have significant impact in terms of morbidity, mortality, and economic burden in COPD. Management of comorbidities should be incorporated into the comprehensive management of COPD as this will also have an effect on the outcome in COPD patients. Various comorbidities reported in COPD include cardiovascular disease, skeletal muscle dysfunction, anemia, metabolic syndrome, and osteoporosis. Osteoporosis is a significant comorbidity in COPD patients. Various risk factors, such as tobacco smoking, systemic inflammation, vitamin D deficiency, and the use of oral or inhaled corticosteroids (ICSs) are responsible for its occurrence in patients with COPD. This review will focus on the prevalence, pathogenesis, risk factors, diagnosis, and treatment of osteoporosis in COPD patients. PMID:25788838

  20. [Advances in the treatment of secondary osteoporosis].

    PubMed

    Galindo Zavala, R; Núñez Cuadros, E; Díaz Cordovés-Rego, G; Urda Cardona, A L

    2014-12-01

    Osteoporosis is being increasingly recognised in paediatric practice as a consequence of the increasing life expectancy of children who suffer from chronic diseases and other factors. There are many non-pharmacological measures that can improve children' bone health, for example, avoiding inflammatory activity and osteotoxic treatments; increasing sun exposure and weight-bearing exercise, and maintaining an adequate nutritional status. Vitamin D and calcium supplements have been proposed as a measure to increase bone mass, but their effect and therapeutic indications are not completely clear. On the other hand, bisphosphonates are currently the only pharmacological alternative for the patients with infantile secondary osteoporosis. However, more studies are required on the therapeutic indications, posology, and long term secondary effects of biphosphonates. The aim of this article is to analyze the scientific evidence of the effectiveness of the therapeutic alternatives for childhood secondary osteoporosis and their safety in children. PMID:25441207

  1. Osteoporosis in Chronic Obstructive Pulmonary Disease

    PubMed Central

    Sarkar, Malay; Bhardwaj, Rajeev; Madabhavi, Irappa; Khatana, Jasmin

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a lifestyle-related chronic inflammatory pulmonary disease associated with significant morbidity and mortality worldwide. COPD is associated with various comorbidities found in all stages of COPD. The comorbidities have significant impact in terms of morbidity, mortality, and economic burden in COPD. Management of comorbidities should be incorporated into the comprehensive management of COPD as this will also have an effect on the outcome in COPD patients. Various comorbidities reported in COPD include cardiovascular disease, skeletal muscle dysfunction, anemia, metabolic syndrome, and osteoporosis. Osteoporosis is a significant comorbidity in COPD patients. Various risk factors, such as tobacco smoking, systemic inflammation, vitamin D deficiency, and the use of oral or inhaled corticosteroids (ICSs) are responsible for its occurrence in patients with COPD. This review will focus on the prevalence, pathogenesis, risk factors, diagnosis, and treatment of osteoporosis in COPD patients. PMID:25788838

  2. Treatment options for thalassemia patients with osteoporosis.

    PubMed

    Terpos, Evangelos; Voskaridou, Ersi

    2010-08-01

    Osteoporosis represents a prominent cause of morbidity in patients with thalassemia. The delay in sexual maturation, the presence of diabetes and hypothyroidism, the parathyroid gland dysfunction, the progressive marrow expansion, the iron toxicity on osteoblasts, the iron chelators, and the deficiency of growth hormone or insulin growth factors have been identified as major causes of osteoporosis in thalassemia. Adequate hormonal replacement, effective iron chelation, improvement of hemoglobin levels, calcium and vitamin D administration, physical activity, and smoking cessation are the main to-date measures for the management of the disease. During the last decade, novel pathogenetic data suggest that the reduced osteoblastic activity, which is believed to be the basic mechanism of bone loss in thalassemia, is accompanied by a comparable or even greater increase in bone resorption. Therefore, the role of bisphosphonates, potent inhibitors of osteoclast activation, arises as a major factor in the management of osteoporosis in thalassemia patients. PMID:20712799

  3. New Antiresorptive Therapies for Postmenopausal Osteoporosis

    PubMed Central

    2015-01-01

    Osteoporosis is a systemic skeletal disease whose risk increases with age and it is common among postmenopausal women. Currently, almost all pharmacological agents for osteoporosis target the bone resorption component of bone remodeling activity. Current antiresorptive agents are effective, but the effectiveness of some agents is limited by real or perceived intolerance, longterm adverse events (AEs), coexisting comorbidities, and inadequate long-term adherence. New antiresorptive therapies that may expand options for the prevention and treatment of osteoporosis include denosumab, combination of conjugated estrogen/bazedoxifene and cathepsin K inhibitors. However, the long-term efficacy and AEs of these antiresorptive therapies need to be confirmed in studies with a longer follow-up period. PMID:26046031

  4. The link between osteoporosis and cardiovascular disease

    PubMed Central

    Farhat, Ghada N.; Cauley, Jane A.

    2008-01-01

    Cardiovascular disease (CVD) and osteoporosis are common age-related conditions associated with significant morbidity, mortality, and disability. Traditionally, these two conditions were considered unrelated and their coexistence was attributed to independent age-related processes. However, an increasing body of biological and epidemiological evidence has provided support for a link between the two conditions that cannot be explained by age alone. Several hypotheses have been proposed to explain the link between osteoporosis and CVD including: 1) shared risk factors, 2) common pathophysiological mechanisms, 3) common genetic factors, or 4) a causal association. This review highlights the epidemiologic literature on the association of bone density with cardiovascular mortality, cardiovascular morbidity, and subclinical measures of atherosclerosis. It also summarizes the different potential mechanisms involved in the link between osteoporosis and CVD. PMID:22460842

  5. Renal Glucose Handling

    PubMed Central

    Ferrannini, Ele; Veltkamp, Stephan A.; Smulders, Ronald A.; Kadokura, Takeshi

    2013-01-01

    OBJECTIVE Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, stimulates glycosuria and lowers glycemia in patients with type 2 diabetes (T2DM). The objective of this study was to assess the pharmacodynamics of ipragliflozin in T2DM patients with impaired renal function. RESEARCH DESIGN AND METHODS Glycosuria was measured before and after a single ipragliflozin dose in 8 nondiabetic subjects and 57 T2DM patients (age 62 ± 9 years, fasting glucose 133 ± 39 mg/dL, mean ± SD) with normal renal function (assessed as the estimated glomerular filtration rate [eGFR]) (eGFR1 ≥90 mL · min–1 · 1.73 m−2), mild (eGFR2 ≥60 to <90), moderate (eGFR3 ≥30 to <60), or severe reduction in eGFR (eGFR4 ≤15 to <30). RESULTS Ipragliflozin significantly increased urinary glucose excretion in each eGFR class (P < 0.0001). However, ipragliflozin-induced glycosuria declined (median [IQR]) across eGFR class (from 46 mg/min [33] in eGFR1 to 8 mg/min [7] in eGFR4, P < 0.001). Ipragliflozin-induced fractional glucose excretion (excretion/filtration) was 39% [27] in the T2DM patients (pooled data), similar to that of the nondiabetic subjects (37% [17], P = ns). In bivariate analysis of the pooled data, ipragliflozin-induced glycosuria was directly related to eGFR and fasting glucose (P < 0.0001 for both, r2 = 0.55), predicting a decrement in 24-h glycosuria of 15 g for each 20 mL/min decline in eGFR and an increase of 7 g for each 10 mg/dL increase in glucose above fasting normoglycemia. CONCLUSIONS In T2DM patients, ipragliflozin increases glycosuria in direct, linear proportion to GFR and degree of hyperglycemia, such that its amount can be reliably predicted in the individual patient. Although absolute glycosuria decreases with declining GFR, the efficiency of ipragliflozin action (fractional glucose excretion) is maintained in patients with severe renal impairment. PMID:23359360

  6. Osteoporosis Health Beliefs among Younger and Older Men and Women

    ERIC Educational Resources Information Center

    Johnson, C. Shanthi; McLeod, William; Kennedy, Laura; McLeod, Katherine

    2008-01-01

    The purpose of this study was to compare osteoporosis health beliefs among different age and gender groups. This study used a cross-sectional design, involved 300 participants that represent both genders and three age groups (18 to 25, 30 to 50, and 50-plus), and assessed osteoporosis health beliefs using the Osteoporosis Health Belief Scale…

  7. Osteoporosis and Arthritis: Two Common but Different Conditions

    MedlinePlus

    ... situation. Most people with arthritis will use pain management strategies at some time. This is not always true for people with osteoporosis. Usually, people with osteoporosis need pain relief when they ... pain management strategies are similar for people with osteoporosis, OA, ...

  8. Transient osteoporosis of the hip in pregnancy.

    PubMed

    Siva, S; Roach, V

    1997-08-01

    Transient osteoporosis of the hip (TOH) is an uncommon condition. This painful regional osteoporosis affects previously healthy women in the third trimester of pregnancy. It is characterized by pain in the affected hip and pronounced osteopenia of the femoral head and neck. It has a relatively short clinical course (average 6 months) and a predictably benign prognosis. Complete clinical and radiological recovery is the rule. The diagnosis is one of exclusion. The cause of the osteopenia is not known, although various aetiological factors have been implicated. A case of TOH occurring in the third trimester of pregnancy with complete recovery within 6 months postpartum is presented. PMID:9325501

  9. Premenopausal bone health: osteoporosis in premenopausal women.

    PubMed

    Abraham, Alice; Cohen, Adi; Shane, Elizabeth

    2013-12-01

    This article will discuss the diagnosis of osteoporosis in premenopausal women and the evaluation and management of those with low-trauma fractures and/or low bone mineral density. As secondary causes (glucocorticoid excess, anorexia nervosa, premenopausal estrogen deficiency, and celiac disease) are commonly the underlying cause of osteoporosis in this population, treatment of the underlying condition should be the focus of management. Additional management options, generally reserved for those with major or multiple fractures and/or ongoing bone loss, will also be described. PMID:24022503

  10. Osteoporosis-pseudoglioma syndrome in South Africa.

    PubMed

    Chetty, M; Stephen, L X G; Roberts, T

    2016-01-01

    The osteoporosis-pseudoglioma syndrome (MIM 259770) is a rare autosomal recessive disorder in which bone fragility and frequent fractures are associated with serious ocular changes. The skeletal manifestations resemble those of osteogenesis imperfecta while hyperplasia of the vitreous, eye and corneal opacities often mimics the appearance of intraocular glioma. This disorder was previously reported in a South African family of Indian stock as 'the ocular form of osteogenesis imperfecta'. Terminological discussion followed and it was suggested that these individuals had osteoporosis-pseudoglioma syndrome. This article describes and depicts the manifestations of the disorder and discusses the nosology. PMID:27245540

  11. Dietary approaches for bone health: lessons from the Framingham Osteoporosis Study

    PubMed Central

    Sahni, Shivani; Mangano, Kelsey M; McLean, Robert R; Hannan, Marian T; Kiel, Douglas P

    2016-01-01

    Osteoporosis is characterized by systemic impairment of bone mass, strength, and microarchitecture, resulting in increased risk for fragility fracture, disability, loss of independence and even death. Adequate nutrition is important in achieving and maintaining optimal bone mass, as well as preventing this debilitating disease. It is widely accepted that adequate calcium and vitamin D intake are necessary for good bone health; however, nutritional benefits to bone go beyond these two nutrients. This review article will provide updated information on all nutrients and foods now understood to alter bone health. Specifically, this paper will focus on related research from the Framingham Osteoporosis Study, an ancillary study of the Framingham Heart Study, with data on more than five thousand adult men and women. PMID:26045228

  12. Management of endocrine disease: Secondary osteoporosis: pathophysiology and management.

    PubMed

    Mirza, Faryal; Canalis, Ernesto

    2015-09-01

    Osteoporosis is a skeletal disorder characterized by decreased mass and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions. PMID:25971649

  13. Bone mineral density: testing for osteoporosis

    PubMed Central

    Sheu, Angela; Diamond, Terry

    2016-01-01

    Summary Primary osteoporosis is related to bone loss from ageing. Secondary osteoporosis results from specific conditions that may be reversible. A thoracolumbar X-ray is useful in identifying vertebral fractures, and dual energy X-ray absorptiometry is the preferred method of calculating bone mineral density. The density of the total hip is the best predictor for a hip fracture, while the lumbar spine is the best site for monitoring the effect of treatment. The T-score is a comparison of the patient’s bone density with healthy, young individuals of the same sex. A negative T-score of –2.5 or less at the femoral neck defines osteoporosis. The Z-score is a comparison with the bone density of people of the same age and sex as the patient. A negative Z-score of –2.5 or less should raise suspicion of a secondary cause of osteoporosis. Clinical risk calculators can be used to predict the 10-year probability of a hip or major osteoporotic fracture. A probability of more than 5% for the hip or more than 20% for any fracture is abnormal and treatment may be warranted. PMID:27340320

  14. The Effect of Fluoride in Osteoporosis.

    ERIC Educational Resources Information Center

    Hedlund, L. R.; Gallagher, J. C.

    1987-01-01

    This article discusses the effect of fluoride on bone tissue and the possible role of fluoride in the treatment of osteoporosis. At present, fluoride treatment should be restricted to clinical trials until its risks and benefits have been further evaluated. (Author/MT)

  15. Better Bones Buddies: An Osteoporosis Prevention Program

    ERIC Educational Resources Information Center

    Schrader, Susan L.; Blue, Rebecca; Horner, Arlene

    2005-01-01

    Although osteoporosis typically surfaces in later life, peak bone mass attained before age 20 is a key factor in its prevention. However, most American children's diets lack sufficient calcium during the critical growth periods of preadolescence and adolescence to achieve peak bone mass. "Better Bones (BB) Buddies" is an educational program…

  16. Osteoporosis: What is the Role of Exercise?

    ERIC Educational Resources Information Center

    Munnings, Frances

    1992-01-01

    Research has not yet identified the best combination of estrogen replacement, calcium, and exercise for fighting osteoporosis, but clinical experience indicates all are needed to prevent the rapid bone loss that occurs in postmenopausal women. Physicians must encourage women to reduce their risk using all available options. (SM)

  17. Osteoporosis Risk Factors in Eighth Grade Students.

    ERIC Educational Resources Information Center

    Lysen, Victoria C.; Walker, Robert

    1997-01-01

    Presents findings from food frequency questionnaires and surveys of 138 Midwestern eighth-grade student-parent pairs. The study examined the incidence of modifiable and nonmodifiable osteoporosis risk factors and compared gender differences. Data analysis indicated that many adolescents possessed several modifiable and nonmodifiable risk factors…

  18. [Drug therapy for primary osteoporosis in men].

    PubMed

    Soen, Satoshi

    2016-07-01

    Overall, drug therapies for osteoporosis in men are less defined than in women, mainly due to the fact that there are fewer RCTs performed in male populations, to the relatively smaller sample sizes, and to the lack of long-term extension studies. In a series of well-designed RCTs, alendronate, risedronate, zoledronic acid, and teriparatide were demonstrated to reduce the risk of new vertebral fractures in men presenting with primary osteoporosis(including osteoporosis associated with low testosterone levels)and to improve the bone mineral density(BMD). In preliminary studies, ibandronate and denosumab also showed their beneficial effects on surrogate outcomes(BMD and markers of bone turnover)in men with osteoporosis. Although direct evidence about their non-vertebral anti-fracture efficacy are lacking, the effects of bisphosphonates, denosumab and teriparatide on surrogate outcomes were similar to those reported in pivotal RCTs undertaken in postmenopausal women, in which vertebral and non-vertebral anti-fracture efficacy have been clearly demonstrated. PMID:27346317

  19. Osteoporosis: Its Prosthodontic Considerations - A Review

    PubMed Central

    Munagapati, Bharathi; Karnati, Rajeev K Reddy; Venkata, Giridhar Reddy Sirupa; Nidudhur, Simhachalam Reddy

    2015-01-01

    Osteoporosis is a disease of bone which is common in middle aged post-menopausal women. The osteoporotic bones will become weak and are prone to fractures. Osteoporosis means “porous bone” is a “silent disease”. Healthy bone microscopically appears like a honeycomb but, in osteoporotic patients the spaces are much bigger. The osteoporotic bone will have less density or mass and the structure of bone tissue is abnormal. As the bone becomes less dense, they become weaker and more likely to fracture. Women are four times more likely to develop osteoporosis than men. Oral health maintenance for adults with osteoporosis is important. Bone weakness and loss may also affect the ridges that hold dentures resulting in poor fitting dentures. The patients require new dentures more often than those who have strong, healthy bones. Best way to handle problems is avoid delaying or postponing the dental treatment. Regular dental visits and healthy lifestyle is necessary in strengthening and maintenance of good bone health. Well balanced diet with high amounts of vitamin-D & calcium with regular physical activity is recommended. PMID:26816999

  20. Management of beta-thalassemia-associated osteoporosis.

    PubMed

    Giusti, Andrea; Pinto, Valeria; Forni, Gian Luca; Pilotto, Alberto

    2016-03-01

    Beta-Thalassemia-associated osteoporosis is a multifactorial and complex condition. Different acquired and genetic factors are involved in its pathogenesis. These factors produce an imbalance in bone remodeling by inhibiting osteoblast activity and increasing osteoclast function, leading to bone loss and increased fracture risk. The management of patients presenting with thalassemia-associated osteoporosis should consist of the implementation of general measures and the prescription of a specific pharmacological agent, with the aim of reducing fracture risk and preventing disability and deterioration of quality of life. General measures include control of anemia, adequate chelation therapy, healthy nutrition and lifestyle, regular exercise, adequate management of comorbid conditions, hormone replacement therapy in patients with hypogonadism, and vitamin D supplementation/therapy. Among the pharmacological agents currently available for the management of osteoporosis in postmenopausal women and men, bisphosphonates have been shown to improve bone mineral density, to reduce bone turnover, and to decrease bone/back pain in patients with thalassemia-associated osteoporosis, with a good profile of safety and tolerability. On the other hand, there are limited experiences with other pharmacological agents (e.g., denosumab or teriparatide). The complexity of this condition presents diagnostic and therapeutic challenges and underscores the importance of a comprehensive and multidisciplinary approach. PMID:27060977

  1. Bisphosphonates adherence for treatment of osteoporosis

    PubMed Central

    2013-01-01

    Background Osteoporosis is a disease of bone metabolism in which bisphosphonates (BPS) are the most common medications used in its treatment, whose main objective is to reduce the risk of fractures. The aim of this study was to conduct a systematic review on BPs adherence for treatment of osteoporosis. Methods Systematic review of articles on BPs adherence for treatment of osteoporosis, indexed on MEDLINE (via PubMed) databases, from inception of databases until January 2013. Search terms were “Adherence, Medication” (MeSH term), “Bisphosphonates” (MeSH term), and “Osteoporosis” (MeSH term). Results Of the 78 identified studies, 27 met the eligibility criteria. Identified studies covered a wide range of aspects regarding adherence and associated factors, adherence and fracture, adherence and BPs dosage. The studies are mostly observational, conducted with women over 45 years old, showing low rates of adherence to treatment. Several factors may influence adherence: socio-economic and cultural, participation of physicians when guidance is given to the patient, the use of bone turnover markers, and use of generic drugs. The monthly dosage is associated with greater adherence compared to weekly dosage. Conclusions Considering the methodological differences between the studies, the results converge to show that adherence to treatment of osteoporosis with BPs is still inadequate. Further experimental studies are needed to evaluate the adherence and suggest new treatment options. PMID:23705998

  2. [New strategies for exercise training in osteoporosis].

    PubMed

    Winkelmann, A; Schilling, S; Neuerburg, C; Mutschler, W; Böcker, W; Felsenberg, D; Stumpf, U

    2015-11-01

    In the prevention and treatment of osteoporosis, movement with muscle strengthening and proprioceptive training plays a major role. This was taken into consideration in the guidelines by the governing body on osteoporosis (Dachverband Osteoporose, DVO) from 2014 on prophylaxis, diagnosis and treatment of osteoporosis and in the DVO guidelines from 2008 on physiotherapy and exercise therapy for osteoporosis. Increases in lumbar bone density of between 0.5 % and 2.5 % can be achieved in women by strengthening exercises with high resistance. With this combination and strengthening of the quadriceps muscle a reduction of falls and hence the fracture risk could also be achieved. In traumatology, training for muscle strengthening is not always possible, especially for elderly patients. Practically relevant alternatives are regular walking and aquatraining, which may also lead to a significant increase in bone mineral density. Furthermore, large effects can be achieved with alternating side whole-body vibration (WBV) training with whole body vibration plates with only 3 days of training per week and with short training periods (15-20 min). Rates of increase in leg strength between 20 % and almost 40 % and in bone density between 0.5 % and 4 % in 6 months have been described. Whether and with what intensity whole body vibration therapy could be used for e.g. more rapid healing of fractures, is currently unclear. Initial positive results have been described in animal models. PMID:26467265

  3. Immunology of Osteoporosis: A Mini-Review.

    PubMed

    Pietschmann, Peter; Mechtcheriakova, Diana; Meshcheryakova, Anastasia; Föger-Samwald, Ursula; Ellinger, Isabella

    2016-01-01

    Osteoporosis is a major cause of fractures and associated morbidity in the aged population. The pathogenesis of osteoporosis is multifactorial; whereas traditional pathophysiological concepts emphasize endocrine mechanisms, it has been recognized that also components of the immune system have a significant impact on bone. Since 2000, when the term 'osteoimmunology' was coined, novel insights into the role of inflammatory cytokines by influencing the fine-tuned balance between bone resorption and bone formation have helped to explain the occurrence of osteoporosis in conjunction with chronic inflammatory reactions. Moreover, the phenomenon of a low-grade, chronic, systemic inflammatory state associated with aging has been defined as 'inflamm-aging' by Claudio Franceschi and has been linked to age-related diseases such as osteoporosis. Given the tight anatomical and physiological coexistence of B cells and the bone-forming units in the bone marrow, a role of B cells in osteoimmunological interactions has long been suspected. Recent findings of B cells as active regulators of the RANK/RANKL/OPG axis, of altered RANKL/OPG production by B cells in HIV-associated bone loss or of a modulated expression of genes linked to B-cell biology in response to estrogen deficiency support this assumption. Furthermore, oxidative stress and the generation of advanced glycation end products have emerged as links between inflammation and bone destruction. PMID:26088283

  4. Decreased Bone Formation Explains Osteoporosis in a Genetic Mouse Model of Hemochromatosiss

    PubMed Central

    Doyard, Mathilde; Chappard, Daniel; Leroyer, Patricia; Roth, Marie-Paule; Loréal, Olivier; Guggenbuhl, Pascal

    2016-01-01

    Osteoporosis may complicate iron overload diseases such as genetic hemochromatosis. However, molecular mechanisms involved in the iron-related osteoporosis remains poorly understood. Recent in vitro studies support a role of osteoblast impairment in iron-related osteoporosis. Our aim was to analyse the impact of excess iron in Hfe-/- mice on osteoblast activity and on bone microarchitecture. We studied the bone formation rate, a dynamic parameter reflecting osteoblast activity, and the bone phenotype of Hfe−/− male mice, a mouse model of human hemochromatosis, by using histomorphometry. Hfe−/− animals were sacrificed at 6 months and compared to controls. We found that bone contains excess iron associated with increased hepatic iron concentration in Hfe−/− mice. We have shown that animals with iron overload have decreased bone formation rate, suggesting a direct impact of iron excess on active osteoblasts number. For bone mass parameters, we showed that iron deposition was associated with bone loss by producing microarchitectural impairment with a decreased tendency in bone trabecular volume and trabecular number. A disorganization of trabecular network was found with marrow spaces increased, which was confirmed by enhanced trabecular separation and star volume of marrow spaces. These microarchitectural changes led to a loss of connectivity and complexity in the trabecular network, which was confirmed by decreased interconnectivity index and increased Minkowski’s fractal dimension. Our results suggest for the first time in a genetic hemochromatosis mouse model, that iron overload decreases bone formation and leads to alterations in bone mass and microarchitecture. These observations support a negative effect of iron on osteoblast recruitment and/or function, which may contribute to iron-related osteoporosis. PMID:26829642

  5. Osteoporosis in German men: a cost-of-illness study.

    PubMed

    Berghaus, Sabine; Müller, Dirk; Gandjour, Afschin; Civello, Daniele; Stock, Stephanie

    2015-06-01

    Costs of male osteoporosis may have increased due to population aging and change of treatment patterns. This cost-of-illness study provides a current estimate of the economic burden of male osteoporosis in Germany. Routine claims data from six German sickness funds were analyzed and extrapolated to the German statutory health insurance (SHI). For men above the age of 50 with at least one ICD-10 osteoporosis-related diagnosis or osteoporosis-related fracture in 2010, direct costs related to osteoporosis were considered based on a payer's perspective. Total direct costs attributable to osteoporosis amounted to €728 million in 2010. The majority of these costs (71%) resulted from inpatient treatment due to fractures. Patients aged 75 and older caused approximately 63% of costs. Male osteoporosis represents a non-negligible economic burden for the German health care system. Targeted prevention and promotion measures should be offered both to men and women. PMID:25495596

  6. Diurnal Variation in Response to Intravenous Glucose*

    PubMed Central

    Whichelow, Margaret J.; Sturge, R. A.; Keen, H.; Jarrett, R. J.; Stimmler, L.; Grainger, Susan

    1974-01-01

    Intravenous glucose tolerance tests (25 g) were performed in the morning and afternoon on 13 apparently normal persons. The individual K values (rate of decline of blood sugar) were all higher in the morning tests, and the mean values were significantly higher in the morning. Fasting blood sugar levels were slightly lower in the afternoon. There was no difference between the fasting morning and afternoon plasma insulin levels, but the levels after glucose were lower in the afternoon. Growth hormone levels were low at all times in non-apprehensive subjects and unaffected by glucose. The results suggest that the impaired afternoon intravenous glucose tolerance, like oral glucose tolerance, is associated with impaired insulin release and insulin resistance. PMID:4817160

  7. Glucose control.

    PubMed

    Preiser, Jean-Charles

    2013-01-01

    Stress-related hyperglycemia is a common finding in acutely ill patients, and is related to the severity and outcome of the critical illness. The pathophysiology of stress hyperglycemia includes hormonal and neural signals, leading to increased production of glucose by the liver and peripheral insulin resistance mediated by the translocation of transmembrane glucose transporters. In one pioneering study, tight glycemic control by intensive insulin therapy in critically ill patients was associated with improved survival. However, this major finding was not confirmed in several other prospective randomized controlled trials. The reasons underlying the discrepancy between the first and the subsequent studies could include nutritional strategy (amount of calories provided, use of parenteral nutrition), case-mix, potential differences in the optimal blood glucose level (BG) in different types of patients, hypoglycemia and its correction, and the magnitude of glucose variability. Therefore, an improved understanding of the physiology and pathophysiology of glycemic regulation during acute illness is needed. Safe and effective glucose control will need improvement in the definition of optimal BG and in the measurement techniques, perhaps including continuous monitoring of insulin algorithms and closed-loop systems. PMID:23075589

  8. Clinical Assessment of Functional Movement in Adults with Visual Impairments

    ERIC Educational Resources Information Center

    Ray, Christopher T.; Horvat, Michael; Williams, Michael; Blasch, Bruce B.

    2007-01-01

    Adults with visual impairments have significantly more health risks than do sighted adults because of a number of factors, including the lower mineral density of their femoral neck bones, which is indicative of reduced weight-bearing exercise; their lesser maximal strength; and their higher rates of stroke, osteoporosis, depression, hypertension,…

  9. Prevention of Bone Loss in a Model of Postmenopausal Osteoporosis through Adrenomedullin Inhibition

    PubMed Central

    Martínez-Herrero, Sonia; Larrayoz, Ignacio M.; Ochoa-Callejero, Laura; Fernández, Luis J.; Allueva, Alexis; Ochoa, Ignacio; Martínez, Alfredo

    2016-01-01

    Despite recent advances in the understanding and treatment options for osteoporosis, this condition remains a serious public health issue. Adrenomedullin (AM) is a regulatory peptide with reported activity on bone remodeling. To better understand this relationship we built an inducible knockout for AM. An outstanding feature of knockout mice is their heavier weight due, in part, to the presence of denser bones. The femur of knockout animals was denser, had more trabeculae, and a thicker growth plate than wild type littermates. The endocrine influence of AM on bone seems to be elicited through an indirect mechanism involving, at least, the regulation of insulin, glucose, ghrelin, and calcitonin gene-related peptide (CGRP). To confirm the data we performed a pharmacological approach using the AM inhibitor 16311 in a mouse model of osteoporosis. Ovariectomized females showed significant bone mass loss, whereas ovariectomized females treated with 16311 had similar bone density to sham operated females. In conclusion, we propose the use of AM inhibitors for the treatment of osteoporosis and other conditions leading to the loss of bone mass. PMID:27445864

  10. Glucose Variability

    PubMed Central

    2013-01-01

    The proposed contribution of glucose variability to the development of the complications of diabetes beyond that of glycemic exposure is supported by reports that oxidative stress, the putative mediator of such complications, is greater for intermittent as opposed to sustained hyperglycemia. Variability of glycemia in ambulatory conditions defined as the deviation from steady state is a phenomenon of normal physiology. Comprehensive recording of glycemia is required for the generation of any measurement of glucose variability. To avoid distortion of variability to that of glycemic exposure, its calculation should be devoid of a time component. PMID:23613565

  11. Prevalence of osteoporosis in patients awaiting total hip arthroplasty

    PubMed Central

    Domingues, Vitor Rodrigues; de Campos, Gustavo Constantino; Plapler, Pérola Grimberg; de Rezende, Márcia Uchôa

    2015-01-01

    Objective: To evaluate the prevalence of osteoporosis in patients awaiting total hip arthroplasty. Method: Twenty-nine patients diagnosed with hip osteoarthritis awaiting primary total arthroplasty of the hip answered WOMAC questionnaire, VAS and questions about habits, osteoporosis and related diseases. Bone mineral densitometry of the lumbar spine and hips and laboratory tests (complete blood count and examination of calcium metabolism) were performed. Weight and height were measured to calculate body mass index (BMI). The evaluated quantitative characteristics were compared between patients with and without osteoporosis using the Mann-Whitney tests. Results: Thirteen men and 16 women with a mean age of 61.5 years old, WOMAC 51.4; EVA 6.4 and BMI 27.6 were evaluated. The prevalence of osteoporosis was 20.7%, and 37.9% had osteopenia. Patients with osteoporosis were older than patients without osteoporosis (p=0.006). The mean bone mineral density of the femoral neck without hip osteoarthritis was lower than the affected side (p=0.007). Thirty-five percent of patients did not know what osteoporosis is. Of these, 30% had osteopenia or osteoporosis. Conclusion: osteoarthritis and osteoporosis may coexist and the population waiting for total hip arthroplasty should be considered at risk for the presence of osteoporosis. Level of Evidence III, Observational Study. PMID:26327793

  12. Spaceflight osteoporosis: current state and future perspective.

    PubMed

    Cappellesso, R; Nicole, L; Guido, A; Pizzol, D

    2015-10-01

    Osteoporosis is one of the established major consequences of long-duration spaceflights in astronauts seriously undermining their health after their returning on Earth. Indeed, astronauts typically lose more bone mass during one month than postmenopausal women on Earth lose in one year. To date, countermeasures mainly consist in exercise and supplementation while pharmacological treatment as those used in postmenopausal women are not routine. However, it is evident that exercise and supplementation alone are not enough to maintain bone homeostasis. In this paper we describe the current countermeasures for bone loss during long-term spaceflight, review the modern treatment which are successfully employed to prevent osteoporosis on Earth and that could be quickly used also for astronauts and finally focus on the recent cellular and molecular understanding of bone homeostasis which might provide the basis for the development of future targeted therapies. PMID:26494042

  13. Osteoporosis diagnostics in patients with rheumatoid arthritis

    PubMed Central

    Dura, Marta; Blumfield, Einat; Żuchowski, Paweł; Waszczak, Marzena; Jeka, Sławomir

    2016-01-01

    Rheumatoid arthritis (RA) is a chronic systemic connective tissue disease. The development of comorbidities often occurs in the course of RA. One of them is osteoporosis, which has serious social and economic effects and may contribute to the increase in the degree of disability and premature death of the patient. Due to the young age in which RA disease occurs, densitometry (DXA) of the lumbar spine is the basic examination in osteoporosis diagnostics. In the course of RA, much more frequently than in healthy persons of the same age, osteoporotic fractures of vertebral bodies occur, which hinder a correct assessment in the DXA test. Rheumatoid arthritis patients often undergo computed tomography (CT) examination of the abdominal cavity for other medical indications than suspected spinal injury. Then, CT examination may also serve for the assessment of bone density, especially in patients with osteoporotic fractures. PMID:27407274

  14. Safety considerations with bisphosphonates for the treatment of osteoporosis.

    PubMed

    Strampel, William; Emkey, Ronald; Civitelli, Roberto

    2007-01-01

    , chills, myalgia and arthralgia. These symptoms are transitory and self-limiting and usually do not recur after subsequent drug administration. Symptoms of influenza-like illness have been associated with both IV and oral bisphosphonates. Osteonecrosis of the jaw has also been associated with IV bisphosphonate treatment, particularly in patients treated with high doses. A small number of patients with cancer and osteoporosis using oral bisphosphonates have also reported this AE. As osteonecrosis of the jaw is difficult to treat and is often associated with dental procedures and poor oral hygiene, preventive measures seem to be the best management option for patients taking bisphosphonates.Overall, the safety and tolerability profile of the nitrogen-containing bisphosphonates is good, and long-term treatment does not appear to carry a risk of serious AEs. By encouraging adherence to administration instructions physicians can minimise certain complications, such as UGI intolerability. By being aware of other potential safety issues, such as renal impairment, influenza-like illness and osteonecrosis of the jaw, physicians can detect these AEs early in the course of treatment. PMID:17722968

  15. Osteoporosis: the emperor has no clothes

    PubMed Central

    Järvinen, T L N; Michaëlsson, K; Aspenberg, P; Sievänen, H

    2015-01-01

    Current prevention strategies for low-trauma fractures amongst older persons depend on the notions that fractures are mainly caused by osteoporosis (pathophysiology), that patients at high risk can be identified (screening) and that the risk is amenable to bone-targeted pharmacotherapy (treatment). However, all these three notions can be disputed. Pathophysiology Most fracture patients have fallen, but actually do not have osteoporosis. A high likelihood of falling, in turn, is attributable to an ageing-related decline in physical functioning and general frailty. Screening Currently available fracture risk prediction strategies including bone densitometry and multifactorial prediction tools are unable to identify a large proportion of patients who will sustain a fracture, whereas many of those with a high fracture risk score will not sustain a fracture. Treatment The evidence for the viability of bone-targeted pharmacotherapy in preventing hip fracture and other clinical fragility fractures is mainly limited to women aged 65–80 years with osteoporosis, whereas the proof of hip fracture-preventing efficacy in women over 80 years of age and in men at all ages is meagre or absent. Further, the antihip fracture efficacy shown in clinical trials is absent in real-life studies. Many drugs for the treatment of osteoporosis have also been associated with increased risks of serious adverse events. There are also considerable uncertainties related to the efficacy of drug therapy in preventing clinical vertebral fractures, whereas the efficacy for preventing other fractures (relative risk reductions of 20–25%) remains moderate, particularly in terms of the low absolute risk reduction in fractures with this treatment. PMID:25809279

  16. [Osteoporosis in men and androgen replacement therapy].

    PubMed

    Tsujimura, Akira; Okuyama, Akihiko

    2003-11-01

    Androgen plays an important role in bone maturation and maintenance of bone mass. Androgen deficiency associated with aging causes osteoporosis for men. With respect to this disease, androgen replacement treatment has been performed for aging male. However, available preparations of androgen are limited in Japan and each of them has both merit and demerit. Establishment of guideline for androgen replacement treatment including criteria of serum testosterone concentration is the problem, which now confronts us. PMID:15775234

  17. Clodronate news of efficacy in osteoporosis

    PubMed Central

    Nardi, Alfredo; Ventura, Lorenzo; Cozzi, Luisella; Tonini, Greta

    2016-01-01

    Summary Clodronate belongs to Bisphosphonates family and it has been studied especially for osteoporosis treatment, Paget’s disease, osteolytic metastases, hypercalcemia malignancy and some childhood skeletal diseases. Besides the osteoporosis treatment, it has been successfully used for treating tumoral osteolysis and for bone localization of multiple myeloma, hypercalcemia malignancy, primary hyperparathyroidism, Paget’s disease and algodystrophy. Filipponi study showed a statistically significant reduction of the incidence of vertebral fractures after 4 years of treatment with clodronate, intravenously administered at a dose of 200 mg every three weeks. Frediani study, published in 2003 on BONE, proved the clodronate efficacy in the prevention of fractures caused by glucocorticoid-induced osteoporosis (GIO). Clodronate doses of 800 mg/day per os and 100 mg i.m./week are substantially equivalent, because the oral absorption is about 1,9%. A higher efficacy on BMD was documented in various works, especially in cohorts of patients with a greater fracture risk, using higher doses (1600 mg per os). This has led to the hypothesis of using clodronate 200 mg i.m. formulation. Clodronate is an osteoporosis drug that can be assumed in different doses (100 mg i.m./week, clodronate 200 mg i.m. every 2 weeks) considering the risk band, identified by algorithms (FRAX o DeFRA), by BMD and by the presence of at least one risk factor. That means that it is possible to envisage a differentiated use of clodronate adapting the doses to the fracture risk and to the severity of pain symptoms, thus promoting a greater adherence to the therapy. To conclude clodronate is helpful in reducing fracture risk, is safe, well tolerated, and has a good rate cost/effectiveness in patients with fracture risk over 7% established with FRAX. PMID:27252741

  18. Prevalence and predictive factors of osteoporosis in systemic sclerosis patients: a case-control study

    PubMed Central

    Marot, Mathilde; Valéry, Antoine; Esteve, Eric; Bens, Guido; Müller, Adelheid; Rist, Stéphanie; Toumi, Hechmi; Lespessailles, Eric

    2015-01-01

    Purpose Investigate the prevalence of osteoporosis in patients with systemic sclerosis (SSc) and describe alterations of bone tissue with High-Resolution peripheral Quantitative Computed Tomography (HR-pQCT). Methods Thirty-three patients and 33 controls matched on age, body mass index (BMI) and menopause were included. Bone mineral density (BMD) was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by dual energy X-ray absorptiometry. Volumetric BMD (vBMD) and bone microarchitecture were measured by HR-pQCT at tibia and radius. Results In patients, BMI was significantly lower, the prevalence of osteoporosis was significantly higher and HR-pQCT analysis showed a significant alteration of the trabecular compartment with a decrease in trabecular vBMD on both sites than in controls. In multivariate analysis, a low lean body mass, presence of anticentromere antibodies and older age were identified as independent factors for decreased BMD at LS (r²=0.43), FN (r²=0.61) and TH (r²=0.73). History or current digital ulcers were also identified as an independent factor for microarchitecture alteration. Conclusion In patients an increased prevalence of osteoporosis was found and HR-pQCT showed impaired trabecular bone compartment. Also, low lean body mass, high age, digital ulcers and ACAs were identified as independent risk factors for bone damage. PMID:25944694

  19. Nandrolone decanoate for men with osteoporosis.

    PubMed

    Hamdy, R C; Moore, S W; Whalen, K E; Landy, C

    1998-03-01

    To compare the efficacy and safety of nandrolone decanoate and calcium (NDC) with those of calcium alone (CAL) in men with idiopathic osteoporosis, a 12-month, randomized, prospective, controlled study, was performed in an outpatient clinic. Twenty-one men with idiopathic osteoporosis (as determined by radiological and dual energy x-ray absorptiometry findings) were randomly allocated to either 50 mg nandrolone decanoate intramuscularly (im) weekly and 1,000 mg oral calcium carbonate daily (NDC group) or to 1,000 mg oral calcium carbonate daily (CAL group). Bone densitometry (total body, left femur, and lumbar spine), serum, and urine biochemical parameters were measured at 3-month intervals. In the NDC group, bone mineral density initially increased, reached a plateau, and then decreased to near baseline levels at 12 months. Increases in lean muscle mass mirrored these changes. Free and total testosterone significantly decreased. Hemoglobin increased in all patients in this group. Patients in the CAL group exhibited no significant change in either total body or bone mineral density or biochemical parameters. Thus, nandrolone decanoate, 50 mg im weekly, transiently increases the bone mass of men with idiopathic osteoporosis in this preliminary study. Careful monitoring is necessary. PMID:10099043

  20. To prevent the osteoporosis playing in advance

    PubMed Central

    Colì, Giuseppe

    2013-01-01

    Summary There are several possibilities for the prevention of primary, secondary and tertiary osteoporosis but till now they have not been promoted enough and bone fragility is thought about only after the onset of a fracture (tertiary prevention). By recent studies and discoveries it is becoming increasingly clear that there is a relationship between growth and development in early childhood and bone health in old age. Suboptimal bone development leads to a reduction in peak bone mass, and a higher risk of osteoporotic fracture later in life. Preventative strategies against osteoporosis can be aimed at either optimizing the peak bone mass obtained, or reducing the rate of bone loss. Optimization of peak bone mass may be more amenable to public health strategies. Technological advances and our knowledge of osteoporosis have increased in the last decade and so tertiary prevention should be considered a failure in the field of public health. If we want to make advances in the osteoporotic field, we must start in childhood, before the bone mass peak is reached and the gold-standard is starting with prevention as soon as possible, also during fetal development. PMID:24133522

  1. Osteoporosis: an increasing concern in pediatric dentistry.

    PubMed

    da Fonseca, Marcio A

    2011-01-01

    Increasing numbers of children are being affected by low bone density and osteoporosis. Bone fractures are the main reason for hospitalization between 10 and 14 years of age and, over the past 3 decades, there has been an increase in the incidence of fractures in children. Childhood factors such as lifestyle, diet, chronic illness, and medications have a vital short-term impact on bone health and a long-term effect on the achievement of peak bone mass, with the potential for morbidity in adulthood. The primary forms of osteoporosis consist of rare inherited conditions, but the secondary forms are becoming more common given that chronically ill children are surviving longer. This subject should be of interest to pediatric dentists, because low mineral density and osteoporosis, together with drugs used to treat them (eg, bisphosphonates), may cause adverse effects in the oral cavity. Furthermore, the pediatric dentist is an important health care professional to counsel patients about healthy lifestyles that can help prevent the condition from an early age. PMID:21703077

  2. Denosumab for the Treatment of Osteoporosis

    PubMed Central

    Zaheer, Sarah; LeBoff, Meryl; Lewiecki, E. Michael

    2015-01-01

    Introduction Low trauma fractures due to osteoporosis are a major health concern worldwide. Despite the availability of many therapeutic compounds to reduce fracture risk, osteoporosis remains undertreated and the burden of osteoporotic fractures remains high. Denosumab is a novel agent that acts to reduce bone turnover, improve bone mineral density, and reduce fracture risk, offering a favorable efficacy and safety profile. Areas covered This review covers the pharmacology and major clinical trials with extension/post-marketing follow-up, including trials for all FDA-approved indications of denosumab to date. Expert Opinion Denosumab is an efficacious and safe osteoporosis treatment option, with current data up to 8 years of continued use showing continued improvement in bone density with sustained fracture risk reduction. Safety profiles overall are similar to placebo, with no new safety concerns in extension trials, though a theoretical increased risk of infection exists with RANKL inhibition. Future considerations include safety of prolonged treatment beyond 8 years, and efficacy/fracture risk after discontinuation or with non-adherence, given the characteristic pharmacodynamic profile of denosumab. PMID:25614274

  3. Studies on the pathophysiology and therapy of osteoporosis.

    PubMed

    Ambrus, J L; Ambrus, J L; Robin, J C; Ambrus, C M; Kahn, E A

    1984-01-01

    Etiologic and pathologic factors in clinical osteoporosis are reviewed. Techniques were developed to determine total skeletal calcium content with in vivo neutron activation analysis and to induce osteoporosis (in about three months) with low calcium diet, corticosteroid or heparin treatment in experimental animals. Genetic influence was demonstrated: C3H/St (Ha) mice were more susceptible to osteoporosis by all three modalities than C57B1/6 (J) mice. Fluoride was ineffective in preventing osteoporosis induced by either of these three modalities. Heparin induced osteoporosis was prevented by conjugated estrogens, progestins or their combinations. Progestins were shown in other studies to inhibit estrogen induced metaplasia and neoplasia. Combining estrogens with progestin may result in an increased therapeutic index for the prevention of postmenopausal osteoporosis. Human and salmon calcitonin, Deca - Durabolin, an anabolic steroid, Mopidamole, a pyrimidopyrimidine derivative, Trental, a methylxanthine derivative, certain 2-thiophene carboxylic acid derivatives and imidazoquinazolines exhibited anti-osteoporotic effects. PMID:6396359

  4. Nigella Sativa reverses osteoporosis in ovariectomized rats

    PubMed Central

    2014-01-01

    Background Osteoporosis poses a significant public health issue. It is a skeletal disorder characterized by compromised bone strength that predisposes to increased risk of fracture. There is a direct relationship between the lack of estrogen after menopause and the development of osteoporosis. About 33% of women over 50 will experience bone fractures as a result of osteoporosis. Nigella Sativa (NS) has been shown to have beneficial effects on bone and joint diseases. The present study was conducted to elucidate the protective effect of Nigella Sativa on osteoporosis produced by ovariectomy in rats. Methods Female Wistar rats aged 12–14 months were divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized supplemented with nigella sativa (OVX-NS) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. After 12 weeks, plasma levels of calcium (Ca+2), phosphorous (Pi), alkaline phosphatase (ALP), amino terminal collagen type 1 telopeptide, malondialdehyde (MDA), nitrates, nitric oxide surrogate, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Histological examination of the liver and the tibia was conducted. Histomorphometric analysis of the tibia was also performed. Results OVX rats showed significant decrease in plasma Ca+2, accompanied by a significant increase in plasma ALP, amino terminal collagen type 1 telopeptide, MDA, nitrates, TNF-α and IL-6. These changes were reversed by NS supplementation in OVX-NS group to be near SHAM levels. Histological examination of the tibias revealed discontinuous eroded bone trabeculae with widened bone marrow spaces in OVX rats accompanied by a significant decrease in both cortical and trabecular bone thickness compared to Sham rats. These parameters were markedly reversed in OVX-NS rats. Histological examination of the liver showed mononuclear cellular infiltration and congestion of blood vessels at the portal area in OVX rats which were not found

  5. Incidence of Osteoporosis in Patients with Urolithiasis

    PubMed Central

    Bijelic, Radojka; Milicevic, Snjezana; Balaban, Jagoda

    2014-01-01

    ABSTRACT Introduction. Clinical researches have shown an increased bone disintegration and lower bone mass in patients with calcium urolithiasis. Goal. The goal of our research was to establish the incidence of osteoporosis in adult patients with calcium urolithiasis, on the basis of measuring mineral bone density, using DEXA method, with a special reflection on age subgroups. Material and methods. Clinical research was prospective and it was implemented at the University Clinical Center of Banja Luka, at the Clinic for Endocrinology, Diabetes and Metabolic Diseases and at the Urology Clinic. Material in this research consisted of patients divided in two groups, a working and a control group. One hundred and twenty (120) patients were included in both these groups, divided in three age subgroups: 20-40, 40-60 and over 60. The working group consisted of the patients with calcium urolithiasis and the control group consisted of patients without calcium urolithiasis. Establishing of mineral bone density at L2-L4 of lumbal spine vertebrae and hip was done for the patients in both these groups, using DEXA method. Results. Analysis of mineral bone density using DEXA method in patients in age groups of working and control groups, as well as in the total sample of working and control groups, have shown that the patients of the working group, over 60, had a decreased mineral bone density (30% of osteopenia and 15% osteoporosis) significantly more expressed when compared to the other two age groups (12.5% in the subgroup 20-40 and 17.5% in the subgroup 40-60), which presents a statistically significant difference (p<0.05). In the control group, when taking into account age groups, osteopenia and osteoporosis were marked in 37.5% and 2.5% in the group of patients over 60, whereas in the youngest population, 5% of osteopenia was found, which presents a statistically significant difference (p<0.05). When observing the total sample of working and control group, there was a

  6. Biological agents in management of osteoporosis.

    PubMed

    Tella, Sri Harsha; Gallagher, J Christopher

    2014-11-01

    Osteoporosis is a skeletal disease associated with an imbalance between formation and resorption, leading to net loss of bone mass, loss of bone microarchitecture, and development of fractures. Bone resorption is primarily due to an activation of osteoclastogenesis and an increase in receptor activator of nuclear factor kappa-B ligand (RANKL) expression, a cytokine involved in the final pathway of the osteoclast cycle.Recent studies of genetic diseases led to the discovery of the wingless-type (Wnt) signaling pathway that plays a major role in bone formation. Further work showed that sclerostin produced by osteocytes and the Dickkopf (DKK1) protein secreted in bone were negative regulators of the Wnt signaling bone formation pathway that act directly by binding to the co-receptors LRP5 and LRP6 of WnT and thereby inhibiting the anabolic Wnt pathway. This understanding of the bone remodeling led to the discovery of new biological drugs that target these pathways and have been evaluated in clinical trials.The current article discusses the role of these newer "biological" agents in management of osteoporosis. Denosumab, a human monoclonal antibody that specifically binds RANKL, blocks the binding of RANK to its ligand markedly reducing bone resorption, increases bone density, and reduces fractures and is approved for osteoporosis. Parathyroid hormone PTH 1-34 (teriparatide) stimulates bone formation through inhibition of sclerostin, DKK1, and frizzled protein; increases BMD; improves microarchitecture; and decreases fractures and is approved for osteoporosis. The anti-sclerostin antibodies (romosozumab, blosozumab) increase bone mass by neutralizing the negative effects of sclerostin on the Wnt signaling pathway. These biologics are being evaluated now in a clinical trial and early data looks promising. Cathepsin K is a proteolytic enzyme that degrades bone matrix and inhibitors such as odanacatib show increasing bone density and perhaps decreased fractures. The

  7. [Diagnostic criteria for primary osteoporosis : year 2012 revision].

    PubMed

    Soen, Satoshi

    2014-03-01

    In 1995, the Japanese Society for Bone and Mineral Metabolism (now the Japanese Society for Bone and Mineral Research) established The Osteoporosis Diagnostic Criteria Review Committee. Following discussion held at the 13th scientific meeting of the Society in 1996, the Committee, with the consensus of its members, proposed diagnostic criteria for primary osteoporosis. The Committee revised those criteria in 1996 and again in 2000. Japanese Society for Bone and Mineral Research and Japan Osteoporosis Society Joint Review Committee for the Revision of the Diagnostic Criteria for Primary Osteoporosis aimed at obtaining international consistency and made a revised edition based on the new findings in 2012. PMID:24576928

  8. The position of strontium ranelate in today's management of osteoporosis.

    PubMed

    Reginster, J-Y; Brandi, M-L; Cannata-Andía, J; Cooper, C; Cortet, B; Feron, J-M; Genant, H; Palacios, S; Ringe, J D; Rizzoli, R

    2015-06-01

    Osteoporosis accounts for about 3 % of total European health-care spending. The low proportion of costs for the pharmacological prevention of osteoporotic fracture means that it is highly cost saving, especially in patient with severe osteoporosis or patients who cannot take certain osteoporosis medications due to issues of contraindications or tolerability. Following recent regulatory changes, strontium ranelate is now indicated in patients with severe osteoporosis for whom treatment with other osteoporosis treatments is not possible, and without contraindications including uncontrolled hypertension, established, current or past history of ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease. We review here today's evidence for the safety and efficacy of strontium ranelate. The efficacy of strontium ranelate in patients complying with the new prescribing information (i.e. severe osteoporosis without contraindications) has been explored in a multivariate analysis of clinical trial data, which concluded that the antifracture efficacy of strontium ranelate is maintained in patients with severe osteoporosis without contraindications and also demonstrated how the new target population mitigates risk. Strontium ranelate is therefore an important alternative in today's management of osteoporosis, with a positive benefit-risk balance, provided that the revised indication and contraindications are followed and cardiovascular risk is monitored. The bone community should be reassured that there remain viable alternatives in patients in whom treatment with other agents is not possible and protection against the debilitating effects of fracture is still feasible in patients with severe osteoporosis. PMID:25868510

  9. Senile osteoporosis: is it an immune-mediated disease?

    PubMed

    De Martinis, M; Di Benedetto, M C; Mengoli, L P; Ginaldi, L

    2006-10-01

    Osteoporosis is a major cause of morbidity in older people. There are a large number of risk factors for the development of senile osteoporosis. However, recent discoveries suggest that these risk factors could exert their effects through immunologically mediated modulation of bone remodelling. Inflamm-ageing itself plays a role in bone remodelling through pro-inflammatory cytokines, which are known to influence osteoclasts and osteoblasts, together with other more recently discovered immunological mediators and transcription factors. Senile osteoporosis is an example of the central role of immune-mediated inflammation in determining bone resorption. In this review, we will discuss the pathogenesis of osteoporosis in the context of immunosenescence. PMID:17109066

  10. What People with Inflammatory Bowel Disease Need to Know about Osteoporosis

    MedlinePlus

    ... information on osteoporosis, contact: NIH Osteoporosis and Related Bone Diseases ~ National Resource Center Website: http://www.bones.nih. ... Pub. No. 16-7900 NIH Osteoporosis and Related Bone Diseases ~ National Resource Center 2 AMS Circle Bethesda, MD ...

  11. P1 - Maxillary Osteoporosis and Genetic Predisposition

    PubMed Central

    Biondi, E.; Delle Rose, G.; Duvina, M.; Civitelli, V.; Brancato, L.; Amunni, F.; Tonelli, P.

    2010-01-01

    Introduction: Osteoporosis is a form of dysmetabolic osteopathy of multifactorial origin, characterised by reduction of the bone matrix and mineral portion and, overall, of bone mass, leading to fragility and increased fracture risk. AETIOPATHOGENESIS -ENDOCRINE FACTORS: ACTH, glycocorticoids, PTH, thyroxine, oestrogen, testosterone-GENETIC FACTORS: Major genes that regulate fundamental characteristics of bone, such as density and quality, and minor genes that regulate individual genetic background [lipoprotein receptor related protein (LRP5), TGF1, BMP, VDR, COL1A1, ER]. The DIAGNOSIS is based on history, clinical findings (vertebral or appendicular fractures), blood chemistry, conventional radiology and bone mass measurement. For the latter, it is possible to use DUAL-ENERGY X-RAY DENSITOMETRY which measures bone mineral content: according to the WHO definition, in osteoporosis bone mineral density (BMD) is more than 2.5 standard deviations below normal. MAXILLARY OSTEOPOROSIS: because of their function as a support for teeth, which leads to the development of the alveolar process, and their role in mastication, the jawbones (maxilla and mandible) differ from all the other bones of the skeleton. This role, also involving the masticatory muscles, prompts bone trophism. In advancing age a marked reduction of the thickness of the maxillary cortical bone is observed, together with increased porosity and constant functional remodelling of the trabecular part, a phenomenon that, as it increases, leads to tooth loss. Only a mandibular area (a bucco-lingual area of cortical bone in front of the mental foramen) remains unmodified, independently of gender, age and tooth loss. Materials and methods: Kemifar® supplies a test which can be used to study several factors (Er, VDR, COL1A1) that predispose to the development of osteoporosis. OsteoResis®Type is a simple, non-invasive test that allows the complete determination, and interpretation, of several genotypes associated

  12. Role of estrogen in avian osteoporosis.

    PubMed

    Beck, M M; Hansen, K K

    2004-02-01

    One of the difficulties associated with commercial layer production is the development of osteoporosis in hens late in the production cycle. In light of this fact and because of hens' unique requirements for Ca, many studies have focused on the regulation of Ca and the role of estrogen in this process. The time course of estrogen synthesis over the productive life of hens has been well documented; increased circulating estrogen accompanies the onset of sexual maturity while decreases signal a decline in egg production prior to a molt. Numbers of estrogen receptors decrease with age in numerous tissues. The parallel changes in calcium-regulating proteins, primarily Calbindin D28K, and in the ability of duodenal cells to transport Ca, are thought to occur as a result of the changes in estrogen, and are also reversible by the molt process. In addition to the traditional model of estrogen action, evidence now exists for a possible nongenomic action of estrogen via membrane-bound receptors, demonstrated by extremely rapid surges of ionized Ca in chicken granulosa cells in response to 17beta-estradiol. Estrogen receptors have also been discovered in duodenal tissue, and tamoxifen, which binds to the estrogen receptor, has been shown to cause a rapid increase in Ca transport in the duodenum. In addition, recent evidence also suggests that mineralization of bone per se may not explain entirely the etiology of osteoporosis in the hen but that changes in the collagen matrix may contribute through decreases in bone elasticity. Taken together, these studies suggest that changes in estrogen synthesis and estrogen receptor populations may underlie the age-related changes in avian bone. As with postmenopausal women, dietary Ca and vitamin D are of limited benefit as remedies for osteoporosis in the hen. PMID:14979570

  13. Rabbiteye blueberry prevents osteoporosis in ovariectomized rats

    PubMed Central

    2014-01-01

    Objective It has been forecasted that the rabbiteye blueberry could inhibit osteoporosis. However, the inhibition and prevention of osteoporosis via rabbiteye blueberry are still elusive. This study was aim to evaluate the anti-osteoporosis effects of rabbiteye blueberry in ovariectomized rats. Methods Thirty rats were randomly divided into three groups of ten rats each as follows: sham-operated group (SG), ovariectomized model control group (OMG), and ovariectomized rabbiteye blueberry treatment group (OBG). The blood mineral levels, the alkaline phosphatase (ALP) activity, and osteoprotegerin (OPG) level were determined. The expression analyses of type I collagen, integrin-β1, and focal adhesion kinase (FAK) were performed. Besides, the bone mineral density (BMD) and bone histomorphometry (BH) were measured. Results The ALP activity in SG and OBG was significantly lower than that in OMG. For the OPG level, the significant increase of OPG level in OBG was indicated compared with the other groups. The mRNA expression levels of type I collagen, integrin-β1, and FAK in OMG were significantly lower than those in other groups. The BMD in OMG were all significantly lower than those in SG and OBG. For BH, blueberry significantly improved the trabecular bone volume fraction, trabecular thickness, mean trabecular bone number, and bone formation rate, and decreased the trabecular separation, the percent of bone resorption perimeter, and mean osteoclast number in OBG compared with OMG. Conclusions The rabbiteye blueberries had an effective inhibition in bone resorption, bone loss, and reduction of bone strength of ovariectomized rats and could improve the BMD, osteogenic activity, and trabecular bone structure. PMID:25102951

  14. Osteoporosis and sarcopenia: two diseases or one?

    PubMed Central

    Reginster, Jean-Yves; Beaudart, Charlotte; Buckinx, Fanny; Bruyère, Olivier

    2016-01-01

    Purpose of review This article reviews recently published evidence for common pathways explaining bone and muscle wasting in normal ageing and pathological conditions. Recent findings Numerous studies support the concept of a bone–muscle unit, where constant cross-talking between the two tissues takes place, involving molecules released by the skeletal muscle secretome, which affects bone, and osteokines secreted by the osteoblasts and osteocytes, which, in turn, impact muscle cells. Summary New chemical entities aiming at concomitantly treating osteoporosis and sarcopenia could be developed by targeting pathways that centrally regulate bone and muscle or emerging pathways that facilitate the communication between the two tissues. PMID:26418824

  15. Idiopathic Juvenile Osteoporosis: A Case Report.

    PubMed

    Altan, Halenur; Tosun, Gül; Şen, Yaşar

    2015-08-01

    Idiopathic Juvenile Osteoporosis (IJO) is a very rare disease, self restrictive and shows marked, spontaneous improvement during adolescence. The major clinical features were pain with difficulty walking, growth retardation, oral and dental abnormalities with radiographically porous bone structure. A 13-year-old male referred to paediatric dentistry clinic for toothache. The observations made with extra-intraoral clinic examination that one revealed short and skinny stature, diffuse caries in deciduous teeth, abraded lower incisor, deep bite and dysmorphic appearance in permanent incisor. This report emphasizes the recognized features of IJO as well as describes facio-dental findings that could aid in the diagnosis and management of these patients. PMID:26436063

  16. Exercise and osteoporosis: Methodological and practical considerations

    NASA Technical Reports Server (NTRS)

    Block, Jon E.; Friedlander, Anne L.; Steiger, Peter; Genant, Harry K.

    1994-01-01

    Physical activity may have important implications for enhancing bone density prior to the initiation of space flight, for preserving bone density during zero gravity, and for rehabilitating the skeleton upon return to Earth. Nevertheless, the beneficial effects of exercise upon the skeleton have not been proven by controlled trials and no consensus exists regarding the type, duration, and intensity of exercise necessary to make significant alterations to the skeleton. The following sections review our current understanding of exercise and osteoporosis, examine some of the methodological shortcomings of these investigations, and make research recommendations for future clinical trials.

  17. Idiopathic Juvenile Osteoporosis: A Case Report

    PubMed Central

    Tosun, Gül; Şen, Yaşar

    2015-01-01

    Idiopathic Juvenile Osteoporosis (IJO) is a very rare disease, self restrictive and shows marked, spontaneous improvement during adolescence. The major clinical features were pain with difficulty walking, growth retardation, oral and dental abnormalities with radiographically porous bone structure. A 13-year-old male referred to paediatric dentistry clinic for toothache. The observations made with extra-intraoral clinic examination that one revealed short and skinny stature, diffuse caries in deciduous teeth, abraded lower incisor, deep bite and dysmorphic appearance in permanent incisor. This report emphasizes the recognized features of IJO as well as describes facio-dental findings that could aid in the diagnosis and management of these patients. PMID:26436063

  18. A Practical Approach to Osteoporosis Management in the Geriatric Population

    PubMed Central

    Liberman, Dan; Cheung, Angela

    2015-01-01

    Osteoporosis is a medical condition that is seen commonly in elderly patients, and it is associated with a large burden of morbidity and mortality. This article provides a practical approach to the workup and management of osteoporosis in patients 65 years or older. PMID:25825609

  19. A Multidisciplinary Osteoporosis Service-Based Action Research Study

    ERIC Educational Resources Information Center

    Whitehead, Dean; Keast, John; Montgomery, Val; Hayman, Sue

    2004-01-01

    Objective: To investigate an existing Trust-based osteoporosis service's preventative activity, determine any issues and problems and use this data to reorganise the service, as part of a National Health Service Executive/Regional Office-commissioned and funded study. Setting: A UK Hospital Trust's Osteoporosis Service. Design & Method: A…

  20. Rural Women and Osteoporosis: Awareness and Educational Needs

    ERIC Educational Resources Information Center

    Matthews, Hollie L.; Laya, Mary; DeWitt, Dawn E.

    2006-01-01

    Context: Little is known about rural women's knowledge about osteoporosis. Purpose: To explore what women from high-prevalence rural communities know about osteoporosis and to assess their learning preferences. Methods: We surveyed 437 women in rural Washington and Oregon. Findings: The response rate was 93% (N = 406). The mean age of respondents…

  1. Premenopausal osteoporosis, an overlooked consequence of anorexia nervosa.

    PubMed

    Teng, Kathryn

    2011-01-01

    Many young women with anorexia nervosa develop premenopausal osteoporosis. In particular, female athletes have a much higher incidence of disordered eating than their peers and therefore are at a much higher risk of stress fractures and other traumatic bone pathology. This review summarizes factors affecting the development of premenopausal osteoporosis in these patients and identifies potential targets for intervention. PMID:21199907

  2. Risk Factors for Osteoporosis Among Middle-Aged Women

    ERIC Educational Resources Information Center

    Turner, Lori W.; Wallace, Lorraine Silver; Perry, Blake Allen; Bleeker, Jeanne

    2004-01-01

    Objective: To investigate the risk factors for osteoporosis among a sample of middle-aged women. Methods: Adipose tissue and bone mineral density levels at the left femur, lumbar spine, and total body were assessed using dual-energy x-ray absorptiometry (DXA). Subjects (n=342) were surveyed regarding a variety of osteoporosis-related risk factors.…

  3. Glucose metabolism and cardiac hypertrophy

    PubMed Central

    Kolwicz, Stephen C.; Tian, Rong

    2011-01-01

    The most notable change in the metabolic profile of hypertrophied hearts is an increased reliance on glucose with an overall reduced oxidative metabolism, i.e. a reappearance of the foetal metabolic pattern. In animal models, this change is attributed to the down-regulation of the transcriptional cascades promoting gene expression for fatty acid oxidation and mitochondrial oxidative phosphorylation in adult hearts. Impaired myocardial energetics in cardiac hypertrophy also triggers AMP-activated protein kinase (AMPK), leading to increased glucose uptake and glycolysis. Aside from increased reliance on glucose as an energy source, changes in other glucose metabolism pathways, e.g. the pentose phosphate pathway, the glucosamine biosynthesis pathway, and anaplerosis, are also noted in the hypertrophied hearts. Studies using transgenic mouse models and pharmacological compounds to mimic or counter the switch of substrate preference in cardiac hypertrophy have demonstrated that increased glucose metabolism in adult heart is not harmful and can be beneficial when it provides sufficient fuel for oxidative metabolism. However, improvement in the oxidative capacity and efficiency rather than the selection of the substrate is likely the ultimate goal for metabolic therapies. PMID:21502371

  4. [Pharmacological treatment of other types of secondary osteoporosis].

    PubMed

    Okazaki, Ryo

    2015-10-01

    This article reviews the treatment strategy for the secondary osteoporosis excluding those caused by diabetes, CKD, endocrine disorders, or glucocorticoid, which proceeding articles deal with. Among numerous possible causes for such secondary osteoporosis, the author has selected osteogenesis imperfecta (OI), osteoporosis associated with gastrectomy or bariatric surgery, inflammatory bowel diseases (IBD), and chronic obstructive pulmonary disease (COPD). For OI, current standard treatment is bisphosphonates (BPs), of which efficacy for fracture inhibition has recently been of issue. Other treatment modalities, e.g. PTH, have just been explored. Osteoporosis associated with gastrectomy, bariatric surgery or IBD, have been treated with vitamin D, calcium, and BPs. Despite high fracture rates, there are almost no treatment data for osteoporosis associated with COPD. PMID:26529940

  5. Deletion of glycerol channel aquaporin-9 (Aqp9) impairs long-term blood glucose control in C57BL/6 leptin receptor–deficient (db/db) obese mice

    PubMed Central

    Spegel, Peter; Chawade, Aakash; Nielsen, Søren; Kjellbom, Per; Rützler, Michael

    2015-01-01

    Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor–deficient (db/db) obese mice on a C57BL/6 × C57BLKS mixed genetic background. Furthermore, shRNA-mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet-induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9wt db/db and Aqp9−/− db/db mice did not differ in body weight and liver TAG contents. On the C57BL/6 genetic background, we observed elevated plasma glucose in Aqp9−/− db/db mice (+1.1 mmol/L, life-time average), while plasma insulin concentration was reduced at the time of death. Glucose levels changed similarly in pentobarbital anesthetized, glucagon challenged Aqp9wt db/db and Aqp9−/− db/db mice. Liver transcriptional profiling did not detect differential gene expression between genotypes. Metabolite profiling revealed a sex independent increase in plasma glycerol (+55%) and glucose (+24%), and reduction in threonate (all at q < 0.1) in Aqp9−/− db/db mice compared to controls. Metabolite profiling thus confirms a role of AQP9 in glycerol metabolism of obese C57BL/6 db/db mice. In this animal model of obesity Aqp9 gene deletion elevates plasma glucose and does not alleviate hepatosteatosis. PMID:26416971

  6. Osteoporosis management in older patients who experienced a fracture

    PubMed Central

    Oertel, Mark J; Graves, Leland; Al-Hihi, Eyad; Leonardo, Vincent; Hopkins, Christina; DeSouza, Kristin; Bhattacharya, Rajib K

    2016-01-01

    Background Fractures in older patients are common, morbid, and associated with increased risk of subsequent fractures. Inpatient and outpatient management and treatment of fractures can be costly. With more emphasis placed on quality care for Medicare beneficiaries, we studied if patients were receiving proper screening for osteoporosis and treatment after diagnosis of fracture. This study aims to determine if adequate screening and treatment for osteoporosis occurs in the postfracture period. Methods A retrospective analysis of Medicare beneficiaries aged 67 years or older was gathered from a single institution in both inpatient and outpatient visits. Based on International Classification of Diseases ninth revision codes, primary diagnosis of fractures of neck and trunk, upper limb, and lower limb were obtained in addition to current procedural terminology codes for fracture procedures. We studied patients who had been screened for osteoporosis with a bone mineral study or received osteoporosis treatment after their fracture. Results Medicare beneficiaries totaling 1,375 patients were determined to have an inclusion fracture between June 1, 2013 and November 30, 2014. At the time of our analysis on December 1, 2014, 1,219 patients were living and included in the analysis. Of these patients, 256 (21.0%) either received osteoporosis testing with bone mineral density or received treatment for osteoporosis. On sex breakdown, 208/820 (25.4%) females received proper evaluation or treatment of osteoporosis in comparison to 48/399 (12.0%) males. This is in comparison to the Centers for Medicare and Medicaid Services’ national average of 19.1% for osteoporosis management in females. Conclusion A minority of studied patients received evaluation or treatment for osteoporosis after their fracture. Postfracture investigation and treatment for osteoporosis in Medicare beneficiaries is inadequate. If improved, Medicare costs could be reduced by prevention of future fractures

  7. Cost-Effectiveness Osteoporosis Treatment Thresholds: The United States Perspective from the National Osteoporosis Foundation Guide Committee

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: Rapid growth of the elderly United States population will result in so many at risk of osteoporosis that economically efficient approaches to osteoporosis care warrant consideration.Methods: A Markov-cohort model of annual United States age-specific incidence of hip, wrist, clinical s...

  8. Osteoporosis and sarcopenia in older age.

    PubMed

    Edwards, M H; Dennison, E M; Aihie Sayer, A; Fielding, R; Cooper, C

    2015-11-01

    Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties include the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition. This article is part of a Special Issue entitled "Muscle Bone Interactions". PMID:25886902

  9. Glucocorticoid-induced osteoporosis in growing rats.

    PubMed

    Lin, Sien; Huang, Jianping; Zheng, Liang; Liu, Yanzhi; Liu, Guihua; Li, Nan; Wang, Kuixing; Zou, Liyi; Wu, Tie; Qin, Ling; Cui, Liao; Li, Gang

    2014-10-01

    This study evaluated whether growing rats were appropriate animal models of glucocorticoid-induced osteoporosis. The 3-month-old male rats were treated with either vehicle or prednisone acetate at 1.5, 3.0, and 6.0 mg/kg/day by oral gavage, respectively. All rats were injected with tetracycline and calcein before sacrificed for the purpose of double in vivo labeling. Biochemistry, histomorphometry, mechanical test, densitometry, micro-CT, histology, and component analysis were performed. We found that prednisone treatments dose dependently decreased body weight, serum biomarkers, biomechanical markers, bone formation, and bone resorption parameters in both tibial and femoral trabecular bone without trabecular bone loss. We also found that significant bone loss happened in femoral cortical bone in the glucocorticoid-treated rats. The results suggested that prednisone not only inhibited bone formation, but also inhibited bone resorption which resulted in poor bone strength but with no cancellous bone loss in growing rats. These data also suggested that the effects of glucocorticoid on bone metabolism were different between cortical bone and trabecular bone, and different between tibia and femur. Growing rats may be a glucocorticoid-induced osteoporosis animal model when evaluated the effects of drugs upon juvenile patients exposed to GC for a long time. PMID:25086673

  10. PIXE studies of osteoporosis preventive treatments

    NASA Astrophysics Data System (ADS)

    Ynsa, M. D.; Pinheiro, T.; Ager, F. J.; Alves, L. C.; Millán, J. C.; Gómez-Zubelbia, M. A.; Respaldiza, M. A.

    2002-04-01

    Particle induced X-ray emission (PIXE) and nuclear microprobe (NMP) have been used in an exploratory work to study elemental alterations in tissues of experimental animals submitted to osteoporosis preventive treatments. Osteopathologies have been associated with several factors, such as hormonal disturbances, metabolic aberrations, low dietary Ca and vitamin D intake, excess of iron, among other possible factors. Hormonal treatments seem to be beneficial to the incorporation of Ca in bone but breast and endometrial cancers constitute significant side effects that cannot be ignored. Wistar female rats were used to test the effect of estrogen therapy in osteoporosis progression. The variations of elemental concentrations in uterus and the Ca content of femoral bones of ovariectomised rats under estrogen therapy were investigated. PIXE, Rutherford backscattering spectrometry and secondary electron microscopy techniques were applied for the characterisation of biological materials, with respect to morphology and trace element distribution determination. The increase of Ca and Fe concentrations in uterus and the variations for Ca distribution patterns in bone of rats submitted to estrogen therapy were the major features observed.

  11. Osteoporosis: Modern Paradigms for Last Century's Bones.

    PubMed

    Kruger, Marlena C; Wolber, Frances M

    2016-01-01

    The skeleton is a metabolically active organ undergoing continuously remodelling. With ageing and menopause the balance shifts to increased resorption, leading to a reduction in bone mineral density and disruption of bone microarchitecture. Bone mass accretion and bone metabolism are influenced by systemic hormones as well as genetic and lifestyle factors. The classic paradigm has described osteoporosis as being a "brittle bone" disease that occurs in post-menopausal, thin, Caucasian women with low calcium intakes and/or vitamin D insufficiency. However, a study of black women in Africa demonstrated that higher proportions of body fat did not protect bone health. Isoflavone interventions in Asian postmenopausal women have produced inconsistent bone health benefits, due in part to population heterogeneity in enteric bacterial metabolism of daidzein. A comparison of women and men in several Asian countries identified significant differences between countries in the rate of bone health decline, and a high incidence rate of osteoporosis in both sexes. These studies have revealed significant differences in genetic phenotypes, debunking long-held beliefs and leading to new paradigms in study design. Current studies are now being specifically designed to assess genotype differences between Caucasian, Asian, African, and other phenotypes, and exploring alternative methodology to measure bone architecture. PMID:27322315

  12. [Precautions before starting a treatment for osteoporosis].

    PubMed

    Breuil, Véronique

    2012-02-01

    To be optimal, the treatment of osteoporosis must be global, including nonpharmacological measures. At the initiation of the treatment, a personalized evaluation of the patient must be realized on diet, physical activity, risk of fall and adhesion of the patient. Dietary calcium is estimated and advices given to attain 1000 in 1200 mg/day and limit excessive coffee, soft drinks and salt intake. Dietary calcium is recommended, but if it is impossible, a complement is prescribed, adapted to the intensity of the deficiency. Serum 25-(OH)-vitamine D is measured and, if below 30 ng/ml, a supplementation prescribed. Low protein intake is looked for and corrected if necessary. Advises are given to limit the alcohol to 2 units/day, stop smoking and to have a regular and high impact physical activity. Subjects at risk of fall must be identified and risk factors corrected if possible. Dental recommandations for the use of bisphosphonates in osteoporosis must be apply. Finally, patient education could be used to optimize patient adherence to pharmacological and non pharmacological anti-osteoporotic treatments. PMID:22408863

  13. Osteoporosis and Sarcopenia in Older Age

    PubMed Central

    Edwards, MH; Dennison, EM; Sayer, A Aihie; Fielding, R; Cooper, C

    2015-01-01

    Osteoporosis and sarcopenia are common in older age and associated with significant morbidity and mortality. Consequently, they are both attended by a considerable socioeconomic burden. Osteoporosis was defined by the World Health Organisation (WHO) in 1994 as a bone mineral density of less than 2.5 standard deviations below the sex-specific young adult mean and this characterisation has been adopted globally. Subsequently, a further step forward was taken when bone mineral density was incorporated into fracture risk prediction algorithms, such as the Fracture Risk Assessment Tool (FRAX®) also developed by the WHO. In contrast, for sarcopenia there have been several diagnostic criteria suggested, initially relating to low muscle mass alone and more recently low muscle mass and muscle function. However, none of these have been universally accepted. This has led to difficulties in accurately delineating the burden of disease, exploring geographic differences, and recruiting appropriate subjects to clinical trials. There is also uncertainty about how improvement in sarcopenia should be measured in pharmaceutical trials. Reasons for these difficulties including the number of facets of muscle health available, e.g. mass, strength, function, and performance, and the various clinical outcomes to which sarcopenia can be related such as falls, fracture, disability and premature mortality. It is imperative that a universal definition of sarcopenia is reached soon to facilitate greater progress in research into this debilitating condition. PMID:25886902

  14. QUS devices for assessment of osteoporosis

    NASA Astrophysics Data System (ADS)

    Langton, Christian

    2002-05-01

    The acronym QUS (Quantitative Ultrasound) is now widely used to describe ultrasound assessment of osteoporosis, a disease primarily manifested by fragility fractures of the wrist and hip along with shortening of the spine. There is currently available a plethora of commercial QUS devices, measuring various anatomic sites including the heel, finger, and tibia. Largely through commercial rather than scientific drivers, the parameters reported often differ significantly from the two fundamental parameters of velocity and attenuation. Attenuation at the heel is generally reported as BUA (broadband ultrasound attenuation, the linearly regressed increase in attenuation between 200 and 600 kHz). Velocity derivatives include bone, heel, TOF, and AdV. Further, velocity and BUA parameters may be mathematically combined to provide proprietary parameters including ``stiffness'' and ``QUI.'' In terms of clinical utility, the situation is further complicated by ultrasound being inherently dependent upon ``bone quality'' (e.g., structure) in addition to ``bone quantity'' (generally expressed as BMD, bone mineral density). Hence the BMD derived WHO criteria for osteoporosis and osteopenia may not be directly applied to QUS. There is therefore an urgent need to understand the fundamental dependence of QUS parameters, to perform calibration and cross-correlation studies of QUS devices, and to define its clinical utility.

  15. Herbal treatment for osteoporosis: a current review.

    PubMed

    Leung, Ping-Chung; Siu, Wing-Sum

    2013-04-01

    Osteoporosis is an aging problem. The declining bone mineral density (BMD) enhances the chances of fractures during minor falls. Effective pharmaceuticals are available for a rapid improvement of BMD. However, hormonal treatment gives serious complications, and bisphosphonates may lead to odd fractures of long bones, resulting from excessive rigidity of the cortical components. Many medicinal herbs used in Traditional Chinese Medicine, known as kidney tonics, have been tested for their effects on bone metabolism in the laboratory and clinically. Three of these, viz. Herba epimedii (, Yín Yáng Huò), Fructus ligustri lucidi (, Nǚ Zhēn Zi), and Fructus psoraleae (, Bǔ Gǔ Zhī) were chosen to form a herbal formula, ELP. ELP was tested on in vitro platforms and was shown to have both osteoblastic and anti- osteoclastic action. ELP tested on ovariectomized rats also showed BMD protection. ELP was then put on a placebo- controlled randomized clinical trial. BMD protection was obvious among those women with the onset of menopause beyond 10 years (P < 0.05). A general protective trend was observed among all women under trial (P > 0.05). Although a thorough literature review on the herbal treatment effects did not give convincing answers to the use of Chinese herbs in osteoporosis, our study supports more research and trials in this area, while we are looking for safe and effective agents to keep the bone metabolism in a balanced state. PMID:24716161

  16. Idiopathic osteoporosis: an evolutionary dys-adaptation?

    PubMed Central

    Alexander, C

    2001-01-01

    Osteoporosis is characterised by simultaneous net bone growth and net resorption on different surfaces, suggesting that systemic factors are not the sole explanation for the findings. The main clinical consequence is fracturing in the largely trabecular bones of the spine, hip, and radius, and the key problem in these areas is finding an explanation for the preferential loss of transverse trabeculae. In normal bone, local maintenance depends on a negative feedback response to intermittent compression strain, and it is concluded, from biomechanical analysis of the response required to achieve negative feedback, that a preferential loss of transverse trabeculae is indicative of a selective deficiency of radial compression loading. The only significant source of radial compression in humans is the induced strain produced by axial tension. This is a necessary component of the lifestyles of quadrupeds and arboreal primates, but in humans occurs only on the convex side when the bone is offset loaded. The resulting strain is a function of the range of movement. It is suggested that the asymmetrical pattern of bone loss in cortical and trabecular osteoporosis reflects chronic underuse of movement range, resulting from the adoption of a bipedal lifestyle. Exercise regimens based on using the whole of the available movement range should better prepare the skeleton to adjust to other factors hostile to bone maintenance.

 PMID:11350841

  17. The Impact of Substance Abuse on Osteoporosis Screening and Risk of Osteoporosis in Women with Psychotic Disorders

    PubMed Central

    Kelly, Deanna L.; Myers, Carol S.; Abrams, Michael T.; Feldman, Stephanie; Park, Junyong; McMahon, Robert P.; Shim, Joo-Cheol

    2013-01-01

    Osteoporosis is a major public health concern. Substance abuse and psychosis may be risk factors, however frequency of screening and disease risk in women with psychotic disorders and substance use disorder (SUD) remains unknown. Methods This study examined rates (FY 2005) of osteoporosis screening and disease risk in Medicaid enrolled women aged 50 to 64 (N=18,953). Four diagnostic groups were characterized: 1) Psychosis; 2) SUD; 3) Major mood disorder and 4) Controls. The interaction of psychosis and SUD on screening and disease prevalence of osteoporosis was tested. Results The prevalence of osteoporosis across the entire population was 6.7%. Four percent of those without an osteoporosis diagnosis received osteoporosis screening with no notable differences between psychosis and controls. Those with SUD, however, had a significant reduction in screening compared to controls (OR=0.61, 95% CI 0.40–0.91, p=0.016). Women with a major mood disorder were more likely to have osteoporosis in their administrative record (OR=1.32, 95% CI=1.03–1.70, p=0.028) compared to controls. Those who were dually diagnosed (SUD and psychosis) in the oldest ages (55–64 years) had a markedly higher prevalence of osteoporosis compared to controls (OR=6.4 CI 1.51–27.6, p=0.012), whereas this interaction (SUD and psychosis) was not significant in the entire population over age 49. Conclusions Osteoporosis screening in the Medicaid population is significantly lower for women with SUD, after adjusting for age, race and Medicaid enrollment category. The prevalence of osteoporosis appears markedly elevated in those with major mood disorders and those over age 55 dually diagnosed with schizophrenia and SUD. PMID:20533029

  18. Clinical grading of spinal osteoporosis: quality of life components and spinal deformity in women with chronic low back pain and women with vertebral osteoporosis.

    PubMed

    Leidig-Bruckner, G; Minne, H W; Schlaich, C; Wagner, G; Scheidt-Nave, C; Bruckner, T; Gebest, H J; Ziegler, R

    1997-04-01

    Clinical consequences of osteoporotic vertebral fractures, such as back pain, functional limitations, and impairment of mood, are often cited as justification for prevention and therapy. But these symptoms are poorly characterized, and a clinical grading system is not available. The aim of this study was to compare clinical measures for spinal deformation and quality of life components between patients with osteoporosis and patients with chronic low back pain (CLBP) and to determine the relationship between spinal deformation and quality of life components. A total of 130 female patients (63 osteoporotic patients, 65 +/- 7.9 years, and 77 CLBP patients, 56 +/- 6.5 years) had a standardized interview on quality of life components (pain, activities of daily life, mood) and clinical measures of spinal deformation (height reduction [HR], distance from occiput to wall [DOW], and distance from iliac crest to ribs [DIR]). Spinal X-rays were reviewed in all patients for the evidence of vertebral fractures. In osteoporotic patients, vertebral deformity was quantified by the spine deformity index (SDI) on X-rays. It was assessed whether subgroups could be identified by a combination of indices for spinal deformation (SDI, HR, DOW) using a cluster analysis. Back pain was a major complaint in both groups, without differences in pain intensity and frequency. Impairment of general well being and mood was found in about one-third of the patients in both groups. Independent of age, the disability score was significantly higher in patients with osteoporosis than in patients with CLBP. Both groups differed with respect to clinical measures of spinal deformity (HR, DOW, DIR). Among osteoporotic patients, parameters of quality of life were not linearly related to the degree of radiologically assessed vertebral deformity, but osteoporotic patients with two or more vertebral fractures tended to have more functional limitations than those with only one fracture. There was, however, a

  19. Glucose test (image)

    MedlinePlus

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  20. Low Blood Glucose (Hypoglycemia)

    MedlinePlus

    ... Other Dental Problems Diabetic Eye Disease Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low ... actions can also help prevent hypoglycemia: Check blood glucose levels Knowing your blood glucose level can help ...