A decrease in functional capacity is one of the most important clinical manifestations of hypertensive heart disease, but its cause is poorly understood. Our purpose was to evaluate potential causes of hypertension-induced exercise intolerance, focusing on identifying the type(s) of cardiac dysfunction associated with the first signs of exercise intolerance during the course of hypertensive heart disease. Exercise capacity was
Marco Guazzi; Daniel A. Brenner; Carl S. Apstein; Kurt W. Saupe
OBJECTIVE A high amount of subcutaneous fat is suggested to explain the observation of lower obesity-associated metabolic risk among Inuit than among Europeans. We examined the association between measures of obesity (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], BMI, waist circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit. RESEARCH DESIGN AND METHODS A total of 3,108 adult Inuit participated in a population-based study. The examination included a 75-g oral glucose tolerance test and anthropometric measurements. VAT and SAT were measured by ultrasound according to a validated protocol. Information on sociodemographic characteristics and health behaviors was obtained by interview. RESULTS Mean SATs were 1.8 and 3.5 cm in men and women, respectively. Mean VATs were 7.0 and 6.3 cm in men and women, respectively. The total prevalence of type 2 diabetes was 9%. Percentage of body fat generally was most strongly associated with all outcomes. Both SAT and VAT were significantly associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward a negative or no association with SAT. CONCLUSIONS High mean values of SAT may to a large extent explain the high WC in Inuit populations, and this is suggested to contribute to the lower observed metabolic risk for a given level of obesity. PMID:23656981
J?rgensen, Marit Eika; Borch-Johnsen, Knut; Stolk, Ronald; Bjerregaard, Peter
Aim. Our aim was to evaluate the uptake of our current screening strategy postpartum and the risk factors for glucose intolerance in women with a recent history of gestational diabetes (GDM). Methods. Retrospective analysis of files of women with a recent history of GDM diagnosed with the Carpenter and Coustan criteria from 01-01-2010 till 31-12-2013. Multivariable logistic regression was used to adjust for confounders. Results. Of all 231 women with a recent history of GDM, 21.4% (46) did not attend the scheduled postpartum OGTT. Of the women tested, 39.1% (66) had glucose intolerance and 5.3% (9) had diabetes. These women were more often overweight (39.7% versus 25.3%, P = 0.009), were more often treated with basal-bolus insulin injections (52.0% versus 17.4%, P = 0.032), and had a lower beta-cell function and lower insulin sensitivity, remaining significant after adjustment for age, BMI, and ethnicity (insulin secretion sensitivity index-2 (ISSI-2) in pregnancy 1.5 ± 0.5 versus 1.7 ± 0.4, P = 0.029; ISSI-2 postpartum 1.5 (1.2–1.9) versus 2.2 (1.8–2.6), P = 0.020; Matsuda index postpartum 3.8 (2.6–6.2) versus 6.0 (4.3–8.8), P = 0.021). Conclusion. Glucose intolerance is frequent in early postpartum and these women have a lower beta-cell function and lower insulin sensitivity. One fifth of women did not attend the scheduled OGTT postpartum. PMID:25180037
Calewaert, Peggy; Devlieger, Roland; Verhaeghe, Johan; Mathieu, Chantal
Non-caloric artificial sweeteners (NAS) are among the most widely used food additives worldwide, regularly consumed by lean and obese individuals alike. NAS consumption is considered safe and beneficial owing to their low caloric content, yet supporting scientific data remain sparse and controversial. Here we demonstrate that consumption of commonly used NAS formulations drives the development of glucose intolerance through induction of compositional and functional alterations to the intestinal microbiota. These NAS-mediated deleterious metabolic effects are abrogated by antibiotic treatment, and are fully transferrable to germ-free mice upon faecal transplantation of microbiota configurations from NAS-consuming mice, or of microbiota anaerobically incubated in the presence of NAS. We identify NAS-altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease, and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects. Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities, thereby calling for a reassessment of massive NAS usage. PMID:25231862
Suez, Jotham; Korem, Tal; Zeevi, David; Zilberman-Schapira, Gili; Thaiss, Christoph A; Maza, Ori; Israeli, David; Zmora, Niv; Gilad, Shlomit; Weinberger, Adina; Kuperman, Yael; Harmelin, Alon; Kolodkin-Gal, Ilana; Shapiro, Hagit; Halpern, Zamir; Segal, Eran; Elinav, Eran
The association between weight history and glucose intolerance was examined in a cross-sectional study consisting of 3,128 Swedish men aged 35-56 years, 52 percent of whom had a family background of diabetes mellitus. Oral glucose tolerance testing detected 55 cases of type 2 (non-insulin-dependent) diabetes and 172 cases of impaired glucose tolerance. Among men with no family history of diabetes,
Sofia Carisson; Per-Gunnar Persson; Michael Alvarsson; Suad Efendic; Anders Norman; Leif Svanstrom; Claes-Goran Ostenson; Valdemar Grill
Neural stem cells (NSCs) were recently revealed to exist in the hypothalamus of adult mice. Here, following our observation showing that a partial loss of hypothalamic NSCs caused weight gain and glucose intolerance, we studied if NSCs-based cell therapy could be developed to control these disorders. While hypothalamus-implanted NSCs failed to survive in mice with obesity, NF-?B inhibition induced survival and neurogenesis of these cells, leading to effects in counteracting obesity and glucose intolerance. To generate an alternative cell source, we revealed that iPS-derived NSCs were converted into htNSCs by neuropeptide treatment. Of note, obesity condition potentiated the transfer of carotid artery-injected NSCs into the hypothalamus. These iPS-derived cells when engineered with NF-?B inhibition were also effective in reducing obesity and glucose intolerance, and neurogenesis towards POMCergic and GABAergic lineages was accountable. In conclusion, building NSCs in the hypothalamus represents a strategy for controlling obesity and glucose disorders. PMID:24749061
Li, Juxue; Tang, Yizhe; Purkayastha, Sudarshana; Yan, Jingqi; Cai, Dongsheng
mTOR inhibition with rapamycin induces a diabetes-like syndrome characterized by severe glucose intolerance, hyperinsulinemia, and hypertriglyceridemia, which is due to increased hepatic glucose production as well as reduced skeletal muscle glucose uptake and adipose tissue PPAR? activity. Herein, we tested the hypothesis that pharmacological PPAR? activation attenuates the diabetes-like syndrome associated with chronic mTOR inhibition. Rats treated with the mTOR inhibitor rapamycin (2 mg·kg(-1)·day(-1)) in combination or not with the PPAR? ligand rosiglitazone (15 mg·kg(-1)·day(-1)) for 15 days were evaluated for insulin secretion, glucose, insulin, and pyruvate tolerance, skeletal muscle and adipose tissue glucose uptake, and insulin signaling. Rosiglitazone corrected fasting hyperglycemia, attenuated the glucose and insulin intolerances, and abolished the increase in fasting plasma insulin and C-peptide levels induced by rapamycin. Surprisingly, rosiglitazone markedly increased the plasma insulin and C-peptide responses to refeeding in rapamycin-treated rats. Furthermore, rosiglitazone partially attenuated rapamycin-induced gluconeogenesis, as evidenced by the improved pyruvate tolerance and reduced mRNA levels of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. Rosiglitazone also restored insulin's ability to stimulate glucose uptake and its incorporation into glycogen in skeletal muscle of rapamycin-treated rats, which was associated with normalization of Akt Ser(473) phosphorylation. However, the rapamycin-mediated impairments of adipose tissue glucose uptake and incorporation into triacylglycerol were unaffected by rosiglitazone. Our findings indicate that PPAR? activation ameliorates some of the disturbances in glucose homeostasis and insulin action associated with chronic rapamycin treatment by reducing gluconeogenesis and insulin secretion and restoring muscle insulin signaling and glucose uptake. PMID:24619883
Festuccia, William T; Blanchard, Pierre-Gilles; Belchior, Thiago; Chimin, Patricia; Paschoal, Vivian A; Magdalon, Juliana; Hirabara, Sandro M; Simões, Daniel; St-Pierre, Philippe; Carpinelli, Angelo; Marette, André; Deshaies, Yves
OBJECTIVE: Glucose intolerance is frequently associated with an altered plasma lipid profile and increased cardiovascular disease risk. Nonetheless, lipid metabolism is scarcely studied in normolipidemic glucose-intolerant patients. The aim of this study was to investigate whether important lipid metabolic parameters, such as the kinetics of LDL free and esterified cholesterol and the transfer of lipids to HDL, are altered in glucose-intolerant patients with normal plasma lipids. METHODS: Fourteen glucose-intolerant patients and 15 control patients were studied; none of the patients had cardiovascular disease manifestations, and they were paired for age, sex, race and co-morbidities. A nanoemulsion resembling a LDL lipid composition (LDE) labeled with 14C-cholesteryl ester and 3H-free cholesterol was intravenously injected, and blood samples were collected over a 24-h period to determine the fractional clearance rate of the labels by compartmental analysis. The transfer of free and esterified cholesterol, triglycerides and phospholipids from the LDE to HDL was measured by the incubation of the LDE with plasma and radioactivity counting of the supernatant after chemical precipitation of non-HDL fractions. RESULTS: The levels of LDL, non-HDL and HDL cholesterol, triglycerides, apo A1 and apo B were equal in both groups. The 14C-esterified cholesterol fractional clearance rate was not different between glucose-intolerant and control patients, but the 3H-free- cholesterol fractional clearance rate was greater in glucose-intolerant patients than in control patients. The lipid transfer to HDL was equal in both groups. CONCLUSION: In these glucose-intolerant patients with normal plasma lipids, a faster removal of LDE free cholesterol was the only lipid metabolic alteration detected in our study. This finding suggests that the dissociation of free cholesterol from lipoprotein particles occurs in normolipidemic glucose intolerance and may participate in atherogenic signaling. PMID:22522760
Bertato, Marina P; Oliveira, Carolina P; Wajchenberg, Bernardo L; Lerario, Antonio C; Maranhao, Raul C
Second generation antipsychotic drugs are routinely used as treatment for psychotic disorders. Many of these compounds, including olanzapine, cause metabolic side-effects such as impaired glucose tolerance and insulin resistance. Individual antidiabetic drugs can help control elevated glucose levels in patients treated with antipsychotics, but the effects of combining antidiabetics, which routinely occurs with Type 2 diabetes mellitus patients, have never been studied. Presently, we compared the effects of the three different antidiabetics metformin (500mg/kg, p.o.), rosiglitazone (30mg/kg, p.o.) and glyburide (10mg/kg, p.o.) on metabolic dysregulation in adult female rats treated acutely with olanzapine. In addition, dual combinations of each of these antidiabetics were compared head-to-head against each other and the individual drugs. The animals received two daily treatments with antidiabetics and were then treated acutely with olanzapine (10mg/kg, i.p.). Fasting glucose and insulin levels were measured, followed by a 2h glucose tolerance test. Olanzapine caused a large and highly significant glucose intolerance compared to vehicle treated rats. Rosiglitazone decreased glucose levels non-significantly, while both metformin and glyburide significantly decreased glucose levels compared to olanzapine-only treated animals. For antidiabetic dual-drug combinations, the rosiglitazone-metformin group showed an unexpected increase in glucose levels compared to all of the single antidiabetic drugs. However, both the metformin-glyburide and rosiglitazone-glyburide groups showed significantly greater reductions in glucose levels following olanzapine than with single drug treatment alone for metformin or rosiglitazone, bringing glucose levels down to values equivalent to vehicle-only treated animals. These findings indicate that further study of antidiabetic dual-drug combinations in patients treated with antipsychotic drugs is warranted. PMID:24140931
Boyda, Heidi N; Procyshyn, Ric M; Asiri, Yahya; Wu, Claire; Wang, Cathy K; Lo, Ryan; Pang, Catherine C Y; Honer, William G; Barr, Alasdair M
Background Obesity leads to an increase in inflammation and insulin resistance. This study determined antioxidant activity of flaxseed and its role in inflammation and insulin resistance in obese glucose intolerant people. Methods Using a randomized crossover design, nine obese glucose intolerant people consumed 40 g ground flaxseed or 40 g wheat bran daily for 12 weeks with a 4-week washout period. Plasma inflammation biomarkers (CRP, TNF-?, and IL-6), glucose, insulin, and thiobaribituric acid reactive substance (TBARS) were measured before and after of each supplementation. Results Flaxseed supplementation decreased TBARS (p = 0.0215) and HOMA-IR (p = 0.0382). Flaxseed or wheat bran supplementation did not change plasma inflammatory biomarkers. A positive relationship was found between TBARS and HOMA-IR (r = 0.62, p = 0.0003). Conclusions The results of the study weakly support that decreased insulin resistance might have been secondary to antioxidant activity of flaxseed. However, the mechanism(s) of decreased insulin resistance by flaxseed should be further determined using flaxseed lignan. PMID:21554710
Numerous animal and clinical investigations have pointed to a potential role of the renin-angiotensin system (RAS) in the development of insulin resistance and diabetes in conditions of expanded fat mass. However, the mechanisms underlying this association remain unclear. We used a transgenic mouse model overexpressing renin in the liver (RenTgMK) to examine the effects of chronic activation of RAS on adiposity and insulin sensitivity. Hepatic overexpression of renin resulted in constitutively elevated plasma angiotensin II (four- to six-fold increase vs. wild-type, WT). Surprisingly, RenTgMK mice developed glucose intolerance despite low levels of adiposity and insulinemia. The transgenics also had lower plasma triglyceride levels. Glucose intolerance in transgenic mice fed a low-fat diet was comparable to that observed in high-fat fed WT mice. These studies demonstrate that overexpression of renin and associated hyperangiotensinemia impair glucose tolerance in a diet-dependent manner and further support a consistent role of RAS in the pathogenesis of diabetes and insulin resistance, independent of changes in fat mass. PMID:23308073
Fletcher, Sarah J.; Kalupahana, Nishan S.; Soltani-Bejnood, Morvarid; Kim, Jung Han; Saxton, Arnold M.; Wasserman, David H.; De Taeye, Bart; Voy, Brynn H.; Quignard-Boulange, Annie; Moustaid-Moussa, Naima
Susceptibility during fasting has been reported for the common vampire bat (Desmodus rotundus), to the point of untimely deaths after only 2-3 nights of fasting. To investigate the underlying physiology of this critical metabolic condition, we analyzed serum insulin levels, pancreatic islets morphometry and immunocytochemistry (ICC), static insulin secretion in pancreas fragments, and insulin signaling mechanism in male vampire bats. A glucose tolerance test (ipGTT) was also performed. Serum insulin was found to be lower in fed vampires compared to other mammals, and was significantly reduced after 24h fasting. Morphometrical analyses revealed small irregular pancreatic islets with reduced percentage of ?-cell mass compared to other bats. Static insulin secretion analysis showed that glucose-stimulated insulin secretion was impaired, as insulin levels did not reach significance under high glucose concentrations, whereas the response to the amino acid leucin was preserved. Results from ipGTT showed a failure on glucose clearance, indicating glucose intolerance due to diminished pancreatic insulin secretion and/or decreased ?-cell response to glucose. In conclusion, data presented here indicate lower insulinemia and impaired insulin secretion in D. rotundus, which is consistent with the limited ability to store body energy reserves, previously reported in these animals. Whether these metabolic and hormonal features are associated with their blood diet remains to be determined. The peculiar food sharing through blood regurgitation, reported to this species, might be an adaptive mechanism overcoming this metabolic susceptibility. PMID:23262275
Freitas, Mariella B; Queiroz, Joicy F; Dias Gomes, Carolinne I; Collares-Buzato, Carla B; Barbosa, Helena C; Boschero, Antonio C; Gonçalves, Carlos A; Pinheiro, Eliana C
Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-? (A?40 and A?42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For A?42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline. PMID:20847403
Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne
Estrogens are known to play a role in modulating metabolic processes within the body. The Aromatase knockout (ArKO) mice have been shown to harbor factors of Metabolic syndrome with central adiposity, hyperinsulinemia and male-specific hepatic steatosis. To determine the effects of estrogen ablation and subsequent replacement in males on whole body glucose metabolism, three- and six-month-old male ArKO mice were subjected to whole body glucose, insulin and pyruvate tolerance tests and analyzed for ensuing metabolic changes in liver, adipose tissue, and skeletal muscle. Estrogen-deficient male ArKO mice showed increased gonadal adiposity which was significantly reduced upon 17?-estradiol (E2) treatment. Concurrently, elevated ArKO serum leptin levels were significantly reduced upon E2 treatment and lowered serum adiponectin levels were restored to wild type levels. Three-month-old male ArKO mice were hyperglycemic, and both glucose and pyruvate intolerant. These phenotypes continued through to 6 months of age, highlighting a loss of glycemic control. ArKO livers displayed changes in gluconeogenic enzyme expression, and in insulin signaling pathways upon E2 treatment. Liver triglycerides were increased in the ArKO males only after 6 months of age, which could be reversed by E2 treatment. No differences were observed in insulin-stimulated ex vivo muscle glucose uptake nor changes in ArKO adipose tissue and muscle insulin signaling pathways. Therefore, we conclude that male ArKO mice develop hepatic glucose intolerance by the age of 3 months which precedes the sex-specific development of hepatic steatosis. This can be reversed upon the administration of exogenous E2. PMID:24520329
Van Sinderen, Michelle L.; Steinberg, Gregory R.; J?rgensen, Sebastian B.; To, Sarah Q.; Knower, Kevin C.; Clyne, Colin D.; Honeyman, Jane; Chow, Jenny D.; Herridge, Kerrie A.; Jones, Margaret E. E.; Simpson, Evan R.; Boon, Wah Chin
Obesity is a major contributor to both glucose intolerance and metabolic syndrome. In this study, we investigated the anti-obesity and anti-hyperglycemic effects of Ephedra sinica on high-fat diet-fed mice. Male ICR mice were divided into four groups; the normal group, the obese and diabetic control group treated with a high-fat diet, the positive control group treated with a high-fat diet containing acarbose, and the experimental group treated with a high-fat diet containing Ephedra sinica. The effects of Ephedra sinica on obesity and glucose intolerance were measured by an oral glucose tolerance test (OGTT), plasma biochemistry, body and epididymal fat weight; the expression of adiponectin, peroxisome-proliferator-activated receptor ? (PPAR-?), tumor necrosis factor ? (TNF-?) and leptin was also determined. Ephedra sinica reduced weight gain and epididymal fat accumulation, improved glucose intolerance on the OGTT, decreased triglycerides and increased high-density lipoprotein cholesterol compared to the controls. Moreover, it reduced weight gain and fasting glucose levels and improved HDL-cholesterol levels more than acarbose. Gene expression analysis revealed that Ephedra sinica upregulated the expression of adiponectin and PPAR-?, and downregulated the expression of TNF-?. From these results, we suggest that Ephedra sinica may reduce obesity and hyperglycemia by increasing PPAR-? and adiponectin and reducing TNF-?, and that it may have the potential to be used clinically as an ingredient in food or drugs effective in obesity-related glucose intolerance treatments. PMID:22969956
Song, Moon-Koo; Um, Jae-Young; Jang, Hyeung-Jin; Lee, Byung-Cheol
The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid-independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction. PMID:24937427
Tolson, Kristen P; Garcia, Christian; Yen, Stephanie; Simonds, Stephanie; Stefanidis, Aneta; Lawrence, Alison; Smith, Jeremy T; Kauffman, Alexander S
The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid–independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction. PMID:24937427
Tolson, Kristen P.; Garcia, Christian; Yen, Stephanie; Simonds, Stephanie; Stefanidis, Aneta; Lawrence, Alison; Smith, Jeremy T.; Kauffman, Alexander S.
The proband, a 42-year-old woman without any symptoms or hypertension, was admitted for examination of accidentally discovered bilateral adrenal masses. Physical examination disclosed bilateral nodular goiter and mild sinus tachycardia. Pheochromocytomas and medullary thyroid carcinomas were revealed by biochemical and histopathological examinations. Hypercholesterolemia and abnormal glucose metabolism returned to normal after bilateral total adrenalectomy and thyroidectomy. Screening examination showed four affected family members. Three of them were also asymptomatic and normotensive. In pheochromocytoma patients, normotension, hypercholesterolemia, and impaired glucose metabolism might be signs of excess secretion of epinephrine rather than norepinephrine. PMID:1678022
Wakasugi, T; Aoyama, T; Hirai, J; Saga, T
Serum calcium concentration has recently been shown to predict cardiovascular mortality in a large health-screening program. Since impaired glucose tolerance (IGT) is an independent cardiovascular risk factor, we examined the association between glucose intolerance and serum calcium in a population-based cohort study. To characterize this association, we measured total serum calcium, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), and 1,25-dihydroxyvitamin D
Nicholas J. Wareham; Christopher D. Byrne; Colin Carr; Nicholas E. Day; Barbara J. Boucher; C. Nicholas Hales
Enhanced de novo lipogenesis (DNL), an adult hepatic adaption, is seen with high carbohydrate or low-fat diets. We hypothesized that ad libitum intake after prenatal calorie restriction will result in adult-onset glucose intolerance and enhanced DNL with modified lipid metabolic gene expression profile. Stable isotopes were used in 15-month-old adult male rat offspring exposed to prenatal (IUGR), pre- and postnatal (IPGR), or postnatal (PNGR) caloric restriction vs. controls (CON). IUGR vs. CON were heavier with hepatomegaly but unchanged visceral white adipose tissue (WAT), glucose intolerant with reduced glucose-stimulated insulin secretion (GSIS), pancreatic ?-cell mass, and total glucose clearance rate but unsuppressed hepatic glucose production. Liver glucose transporter (Glut) 1 and DNL increased with decreased hepatic acetyl-CoA carboxylase (ACC) and fatty acid synthase but increased WAT fatty acid transport protein-1 and peroxisomal proliferator-activated receptor-?, resistin, and visfatin gene expression. In contrast, PNGR and IPGR were lighter, had reduced visceral WAT, and were glucose tolerant with unchanged hepatic glucose production but with increased GSIS, ?-cell mass, glucose clearance rate, and WAT insulin receptor. Hepatic Glut1 and DNL were also increased in lean IPGR and PNGR with increased hepatic ACC, phosphorylated ACC, and pAMPK and reduced WAT fatty acid transport protein-1, peroxisomal proliferator-activated receptor-?, and ACC?. We conclude the following: 1) the heavy, glucose-intolerant and insulin-resistant IUGR adult phenotype is ameliorated by postnatal caloric restriction; 2) increased DNL paralleling hepatic Glut1 is a biomarker of exposure to early caloric restriction rather than the adult metabolic status; 3) hepatic lipid enzyme expression reflects GSIS rather than DNL; and 4) WAT gene expression reflects an obesogenic vs. lean phenotype. PMID:23183174
Thamotharan, Manikkavasagar; Dai, Yun; Lagishetty, Venu; Matveyenko, Aleksey V.; Lee, W. N. Paul
Diabetes mellitus is one of the most frequent co-morbidities of ulcerative colitis patients. The epidemiological association of these diseases suggested a genetic sharing and has challenged gene identification. Diabetes co-morbidity in ulcerative colitis has also relevant clinical and therapeutic implications, with potential clinical impact on the follow up and outcome of patients. These diseases share specific complications, such as neuropathy, hepatic steatosis, osteoporosis and venous thrombosis. It is still unknown whether the coexistence of these diseases may increase their occurrence. Diabetes and hyperglycaemia represent relevant risk factors for postoperative complications and pouch failure in ulcerative colitis. Medical treatment of ulcerative colitis in patients with diabetes mellitus may be particularly challenging. Corticosteroids are the treatment of choice of active ulcerative colitis. Their use may be associated with the onset of glucose intolerance and diabetes, with difficult control of glucose levels and with complications in diabetic patients. Epidemiologic and genetic evidences about diabetes co-morbidity in ulcerative colitis patients and shared complications and treatment of patients with these diseases have been discussed in the present review. PMID:24707133
Maconi, Giovanni; Furfaro, Federica; Sciurti, Roberta; Bezzio, Cristina; Ardizzone, Sandro; de Franchis, Roberto
This study describes the prevalence on glucose intolerance by race and ethnicity in the United States Virgin Islands. A population-based sample of 1026 individuals 20 years of age or older was recruited on the island of St. Croix, U.S. Virgin Islands, where 80% of the population classify their race as African American and 20% indicate their ethnicity as Hispanic. American Diabetes Association (ADA) criteria was used to classify glucose tolerance for the entire sample. Persons 40 years of age or older (405) were also administered a 2-h oral glucose tolerance test. Among the major race/ethnic groups, the prevalence of diabetes in patients 20 years of age or older (age-adjusted to the 1995 world population) was 14.1% for non-Hispanic blacks (n = 712), 12.1% for Hispanic blacks (n = 145), 13.5% for Hispanic whites (n = 70) and 1.2% for non-Hispanic whites (n = 37). In each group, the prevalence of diabetes increased with age and appeared higher for men. Among individuals 40 years of age or older a slightly higher prevalence of newly diagnosed diabetes was found when using World Health Organization (WHO) criteria compared to ADA criteria (WHO 10.3%, ADA 7.7% for black non-Hispanic persons and WHO 10.4%, ADA 6.0% for all other groups combined). The prevalence of diabetes for African Americans residing in the U.S. Virgin Islands is similar to rates for the African-American population on the United States mainland and is double that of estimates for blacks on neighboring islands. PMID:11918382
Tull, Eugene S.; LaPorte, Ronald; Kriska, Andrea; Mark, Joseph; Hatcher, Ann T.
Background Increased myocardial lipid accumulation has been described in patients with pre- and overt type 2 diabetes and could underlie the development of left-ventricular dysfunction in metabolic diseases (diabetic cardiomyopathy). Since women with prior gestational diabetes (pGDM) display a generally young population at high risk of developing diabetes and associated cardiovascular complications, we aimed to assess whether myocardial lipid accumulation can be detected at early stages of glucose intolerance and relates to markers of hepatic steatosis (Fatty Liver Index), cardiac function, insulin sensitivity and secretion. Methods Myocardial lipid content (MYCL), left-ventricular function (1H-magnetic-resonance-spectroscopy and -imaging), insulin sensitivity/secretion (oral glucose tolerance test) and the fatty liver index (FLI) were assessed in 35 pGDM (45.6±7.0 years, 28.3±4.8 kg/m2) and 14 healthy control females (CON; 44.7±9.8 years, 26.1±2.5 kg/m2), matching for age and body-mass-index (each p>0.1). Results Of 35 pGDM, 9 displayed normal glucose tolerance (NGT), 6 impaired glucose regulation (IGR) and 20 had been already diagnosed with type 2 diabetes (T2DM). MYCL and cardiac function were comparable between pGDM and CON; in addition, no evidence of left-ventricular dysfunction was observed. MYCL was inversely correlated with the ejection fraction in T2DM (R?=??0.45, p<0.05), while the FLI was tightly correlated with metabolic parameters (such as HbA1C, fasting plasma glucose and HDL-cholesterol) and rose along GT-groups. Conclusions There is no evidence of cardiac steatosis in middle-aged women with prior gestational diabetes, suggesting that cardiac complications might develop later in the time-course of diabetes and may be accelerated by the co-existence of further risk factors, whereas hepatic steatosis remains a valid biomarker for metabolic diseases even in this rather young female cohort. PMID:24621572
Winhofer, Yvonne; Krssak, Martin; Wolf, Peter; Tura, Andrea; Anderwald, Christian-Heinz; Kosi, Lana; Reiter, Gert; Pacini, Giovanni; Trattnig, Siegfried; Luger, Anton; Krebs, Michael; Kautzky-Willer, Alexandra
Glucose intolerance and noninsulin-dependent diabetes are commonly associated with hypertension. Epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. When hypertensive patients whether obese or of normal weight are compared with matched normotensive control subjects, an increased plasma insulin response to a glucose challenge
The objective of this study was to examine, using the new WHO criteria for diabetes mellitus, whether insulin and glucose before and after an oral glucose tolerance test would predict cardiovascular mortality in hypertensive men with normal fasting blood glucose. A standard oral glucose challenge was performed after an overnight fast in 113 hypertensive men with either hypercholesterolaemia or smoking.
Metabolic inflammation may contribute to the pathogenesis of obesity and its comorbidities, including type 2 diabetes and cardiovascular disease. Previously, we showed that the actin-binding protein profilin-1 (pfn) plays a role in atherogenesis because pfn heterozygote mice (PfnHet) exhibited a significant reduction in atherosclerotic lesion burden and vascular inflammation. In the current study, we tested whether pfn haploinsufficiency would also limit diet-induced adipose tissue inflammation and insulin resistance (IR). First, we found that a high-fat diet (HFD) upregulated pfn expression in epididymal and subcutaneous white adipose tissue (WAT) but not in the liver or muscle of C57BL/6 mice compared with normal chow. Pfn expression in WAT correlated with F4/80, an established marker for mature macrophages. Of note, HFD elevated pfn protein levels in both stromal vascular cells and adipocytes of WAT. We also found that PfnHet were significantly protected from HFD-induced glucose intolerance observed in pfn wild-type mice. With HFD, PfnHet displayed blunted expression of systemic and WAT proinflammatory cytokines and decreased accumulation of adipose tissue macrophages, which were also preferentially biased toward an M2-like phenotype; this correlated with preserved frequency of regulatory T cells. Taken together, the findings indicate that pfn haploinsufficiency protects against diet-induced IR and inflammation by modulating WAT immune homeostasis. PMID:23884883
Romeo, Giulio R; Pae, Munkyong; Eberlé, Delphine; Lee, Jongsoon; Shoelson, Steven E
OBJECTIVE: To assess whether active and passive smokers are more likely than non-smokers to develop clinically relevant glucose intolerance or diabetes.\\u000aDESIGN: Coronary artery risk development in young adults (CARDIA) is a prospective cohort study begun in 1985-6 with 15 years of follow-up.\\u000aSETTING: Participants recruited from Birmingham, Alabama; Chicago, Illinois; Minneapolis, Minnesota; and Oakland, California,\\u000aUSA. PARTICIPANTS: Black and
Thomas K. Houston; Sharina D. Person; Mark J. Pletcher; Kiang Liu; Carlos Iribarren; Catarina I. Kiefe
This article evaluates diagnostic sensitivity of minimal F-wave latency, sural/radial amplitude ratio (SRAR), dorsal sural/radial amplitude ratio (DSRAR), sympathetic skin response (SSR), and R-R interval variability (RRIV) for detecting early polyneuropathy in patients with glucose intolerance and diabetic patients. F-wave latencies were more prolonged in diabetic patients with normal and abnormal nerve conduction studies than control subjects (p < .001). SRAR was lower, SSR latency was more prolonged, and RRIV was lower in diabetic patients with abnormal nerve conduction studies than healty controls (p < .001). SSR latency was more prolonged and RRIV was lower in diabetic patients with normal nerve conduction studies than healty controls (p < .01, p < .05, respectively). DSRAR was lower in diabetic patients with normal and abnormal nerve conduction studies than control subjects (p < .001). DSRAR was also lower in patients with glucose intolerance than control subjects (p < .01). DSRAR was the most sensitive and specific test in either of diabetic patients with normal nerve conduction studies (sensitivity 66%, specificity 90%) and diabetic patients with abnormal nerve conduction studies (sensitivity 100%, specificity 90%). DSRAR is the most reliable method for detection of early nerve pathology. Patients with glucose intolerance might have subclinical neuropathy that can be demonstrated with DSRAR analysis. PMID:16753899
Turgut, Nilda; Güldiken, Sibel; Balci, Kemal; Tugrul, Armagan; Berberoglu, Ufuk; Altun, Betül Ugur
Background Diet-induced obesity is a rising health concern which can lead to the development of glucose intolerance and muscle insulin resistance and, ultimately, type II diabetes mellitus. This research investigates the associations between glucose intolerance or muscle insulin resistance and tissue specific changes during the progression of diet-induced obesity. Methodology C57BL/6J mice were fed a normal or high-fat diet (HFD; 60% kcal fat) for 3 or 8 weeks. Disease progression was monitored by measurements of body/tissue mass changes, glucose and insulin tolerance tests, and ex vivo glucose uptake in intact muscles. Lipid metabolism was analyzed using metabolic chambers and ex vivo palmitate assays in intact muscles. Skeletal muscle, liver and adipose tissues were analyzed for changes in inflammatory gene expression. Plasma was analyzed for insulin levels and inflammatory proteins. Histological techniques were used on muscle and liver cryosections to assess metabolic and morphological changes. Principal Findings/Conclusions A rapid shift in whole body metabolism towards lipids was observed with HFD. Following 3 weeks of HFD, elevated total lipid oxidation and an oxidative fiber type shift had occurred in the skeletal muscle, which we propose was responsible for delaying intramyocellular lipid accumulation and maintaining muscle’s insulin sensitivity. Glucose intolerance was present after three weeks of HFD and was associated with an enlarged adipose tissue depot, adipose tissue inflammation and excess hepatic lipids, but not hepatic inflammation. Furthermore, HFD did not significantly increase systemic or muscle inflammation after 3 or 8 weeks of HFD suggesting that early diet-induced obesity does not cause inflammation throughout the whole body. Overall these findings indicate skeletal muscle did not contribute to the development of HFD-induced impairments in whole-body glucose tolerance following 3 weeks of HFD. PMID:23951235
Trajcevski, Karin E.; O'Neill, Hayley M.; Wang, David C.; Thomas, Melissa M.; Al-Sajee, Dhuha; Steinberg, Gregory R.; Ceddia, Rolando B.; Hawke, Thomas J.
Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in ?80–95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels ?4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance. PMID:20802159
Brown, J. Mark; Betters, Jenna L.; Lord, Caleb; Ma, Yinyan; Han, Xianlin; Yang, Kui; Alger, Heather M.; Melchior, John; Sawyer, Janet; Shah, Ramesh; Wilson, Martha D.; Liu, Xiuli; Graham, Mark J.; Lee, Richard; Crooke, Rosanne; Shulman, Gerald I.; Xue, Bingzhong; Shi, Hang; Yu, Liqing
Objective This study aimed to determine the contribution of individual and contextual socioeconomic status (SES) to the prevalence of diabetes mellitus and glucose intolerance in the adult population in rural southwest China. Methods A population-based cross-sectional study of diabetes was performed in 4801(2152 men) Chinese adults (?25 years old). Multilevel logistic regression model was used to examine the association between individuals’ and townships’ variables and the prevalence of diabetes mellitus and glucose intolerance. Results The age-and gender-standardized prevalence of diabetes mellitus and glucose intolerance were 7.1% (3.6% for undiagnosed) and 8.8% in adults aged ?25 years, respectively, and increasing with age. Females were more likely to develop diabetes than males. The probability of developing diabetes increased with BMI. Both contextual and individual educational level and yearly household income were found to be negatively associated with the prevalence of diabetes. Residence in communities with a higher percentage of ethnic minorities was associated with higher prevalence of diabetes. Smoking had a protective effect for diabetes, drinking had a positive association with diabetes mellitus and glucose intolerance. Conclusions Diabetes mellitus and glucose intolerance are common in rural adults of southwest China by international standards. These results indicate that diabetes mellitus has become a major public health problem in rural areas in southwest China, and strategies aimed at the prevention and treatment of diabetes mellitus and glucose intolerance are needed. PMID:23874667
Wang, Ke-wei; Shu, Zhan-kun; Cai, Le; Wu, Jun-Qing; Wei, Wei
Type 2 (non-insulin-dependent) diabetes is emerging as a leading chronic non-communicable disease among the adult Kuwaiti population. Based on the World Health Organization and similar reports the projected estimates for subjects suffering from type 2 diabetes by the years 2000 and 2010 show a striking tendency to high rates of the disease in our area. We report the prevalence rates of glucose intolerance among a relatively young adult Kuwaiti population below 50 years of age and the effect of implementing the recent 1997 American Diabetes Association diagnostic criteria on the frequency of type 2 diabetes, impaired glucose tolerance and impaired fasting glucose among this group. The overall prevalence rate for the three categories of glucose intolerance reached as high as 15.8% (95% CI, 14.2 to 17.4). Age, though all subjects were below 50 years, parental history of type 2 diabetes, diastolic blood pressure and serum triglycerides were found to be significant associated risk factors for the development of type 2 diabetes. Obesity was an apparent significant factor associated with the three forms of glucose intolerance (p < 0.001). Obesity and physical inactivity were documented in both non-diabetic and more so in diabetic Kuwaiti adults, which should form the basis of any immediate intervention programme. An integrated approach to the prevention of the described critical risk factors associated with type 2 diabetes is highly recommended in Kuwait. Research, focused on genetics of type 2 diabetes in the highly susceptible Kuwaiti population, should be planned. PMID:10664317
Abdella, N; Al Nakhi, A; Al Arouj, M; Assoussi, A; Moussa, M
Thyroid hormones (TH) play an important regulatory role in energy expenditure regulation and are key regulators of mitochondrial activity. We have previously identified a mitochondrial triiodothyronine (T3) receptor (p43) which acts as a mitochondrial transcription factor of the organelle genome, which leads in vitro and in vivo, to a stimulation of mitochondrial biogenesis. Recently, we generated mice carrying a specific p43 invalidation. At 2 months of age, we reported that p43 depletion in mice induced a major defect in insulin secretion both in vivo and in isolated pancreatic islets, and a loss of glucose-stimulated insulin secretion. The present study was designed to determine whether p43 invalidation influences life expectancy and modulates blood glucose and insulin levels as well as glucose tolerance or insulin sensitivity during aging. We report that from 4 months old onwards, mice lacking p43 are leaner than wild-type mice. p43?/? mice also have a moderate reduction of life expectancy compared to wild type. We found no difference in blood glucose levels, excepted at 24 months old where p43?/? mice showed a strong hyperglycemia in fasting conditions compared to controls animals. However, the loss of glucose-stimulated insulin secretion was maintained whatever the age of mice lacking p43. If up to 12 months old, glucose tolerance remained unchanged, beyond this age p43?/? mice became increasingly glucose intolerant. In addition, if up to 12 months old p43 deficient animals were more sensitive to insulin, after this age we observed a loss of this capacity, culminating in 24 months old mice with a decreased sensitivity to the hormone. In conclusion, we demonstrated that during aging the depletion of the mitochondrial T3 receptor p43 in mice progressively induced an increased glycemia in the fasted state, glucose intolerance and an insulin-resistance several features of type-2 diabetes. PMID:24098680
Bertrand, Christelle; Blanchet, Emilie; Pessemesse, Laurence; Annicotte, Jean Sebastien; Feillet-Coudray, Christine; Chabi, Beatrice; Levin, Jonathan; Fajas, Lluis; Cabello, Gerard; Wrutniak-Cabello, Chantal; Casas, Francois
Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness. PMID:22745735
Kunkel, Steven D.; Elmore, Christopher J.; Bongers, Kale S.; Ebert, Scott M.; Fox, Daniel K.; Dyle, Michael C.; Bullard, Steven A.; Adams, Christopher M.
Insufficient plasma insulin levels caused by deficits in both pancreatic ?-cell function and mass contribute to the pathogenesis of type 2 diabetes. This loss of insulin-producing capacity is termed ?-cell decompensation. Our work is focused on defining the role(s) of guanine nucleotide-binding protein (G protein) signaling pathways in regulating ?-cell decompensation. We have previously demonstrated that the ?-subunit of the heterotrimeric Gz protein, G?z, impairs insulin secretion by suppressing production of cAMP. Pancreatic islets from G?z-null mice also exhibit constitutively increased cAMP production and augmented glucose-stimulated insulin secretion, suggesting that G?z is a tonic inhibitor of adenylate cyclase, the enzyme responsible for the conversion of ATP to cAMP. In the present study, we show that mice genetically deficient for G?z are protected from developing glucose intolerance when fed a high fat (45 kcal%) diet. In these mice, a robust increase in ?-cell proliferation is correlated with significantly increased ?-cell mass. Further, an endogenous G?z signaling pathway, through circulating prostaglandin E activating the EP3 isoform of the E prostanoid receptor, appears to be up-regulated in insulin-resistant, glucose-intolerant mice. These results, along with those of our previous work, link signaling through G?z to both major aspects of ?-cell decompensation: insufficient ?-cell function and mass. PMID:22457354
Kimple, Michelle E.; Moss, Jennifer B.; Brar, Harpreet K.; Rosa, Taylor C.; Truchan, Nathan A.; Pasker, Renee L.; Newgard, Christopher B.; Casey, Patrick J.
We examined antepartum clinical characteristics along with measures of glucose tolerance, insulin sensitivity, pancreatic -cell function, and body composition in Latino women with gestational diabetes mellitus (GDM) for their ability to predict type 2 diabetes or impaired glucose tolerance (IGT) within 6 months after delivery. A total of 122 islet cell antibody-negative women under- went oral and intravenous glucose tolerance
Thomas A. Buchanan; Anny Xiang; Siri L. Kjos; W. P. Lee; Enrique Trigo; Isabel Nader; E. Anne Bergner; Jerry P. Palmer; Ruth K. Peters
Aims The ability of dietary enrichment with monounsaturated (MUFA), n-3, or n-6 polyunsaturated fatty acids (PUFA) to reverse glucose intolerance and vascular dysfunction resulting from excessive dietary saturated fatty acids is not resolved. We hypothesized that partial replacement of dietary saturated fats with n-3 PUFA enriched menhaden oil (MO) would provide greater improvement in glucose tolerance and vascular function compared to n-6 enriched safflower oil (SO) or MUFA-enriched olive oil (OO). Material and Methods We fed mice a high saturated fat diet (60% kcal from lard) for 12 weeks before substituting half the lard with MO, SO or OO for an additional 4 weeks. At the end of 4 weeks, we assessed glucose tolerance, insulin signaling and reactivity of isolated pressurized gracilis arteries. Results After 12 weeks of saturated fat diet, body weights were elevated and glucose tolerance abnormal compared to mice on control diet (13% kcal lard). Diet substituted with MO restored basal glucose levels, glucose tolerance, and indices of insulin signaling (phosphorylated Akt) to normal whereas restoration was limited for SO and OO substitutions. Although dilation to acetylcholine was reduced in arteries from mice on HF, OO and SO diets compared to normal diet, dilation to acetylcholine was fully restored and constriction to phenylephrine reduced in MO fed mice compared to normal. Conclusion We conclude that short term enrichment of an ongoing high fat diet with n-3 PUFA rich MO but not MUFA rich OO or n-6 PUFA rich SO reverses glucose tolerance, insulin signaling, and vascular dysfunction. PMID:22950668
Lamping, KL; Nuno, DW; Coppey, LJ; Holmes, AJ; Hu, S; Oltman, CL; Norris, AW; Yorek, MA
The association of insulin resistance and hyperinsulinemia to blood pressure has remained controversial. We examined the association of insulinemia to hypertension and blood pressure using baseline measurements for participants of the Diabetes Prevention Program (DPP). The DPP is a multicenter randomized controlled trial of 3819 participants with impaired glucose tolerance, and is designed to evaluate interventions for the delay or prevention of type 2 diabetes. The relationship between hypertension and insulinemia is described overall and by ethnicity. The effects of demographics (age and gender), adiposity, and glucose on the relationship are also presented. Asian Americans and African Americans had a similarly high prevalence of hypertension as did whites; American Indians had a lower prevalence of hypertension. Among participants not on antihypertensive medications, systolic blood pressure was significantly (but weakly) correlated with fasting insulin (r=0.12), homeostasis model assessment of insulin resistance (HOMA IR; r=0.13), and fasting proinsulin (r=0.10) when adjusted for age and gender (all, P<0.001). Systolic blood pressure showed similar correlations to fasting insulin in each ethnic group. After further adjustment for body mass index, the association of fasting insulin to systolic and diastolic blood pressures weakened considerably but remained significant (systolic: r=0.06, P=0.002; DBP: r=0.06, P<0.001). We conclude that a weak but significant association between insulin, (and proinsulin and HOMA IR) and blood pressure exists but is largely explained by overall adiposity. This association is similar among ethnicities, with the possible exception of Hispanics. The relation between insulin concentrations and blood pressure explains relatively little of the ethnic differences in hypertensive prevalence. PMID:12411462
Rapamycin, an inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, extends the life span of yeast, worms, flies, and mice. Interventions that promote longevity are often correlated with increased insulin sensitivity, and it therefore is surprising that chronic rapamycin treatment of mice, rats, and humans is associated with insulin resistance (J Am Soc Nephrol., 19, 2008, 1411; Diabetes, 00, 2010, 00; Science, 335, 2012, 1638). We examined the effect of dietary rapamycin treatment on glucose homeostasis and insulin resistance in the genetically heterogeneous HET3 mouse strain, a strain in which dietary rapamycin robustly extends mean and maximum life span. We find that rapamycin treatment leads to glucose intolerance in both young and old HET3 mice, but in contrast to the previously reported effect of injected rapamycin in C57BL/6 mice, HET3 mice treated with dietary rapamycin responded normally in an insulin tolerance test. To gauge the overall consequences of rapamycin treatment on average blood glucose levels, we measured HBA1c. Dietary rapamycin increased HBA1c over the first 3 weeks of treatment in young animals, but the effect was lost by 3 months, and no effect was detected in older animals. Our results demonstrate that the extended life span of HET3 mice on a rapamycin diet occurs in the absence of major changes in insulin sensitivity and highlight the importance of strain background and delivery method in testing effects of longevity interventions. PMID:23648089
Lamming, Dudley W; Ye, Lan; Astle, Clinton M; Baur, Joseph A; Sabatini, David M; Harrison, David E
Ceramides increase during obesity and promote insulin resistance. Ceramides vary in acyl-chain lengths from C14:0 to C30:0 and are synthesized by six ceramide synthase enzymes (CerS1-6). It remains unresolved whether obesity-associated alterations of specific CerSs and their defined acyl-chain length ceramides contribute to the manifestation of metabolic diseases. Here we reveal that CERS6 mRNA expression and C16:0 ceramides are elevated in adipose tissue of obese humans, and increased CERS6 expression correlates with insulin resistance. Conversely, CerS6-deficient (CerS6(?/?)) mice exhibit reduced C16:0 ceramides and are protected from high-fat-diet-induced obesity and glucose intolerance. CerS6 deletion increases energy expenditure and improves glucose tolerance, not only in CerS6(?/?) mice, but also in brown adipose tissue- (CerS6(?BAT)) and liver-specific (CerS6(?LIVER)) CerS6 knockout mice. CerS6 deficiency increases lipid utilization in BAT and liver. These experiments highlight CerS6 inhibition as a specific approach for the treatment of obesity and type 2 diabetes mellitus, circumventing the side effects of global ceramide synthesis inhibition. PMID:25295788
Turpin, Sarah M; Nicholls, Hayley T; Willmes, Diana M; Mourier, Arnaud; Brodesser, Susanne; Wunderlich, Claudia M; Mauer, Jan; Xu, Elaine; Hammerschmidt, Philipp; Brönneke, Hella S; Trifunovic, Aleksandra; LoSasso, Giuseppe; Wunderlich, F Thomas; Kornfeld, Jan-Wilhelm; Blüher, Matthias; Krönke, Martin; Brüning, Jens C
Background: The delivery of excess maternal nutrients to the fetus is known to increase the risk of macrosomia, even among infants of women without gestational diabetes mellitus. With the current obesity epidemic, maternal adiposity and its associated effects on circulating adipokines and inflammatory proteins may now have a greater impact on fetal growth. We sought to evaluate the independent effects of maternal glycemia, lipids, obesity, adipokines and inflammation on infant birth weight. Methods: We included 472 women who underwent an oral glucose tolerance test in late pregnancy and were found not to have gestational diabetes; 104 (22.0%) had gestational impaired glucose tolerance. We also measured fasting levels of insulin, low-and high-density lipoprotein cholesterol, triglycerides, leptin, adiponectin and C-reactive protein. Obstetric outcomes were assessed at delivery. Results: The mean birth weight was 3481 g (standard deviation 493 g); 68 of the infants were large for gestational age. On multiple linear regression analysis, positive determinants of birth weight were length of gestation, male infant, weight gain during pregnancy up to the time of the oral glucose tolerance test, body mass index (BMI) before pregnancy and impaired glucose tolerance in pregnancy. Leptin, adiponectin and C-reactive protein levels were each negatively associated with birth weight. On logistic regression analysis, the significant metabolic predictors of having a large-for-gestational-age infant were BMI before pregnancy (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.05–1.27, per 1 kg/m2 increase), weight gain during pregnancy up to the time of the oral glucose tolerance test (OR 1.12, 95% CI 1.05–1.19, per 1 kg increase) and leptin level (OR 0.50, 95% CI 0.30–0.82, per 1 standard deviation change). Interpretation: Among women without gestational diabetes, maternal adiposity and leptin levels were the strongest metabolic determinants of having a large-for-gestational-age infant rather than glucose intolerance and lipid levels. PMID:22619341
Retnakaran, Ravi; Ye, Chang; Hanley, Anthony J.G.; Connelly, Philip W.; Sermer, Mathew; Zinman, Bernard; Hamilton, Jill K.
Orexin-A (a neuropeptide in the hypothalamus) plays an important role in many physiological functions, including the regulation of glucose metabolism. We have previously found that the development of post-ischemic glucose intolerance is one of the triggers of ischemic neuronal damage, which is suppressed by hypothalamic orexin-A. Other reports have shown that the communication system between brain and peripheral tissues through the autonomic nervous system (sympathetic, parasympathetic and vagus nerve) is important for maintaining glucose and energy metabolism. The aim of this study was to determine the involvement of the hepatic vagus nerve on hypothalamic orexin-A-mediated suppression of post-ischemic glucose intolerance development and ischemic neuronal damage. Male ddY mice were subjected to middle cerebral artery occlusion (MCAO) for 2 h. Intrahypothalamic orexin-A (5 pmol/mouse) administration significantly suppressed the development of post-ischemic glucose intolerance and neuronal damage on day 1 and 3, respectively after MCAO. MCAO-induced decrease of hepatic insulin receptors and increase of hepatic gluconeogenic enzymes on day 1 after was reversed to control levels by orexin-A. This effect was reversed by intramedullary administration of the orexin-1 receptor antagonist, SB334867, or hepatic vagotomy. In the medulla oblongata, orexin-A induced the co-localization of cholin acetyltransferase (cholinergic neuronal marker used for the vagus nerve) with orexin-1 receptor and c-Fos (activated neural cells marker). These results suggest that the hepatic branch vagus nerve projecting from the medulla oblongata plays an important role in the recovery of post-ischemic glucose intolerance and mediates a neuroprotective effect by hypothalamic orexin-A. PMID:24759941
Harada, Shinichi; Yamazaki, Yui; Koda, Shuichi; Tokuyama, Shogo
Several epidemiological evidences indicate that consumption of coffee is associated with a lower risk of type 2 diabetes mellitus (T2DM) however; there is dearth of experimental data to support these observations. Given that associations do not necessarily infer causality, the present study was designed to investigate the effect of coffee consumption on glucose regulation, T2DM and the probable mechanisms of action, using an animal model. The effect of coffee (2-fold dilution) by oral gavage on normal and high sucrose-solution (HSS) fed (30 % w/v) rats was evaluated. The results showed that consumption of coffee significantly increase glucose tolerance and insulin sensitivity (p<0.05) along with significant improvement in SOD and GSH activities. In addition, lipid indices such as TG and LDL as well as the lipid peroxidation marker (MDA) were markedly reduced (p<0.05) in rats fed with coffee compared with that of the HSS fed rats. These findings suggest that coffee consumption improves insulin sensitivity, glucose tolerance in HSS-fed rat possibly via inhibition of oxidative stress. PMID:24937394
Morakinyo, A O; Adekunbi, D A; Dada, K A; Adegoke, O A
Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepressor splicing from NCoR? to NCoR?, which appears to help regulate this differentiation process. We report here that mimicking this development switch in mice by a splice-specific whole-animal ablation of NCoR? is very different from a whole-animal or tissue-specific total NCoR knockout and produces significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoR?(-/-) mice are protected against diet-induced glucose intolerance despite enhanced adiposity and the presence of multiple additional, prodiabetic phenotypic changes. Our results indicate that the change in NCoR splicing during normal development both helps drive normal adipocyte differentiation and plays a key role in determining a metabolically appropriate storage of excess calories. We also conclude that whole-gene "knockouts" fail to reveal how important gene products are customized, tailored, and adapted through alternative mRNA splicing and thus do not reveal all the functions of the protein products of that gene. PMID:25182530
Goodson, Michael L; Young, Briana M; Snyder, Chelsea A; Schroeder, Amy C; Privalsky, Martin L
Alterations of the gut microbiota and mucosal barrier are linked with metabolic diseases. Our aim was to investigate the potential benefit of the potential probiotic Bifidobacterium animalis ssp. lactis 420 in reducing high-fat diet-induced body weight gain and diabetes in mice. In the obesity model, C57Bl/6J mice were fed a high-fat diet (60 energy %) for 12 weeks, and gavaged daily with B. lactis 420 (109 cfu) or vehicle. In the diabetes model, mice were fed a high-fat, ketogenic diet (72 energy % fat) for 4 weeks, with a 6-week subsequent treatment with B. lactis 420 (108-1010 cfu/day) or vehicle, after which they were analysed for body composition. We also analysed glucose tolerance, plasma lipopolysaccharide and target tissue inflammation using only one of the B. lactis 420 groups (109 cfu/day). Intestinal bacterial translocation and adhesion were analysed in a separate experiment using an Escherichia coli gavage. Body fat mass was increased in both obese (10.7±0.8 g (mean ± standard error of mean) vs. 1.86±0.21 g, P<0.001) and diabetic mice (3.01±0.4 g vs. 1.14±0.15 g, P<0.001) compared to healthy controls. Treatment with B. lactis 420 significantly decreased fat mass in obese (7.83 ± 0.67 g, P=0.007 compared to obese with vehicle) and diabetic mice (1.89 ± 0.16 g, P=0.02 for highest dose). This was reflected as reduced weight gain and improved glucose tolerance. Furthermore, B. lactis 420 decreased plasma lipopolysaccharide levels (P<0.001), liver inflammation (P=0.04), and E. coli adhesion in the distal gut (P<0.05). In conclusion, B. lactis 420 reduces fat mass and glucose intolerance in both obese and diabetic mice. Reduced intestinal mucosal adherence and plasma lipopolysaccharide suggest a mechanism related to reduced translocation of gut microbes. PMID:25062610
Stenman, L K; Waget, A; Garret, C; Klopp, P; Burcelin, R; Lahtinen, S
Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 ?-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet. PMID:24742673
Fjære, Even; Aune, Ulrike L; Røen, Kristin; Keenan, Alison H; Ma, Tao; Borkowski, Kamil; Kristensen, David M; Novotny, Guy W; Mandrup-Poulsen, Thomas; Hudson, Brian D; Milligan, Graeme; Xi, Yannan; Newman, John W; Haj, Fawaz G; Liaset, Bjørn; Kristiansen, Karsten; Madsen, Lise
Endocannabinoids regulate energy balance and lipid metabolism by stimulating the cannabinoid receptor type 1 (CB1). Genetic deletion and pharmacological antagonism have shown that CB1 signaling is necessary for the development of obesity and related metabolic disturbances. However, the sufficiency of endogenously produced endocannabinoids to cause hepatic lipid accumulation and insulin resistance, independent of food intake, has not been demonstrated. Here, we show that a single administration of isopropyl dodecylfluorophosphonate (IDFP), perhaps the most potent pharmacological inhibitor of endocannabinoid degradation, increases hepatic triglycerides (TG) and induces insulin resistance in mice. These effects involve increased CB1 signaling, as they are mitigated by pre-administration of a CB1 antagonist (AM251) and in CB1 knockout mice. Despite the strong physiological effects of CB1 on hepatic lipid and glucose metabolism, little is known about the downstream targets responsible for these effects. To elucidate transcriptional targets of CB1 signaling, we performed microarrays on hepatic RNA isolated from DMSO (control), IDFP and AM251/IDFP-treated mice. The gene for the secreted glycoprotein lipocalin 2 (lcn2), which has been implicated in obesity and insulin resistance, was among those most responsive to alterations in CB1 signaling. The expression pattern of IDFP mice segregated from DMSO mice in hierarchal cluster analysis and AM251 pre-administration reduced (>50%) the majority (303 of 533) of the IDFP induced alterations. Pathway analysis revealed that IDFP altered expression of genes involved in lipid, fatty acid and steroid metabolism, the acute phase response, and amino acid metabolism in a CB1-dependent manner. PCR confirmed array results of key target genes in multiple independent experiments. Overall, we show that acute IDFP treatment induces hepatic TG accumulation and insulin resistance, at least in part through the CB1 receptor, and identify novel cannabinoid responsive genes. PMID:22073164
Ruby, Maxwell A.; Nomura, Daniel K.; Hudak, Carolyn S. S.; Barber, Anne; Casida, John E.; Krauss, Ronald M.
Insulin is believed to regulate glucose homeostasis mainly via direct effects on the liver, muscle, and adipose tissues. The contribution of insulin's central nervous system effects to disorders of glucose metabolism has received less attention. To evaluate whether postnatal reduction of insulin receptors (IRs) within the ventromedial hypothalamus (VMH), a brain region critical for glucose sensing, contributes to disorders of peripheral glucose metabolism, we microinjected a lentiviral vector expressing an antisense sequence to knockdown IRs or a control lentiviral vector into the VMH of nonobese nondiabetic rats. After 3–4 mo, we assessed 1) glucose tolerance, 2) hepatic insulin sensitivity, and 3) insulin and glucagon secretion, using the glucose clamp technique. Knockdown of IRs locally in the VMH caused glucose intolerance without altering body weight. Increments of plasma insulin during a euglycemic clamp study failed to suppress endogenous glucose production and produced a paradoxical rise in plasma glucagon in the VMH-IR knockdown rats. Unexpectedly, these animals also displayed a 40% reduction (P < 0.05) in insulin secretion in response to an identical hyperglycemic stimulus (?220 mg/dl). Our data demonstrate that chronic suppression of VMH-IR gene expression is sufficient to impair glucose metabolism as well as ?-cell and ?-cell function in nondiabetic, nonobese rats. These data suggest that insulin resistance within the VMH may be a significant contributor to the development of type 2 diabetes. PMID:21828334
Chan, Owen; Zhu, Wanling; Horblitt, Adam M.; Grillo, Claudia A.; Wilson, Steven; Reagan, Lawrence; Sherwin, Robert S.
Maternal nutrition may influence metabolic profiles in offspring. We aimed to investigate the effect of maternal folic acid supplement on glucose metabolism in mouse offspring fed a high-fat diet (HFD). Sixty C57BL/6 female mice were randomly assigned into three dietary groups and fed the AIN-93G diet containing 2 (control), 5 (recommended folic acid supplement, RFolS) or 40 (high folic acid supplement, HFolS) mg folic acid/kg of diet. All male offspring were fed HFD for eight weeks. Physiological, biochemical and genetic variables were measured. Before HFD feeding, developmental variables and metabolic profiles were comparable among each offspring group. However, after eight weeks of HFD feeding, the offspring of HFolS dams (Off-HFolS) were more vulnerable to suffer from obesity (p=0.009), glucose intolerance (p<0.001) and insulin resistance (p<0.001), compared with the controls. Off-HFolS had reduced serum adiponectin concentration, accompanied with decreased adiponectin mRNA level but increased global DNA methylation level in white adipose tissue. In conclusion, our results suggest maternal HFolS exacerbates the detrimental effect of HFD on glucose intolerance and insulin resistance in male offspring, implying that HFolS during pregnancy should be adopted cautiously in the general population of pregnant women to avoid potential deleterious effect on the metabolic diseases in their offspring. PMID:24736781
Huang, Yifan; He, Yonghan; Sun, Xiaowei; He, Yujie; Li, Ying; Sun, Changhao
It has been hypothesized that freeze-tolerance in anurans evolved from a predisposition for dehydration tolerance. To test this hypothesis, we dehydrated summer/fall-collected and winter acclimated freeze-tolerant chorus frogs and dehydration-tolerant, but freeze-intolerant, Woodhouse's and Great Plains toads to 25% and 50% body water loss (BWL). Following treatments, we measured glucose, glycogen, and glycogen phosphorylase and glycogen synthetase (summer/fall only) activities in liver and leg muscle. Hepatic glucose levels were not significantly altered by dehydration in either summer/fall-collected frogs or toads. Conversely, winter acclimated frogs did show an increment (2.9-fold) in hepatic glucose with dehydration, accompanied by a reduction in hepatic glycogen levels. Winter acclimated toads did not mobilize hepatic glucose in response to dehydration. Further, hepatic glycogen and phosphorylase activities did not vary in any consistent manner with dehydration in winter toads. Mean leg muscle glucose values were elevated at 50% BWL relative to other treatments, significantly so compared to 25% BWL for summer/fall-collected frogs. The pattern of hepatic glucose mobilization with dehydration in winter frogs is consistent with that in other freeze-tolerant frog species, and provides additional support for the hypothesis that freezing tolerance evolved from a capacity for dehydration tolerance. However, the lack of hepatic glucose mobilization in response to dehydration in fall frogs suggests that a seasonal component to dehydration-induced regulation of glucose metabolism exists in chorus frogs. Furthermore, the absence of a dehydration-induced mobilization of hepatic glucose at both seasons in toads suggests that this dehydration response is not universal for terrestrial anurans. PMID:15181646
Edwards, Joshua Ronald; Jenkins, Jennifer Lynn; Swanson, David Leslie
Elevated 2-h plasma glucose concentration (2hPG) from an oral glucose tolerance (OGTT) test more strongly predicts risk of subsequent cardiovascular disease than fasting plasma glucose (FPG), but the association between these glucose measurements and hypertension risk is less clear. We examined the association between 2hPG, FPG and risk of hypertension. We conducted a prospective observational study (The Australian Diabetes, Obesity
E J Boyko; E L M Barr; P Z Zimmet; J E Shaw
OBJECTIVE Subjects who are normal glucose tolerant (NGT) are considered at low risk, even if a plasma glucose value ?155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) is able to identify NGT subjects at high risk for type 2 diabetes and subclinical organ damage. Hyperuricemia is associated with several risk factors for cardiovascular diseases such as hypertension, insulin resistance, and diabetes. However, it is unknown whether uric acid (UA) is able to affect 1-h postload plasma glucose in hypertensive NGT subjects. RESEARCH DESIGN AND METHODS From a cohort of ?1,200 uncomplicated hypertensive outpatients who underwent OGTT, we selected 955 subjects (548 men and 407 women) aged 45.6 ± 10.1 years. Laboratory evaluations were performed, and estimated glomerular filtration rate was assessed by using the new equation proposed by investigators in the Chronic Kidney Disease Epidemiology Collaboration. RESULTS Considering different stepwise multivariate linear regression models, UA was the major predictor of 1-h postload glucose in the entire population, with NGT ?155 subjects, impaired glucose tolerant, and type 2 diabetic patients accounting for 26.0% (P < 0.0001), 25.3% (P < 0.0001), 13.5% (P < 0.0001), and 13.5% (P = 0.003) of its variation in the respective models. CONCLUSIONS We documented that in hypertensive NGT ?155 subjects, UA is strongly associated with 1-h postload glucose, similarly to what is observed in impaired glucose tolerant and diabetic patients. PMID:22011411
Perticone, Francesco; Sciacqua, Angela; Perticone, Maria; Arturi, Franco; Scarpino, Paola Elisa; Quero, Michele; Sesti, Giorgio
We examined the antidiabetic property of Boehmeria nivea (L.) Gaud. Ethanolic extract of Boehmeria nivea (L.) Gaud. (EBN) increased the uptake of 2-[N-(nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose in C2C12 myotubes. To examine the mechanisms underlying EBN-mediated increase in glucose uptake, we examined the transcriptional activity and expression of peroxisome proliferator-activated receptor gamma (PPAR-?), a pivotal target for glucose metabolism in C2C12 myotubes. We found that the EBN increased both the transcriptional activity and mRNA expression levels of PPAR-?. In addition, we measured phosphorylation and expression levels of other targets of glucose metabolism, such as AMP-activated protein kinase (AMPK) and protein kinase B (Akt/PKB). We found that EBN did not alter the phosphorylation or expression levels of these proteins in a time- or dose-dependent manner, which suggested that EBN stimulates glucose uptake through a PPAR-?-dependent mechanism. Further, we investigated the antidiabetic property of EBN using mice fed a high-fat diet (HFD). Administration of 0.5% EBN reduced the HFD-induced increase in body weight, total cholesterol level, and fatty liver and improved the impaired fasting glucose level, blood insulin content, and glucose intolerance. These results suggest that EBN had an antidiabetic effect in cell culture and animal systems and may be useful for preventing diabetes. PMID:23690860
Kim, Sung Hee; Sung, Mi Jeong; Park, Jae Ho; Yang, Hye Jeong; Hwang, Jin-Taek
Emerging evidence has demonstrated that saturated fatty acids prime pro-IL-1? production and inflammasome-mediated IL-1? activation is critical in obesity-associated insulin resistance (IR). Nonetheless, IL-1 receptor I-deficient (IL-1RI(-/-)) mice develop mature-onset obesity despite consuming a low-fat diet (LFD). With this apparent contradiction, the present study evaluated whether IL-1RI(-/-) mice were protected against long-term (6 mo) high-fat diet (HFD)-induced IR. Male wild-type and IL-1RI(-/-) mice were fed LFD or HFD for 3 or 6 mo, and glucose and insulin tolerance tests were performed. Adipose insulin sensitivity, cytokine profiles, and adipocyte morphology were assessed. The adipogenic potential of stromal vascular fraction was determined. Hepatic lipid accumulation and insulin sensitivity were characterized. IL-1RI(-/-) mice developed glucose intolerance and IR after 6 mo HFD compared with 3 mo HFD, coincident with enhanced weight gain, hyperinsulinemia, and hyperleptinemia. The aggravated IR phenotype was associated with loss of adipose functionality, switch from adipocyte hyperplasia to hypertrophy and hepatosteatosis. Induction of adipogenic genes was reduced in IL-1RI(-/-) preadipocytes after 6 mo HFD compared with 3 mo HFD. Obese LFD-IL-1RI(-/-) mice exhibited preserved metabolic health. IL-1RI(-/-) mice develop glucose intolerance and IR after 6 mo HFD intervention. While mature-onset obesity is evident in LFD-IL-1RI(-/-) mice, the additional metabolic insult of HFD was required to drive adipose inflammation and systemic IR. These findings indicate an important interaction between dietary fat and IL-1, relevant to optimal metabolic health. PMID:23921145
McGillicuddy, Fiona C; Reynolds, Clare M; Finucane, Orla; Coleman, Eilish; Harford, Karen A; Grant, Christine; Sergi, Domenico; Williams, Lynda M; Mills, Kingston H G; Roche, Helen M
Emerging evidence has demonstrated that saturated fatty acids prime pro-IL-1? production and inflammasome-mediated IL-1? activation is critical in obesity-associated insulin resistance (IR). Nonetheless, IL-1 receptor I-deficient (IL-1RI?/?) mice develop mature-onset obesity despite consuming a low-fat diet (LFD). With this apparent contradiction, the present study evaluated whether IL-1RI?/? mice were protected against long-term (6 mo) high-fat diet (HFD)-induced IR. Male wild-type and IL-1RI?/? mice were fed LFD or HFD for 3 or 6 mo, and glucose and insulin tolerance tests were performed. Adipose insulin sensitivity, cytokine profiles, and adipocyte morphology were assessed. The adipogenic potential of stromal vascular fraction was determined. Hepatic lipid accumulation and insulin sensitivity were characterized. IL-1RI?/? mice developed glucose intolerance and IR after 6 mo HFD compared with 3 mo HFD, coincident with enhanced weight gain, hyperinsulinemia, and hyperleptinemia. The aggravated IR phenotype was associated with loss of adipose functionality, switch from adipocyte hyperplasia to hypertrophy and hepatosteatosis. Induction of adipogenic genes was reduced in IL-1RI?/? preadipocytes after 6 mo HFD compared with 3 mo HFD. Obese LFD-IL-1RI?/? mice exhibited preserved metabolic health. IL-1RI?/? mice develop glucose intolerance and IR after 6 mo HFD intervention. While mature-onset obesity is evident in LFD-IL-1RI?/? mice, the additional metabolic insult of HFD was required to drive adipose inflammation and systemic IR. These findings indicate an important interaction between dietary fat and IL-1, relevant to optimal metabolic health. PMID:23921145
McGillicuddy, Fiona C.; Reynolds, Clare M.; Finucane, Orla; Coleman, Eilish; Harford, Karen A.; Grant, Christine; Sergi, Domenico; Williams, Lynda M.; Mills, Kingston H. G.
Oral Supplementation with Non-Absorbable Antibiotics or Curcumin Attenuates Western Diet-Induced Atherosclerosis and Glucose Intolerance in LDLR-/- Mice - Role of Intestinal Permeability and Macrophage Activation
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR?/? mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR?/? mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases. PMID:25251395
Ghosh, Siddhartha S.; Bie, Jinghua; Wang, Jing; Ghosh, Shobha
A 64-year-old woman with end-stage renal disease and retinopathy secondary to type 2 diabetes mellitus presented with recurrent episodes of left ocular pain and acute loss of visual acuity during hemodialysis. During these episodes, markedly elevated intraocular pressures were measured. Several local and systemic antiglaucoma drugs were administered without improvement of intraocular pressure, resulting in the necessity of a glaucoma drainage device (Ahmed valve). Due to a local infection, it had to be removed, after which intraocular pressure elevations recurred during hemodialysis. Assuming that intraocular changes in osmolality during hemodialysis caused the intraocular pressure increases, intradialytic administration of a 20% glucose solution (100mL/h) was initiated. This completely abrogated the development of both intraocular pain and increases in intraocular pressure. PMID:24189474
Saritas, Turgay; Koutsonas, Antonis; Walter, Peter; Floege, Jürgen; Krüger, Thilo
Metabolic syndrome (MetS) is a health problem throughout the world and is associated with cardiovascular disease and diabetes. Thus, the purpose of the present work was to evaluate the effects of a dietary pattern (DP; soy protein, nopal, chia seed, and oat) on the biochemical variables of MetS, the AUC for glucose and insulin, glucose intolerance (GI), the relationship of the presence of certain polymorphisms related to MetS, and the response to the DP. In this randomized trial, the participants consumed their habitual diet but reduced by 500 kcal for 2 wk. They were then assigned to the placebo (P; n = 35) or DP (n = 32) group and consumed the reduced energy diet plus the P or DP beverage (235 kcal) minus the energy provided by these for 2 mo. All participants had decreases in body weight (BW), BMI, and waist circumference during the 2-mo treatment (P < 0.0001); however, only the DP group had decreases in serum TG, C-reactive protein (CRP), and AUC for insulin and GI after a glucose tolerance test. Interestingly, participants in the DP group with MetS and the ABCA1 R230C variant had a greater decrease in BW and an increase in serum adiponectin concentration after 2 mo of dietary treatment than those with the ABCA1 R230R variant. The results from this study suggest that lifestyle interventions involving specific DP for the treatment of MetS could be more effective if local foods and genetic variations of the population are considered. PMID:22090467
Guevara-Cruz, Martha; Tovar, Armando R; Aguilar-Salinas, Carlos A; Medina-Vera, Isabel; Gil-Zenteno, Lidia; Hernández-Viveros, Isaac; López-Romero, Patricia; Ordaz-Nava, Guillermo; Canizales-Quinteros, Samuel; Guillen Pineda, Luz E; Torres, Nimbe
OBJECTIVE To address whether glucose tolerance status, and in particular 1-h postload plasma glucose levels, may affect diastolic function in 161 never-treated hypertensive white subjects. Impaired left ventricular relaxation, an early sign of diastolic dysfunction, represents the first manifestation of myocardial involvement in diabetic cardiomyopathy. A plasma glucose value ?155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes and with subclinical organ damage. RESEARCH DESIGN AND METHODS Subjects underwent OGTT and standard echocardiography. Diastolic function was assessed by pulsed Doppler transmitral flow velocity and tissue Doppler imaging. Insulin sensitivity was assessed by Matsuda index. RESULTS Among the participants, 120 had NGT, 26 had impaired glucose tolerance (IGT), and 15 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided NGT subjects as follows: NGT <155 mg/dL (n = 90) and NGT ?155 mg/dL (n = 30). Those with NGT ?155 mg/dL had higher left atrium dimensions (P < 0.0001) and isovolumetric relaxation time (IVRT) (P = 0.037) than those with NGT <155 mg/dL. By contrast, early/late transmitral flow velocity and all tissue Doppler parameters were significantly lower in those with NGT ?155 mg/dL than in those with NGT<155 mg/dL. At multiple regression analysis, 1-h glucose was the major determinant of left atrium area, IVRT, septal e?, septal e?-to-a? ratio, lateral e?, and lateral e?-to-a? ratio. CONCLUSIONS The main finding of this study is that 1-h postload plasma glucose is associated with left ventricular diastolic dysfunction. Subjects with NGT ?155 mg/dL had significantly worse diastolic function than those with NGT<155 mg/dL. PMID:21911775
Sciacqua, Angela; Miceli, Sofia; Greco, Laura; Arturi, Franco; Naccarato, Paola; Mazzaferro, Deborah; Tassone, Eliezer J.; Turano, Laura; Martino, Francesco; Sesti, Giorgio; Perticone, Francesco
Objectives To determine the main predictors of all-cause and cardiovascular (CV) mortality in a rural West Indian population in Plymouth, Tobago over 30 years. Methods Questionnaire survey for CV risk factors and alcohol consumption patterns administered at baseline in 1976 with 92.5% response rate. 831/832 patients were followed up until 2005 or death. Results Hypertension (>140/90 mm Hg) was prevalent in 48% of men and 44% of women, and 21% of men and 17% of women had diabetes. Evidence showed most predictors for all cause and cardiovascular mortality having the main effects at ages <60 years, (p-value for interaction<0.01) but no risk factors having sex-specific effects on mortality. The main predictors of all-cause mortality at age <60 years in the fully adjusted model were high sessional alcohol intake (hazard ratio (HR) 2.04, 95% CI 1.10-3.80), severe hypertension >160/95 mm Hg (HR 1.68, 95% CI 1.09-2.60), diabetes (HR 3.28, 95% CI 1.89-5.69), and BMI (HR 1.04, 95% CI 1.00-1.07). The main predictors of cardiovascular mortality were similar in the fully adjusted model: high sessional alcohol intake (HR 2.47 95% CI 1.10-5.57), severe hypertension (HR 2.78 95% CI 1.56-4.95), diabetes (HR 3.68 95% CI 1.77-7.67) and additionally LVH, (HR 5.54 95% CI 1.38-22.26), however BMI did not show independent effects. For men, high sessional alcohol intake explains 27% of all cause mortality, and 40% of cardiovascular mortality at age <60 yrs. In adults aged <60 years, the attributable risk fraction for IGT/Diabetes and all cause mortality and cardiovascular mortality is 28% in women vs. 11% in men, and 22% in women vs. 6% in men respectively. Conclusions In this Afro-Caribbean population we found that a major proportion of deaths are attributable to high sessional alcohol intake (in males), diabetes, and hypertension and these risk factors primarily operate in those below 60 years. PMID:21283617
Molokhia, Mariam; Nitsch, Dorothea; Patrick, Alan Leslie; McKeigue, Paul
Williams–Beuren syndrome is a neurodevelopmental disorder mainly characterized by dysmorphic features, vascular stenoses,\\u000a abnormalities of calcium and glucose metabolism, and mental retardation with visuospatial deficits, caused by de novo deletion\\u000a of 26–28 genes at 7q11.23. Clinical–molecular correlations have defined critically deleted genes as likely responsible for\\u000a several aspects of the phenotype, but the precise biological pathways affected are mostly unknown.
Anna Antonell; Mireia Vilardell; Luis A. Pérez Jurado
OBJECTIVE Left ventricular hypertrophy (LVH), an independent risk factor for cardiovascular (CV) morbidity and mortality, recognizes a multifactorial pathogenesis. A plasma glucose value ?155 mg/dL for the 1-h postload plasma glucose during an oral glucose tolerance test (OGTT) identifies subjects with normal glucose tolerance (NGT) at high risk for type 2 diabetes. We addressed the question if glucose tolerance status, particularly 1-h postload plasma glucose levels, affects left ventricular mass (LVM) and cardiac geometry in essential hypertension. RESEARCH DESIGN AND METHODS We enrolled 767 never-treated hypertensive subjects, 393 women and 374 men (mean age 49.6 ± 8.5 years). All patients underwent an OGTT for the evaluation of glucose tolerance and standard echocardiography. LVM was calculated using the Devereux formula and normalized by body surface area (LVM index [LVMI]). Insulin sensitivity was assessed by the Matsuda index. Among all participants, 514 had NGT, 168 had impaired glucose tolerance (IGT), and 85 had type 2 diabetes. According to the 1-h postload plasma glucose cutoff point of 155 mg/dL, we divided normotolerant subjects into two groups: NGT <155 mg/dL (n = 356) and NGT ?155 mg/dL (n = 158). RESULTS Subjects in the NGT ?155 mg/dL group had worse insulin sensitivity than subjects in the NGT <155 mg/dL group (Matsuda index 63.9 vs. 88.8; P < 0.0001). Men with NGT ?155 mg/dL had a higher LVMI than men with NGT <155 mg/dL (126.6 vs. 114.3 g/m2; P = 0.002) and a different LVH prevalence (41.1 vs. 25.8%; P < 0.0001). At multiple regression analysis, 1-h glucose resulted in the major determinant of LVMI in normotolerant, IGT, and diabetic groups. CONCLUSIONS These data show that NGT ?155 mg/dL subjects, compared with NGT <155 mg/dL subjects, have a higher LVMI and a greater prevalence of LVH similar to that of IGT and diabetic patients. PMID:21515837
Sciacqua, Angela; Miceli, Sofia; Carullo, Giuseppe; Greco, Laura; Succurro, Elena; Arturi, Franco; Sesti, Giorgio; Perticone, Francesco
Background A plasma glucose value ?155 mg/dl for 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes and with subclinical organ damage. We designed this study to address if 25-hydroxyvitamin D [25(OH)D] circulating levels are associated with glucose tolerance status, and in particular with 1-hour post-load plasma glucose levels. Methods We enrolled 300 consecutive Caucasian hypertensive never-treated outpatients (160 men and 140 women, aged 52.9?±?9.2 years). Subjects underwent OGTT and measurements of 25(OH)D and standard laboratory tests. Estimated glomerular filtration rate (e-GFR) was calculated by CKD-EPI formula and insulin sensitivity was assessed by Matsuda-index. Results Among participants, 230 were NGT, 44 had impaired glucose tolerance (IGT) and 26 had type-2 diabetes. According to 1-h post-load plasma glucose cut-off point of 155 mg/dL, we divided NGT subjects into: NGT?155 (n?=?156) and NGT?>?155 mg/dL (n?=?74). NGT???155 had higher significant fasting and post-load glucose and insulin, parathyroid hormone and hs-CRP levels than NGT?155. On the contrary, Matsuda-index, e-GFR, and 25(OH)D were significantly lower in NGT???155 than NGT?155 subjects. In the multiple regression analysis, 25(OH)D levels resulted the major determinant of 1-h post-load plasma glucose in all population and in the four groups of glucose tolerance status. In the whole population, Matsuda-index, hs-CRP and e-GFR explained another 12.2%, 6.7% and 1.7% of its variation. Conclusions Our data demonstrate a significant and inverse relationship between 25(OH)D levels and glucose tolerance status, particularly with 1-h post-load glucose. PMID:24555478
Hypertensive patients have higher prevalence of insulin resistance and are at increased risk of developing type 2 diabetes mellitus (DM). There is scarcity of data on the relationship between antihypertensive therapies and glycaemic control in Indian population. Thus, the present study was designed to investigate such association among Indian population in a University teaching hospital.The study was carried out on 177 hypertensive patients (with new onset of diabetes or without diabetes) visiting the OPD of medicine department at Majeedia hospital, New Delhi. The drug history of hypertensive patients and blood glucose levels following 1-5 yrs of antihypertensive therapy were recorded.The gender distribution of hypertensive patients reveals a higher percentage of incidences in males (53.7%) as compared to females (46.3%). Hypertensive patient without DM on beta blockers and on thiazide shows higher incidence of impaired glucose tolerance (IGT) (17.5%, 18.5%) and DM (10%, 11%) as compared to patient receiving other antihypertensive therapy. While in patients of new onset diabetes the incidence was higher with ?-blockers (56.2%) than with thiazides (31.3%) followed by calcium channel blockers (CCBs) (12.5%). There was proportionate increase in incidence with the duration of therapy (3-5 years). None of the patients who were on ACE inhibitors or on angiotensin receptor blockers (ARBs) reported any incidence of IGT or DM.To conclude, ?-blockers and thiazides increases the risk of type 2 diabetes mellitus with long term antihypertensive therapy requiring regular monitoring. CCBs have lowered risks while ACE inhibitors and ARBs are relatively free of such metabolic adverse effects. PMID:24132701
Ahmad, M A; Kapur, P; Khanam, R; Akhtar, M; Khan, G H; Anwar, M J; Vohora, D
The contribution of peroxisomal proliferator-activated receptor (PPAR)-? agonism in pancreatic ?-cells to the antidiabetic actions of thiazolidinediones has not been clearly elucidated. Genetic models of pancreatic ?-cell PPAR? ablation have revealed a potential role for PPAR? in ?-cell expansion in obesity but a limited role in normal ?-cell physiology. Here we overexpressed PPAR?1 or PPAR?2 specifically in pancreatic ?-cells of mice subjected to high-fat feeding using an associated adenovirus (?-PPAR?1-HFD and ?-PPAR?2-HFD mice). We show ?-cell-specific PPAR?1 or PPAR?2 overexpression in diet-induced obese mice exacerbated obesity-induced glucose intolerance with decreased ?-cell mass, increased islet cell apoptosis, and decreased plasma insulin compared with obese control mice (?-eGFP-HFD mice). Analysis of islet lipid composition in ?-PPAR?2-HFD mice revealed no significant changes in islet triglyceride content and an increase in only one of eight ceramide species measured. Interestingly ?-PPAR?2-HFD islets had significantly lower levels of lysophosphatidylcholines, lipid species shown to enhance insulin secretion in ?-cells. Gene expression profiling revealed increased expression of uncoupling protein 2 and genes involved in fatty acid transport and ?-oxidation. In summary, transgenic overexpression of PPAR? in ?-cells in diet-induced obesity negatively impacts whole-animal carbohydrate metabolism associated with altered islet lipid content, increased expression of ?-oxidative genes, and reduced ?-cell mass. PMID:25051434
Hogh, K-Lynn N; Craig, Michael N; Uy, Christopher E; Nygren, Heli; Asadi, Ali; Speck, Madeline; Fraser, Jordie D; Rudecki, Alexander P; Baker, Robert K; Oreši?, Matej; Gray, Sarah L
The Hyde Amendment and Roman Catholic attempts to put restrictions on Title X funding have been criticized for being intolerant. However, such criticism fails to appreciate that there are two competing notions of tolerance, one focusing on the limits of state force and accepting pluralism as unavoidable, and the other focusing on the limits of knowledge and advancing pluralism as a good. These two types of tolerance, illustrated in the writings of John Locke and J.S. Mill, each involve an intolerance. In a pluralistic context where the free exercise of religion is respected, John Locke's account of tolerance is preferable. However, it (in a reconstructed form) leads to a minimal state. Positive entitlements to benefits like artificial contraception or nontherapeutic abortions can legitimately be resisted, because an intolerance has already been shown with respect to those that consider the benefit immoral, since their resources have been coopted by taxation to advance an end that is contrary to their own. There is a sliding scale from tolerance (viewed as forbearance) to the affirmation of communal integrity, and this scale maps on to the continuum from negative to positive rights. PMID:8051515
We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis. PMID:9180626
Rosenthal, T; Erlich, Y; Rosenmann, E; Cohen, A
Objectives Pulse wave velocity (PWV) is a surrogate end-point for cardiovascular morbidity and mortality. A plasma glucose value ?155 mg/dl for the 1-hour post-load plasma glucose during an oral glucose tolerance test (OGTT) is able to identify subjects with normal glucose tolerance (NGT) at high-risk for type-2 diabetes (T2D) and for subclinical organ damage. Thus, we addressed the question if 1-hour post-load plasma glucose levels, affects PWV and its central hemodynamic correlates, as augmentation pressure (AP) and augmentation index (AI). Methods We enrolled 584 newly diagnosed hypertensives. All patients underwent OGTT and measurements of PWV, AP and AI. Insulin sensitivity was assessed by Matsuda-index. Results Among participants, 424 were NGT and 160 had impaired glucose tolerance (IGT). Of 424 NGT, 278 had 1-h post-load plasma glucose <155 mg/dl (NGT<155) and 146 had 1-h post-load plasma glucose ?155 mg/dl (NGT?155). NGT?155 had a worse insulin sensitivity and higher hs-CRP than NGT<155, similar to IGT subjects. In addition, NGT ?155 in comparison with NGT<155 had higher central systolic blood pressure (134±12 vs 131±10 mmHg), as well as PWV (8.4±3.7 vs 6.7±1.7 m/s), AP (12.5±7.1 vs 9.8±5.7 mmHg) and AI (29.4±11.9 vs 25.1±12.4%), and similar to IGT. At multiple regression analysis, 1-h post-load plasma glucose resulted the major determinant of all indices of vascular stiffness. Conclusion Hypertensive NGT?155 subjects, compared with NGT<155, have higher PWV and its hemodynamic correlates that increase their cardiovascular risk profile. PMID:23028545
Sciacqua, Angela; Maio, Raffaele; Miceli, Sofia; Pascale, Alessandra; Carullo, Giuseppe; Grillo, Nadia; Arturi, Franco; Sesti, Giorgio; Perticone, Francesco
Summary A representative sample (n=2140) of the Israeli Jewish population aged 40–70 (excluding known diabetic patients), whose body mass index had been measured 10 years earlier, underwent an oral glucose tolerance test and redetermination of body mass index. Irrespective of weight changes, high concurrent and high past body mass index values ( 27) were associated with similarly increased rates of glucose
M. Modan; A. Karasik; H. Halkin; Z. Fuchs; A. Lusky; A. Shitrit; B. Modan
Oral supplementation with non-absorbable antibiotics or curcumin attenuates western diet-induced atherosclerosis and glucose intolerance in LDLR-/- mice--role of intestinal permeability and macrophage activation.
Association between circulating lipopolysaccharide (LPS) and metabolic diseases (such as Type 2 Diabetes and atherosclerosis) has shifted the focus from Western diet-induced changes in gut microbiota per se to release of gut bacteria-derived products into circulation as the possible mechanism for the chronic inflammatory state underlying the development of these diseases. Under physiological conditions, an intact intestinal barrier prevents this release of LPS underscoring the importance of examining and modulating the direct effects of Western diet on intestinal barrier function. In the present study we evaluated two strategies, namely selective gut decontamination and supplementation with oral curcumin, to modulate Western-diet (WD) induced changes in intestinal barrier function and subsequent development of glucose intolerance and atherosclerosis. LDLR-/- mice were fed WD for 16 weeks and either received non-absorbable antibiotics (Neomycin and polymyxin) in drinking water for selective gut decontamination or gavaged daily with curcumin. WD significantly increased intestinal permeability as assessed by in vivo translocation of FITC-dextran and plasma LPS levels. Selective gut decontamination and supplementation with curcumin significantly attenuated the WD-induced increase in plasma LPS levels (3.32 vs 1.90 or 1.51 EU/ml, respectively) and improved intestinal barrier function at multiple levels (restoring intestinal alkaline phosphatase activity and expression of tight junction proteins, ZO-1 and Claudin-1). Consequently, both these interventions significantly reduced WD-induced glucose intolerance and atherosclerosis in LDLR-/- mice. Activation of macrophages by low levels of LPS (50 ng/ml) and its exacerbation by fatty acids is likely the mechanism by which release of trace amounts of LPS into circulation due to disruption of intestinal barrier function induces the development of these diseases. These studies not only establish the important role of intestinal barrier function, but also identify oral supplementation with curcumin as a potential therapeutic strategy to improve intestinal barrier function and prevent the development of metabolic diseases. PMID:25251395
Ghosh, Siddhartha S; Bie, Jinghua; Wang, Jing; Ghosh, Shobha
Type 2 Diabetes is a global health burden and based on current estimates will become an even larger problem in the future. Developing new strategies to prevent and treat diabetes is a scientific challenge of high priority. The stomach hormone ghrelin has been associated with playing a role in the regulation of glucose homeostasis. However, its precise mechanism and impact on whole glucose metabolism remains to be elucidated. This study aims to clarify the role of the two ghrelin isoforms acyl- and desacyl ghrelin in regulating glucose homeostasis. Therefore ghrelin activating enzyme Ghrelin-O-acyltransferase (GOAT) was ablated in leptin-deficient ob/ob mice to study whether specific acyl ghrelin deficiency or desacyl ghrelin abundance modifies glucose tolerance on a massively obese background. As targeted deletion of acyl ghrelin does not improve glucose homeostasis in our GOAT-ob/ob mouse model we conclude that neither acyl ghrelin nor the increased ratio of desacyl/acyl ghrelin is crucial for controlling glucose homeostasis in the here presented model of massive obesity induced by leptin deficiency. PMID:23630616
Kirchner, Henriette; Heppner, Kristy M.; Holland, Jenna; Kabra, Dhiraj; Tschop, Matthias H.; Pfluger, Paul T.
Arterial hypertension (AH) and diabetes mellitus (DM) are established cardiovascular risk factors. Impaired glucose homeostasis (IGH; impaired fasting glucose or/and impaired glucose tolerance) or pre-diabetes, obesity, and DM family history identify individuals at risk for type 2 DM in whom preventive interventions are necessary. The aim of this study was to determine the glycemic profile in non-diabetic Greek adult hypertensive men and women according to DM family history and the obesity status. Diabetes family history, obesity markers (waist-to-hip ratio, WHR; body mass index, BMI), glycemic parameters (fasting and 2-hour post-load plasma glucose, if necessary; glycated hemoglobin, HbA1c; fasting insulin), insulin resistance indices (homeostasis model assessment, HOMA; quantitative insulin sensitivity check index, QUICKI; Bennett; McAuley), and IGH prevalence were determined in a large cohort of 11,540 Greek hypertensives referred to our institutions. Positive DM family history was associated with elevated fasting glucose (98.6 ± 13.1 vs 96.5 ± 12.3 mg/dL), HbA1c (5.58% ± 0.49% vs 5.50% ± 0.46%), fasting insulin (9.74 ± 4.20 vs 9.21 ± 3.63 ?U/mL) and HOMA (2.43 ± 1.19 vs 2.24 ± 1.01) values, lower QUICKI (0.342 ± 0.025 vs 0.345 ± 0.023), Bennett (0.285 ± 0.081 vs 0.292 ± 0.078) and McAuley (6.73 ± 3.43 vs 6.95 ± 3.44) values, and higher IGH prevalence (45.3% vs 38.7%); P < .01 for all comparisons. The difference in the prevalence of IGH according to DM family history was significant (P < .01) in both genders and every WHR and BMI subgroup (except for women with BMI <20 kg/m(2)). Non-diabetic hypertensives with positive DM family history present with higher IGH prevalence and worse glycemic indices levels compared with those with negative family history, especially in the higher WHR/BMI subgroups. PMID:23562108
Vyssoulis, Gregory P; Liakos, Charalampos I; Karpanou, Eva A; Triantafyllou, Athanasios I; Michaelides, Andreas P; Tzamou, Vanessa E; Markou, Maria I; Stefanadis, Christodoulos I
Dietary intolerances to fructose, fructans and FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) are common, yet poorly recognized and managed. Over the last decade, they have come to the forefront because of new knowledge on the mechanisms and treatment of these conditions. Patients with these problems often present with unexplained bloating, belching, distension, gas, abdominal pain, or diarrhea. Here, we have examined the most up-to-date research on these food-related intolerances, discussed controversies, and have provided some guidelines for the dietary management of these conditions. Breath testing for carbohydrate intolerance appears to be standardized and essential for the diagnosis and management of these conditions, especially in the Western population. While current research shows that the FODMAP diet may be effective in treating some patients with irritable bowel syndrome, additional research is needed to identify more foods items that are high in FODMAPs, and to assess the long-term efficacy and safety of dietary interventions. PMID:24357350
Fedewa, Amy; Rao, Satish S C
Fructose in sweetened beverages (SB) increases the risk for metabolic and cardiorenal disorders, and these effects are in part mediated by a secondary increment in uric acid (UA). Rodents have an active uricase, thus requiring large doses of fructose to increase plasma UA and to induce metabolic syndrome and renal hemodynamic changes. We therefore hypothesized that the effects of fructose in rats might be enhanced in the setting of uricase inhibition. Four groups of male Sprague-Dawley rats (n = 7/group) were studied during 8 wk: water + vehicle (V), water + oxonic acid (OA; 750 mg/k BW), sweetened beverage (SB; 11% fructose-glucose combination) + V, and SB + OA. Systemic blood pressure, plasma UA, triglycerides (TG), glucose and insulin, glomerular hemodynamics, renal structural damage, renal cortex and liver UA, TG, markers of oxidative stress, mitDNA, fructokinase, and fatty liver synthase protein expressions were evaluated at the end of the experiment. Chronic hyperuricemia and SB induced features of the metabolic syndrome, including hypertension, hyperuricemia, hyperglycemia, and systemic and hepatic TG accumulation. OA alone also induced glomerular hypertension, and SB alone induced insulin resistance. SB + OA induced a combined phenotype including metabolic and renal alterations induced by SB or OA alone and in addition also acted synergistically on systemic and glomerular pressure, plasma glucose, hepatic TG, and oxidative stress. These findings explain why high concentrations of fructose are required to induce greater metabolic changes and renal disease in rats whereas humans, who lack uricase, appear to be much more sensitive to the effects of fructose. PMID:23303409
Tapia, Edilia; Cristobal, Magdalena; Garcia-Arroyo, Fernando E.; Soto, Virgilia; Monroy-Sanchez, Fabiola; Pacheco, Ursino; Lanaspa, Miguel A.; Roncal-Jimenez, Carlos A.; Cruz-Robles, David; Ishimoto, Takuji; Madero, Magdalena; Johnson, Richard J.
Hypertension is the most common modifiable risk factor for cardiovascular disease. Antihypertensive treatment substantially reduces the risk of heart failure, stroke, and myocardial infarction. Current guidelines recommend screening all adults for high blood pressure (BP). Lifestyle modifications to help control high BP include weight loss, exercise, moderation of alcohol intake, and a diet low in sodium and saturated fats and high in fruits and vegetables. Out-of-office BP monitoring should be used to confirm suspected white coat effect, especially in patients with apparent resistant hypertension. PMID:23402468
Winter, Katherine H; Tuttle, Laura A; Viera, Anthony J
Hypertension is a forum for the presentation of scientific investigation of the highest quality in the broad field of cardiovascular regulation as it may affect high blood pressure research. The editors are interested in receiving original articles that deal with either basic or clinical research in the fields of biochemistry, cellular and molecular biology, immunology, physiology, pharmacology, and epidemiology. In
Allyn L. Mark; Francois M. Abboud; Gerald F. DiBona; Donald D. Heistad; Larry S. Tobacman; Victor J. Dzau; Carlos Ferrario; Eduardo Marban; Suzanne Oparil; Henry W. Overbeck; Stephen M. Schwartz; Karen Potvin Klein; Connie J. Nelson; John D. Baxter; Kathleen H. Berecek; Edward H. Blaine; Mordecai P. Blaustein; Barry M. Brenner; Michael J. Brody; Hans R. Brunner; Aram V. Chobanian; Robert J. Cody; Allen W. Cowley Jr.; Michael J. Dunn; Alvan R. Feinstein; D. Fink; S. Floras; Ronald H. Freeman; Edward D. Frohlich; Detlev Ganten; Haralambos P. Gavras; Celso E. Gomez-Sanchez; W. Gross; Oregon Willa Hsueh; Tadashi Inagami; I. Johnston; Stevo Julius; Norman M. Kaplan; Paul I. Korner; Theodore A. Kotchen; Eduardo M. Krieger; Brazil Kai Lau; Ronald M. Lauer; Jean-Francois Liard; Marshall D. Lindheimer; Friedrich C. Luft; Giuseppe Mancia; Harry S. Margolius; David A. McCarron; Oregon John; C. McGiff; Trefor O. Morgan; Michael J. Mulvany; Kazuo Murakami; Gary Nicholls; Michael J. Peach; Marc A. Pfeffer; V. Postnov; Morton P. Printz; John P. Rapp; John L. Reid; Donald J. Reis; J. Carlos Romero; E. Safar; A. Guillermo Scicli; T. Shepherd; Thomas Unger; Paul M. Vanhoutte; Stephen F. Vatner; Ronald G. Victor; B. Gunnar Wallin; Gordon H. Williams; Roger R. Williams; Vermont Margaret Foti; Mary Jane Jesse; Clyde E. Johnson; Ben G. Zimmerman
Women who develop gestational diabetes mellitus or impaired glucose tolerance during pregnancy are at substantially increased risk for type 2 diabetes and comorbidities after pregnancy. Little is known about the role of genetic factors and their interactions with environmental factors in determining the transition from gestational diabetes mellitus to overt type 2 diabetes mellitus. These critical data gaps served as the impetus for this Diabetes & Women's Health study with the overall goal of investigating genetic factors and their interactions with risk factors amenable to clinical or public health interventions in relation to the transition of gestational diabetes mellitus to type 2 diabetes mellitus. To achieve the goal efficiently, we are applying a hybrid design enrolling and collecting data longitudinally from approximately 4000 women with a medical history of gestational diabetes mellitus in two existing prospective cohorts, the Nurses' Health Study II and the Danish National Birth Cohort. Women who had a medical history of gestational diabetes mellitus in one or more of their pregnancies are eligible for the present study. After enrollment, we follow study participants for an additional 2 years to collect updated information on major clinical and environmental factors that may predict type 2 diabetes mellitus risk as well as with biospecimens to measure genetic and biochemical markers implicated in glucose metabolism. Newly collected data will be appended to the relevant existing data for the creation of a new database inclusive of genetic, epigenetic and environmental data. Findings from the study are critical for the development of targeted and more effective strategies to prevent type 2 diabetes mellitus and its complications in this high-risk population. PMID:24828694
Zhang, Cuilin; Hu, Frank B; Olsen, Sjurdur F; Vaag, Allan; Gore-Langton, Robert; Chavarro, Jorge E; Bao, Wei; Yeung, Edwina; Bowers, Katherine; Grunnet, Louise G; Sherman, Seth; Kiely, Michele; Strøm, Marin; Hansen, Susanne; Liu, Aiyi; Mills, James; Fan, Ruzong
Objective To test if pancreatic beta-cell genetic frailty and hypertension interact in their associations with change over time in fasting glucose (?FG) or type-2 diabetes (T2D) risk. Methods and results We pooled data from 3,471 Framingham Offspring Study participants into 6 ~4-yr periods (15,852 person-exams; mean age 52; 54% women). We defined two genetic exposures reflecting beta-cell genetic risk burden: single nucleotide polymorphism (SNP) score counts of FG- and T2D–associated risk alleles at 16 and 33 putative beta-cell loci, respectively; and three hypertension exposures: 1)hypertension vs. no-hypertension; 2)treated vs. untreated-hypertension; and 3)five mutually-exclusive anti-hypertensive categories (beta-blockers, thiazides, renin-angiotensin system agents, combinations, others) vs. untreated-hypertension. We tested ~4-year mean ?FG or odds of T2D by per-risk allele score change and hypertension category, seeking genetic score-by-hypertension interaction. Genetic scores increased ~4-yr ?FG (0.6 mg/dl per-risk allele; p=8.9×10?16) and T2D–risk (~17% per-risk allele; p=2.1×10?7). Versus no-hypertension, hypertension conferred higher ?FG (2.6 vs. 1.7 mg/dl; p<0.0001) and T2D–risk (OR=2.9, 95% CI [2.8–3.0]; p<0.0001). Versus untreated-hypertension, treated hypertension conferred higher ?FG (3.4 vs. 3.0 mg/dl; p<0.0001) and T2D–risk (OR=1.4 [1.3–1.5]; p=0.02). Beta-blockers (OR=1.6 [1.1–2.4]), combinations (OR=1.6 [1.1–2.5]) and others (OR=2.0 [1.4–2.9]) increased T2D–risk (all p<0.02). In joint models including interaction terms, all genetic score-by-hypertension interaction terms were p>0.05. In joint models without interaction, FG-SNP or T2D–SNP genetic scores (both p<0.001) and hypertension (p<0.0001) independently increased ?FG or T2D–risk. Conclusion Hypertension, hypertension treatment and common FG-/T2D–SNP genetic scores independently predicted ?FG and T2D incidence, but did not modify each other’s association with ?FG or T2D risk. PMID:23425704
de Miguel-Yanes, JM; Porneala, B; Pencina, MJ; Fox, CS; Florez, JC; Siscovick, DS; Dupuis, J; Meigs, JB
BackgroundVitamin D might have an influence on glucose concentrations, due to the presence of VDR receptors on the pancreas. We established an experimental model of type 2 diabetes in spontaneously hypertensive rats (SHR) and Wistar rats in order to investigate the glycemic response.
Rosane de Souza Santos; Lucia Marques Vianna
MCGILLIVRAY1 has suggested that lactose intolerance in Asians is limited to ``selected groups of adult students in unfamiliar surroundings'' (studying abroad) and that it is ``a rare condition which must be seen against the background of malnutrition''.
G. Flatz; C. H. SAENGUDOM; T. SANGUANBHOKHAI
A complex but crucial relationship exists between blood volume and blood pressure in human subjects; it has been recognized that in essential hypertension, renovascular hypertension, and pheochromocytoma, the relationship between plasma volume and diastolic blood pressure is an inverse one. This phenomenon has not been studied in individuals with low normal and reduced blood pressures. Orthostatic intolerance is a commonly encountered abnormality in blood pressure regulation often associated with tachycardia in the standing position. Most of these patients have varying degrees of reduced blood volume. We tested the hypothesis that the relationship previously found between plasma volume and diastolic blood pressure in pressor states would also hold in orthostatic intolerance. We studied 16 patients with a history of symptomatic orthostatic intolerance associated with an elevation in plasma norepinephrine in the upright posture and hypovolemia in 9 patients and normovolemia in 7 patients. Our studies demonstrate an inverse relationship between plasma volume and diastolic blood pressure in patients with orthostatic intolerance. This finding also holds for the change in diastolic blood pressure in response to upright posture. In this relationship, patients with orthostatic intolerance with high plasma norepinephrine resemble those with essential hypertension, renovascular hypertension, and pheochromocytoma. We conclude that in a variety of conditions at both ends of the blood pressure spectrum, the seemingly paradoxical association of hypovolemia and diastolic blood pressure is preserved.
Jacob, G.; Biaggioni, I.; Mosqueda-Garcia, R.; Robertson, R. M.; Robertson, D.
Diabetes mellitus and hypertension diseases are frequently found in the same patient, which if untreated predispose to atherosclerotic and kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through dispersive near-infrared Raman spectroscopy. Urine samples were collected from patients with diabetes and hypertension but no complications (LG), high degree of complications (HG), and control ones: one fraction was submitted to biochemical tests and another one was stored frozen (-20°C) until spectral analysis. Samples were warmed up and placed in an aluminum sample holder for Raman spectra collection using a dispersive spectrometer (830 nm wavelength, 300 mW laser power and 20 s exposure time). Spectra were then submitted to Principal Components Analysis. The PCA loading vectors 1 and 3 revealed spectral features of urea/creatinine and glucose, respectively; the PCA scores showed that patients with diabetes/hypertension (LG and HG) had higher amount of glucose in the urine compared to the normal group (p < 0.05), which can bring serious consequences to patients. Also, the PCA scores showed that the amount of urea decreased in the groups with diabetes/hypertension (p < 0.05), which generates the same concern as it is a marker that has a strong importance in the metabolic changes induced by such diseases. These results, applied to the analysis of urine of patients with diabetes/hypertension, can lead to early diagnostic information of complications and a possible disease prognosis in the patients where no complications from diabetes and hypertension were found.
Bispo, Jeyse A. M.; Silveira, Landulfo; Vieira, Elzo E. d. S.; Fernandes, Adriana B.
Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)
Background Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. Methods Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. Results Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). Conclusions These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension. PMID:21906391
Orthostatic intolerance (OI) is a cause of significant disability in otherwise healthy women seen by gynecologists. Orthostatic tachycardia is often the most obvious hemodynamic abnormality found in OI patients, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety, and, in some cases, fainting (syncope). It is the most common disorder of blood pressure regulation after essential hypertension, and patients with OI are traditionally women of childbearing age. Estimates suggest that at least 500,000 Americans suffer from some form of OI, and such patients comprise the largest group referred to centers specialized in autonomic disorders. This article reviews recent advances made in the understanding of this condition, potential pathophysiological mechanisms contributing to orthostatic intolerance, and therapeutic alternatives currently available for the management of these patients.
Ali, Y. S.; Daamen, N.; Jacob, G.; Jordan, J.; Shannon, J. R.; Biaggioni, I.; Robertson, D.
... fully digest lactose found in human milk and infant formulas. But at some point after being weaned, most children in the world begin to make less lactase. Most people with primary lactose ... lactose intolerance . Infants born with this rare type make no lactase ...
A high incidence (minimum 20\\/26, maximum 24\\/26) of lactose intolerance was found in a group of adult Arab subjects. A selective reduction of intestinallactase activity was present in 4 subjects in whom a suction biopsy was performed.
H. W. Rotthauwe; M. O. El-Schallah; G. Flatz
... intolerance. On this page: Lactose intolerance Food additives Gluten intolerance Food poisoning Histamine toxicity Other conditions Lactose ... are listed on ingredient labels. back to top Gluten intolerance Gluten is a part of wheat, barley, ...
It has been proved that cilnidipine has N-type calcium channels inhibitory activity as well as L-type calcium channels and inhibits excessive release of norepinephrine from the sympathetic nerve ending. This study was undertaken to compare the efficacy of amlodipine (an inhibitor of L-type calcium channels) and cilnidipine (an inhibitor of both L-type and N-type calcium channels) in patients with hypertension and type II diabetes mellitus. Seventy-seven hypertensive patients were divided into two groups according to presence/absence of type II diabetes mellitus. In these two groups of patients, the effects of amlodipine and cilnidipine on glucose and lipid metabolism and renal function were compared. As for glucose and lipid metabolism, homeostasis model assessment insulin resistance (HOMA-R) level in the non-diabetic group and triglyceride in the diabetes group were significantly lower with cilnidipine than with amlodipine. As regards renal function in the diabetic group, estimated glomerular filtration rate (eGFR) was significantly higher and urinary albumin/creatinine ratio was significantly lower with cilnidipine than with amlodipine. Cilnidipine which inhibits N-type calcium channels is more useful for patients with hypertension and diabetes mellitus from its effects on glucose and lipid metabolism and renal function. PMID:20337636
Masuda, Takashi; Ogura, Misao N; Moriya, Tatsumi; Takahira, Naonobu; Matsumoto, Takuya; Kutsuna, Toshiki; Hara, Miyako; Aiba, Naoko; Noda, Chiharu; Izumi, Tohru
"Multiculturalism", "pluralism" and "tolerance" have become buzz words in applied ethics. While serious and well thought out work is going on in these areas, a misunderstanding of the importance of tolerance, and the difficulties raised by multicultural moral conflict seems common. In this paper I argue that intolerance of some cultural traditions is morally required, and suggest that the forging of a moral mono-culture is preferable to pluralism. Key Words: Pluralism • multicultural • tolerance • relativism PMID:11129841
The authors report results of allergological history, of passive haemagglutination reaction, lymphocytes blast transformation and leucocytes migration inhibition tests in 100 patients suffering from affections involving the gastro-intestinal tract. Control investigations were carried out in 20 practically healthy individuals. From these results the authors conclude that the data of the allergological history and clinical symptoms of the cow milk intolerance are determined, above all, by the immuno-allergic mechanisms, this being confirmed by the results of the "in vitro" methods characterizing the humoral and cellular types of the immunological reactivity. PMID:988940
Martynov, S M; Fedorenko, T A
Influence of telmisartan on insulin response after glucose loading in obese patients with hypertension: ARB Trial of hypertension in obese patients with hyperinsulinemia assessed by oral glucose tolerance test (ATHLETE)
Introduction The number of patients with both hypertension and obesity has been increasing in Japan. Many of these patients may also have\\u000a insulin resistance. Telmisartan, an angiotensin II receptor blocker (ARB), selectively activates peroxisome proliferatoractivated\\u000a receptor (PPAR)-gamma, and this effect is considered to markedly improve insulin resistance in obese patients with hypertension.\\u000a We compared the antihypertensive and insulin resistance-improving effects of
Yutaka Mori; Takaaki Tanaka; Kenichi Matsuura; Junichi Yokoyama; Kazunori Utsunomiya
't traditionally include dairy products in their diets.3 There are three main types of lactose intolerance patients with lactose intolerance may believe they are allergic to milk or milk products. A milk allergy Lactose Intolerance: Information for Health Care
Rau, Don C.
... sugar found in milk and other dairy products. Lactose is normally broken down by an enzyme called lactase, which is produced by cells in ... Health Professionals What glossary definitions help with understanding lactose intolerance? autosomal ; ... incidence ; inherited ; intestine ; malabsorption ; population ; ...
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
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
J.-L. Chiasson; R. G. Josse; R. Gomis; M. Hanefeld; A. Karasik; M. Laakso
A new mathematical model of short-term glucose regulation by insulin is proposed to exploit the oral glucose tolerance test (OGTT), which is commonly used for clinical diagnosis of glucose intolerance and diabetes. Contributions of endogenous and exogenous sources to measured plasma glucose concentrations have been separated by means of additional oral administration and constant intravenous infusion of glucose labeled with
Karl Thomaseth; Alessandra Pavan; Rachele Berria; Leonard Glass; Ralph Defronzo; Amalia Gastaldelli
Although gestational diabetes mellitus (GDM) is associated with an increased risk of maternal and neonatal morbidity, there is no consensus as to the optimal approach of nutritional management in these patients. The present study was designed to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) eating plan on glucose tolerance and lipid profiles of pregnant women with GDM. The present randomised controlled clinical trial was performed among thirty-four women diagnosed with GDM at 24-28 weeks of gestation. Subjects were randomly assigned to consume either the control diet (n 17) or the DASH eating pattern (n 17) for 4 weeks. The control diet was designed to contain 45-55% carbohydrates, 15-20% protein and 25-30% total fat. The macronutrient composition of the DASH diet was similar to the control diet; however, the DASH diet was rich in fruits, vegetables, whole grains and low-fat dairy products, and contained lower amounts of saturated fats, cholesterol and refined grains with a total of 2400 mg Na/d. Fasting blood samples were taken at baseline and after 4 weeks of intervention to measure fasting plasma glucose, glycated Hb (HbA1c) and lipid profiles. Participants underwent a 3 h oral glucose tolerance tests and blood samples were collected at 60, 120 and 180 min to measure plasma glucose levels. Adherence to the DASH eating pattern, compared with the control diet, resulted in improved glucose tolerance such that plasma glucose levels reduced at 60 (21·86 v. 20·45 mmol/l, Pgroup = 0·02), 120 (22·3 v. 0·2 mmol/l, Pgroup = 0·001) and 180 min (21·7 v. 0·22 mmol/l, Pgroup = 0·002) after the glucose load. Decreased HbA1c levels (20·2 v. 0·05 %, Pgroup = 0·001) was also seen in the DASH group compared with the control group. Mean changes for serum total (20·42 v. 0·31 mmol/l, Pgroup = 0·01) and LDL-cholesterol (20·47 v. 0·22 mmol/l, Pgroup = 0·005), TAG (20·17 v. 0·34 mmol/l, Pgroup = 0·01) and total:HDL-cholesterol ratio (20·6 (SD 0·9) v. 0·3 (SD 0·8), Pgroup = 0·008) were significantly different between the two diets. Additionally, consumption of the DASH diet favourably influenced systolic blood pressure (22·6 v. 1·7 mmHg, Pgroup = 0·001). Mean changes of fasting plasma glucose (20·29 v. 0·15 mmol/l, Pgroup = 0·09) were nonsignificant comparing the DASH diet with the control diet. In conclusion, consumption of the DASH eating pattern for 4 weeks among pregnant women with GDM resulted in beneficial effects on glucose tolerance and lipid profiles compared with the control diet. PMID:23148885
Asemi, Zatollah; Tabassi, Zohreh; Samimi, Mansooreh; Fahiminejad, Taherh; Esmaillzadeh, Ahmad
Background: The definition and treatment of glucose intolerance during pregnancy are matters of intense controversy. Our goal was to examine the value of the 75-g oral glucose tolerance test (OGTT) in terms of its ability to predict birth weight per- centile in a group of women with singleton pregnancies who received minimal treatment for their glucose intolerance. Methods: We reviewed
Christian Ouzilleau; Marie-Andrée Roy; Louiselle Leblanc; André Carpentier; Pierre Maheux
Glucose homeostasis in mammals is maintained by insulin secre- tion from the b-cells of the islets of Langerhans. Type 2 diabetes results either from primary b-cell failure alone and\\/or a failure to secrete enough insulin to overcome insulin resistance. Here, we show that continuous infusion of glucagon-like peptide-1 (7-36) (GLP-1; an insulinotropic agent), to young and old animals, had effects
RICCARDO PERFETTI; JIE ZHOU; MAIRE E. DOYLE; JOSEPHINE M. EGAN
Food intolerance is an adverse reaction to a particular food or ingredient that may or may not be related to the immune system.\\u000a A deficiency in digestive enzymes can also cause some types of food intolerances like lactose and gluten intolerance. Food\\u000a intolerances may cause unpleasant symptoms, including nausea, bloating, abdominal pain, and diarrhea, which usually begin\\u000a about half an
Oner Ozdemir; Emin Mete; Ferhat Catal; Duygu Ozol
Dairy foods contribute nine essential nutrients to the diet including calcium, potassium and vitamin D; nutrients identified by the 2010 Dietary Guidelines for Americans as being "of public health concern" within the U.S. population. Milk and milk product intake is associated with better diet quality and has been associated with a reduced risk of chronic diseases or conditions including hypertension, cardiovascular disease, metabolic syndrome, Type 2 Diabetes and osteoporosis. Some research also indicates dairy food intake may be linked to reduced body fat, when accompanied by energy-restriction. On average, both African Americans and Hispanic Americans consume less than the recommended levels of dairy foods, and perceived or actual lactose intolerance can be a primary reason for limiting or avoiding dairy intake. True lactose intolerance prevalence is not known because healthcare providers do not routinely measure for it, and no standardized assessment method exists. Avoiding dairy may lead to shortfalls of essential nutrients and increased susceptibility to chronic disease. This updated Consensus Statement aims to provide the most current information about lactose intolerance and health, with specific relevance to the African American and Hispanic American communities. Topics covered include diagnostic considerations, actual and recommended dairy food intake and levels of consumption of key dairy nutrients among African Americans and Hispanic Americans; prevalence of self-reported lactose intolerance among various racial/ethnic groups; the association between dairy food intake, lactose intolerance and chronic disease; and research-based management recommendations for those with lactose intolerance. PMID:24079212
Bailey, Rahn K; Fileti, Cecelia Pozo; Keith, Jeanette; Tropez-Sims, Susanne; Price, Winston; Allison-Ottey, Sharon Denise
BACKGROUND AND PURPOSE: Orthostatic and other stresses trigger tachycardia associated with symptoms of tremulousness, shortness of breath, dizziness, blurred vision, and, often, syncope. It has been suggested that paradoxical cerebral vasoconstriction during head-up tilt might be present in patients with orthostatic intolerance. We chose to study middle cerebral artery (MCA) blood flow velocity (BFV) and cerebral vasoregulation during tilt in patients with orthostatic intolerance (OI). METHODS: Beat-to-beat BFV from the MCA, heart rate, CO2, blood pressure (BP), and respiration were measured in 30 patients with OI (25 women and 5 men; age range, 21 to 44 years; mean age, 31.3+/-1.2 years) and 17 control subjects (13 women and 4 men; age range, 20 to 41 years; mean age, 30+/-1.6 years); ages were not statistically different. These indices were monitored during supine rest and head-up tilt (HUT). We compared spontaneous breathing and hyperventilation and evaluated the effect of CO2 rebreathing in these 2 positions. RESULTS: The OI group had higher supine heart rates (P<0.001) and cardiac outputs (P<0.01) than the control group. In response to HUT, OI patients underwent a greater heart rate increment (P<0.001) and greater reductions in pulse pressure (P<0.01) and CO2 (P<0.001), but total systemic resistance failed to show an increment. Among the cerebrovascular indices, all BFVs (systolic, diastolic, and mean) decreased significantly more, and cerebrovascular resistance (CVR) was increased in OI patients (P<0.01) compared with control subjects. In both groups, hyperventilation induced mild tachycardia (P<0.001), a significant reduction of BFV, and a significant increase of CVR associated with a fall in CO2. Hyperventilation during HUT reproduced hypocapnia, BFV reduction, and tachycardia and worsened symptoms of OI; these symptoms and indices were improved within 2 minutes of CO2 rebreathing. The relationships between CO2 and BFV and heart rate were well described by linear regressions, and the slope was not different between control subjects and patients with OI. CONCLUSIONS: Cerebral vasoconstriction occurs in OI during orthostasis, which is primarily due to hyperventilation, causing significant hypocapnia. Hypocapnia and symptoms of orthostatic hypertension are reversible by CO2 rebreathing.
Novak, V.; Spies, J. M.; Novak, P.; McPhee, B. R.; Rummans, T. A.; Low, P. A.
Although hypoxia is detrimental to most cell types, it aids survival of progenitor cells and is associated with diseases like cancer and pulmonary hypertension in humans. Therefore, understanding the underlying mechanisms that promote survival of progenitor cells in hypoxia and then developing novel therapies to stop their growth in hypoxia-associated human diseases is important. Here we demonstrate that the proliferation and growth of human CD133(+) progenitor cells, which contribute to tumorigenesis and the development of pulmonary hypertension, are increased when cultured under hypoxic conditions. Furthermore, glucose-6-phosphate dehydrogenase (G6PD) activity was increased threefold in hypoxic CD133(+) cells. The increased G6PD activity was required for CD133(+) cell proliferation, and their growth was arrested by G6PD inhibition or knockdown. G6PD activity upregulated expression of HIF1?, cyclin A, and phospho-histone H3, thereby promoting CD133(+) cell dedifferentiation and self-renewal and altering cell cycle regulation. When CD133(+) cells were cocultured across a porous membrane from pulmonary artery smooth muscle cells (PASMCs), G6PD-dependent H2O2 production and release by PASMCs recruited CD133(+) cells to the membrane, where they attached and expressed smooth muscle markers (?-actin and SM22?). Inhibition of G6PD reduced smooth muscle marker expression in CD133(+) cells under normoxia but not hypoxia. In vivo, CD133(+) cells colocalized with G6PD(+) cells in the perivascular region of lungs from rats with hypoxia-induced pulmonary hypertension. Finally, inhibition of G6PD by dehydroepiandrosterone in pulmonary arterial hypertensive rats nearly abolished CD133(+) cell accumulation around pulmonary arteries and the formation of occlusive lesions. These observations suggest G6PD plays a key role in increasing hypoxia-induced CD133(+) cell survival in hypertensive lungs that differentiate to smooth muscle cells and contribute to pulmonary arterial remodeling during development of pulmonary hypertension. PMID:25063801
Chettimada, Sukrutha; Joshi, Sachindra Raj; Alzoubi, Abdallah; Gebb, Sarah A; McMurtry, Ivan F; Gupte, Rakhee; Gupte, Sachin A
Individuals within gluten intolerance communities, whether online or in support group settings, regularly discuss their narrative experiences with illness and diagnosis, culminating in the identification of gluten intolerance as being the source of what may have been years of suffering. In this way their experiences with illness and the social interactions that have accompanied their illness are structured into a
A 53 year old woman with hypercholesterolemia treated with statins, with no history of cardiovascular disease, was referred to the Hypertension and Vascular Risk Unit for management of hypertension resistant to 4 antihypertensive agents at full doses. The patient had obesity, with a body mass index of 36.3kg/m(2) and office blood pressure 162/102mm Hg. Physical examination showed no data of interest. Analysis: glucose 120mg/dl, glycated Hb: 6.4%, albuminuria 68mg/g, kidney function and study of the renin angiotensin system and other biochemical parameters were normal. Echocardiography: left ventricular mass, 131g/m(2) (normal, <110g/m(2)). True resistant hypertension was confirmed by ambulatory monitoring of blood pressure during 24h (153/89mm Hg). Spironolactone treatment (25mg/day) was added and was well tolerated, with no change in renal function and kaliemia within normal (4.1mmol/l) following the treatment. After 8 weeks, blood pressure was well controlled: office blood pressure 132/86mm Hg and 24h-ambulatory blood pressure: 128/79mm Hg. PMID:23827205
Armario, P; Oliveras, A; de la Sierra, A
Correlating the amount of urea, creatinine, and glucose in urine from patients with diabetes mellitus and hypertension with the risk of developing renal lesions by means of Raman spectroscopy and principal component analysis
Patients with diabetes mellitus and hypertension (HT) diseases are predisposed to kidney diseases. The objective of this study was to identify potential biomarkers in the urine of diabetic and hypertensive patients through Raman spectroscopy in order to predict the evolution to complications and kidney failure. Urine samples were collected from control subjects (CTR) and patients with diabetes and HT with no complications (lower risk, LR), high degree of complications (higher risk, HR), and doing blood dialysis (DI). Urine samples were stored frozen (-20°C) before spectral analysis. Raman spectra were obtained using a dispersive spectrometer (830-nm, 300-mW power, and 20-s accumulation). Spectra were then submitted to principal component analysis (PCA) followed by discriminant analysis. The first PCA loading vectors revealed spectral features of urea, creatinine, and glucose. It has been found that the amounts of urea and creatinine decreased as disease evoluted from CTR to LR/HR and DI (PC1, p<0.05), and the amount of glucose increased in the urine of LR/HR compared to CTR (PC3, p<0.05). The discriminating model showed better overall classification rate of 70%. These results could lead to diagnostic information of possible complications and a better disease prognosis.
Bispo, Jeyse Aliana Martins; de Sousa Vieira, Elzo Everton; Silveira, Landulfo; Fernandes, Adriana Barrinha
To clarify whether the long-acting calcium-channel blocker amlodipine restores insulin insensitivity in essential hypertension, insulin sensitivity tests were performed at the physiological steady-state insulin level (45 to 55 ?U\\/mL) before and after amlodipine (2.5 to 7.5 mg\\/d) administration for 2 to 4 months in borderline and mild essential hypertensive subjects. Instead of somatostatin, Sandostatin (Sandoz, Basel, Switzerland) was used for
Y. Harano; A. Kageyama; J. Hirose; Y. Asakura; T. Yokota; M. Ikebuchi; M. Suzuki; T. Omae
The autonomic nervous system, adequate blood volume, and intact skeletal and respiratory muscle pumps are essential components for rapid cardiovascular adjustments to upright posture (orthostasis). Patients lacking sufficient blood volume or having defective sympathetic adrenergic vasoconstriction develop orthostatic hypotension (OH), prohibiting effective upright activities. OH is one form of orthostatic intolerance (OI) defined by signs, such as hypotension, and symptoms, such as lightheadedness, that occur when upright and are relieved by recumbence. Mild OI is commonly experienced during intercurrent illnesses and when standing up rapidly. The latter is denoted “initial OH” and represents a normal cardiovascular adjustment to the blood volume shifts during standing. Some people experience episodic acute OI, such as postural vasovagal syncope (fainting), or chronic OI, such as postural tachycardia syndrome, which can significantly reduce quality of life. The lifetime incidence of ?1 fainting episodes is ?40%. For the most part, these episodes are benign and self-limited, although frequent syncope episodes can be debilitating, and injury may occur from sudden falls. In this article, mechanisms for OI having components of adrenergic hypofunction, adrenergic hyperfunction, hyperpnea, and regional blood volume redistribution are discussed. Therapeutic strategies to cope with OI are proposed. PMID:23569093
Post-flight orthostatic intolerance is a dramatic physiological consequence of human adaptation to microgravity made inappropriate by a sudden return to 1-G. The immediate mechanism is almost always a failure to maintain adequate tissue perfusion, specifically perfusion of the central nervous system, but vestibular dysfunction may occasionally be the primary cause. Orthostatic intolerance is present in a wide range of clinical disorders of the nervous and cardiovascular systems. The intolerance that is produced by spaceflight and 1-G analogs (bed rest, head-down tilt at a moderate angle, water immersion) is different from its clinical counterparts by being only transiently present in subjects who otherwise have normal cardiovascular and regulatory systems. However, the same set of basic pathophysiological elements should be considered in the analysis of any form of orthostatic intolerance.
Blomqvist, C. G.; Buckey, J. C.; Gaffney, F. A.; Lane, L. D.; Levine, B. D.; Watenpaugh, D. E.
Fifty-nine per cent of a series of patients with ulcerative colitis were found to have lactose intolerance by a lactose-tolerance test. It appears likely that the inflamed, irritated bowel of patients with ulcerative colitis cannot handle the osmotic-acid load and that lactose intolerance imposes an extra burden upon the inflamed bowel. Therefore, a lactose-free diet is advisable in patients with
Henry J. Binder; Joyce D. Gryboski; Walter R. Thayer; Howard M. Spiro
For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome (MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes. PMID:25276291
Mulè, Giuseppe; Calcaterra, Ilenia; Nardi, Emilio; Cerasola, Giovanni; Cottone, Santina
For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome (MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.
Mule, Giuseppe; Calcaterra, Ilenia; Nardi, Emilio; Cerasola, Giovanni; Cottone, Santina
Despite repeated emphasis in the Dietary Guidelines for Americans on the importance of calcium in the adult American diet and the recommendation to consume 3 dairy servings a day, dairy intake remains well below recommendations. Insufficient health professional awareness of the benefits of calcium and concern for lactose intolerance are among several possible reasons, This mini-review highlights both the role of calcium (and of dairy, its principal source in modern diets) in health maintenance and reviews the means for overcoming lactose intolerance (real or perceived). PMID:23493531
Heaney, Robert P
This essay argues that some proponents of multicultural education (ME) appear to teach intolerance of certain kinds of speech. The essay argues, in support, the down-playing of tolerance in ME as cultural respect, accommodation, and harmony are stronger candidates as virtues. The essay goes on to point out that ME does not teach cultural…
Heslep, Robert D.
Women with polycystic ovary syndrome (PCOS) are insulin resis- tant, have insulin secretory defects, and are at high risk for glucose intolerance. We performed this study to determine the prevalence of glucose intolerance and parameters associated with risk for this in PCOS women. Two-hundred and fifty-four PCOS women, aged 14 - 44 yr, were prospectively evaluated at 2 centers, 1
RICHARD S. LEGRO; ALLEN R. KUNSELMAN; WILLIAM C. DODSON; ANDREA DUNAIF
Effects of rosuvastatin combined with olmesartan, irbesartan, or telmisartan on indices of glucose metabolism in greek adults with impaired fasting glucose, hypertension, and mixed hyperlipidemia: A 24-week, randomized, open-label, prospective study
Background: Statin therapy has been reported to be associated with new-onset diabetes. Angiotensin II-receptor blockers (ARBs) are effective antihypertensive drugs that have been reported to activate peroxisome proliferator-activated receptor ? (PPAR?) to differing extents, with favorable effects on glucose metabolism and the incidence of new-onset diabetes. Among the ARBs, telmisartan is a partial activator of PPAR?, irbesartan is a weak
Christos V. Rizos; Haralampos J. Milionis; Michael S. Kostapanos; Matilda Florentin; Christina E. Kostara; Moses S. Elisaf; Evangelos N. Liberopoulos
Neurons have a constantly high glucose demand, and unlike muscle cells they cannot accommodate episodic glucose uptake under the influence of insulin. Neuronal glucose uptake depends on the extracellular concentration of glucose, and cellular damage can ensue after persistent episodes of hyperglycaemia — a phenomenon referred to as glucose neurotoxicity. This article reviews the pathophysiological manifestation of raised glucose in
David R. Tomlinson; Natalie J. Gardiner
'Food intolerance' is often confused with a range of adverse symptoms which may be coincidental to ingestion of food. 'Food intolerance' is defined as a reaction in which symptoms must be objectively reproducible and not known to involve an immunological mechanism. A more precise term is non-allergic food hypersensitivity, which contrasts with food allergies which are due to an immunological mechanism. Some children will experience food reactions to food additives. Reported symptoms range from urticaria/angioedema to hyperactive behaviours. While parents/carers report that over one fifth of children experience of food reaction, only 1 in 20 of these are confirmed to have a non-allergic food hypersensitivity on testing. PMID:22320279
Turner, Paul J; Kemp, Andrew S
Strict criteria for the diagnosis of temporary gluten intolerance are formulated in the light of the case of an 8-week-old infant with severe diarrhoea and failure to thrive, who recovered on an elimination diet that was gluten-free. 8 weeks later an oral challenge with 2.5 g twice daily of powdered gluten for one day produced diarrhoea, weight loss, and impaired
A S McNeish; C J Rolles; L J Arthur
Upright posture imposes a substantial gravitational stress on the body, for which we are able to compensate, in large part because of the autonomic nervous system. Alteration in autonomic function, therefore, may lead to orthostatic intolerance. On one extreme, patients with autonomic failure caused by degenerative loss of autonomic function are severely disabled by orthostatic hypotension and may faint whenever they stand up. Fortunately, such patients are relatively rare. On the other hand, disabling orthostatic intolerance can develop in otherwise normal young people. These patients can be severely impaired by symptoms of fatigue, tachycardia, and shortness of breath when they stand up. The actual incidence of this disorder is unknown, but these patients make up the largest group of patients referred to centers that specialize in autonomic disorders. We will review recent advances made in the understanding of this condition, potential pathophysiological mechanisms that contribute to orthostatic intolerance, therapeutic alternatives currently available for the management of these patients, and areas in which more research is needed.
Jacob, G.; Biaggioni, I.; Robertson, D. (Principal Investigator)
Glucose plays a key role as energy source in the majority of mammals, but its importance in fish appears limited. Until now,\\u000a the physiological basis for such apparent glucose intolerance in fish has not been fully understood. A distinct regulation\\u000a of hepatic glucose utilization (glycolysis) and production (gluconeogenesis) may be advanced to explain the relative inability\\u000a of fish to efficiently
P. Enes; S. Panserat; S. Kaushik; A. Oliva-Teles
PURPOSE: Orthostatic intolerance is the cause of significant disability in otherwise normal patients. Orthostatic tachycardia is usually the dominant hemodynamic abnormality, but symptoms may include dizziness, visual changes, discomfort in the head or neck, poor concentration, fatigue, palpitations, tremulousness, anxiety and, in some cases, syncope. It is the most common disorder of blood pressure regulation after essential hypertension. There is a predilection for younger rather than older adults and for women more than men. Its cause is unknown; partial sympathetic denervation or hypovolemia has been proposed. METHODS AND MATERIALS: We tested the hypothesis that reduced plasma renin activity, perhaps from defects in sympathetic innervation of the kidney, could underlie a hypovolemia, giving rise to these clinical symptoms. Sixteen patients (14 female, 2 male) ranging in age from 16 to 44 years were studied. Patients were enrolled in the study if they had orthostatic intolerance, together with a raised upright plasma norepinephrine (> or = 600 pg/mL). Patients underwent a battery of autonomic tests and biochemical determinations. RESULTS: There was a strong positive correlation between the blood volume and plasma renin activity (r = 0.84, P = 0.001). The tachycardic response to upright posture correlated with the severity of the hypovolemia. There was also a correlation between the plasma renin activity measured in these patients and their concomitant plasma aldosterone level. CONCLUSIONS: Hypovolemia occurs commonly in orthostatic intolerance. It is accompanied by an inappropriately low level of plasma renin activity. The degree of abnormality of blood volume correlates closely with the degree of abnormality in plasma renin activity. Taken together, these observations suggest that reduced plasma renin activity may be an important pathophysiologic component of the syndrome of orthostatic intolerance.
Jacob, G.; Robertson, D.; Mosqueda-Garcia, R.; Ertl, A. C.; Robertson, R. M.; Biaggioni, I.
Celiac disease is associated with several genetic disorders, but its association with hereditary fructose intolerance is rare. Hereditary fructose intolerance is a rare autosomal recessive disease of fructose metabolism presenting as vomiting after intake of fructose. An association between these two distinct genetic gastrointestinal disorders is important as treatment failure of celiac disease calls for careful evaluation for hereditary fructose intolerance. We report a patient with an association of these two disorders. PMID:22461154
Bharadia, Lalit; Shivpuri, Deepak
Eating an unbalanced diet during pregnancy may induce long-term health consequences in offspring, in particular obesity, insulin resistance, and hypertension. We tested the hypothesis that a maternal diet rich in simple sugars predispose mouse offspring to obesity, glucose intolerance, and cardiovascular diseases in adulthood. Female C57BL/6J mice were fed either a standard chow or a sucrose-rich diet (26% of total energy) 6 weeks prior to mating, throughout pregnancy and lactation. Offspring of control dams (OC) and high sucrose fed dams (OSF) were weaned onto standard control chow, and metabolic and cardiovascular parameters determined at 3 months of age. Both male and female OSF were hyperphagic by 4 weeks of age and females were heavier than OC at 6 weeks. At 3 months, female OSF showed a significant increase in inguinal fat pad mass, whereas skeletal muscle mass (tibialis anterior) and locomotor activity were decreased relative to OC. A 10-fold increase in fasting serum insulin in female OSF vs. OC at 3 months (Insulin [pmol/L] mean ± SEM, OSF, 200.3 ± 16.1, vs. OC, 20.3 ± 1.8, n = 6 P < 0.001), was associated with impaired glucose tolerance (AUC [mmol/L min] mean ± SEM, OSF 1437.4 ± 124.2 vs. OC, 1076.8 ± 83.9, n = 6, P < 0.05). Both male and female OSF were hypertensive as assessed by radiotelemetry (night-time systolic arterial pressure (SAP) [mmHg] mean ± SEM, male OSF, 128 ± 1 vs. OC, 109 ± 1, n = 6, P < 0.01; female OSF, 130 ± 1 vs. OC, 118 ± 1, n = 6, P < 0.05). Analysis of heart rate variability (HRV) demonstrated an increased low:high frequency ratio in male and female OSF (P < 0.05), indicative of heightened sympathetic efferent tone. Renal tissue noradrenaline (NA) content was markedly raised in the OSF vs. OC (NA [pg/ml/mg tissue] mean ± SEM, male OSF, 2.28 ± 0.19 vs. OC 0.84 ± 0.09, n = 6, P < 0.01). Exposure to a maternal diet rich in sucrose led to obesity and glucose intolerance in female mice offspring, and hypertension in both sexes. PMID:23423541
Samuelsson, Anne-Maj; Matthews, Phillippa A.; Jansen, Eugene; Taylor, Paul D.; Poston, Lucilla
Hypertension plays a major role in the development and progression of micro- and macrovascular disease. Moreover, increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance. As a result the need for a comprehensive management of hypertensive patients is critical. However, the various antihypertensive drug categories have different effects on glucose metabolism. Indeed, angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis. Calcium channel blockers (CCBs) have an overall neutral effect on glucose metabolism. However, some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis. On the other hand, diuretics and ?-blockers have an overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well as nebivolol seem to differentiate themselves from the rest of the ?-blockers class, being more attractive options regarding their effect on glucose homeostasis. The adverse effects of some blood pressure lowering drugs on glucose metabolism may, to an extent, compromise their cardiovascular protective role. As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment, especially in patients which are at high risk for developing diabetes. PMID:25068013
Rizos, Christos V; Elisaf, Moses S
PURPOSE This study extends previous community-based studies on the prevalence and clinical characteristics of chemical intolerance in a sample of primary care clinic patients. We evaluated comorbid medical and psychiatric disorders, functional status, and rates of health care use. METHODS A total of 400 patients were recruited from 2 family medicine clinic waiting rooms in San Antonio, Texas. Patients completed the validated Quick Environmental Exposure and Sensitivity Inventory (QEESI) to assess chemical intolerance; the Primary Care Evaluation of Mental Disorders (PRIME-MD) screen for possible psychiatric disorders; the Dartmouth–Northern New England Primary Care Cooperative Information Project (Dartmouth COOP) charts for functional status; and the Healthcare Utilization Questionnaire. RESULTS Overall, 20.3% of the sample met criteria for chemical intolerance. The chemically intolerant group reported significantly higher rates of comorbid allergies and more often met screening criteria for possible major depressive disorder, panic disorder, generalized anxiety disorder, and alcohol abuse disorder, as well as somatization disorder. The total number of possible mental disorders was correlated with chemical intolerance scores (P <.001). Controlling for demographics, patients with chemical intolerance were significantly more likely to have poorer functional status, with trends toward increased medical service use when compared with non–chemically intolerant patients. After controlling for comorbid psychiatric conditions, the groups differed significantly only regarding limitations of social activities. CONCLUSIONS Chemical intolerance occurs in 1 of 5 primary care patients yet is rarely diagnosed by busy practitioners. Psychiatric comorbidities contribute to functional limitations and increased health care use. Chemical intolerance offers an etiologic explanation. Symptoms may resolve or improve with the avoidance of salient chemical, dietary (including caffeine and alcohol), and drug triggers. Given greater medication intolerances in chemical intolerance, primary care clinicians could use the QEESI to identify patients for appropriate triage to comprehensive nonpharmacologic care. PMID:22778124
Katerndahl, David A.; Bell, Iris R.; Palmer, Raymond F.; Miller, Claudia S.
A 5 year, ten wave longitudinal study of 338 adolescents assessed the association between two forms of cognitive vulnerability (intolerance of uncertainty and fear of anxiety) and worry. Multilevel mediational analyses revealed a bidirectional and reciprocal relation between intolerance of uncertainty and worry in which change in one variable…
Dugas, Michel J.; Laugesen, Nina; Bukowski, William M.
Background\\/Aims: Acquired lactase deficiency is a common cause of gastrointestinal symptoms but its etiology remains unclear. Celiac disease could lead to lactase deficiency and is much more common than previously suspected. Several studies have highlighted the prevalence of lactose intolerance in celiac disease, but studies assessing the prevalence of celiac disease in lactose intolerance are lacking. We evaluated the prevalence
Veronica Ojetti; Gabriella Nucera; Alessio Migneco; Maurizio Gabrielli; Cristiano Lauritano; Silvio Danese; Maria Assunta Zocco; Enrico Celestino Nista; Giovanni Cammarota; Antonino De Lorenzo; Giovanni Gasbarrini; Antonio Gasbarrini
Sympathetic circulatory control is key to the rapid cardiovascular adjustments that occur within seconds of standing upright (orthostasis) and which are required for bipedal stance. Indeed, patients with ineffective sympathetic adrenergic vasoconstriction rapidly develop orthostatic hypotension, prohibiting effective upright activities. One speaks of orthostatic intolerance (OI) when signs, such as hypotension, and symptoms, such as lightheadedness, occur when upright and are relieved by recumbence. The experience of transient mild OI is part of daily life. However, many people experience episodic acute OI as postural faint or chronic OI in the form of orthostatic tachycardia and orthostatic hypotension that significantly reduce the quality of life. Potential mechanisms for OI are discussed including forms of sympathetic hypofunction, forms of sympathetic hyperfunction, and OI that results from regional blood volume redistribution attributable to regional adrenergic hypofunction. PMID:22678960
Metabolic syndrome (MetSyndr), a constellation of abnormalities [obesity, glucose intolerance, insulin resistance (IR), dyslipidemia (low HDL-cholesterol, high LDL-cholesterol and triglycerides (TG)], and elevated blood pressure (BP)], increases the risk of cardiovascular (CV) disease and premature death. From 10% to 30% of the adult population in industrialized countries has MetSyndr, which effectively predicts the development of type 2 diabetes mellitus (T2D) and CV disease. Because of the complex etiology of MetSyndr, a multi-targeted, integrated therapeutic approach is required to simultaneously treat high BP, obesity, lipid disorders and T2D (if present), to fully protect CV, cerebrovascular and renal systems. If lifestyle modification (weight control, diet, exercise, smoking cessation, moderation of alcohol intake) is ineffective, pharmaco-theraphy should be added to treat simultaneously the lipid- and non-lipid CV risk factors. Patients with HTN and MetSyndr should be started on angiotensin-converting enzyme (ACE) inhibitors, unless contraindicated. The ACE inhibitors and angiotensin receptor blockers (ARBs) reduce the odds of developing new onset T2D and also decrease albuminuria. The ACE inhibitors provide cardioprotective and renoprotective benefits beyond their effect on BP; they also improve IR. The ARBs are renoprotective in addition to being cardioprotective. Long-acting calcium channel blockers are also recommended in hypertensive patients with MetSyndr; these drugs also improve IR. Thiazides (at low doses) and selected ss-blockers can be given to patients with HTN and MetSyndr. Celiprolol in combination with diuretics has a favorable effect on glucose tolerance and IR in patients with HTN and MetSyndr, and spironolactone added to ACE inhibitor or ARB therapy provides additional reno- and CV protective benefits in patients with diabetic nephropathy. Carvedilol, a ss-blocker with vasodilating properties, added to ACE inhibitor or ARB therapy, is effective in preventing worsening of microalbuminuria in patients with HTN and MetSyndr; it also improves IR and glycemic control. Most patients eventually require two or more antihypertensive drugs to reach BP goal. It is recommended that therapy in patients whose BP is more than 20/10 mm Hg above target at diagnosis be initiated with a combination of antihypertensive drugs, administered either as individual drugs or as fixed-dose formulations. Treatment with fixed-dose combinations, such as irbesartan + hydrochlorothiazide provides good BP control in more than two-thirds of hypertensive patients with MetSyndr. Lipid and BP targets are reached in a high percent of patients with HTN and CV disease treated with a combination of amlodipine + atorvastatin. In conclusion, hypertensive patients with the MetSyndr be treated aggressively for each component of the syndrome to provide CV, cerebrovascular and renal protection. PMID:17667215
Israili, Zafar H; Lyoussi, Badiâa; Hernández-Hernández, Rafael; Velasco, Manuel
The effect of hypertension on non-alcoholic fatty liver disease (NAFLD) remains unclear at the molecular level. In this study, we investigated the effects of hypertension on the degree of hepatic steatosis, liver injury and hepatic fibrosis induced by a choline-deficient L-amino acid-defined (CDAA) diet in spontaneously hypertensive rats (SHRs). Seven-week-old male SHRs were fed standard chow with high or normal salt concentrations for 7 weeks, followed by a CDAA diet containing high or normal salt for an additional 8 or 24 weeks. Hepatic steatosis was assessed using hepatic triglyceride levels and Oil red O staining. Hepatic fibrosis was evaluated using Sirius red and Azan staining. Systolic blood pressure (SBP) gradually increased with a high-salt diet and was significantly higher after 7 weeks of feeding with high-salt vs. normal-salt chow. After 8 weeks on the CDAA diet, the degree of hepatic steatosis did not differ between the high-salt and normal-salt groups; however, alanine aminotransferase and fasting blood glucose levels were significantly higher and hepatic mRNA levels for interleukin (IL)-10 and heme oxygenase (HO)-1 were significantly lower in the high-salt group compared with the normal-salt group. After 24 weeks on the CDAA diet, the high-salt group had significantly more severe hepatic fibrosis and a higher hepatic mRNA expression of ?-smooth muscle actin and lower hepatic IL-10 and HO-1 mRNA levels compared with the normal-salt group. In conclusion, our results indicate that hypertension is a potential risk factor for liver injury and hepatic fibrosis through glucose intolerance and decreased IL-10-mediated or HO-1-induced anti-inflammatory mechanisms. PMID:24190226
Arima, Shiho; Uto, Hirofumi; Ibusuki, Rie; Kumamoto, Ryo; Tanoue, Shirou; Mawatari, Seiichi; Oda, Kohei; Numata, Masatsugu; Fujita, Hiroshi; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito
ObjectivesThe objective of this work was to evaluate the effect of different glucose levels on the ATP, ADP and AMP hydrolysis in the platelets of diabetic, hypertensive and diabetic\\/hypertensive participants.
Gilberto Inácio Lunkes; Daniéle Sausen Lunkes; Daniela Leal; Maria do Carmo Araújo; Maísa Corrêa; Lara Becker; Cintia Saydelles da Rosa; Vera Maria Morsch; Maria Rosa Chitolina Schetinger
Pancreatic resection results in hormonal abnormalities that are dependent on the extent and location (proximal versus distal) of the resected portion of the gland. The form of glucose intolerance which results from pancreatic resection is termed pancreatogenic diabetes. It is associated with features distinct from both type I (insulin-dependent) and type II (insulin-independent, or adult-onset) diabetes. Hepatic insulin resistance with
Lori A. Slezak; Dana K. Andersen
Context: Little is known about exercise intolerance or the utility of an exercise evaluation in patients with postconcussion syndrome (PCS). Objective: To assess exercise intolerance in male and female patients with PCS. Design: Cross-sectional study. Setting: Laboratory setting. Patients or Other Participants: Participants included a convenience sample of 34 patients with PCS (17 males, 17 females; age = 25.9 ± 10.9 years) and 22 uninjured individuals on whom we gathered historical deidentified laboratory data (control group; 11 males, 11 females; age = 23.3 ± 6.2 years). Main Outcome Measure(s): Self-reported symptoms, heart rate, systolic and diastolic blood pressures (BPs), and the Borg rating of perceived exertion were measured before, during each minute of, and immediately after a graded treadmill exercise test (Balke protocol). Exercise was stopped when participants could no longer maintain the effort or reported the onset of or increase in PCS symptoms. Results: Exercise test duration (8.5 ± 4.4 minutes versus 17.9 ± 3.6 minutes; t51 = 1.8, P < .001), heart rate (142.8 ± 24.1 versus 175.2 ± 17.4; t54 = ?5.5, P < .001), and systolic BP (142.1 ± 18.3 mm Hg versus 155.5 ± 24.5 mm Hg; t53 = 2.3, P = .02) were lower, and diastolic BP (78.4 ± 10.2 mm Hg versus 73.5 ± 11.7 mm Hg; t53 = 2.2, P = .03) was higher at test cessation in the PCS than control group. Cox regression showed the odds of a shorter exercise duration were nearly 8 times greater in the PCS than control group (hazard ratio = 7.93; 95% confidence interval = 3.39, 18.56). In the general linear models that adjusted for differences in test duration, rating of perceived exertion was the only physiologic measure to show an overall difference between groups, with the control group reporting higher ratings than the PCS group (t53 = ?6.0, P < .001). Within the PCS group, systolic BP was the only measure to show a sex effect, with males showing higher pressure readings than females throughout the exercise tests (t31 = 2.8, P = .009). Conclusions: Patients with PCS had a symptom-limited response to exercise, and the treadmill test was a potentially useful tool to monitor the recovery from PCS. PMID:23952041
Kozlowski, Karl F.; Graham, James; Leddy, John J.; Devinney-Boymel, Lee; Willer, Barry S.
Essential hypertension can be defined as a rise in blood pressure of unknown cause that increases risk for cerebral, cardiac, and renal events. In industrialised countries, the risk of becoming hypertensive (blood pressure >140/90 mm Hg) during a lifetime exceeds 90%. Essential hypertension usually clusters with other cardiovascular risk factors such as ageing, being overweight, insulin resistance, diabetes, and hyperlipidaemia. Subtle target-organ damage such as left-ventricular hypertrophy, microalbuminuria, and cognitive dysfunction takes place early in the course of hypertensive cardiovascular disease, although catastrophic events such as stroke, heart attack, renal failure, and dementia usually happen after long periods of uncontrolled hypertension only. All antihypertensive drugs lower blood pressure (by definition) and this decline is the best determinant of cardiovascular risk reduction. However, differences between drugs exist with respect to reduction of target-organ disease and prevention of major cardiovascular events. Most hypertensive patients need two or more drugs for blood-pressure control and concomitant statin treatment for risk factor reduction. Despite the availability of effective and safe antihypertensive drugs, hypertension and its concomitant risk factors remain uncontrolled in most patients. PMID:17707755
Messerli, Franz H; Williams, Bryan; Ritz, Eberhard
Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.
Shapiro, R. E.; Winters, B.; Hales, M.; Barnett, T.; Schwinn, D. A.; Flavahan, N.; Berkowitz, D. E.
Hyponatremia due to intolerance to water is a frequent clinical condition and associated with increased mortality. Besides the well known neurological symptoms, gait disturbances, falls, fractures and osteoporosis have also been described recently in patients with chronic hyponatremia. Acute hyponatremia is a more dramatic situation and needs rapid action when severe neurological symptoms are present. Hypertonic saline is recommended to treat this condition until relief of severe symptoms. The causes of hyponatremia have to be carefully examined. Especially diuretics, antidepressants and endocrine causes, e.g. hypothyroidism, hypocortisolism and hypoaldosteronism should be excluded by examination of the patient history, clinical examination and by laboratory tests. Patients should be classified as being euvolemic, hypovolemic or hypervolemic. Whereas acute hyponatremia with severe symptom should be treated with hypertonic saline, euvolemic hyponatremia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) with mild and moderate symptoms can now be treated with tolvaptan, a selective V(2)-vasopressin antagonist. Oral tolvaptan has been shown to be an effective and potent aquaretic to treat hyponatremia caused by SIADH as evidenced by a simultaneous increase in serum sodium and a decrease in urine osmolality. The condition of patients with mild or moderate hyponatremia is also improved. Side effects associated with tolvaptan include increased thirst, dry mouth, polyuria and hypernatremia. Rapid increases in serum sodium should be avoided by close monitoring in a hospital setting. PMID:22911166
To provide an overview on the role of gut immunity, nervous system and motility patterns in the development of feeding intolerance in newborns. Maturation of the GI is important not only for digestion and absorption, but for endocrine and exocrine function as well. There is little data available about the development of the motility function and of the mucosal barrier of the human gut, and in particular about the motility patterns and mucosal changes in newborns during early days of life. It is known that functional maturation of the gastrointestinal tract is quite different over time with respect to its anatomical development. Besides, the gastrointestinal tract through innate and specific immunologic factors, acts as a defense against ingested antigens. In addition to the mucous membrane integrity and digestion, numerous specific immunologic cells and mediators orchestrate such defensive mechanisms. In case of food antigens, the outcome is usually in favor of tolerance. Defects in that barrier, however, can lead to the development of aberrant immunologic responses, including hypersensitivity reactions. It is obvious that an appropriate feeding regimen during early infancy is in favor of food tolerance. However, in addition to genetic predisposition, development of tolerance is facilitated by an adequate gut barrier (immune or nonimmune), well-coordinated GI motility and nervous network, and appropriate food regimen. PMID:21942596
Indrio, Flavia; Riezzo, Giuseppe; Cavallo, Luciano; Di Mauro, Antonio; Francavilla, Ruggiero
Intolerance to certain foods can cause a range of gut and systemic symptoms. The possibility that these can be caused by lactose has been missed because of "hidden" lactose added to many foods and drinks inadequately labelled, confusing diagnosis based on dietary removal of dairy foods. Two polymorphisms, C/T13910 and G/A22018, linked to hypolactasia, correlate with breath hydrogen and symptoms after lactose. This, with a 48 hour record of gut and systemic symptoms and a six hour breath hydrogen test, provides a new approach to the clinical management of lactose intolerance. The key is the prolonged effect of dietary removal of lactose. Patients diagnosed as lactose intolerant must be advised of "risk" foods, inadequately labelled, including processed meats, bread, cake mixes, soft drinks, and lagers. This review highlights the wide range of systemic symptoms caused by lactose intolerance. This has important implications for the management of irritable bowel syndrome, and for doctors of many specialties. PMID:15749792
Matthews, S; Waud, J; Roberts, A; Campbell, A
Lactose malabsorption is a common condition caused by reduced expression or activity of lactase in the small intestine. In such patients, lactose intolerance is characterized by abdominal symptoms (e.g. nausea, bloating, and pain) after ingestion of dairy products. The genetic basis of lactose malabsorption is established and several tests for this condition are available, including genetic, endoscopic, and H2-breath tests. In contrast, lactose intolerance is less well understood. Recent studies show that the risk of symptoms after lactose ingestion depends on the dose of lactose, lactase expression, intestinal flora, and sensitivity of the gastrointestinal tract. Lactose intolerance has recently been defined as symptoms developing after ingestion of lactose which do not develop after placebo challenge in a person with lactose maldigestion. Such blinded testing might be especially important in those with functional gastrointestinal diseases in whom self-reported lactose intolerance is common. However, placebo-controlled testing is not part of current clinical practice. Updated protocols and high-quality outcome studies are needed. Treatment options of lactose intolerance include lactose-reduced diet and enzyme replacement. Documenting the response to multiple doses can guide rational dietary management; however, the clinical utility of this strategy has not been tested. This review summarizes the genetic basis, diagnosis, and treatment of lactose malabsorption and intolerance. PMID:24917953
Pohl, Daniel; Fruhauf, Heiko; Fried, Michael; Vavricka, Stephan R; Fox, Mark
An attempt was made to measure the response to an announcement of hypertension screening at the Goddard Space Center, to compare the results to those of previous statistics. Education and patient awareness of the problem were stressed.
Foulke, J. M.
\\u000a Hypertension as a clinical problem in newborn infants was first recognized in the 1970s (1). However, recent advances in our ability to identify, evaluate, and care for prmature infants have lead to an increased awareness\\u000a of neonatal hypertension, not only in the neonatal intensive care unit (NICU) but also in the neonatal follow-up clinic. This\\u000a chapter will focus on the
Joseph T. Flynn
Background Gastrointestinal symptoms and malabsorption following fructose ingestion (fructose intolerance) are common in functional gastrointestinal disorders (FGID). The underlying mechanism is unclear, but is hypothesized to be related an abnormality of intestinal fructose transporter proteins. Objective To assess the expression of the main intestinal fructose transporter proteins, glucose transport protein 5 (GLUT5) and 2 (GLUT2), in FGID. Methods The expression of GLUT5 and GLUT2 protein and mRNA in small intestinal biopsy tissue was investigated using real-time reverse-transcription PCR and Western immunoblotting in 11 adults with FGID and fructose intolerance ascertained by breath testing and in 15 controls. Results Median expression levels of GLUT5 mRNA normalized to beta-actin were 0.18 (interquartile range, IQR, 0.13–0.21) in patients and 0.17 (IQR 0.12–0.19) in controls (p?>?0.05). Respective levels of GLUT2 mRNA were 0.26 (IQR 0.20–0.31) and 0.26 (IQR 0.19–0.31) (p?>?0.05). Median expression levels of GLUT5 protein normalized to alpha-tubulin were 0.95 (IQR 0.52–1.68) in patients and 0.95 (IQR 0.59–1.15) in controls (p?>?0.05). Respective protein expression levels for GLUT2 were 1.56 (IQR 1.06–2.14) and 1.35 (IQR 0.96–1.79) (p?>?0.05). Conclusions Human fructose intolerance may not be associated with marked changes in GLUT5 and GLUT2 expression. Replication of these results in a larger subject group, including measures of transporter activation and membrane and subcellular localization, is warranted. PMID:24918004
Li, Xinhua; Ho, Sherry SY; Leong, Sai Mun; Wong, Reuben K; Koay, Evelyn SC; Ferraris, Ronaldo P
Hypertension is a growing public health problem worldwide. Only 37% of American hypertensives currently have their blood pressures controlled. Hypertension is traditionally diagnosed in the medical office, but both home and ambulatory blood pressure monitoring can help. Lifestyle modifications are recommended for everyone who has higher than "normal" blood pressure (<120/80 mm Hg). Voluminous clinical trial data support beginning drug therapy with low-dose chlorthalidone, unless the patient has a specific indication for a different drug. Additional drugs (typically in the sequence, angiotensin converting-enzyme inhibitor or angiotensin receptor blocker, calcium antagonist, beta-blocker, alpha-blocker, aldosterone antagonist, direct vasodilator, and centrally acting alpha(2)-agonist) can be added to achieve the blood pressure goal (usually <140/90 mm Hg, but <130/80 mm Hg for diabetics and those with chronic kidney disease). Special circumstances exist for treatment of hypertension in pregnancy, in childhood, in the elderly, and in both extremes of blood pressure (pre-hypertension or hypertensive emergencies). PMID:17398315
Elliott, William J
A 75 g oral glucose tolerance test was performed in 212 pregnant women with no predisposing factors suggesting glucose intolerance to establish the normal pattern of glucose metabolism in pregnancy. Reference values for the test were established for the middle of pregnancy (14-20 weeks, n=43) and late pregnancy (28-37 weeks, n=168). One woman was excluded because she had diabetes that
M Hatem; F Anthony; P Hogston; D J F Rowe; K J Dennis
Up-regulation of the Sirtuin 1 (Sirt1) and Peroxisome Proliferator-activated Receptor ? Coactivator-1? (PGC-1?) Genes in White Adipose Tissue of Id1 Protein-deficient Mice: IMPLICATIONS IN THE PROTECTION AGAINST DIET AND AGE-INDUCED GLUCOSE INTOLERANCE.
Id1, a helix-loop-helix (HLH) protein that inhibits the function of basic HLH E protein transcription factors in lymphoid cells, has been implicated in diet- and age-induced obesity by unknown mechanisms. Here we show that Id1-deficient mice are resistant to a high fat diet- and age-induced obesity, as revealed by reduced weight gain and body fat, increased lipid oxidation, attenuated hepatosteatosis, lower levels of lipid droplets in brown adipose tissue, and smaller white adipocytes after a high fat diet feeding or in aged animals. Id1 deficiency improves glucose tolerance, lowers serum insulin levels, and reduces TNF? gene expression in white adipose tissue. Id1 deficiency also increased expression of Sirtuin 1 and peroxisome proliferator-activated receptor ? coactivator 1?, regulators of mitochondrial biogenesis and energy expenditure, in the white adipose tissue. This effect was accompanied by the elevation of several genes encoding proteins involved in oxidative phosphorylation and fatty acid oxidation, such as cytochrome c, medium-chain acyl-CoA dehydrogenase, and adipocyte protein 2. Moreover, the phenotype for Id1 deficiency was similar to that of mice expressing an E protein dominant-positive construct, ET2, suggesting that the balance between Id and E proteins plays a role in regulating lipid metabolism and insulin sensitivity. PMID:25190816
Zhao, Ying; Ling, Flora; Griffin, Timothy M; He, Ting; Towner, Rheal; Ruan, Hong; Sun, Xiao-Hong
In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific /sup 125/I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific /sup 125/I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity.
Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.
... ENews Home > Lung Disease > Primary Pulmonary Hypertension Primary Pulmonary Hypertension Primary pulmonary hypertension (PPH) is a rare lung ... Lung Association also provides patients with information about pulmonary arterial hypertension (PAH). In-Depth Resources Symptoms, Diagnosis and Treatment ...
The NMR methods for the measurement of intracellular free Na+, K+, Mg2+, Ca2+, and H+ are introduced. The recent literature is then presented showing applications of these methods to cells and tissues from hypertensive animal model systems, and humans with essential hypertension. The results support the hypothesis of consistent derangement of the intracellular ionic environment in hypertension. The theory that this derangement may be a common link in the disease states of high blood pressure and abnormal insulin and glucose metabolism, which are often associated clinically, is discussed.
Veniero, Joseph C.; Gupta, R. K.
Current pharmacotherapy for chronic obstructive pulmonary dis- ease (COPD) relieves symptoms and reduces exacerbation through improving airflow limitation. Such drugs do not effectively improve exercise tolerance due in part to pulmonary hypertension associ- ated with severe COPD, nor impact on its increased morbidity and mortality. Exercise intolerance is often improved (temporarily) by lung volume reduction surgery and pulmonary rehabilitation. Am-
Among 160 consecutive patients referred to the Clinic of Occupational Medicine, Rigshospitalet, for symptoms connected with exposure to organic solvents, 20 exhibited symptoms of acquired intolerance to minor amounts of organic solvents. Later, an additional 30 consecutive patients with symptoms of acquired intolerance were included, yielding a total of 43 men and 7 women. The characteristics of the clinical syndrome described are complaints of dizziness, nausea, and weakness after exposure to minimal solvent vapor concentrations. After having tolerated long-term occupational exposure to moderate or high air concentrations of various organic solvents, the patients became intolerant within a short period of time. Since dizziness was a frequent complaint, we tried to obtain a measure of the patients' complaints using vestibular tests. As a diagnostic test the combined vestibular tests had a sensitivity of 0.55 and a specificity of 0.87. No differences between patients with and without intolerance could be detected by the vestibular tests used. We conclude that acquired intolerance to organic solvents is a new but characteristic and easily recognizable syndrome, often with severe consequences for the patient's working ability.
Gyntelberg, F.; Vesterhauge, S.; Fog, P.; Isager, H.; Zillstorff, K.
Environmental intolerance (EI) is characterized by attribution of several, multisystem symptoms to specific environmental exposures, such as exposure to odorous/pungent chemicals, certain buildings, electromagnetic fields (EMFs) and everyday sounds. The symptoms are medically unexplained, non-specific and the symptoms overlap between different types of EI. To approach the issue of underlying mechanisms the matter of overlap in prevalence between intolerances can provide valuable information. The aim of the study was to examine if the overlap between intolerance to odorous/pungent chemicals, certain buildings, EMFs and sounds is larger than the expected overlap if no association would exist between them. The study was using cross-sectional data from the Västerbotten Environmental Health Study in Sweden; a large questionnaire-based survey. 8520 adults (18-79 years) were randomly selected after stratification for age and sex, of whom 3406 (40%) participated. Individuals with the four types of intolerance were identified either through self-report, or by having been physician-diagnosed with a specific EI. The overlaps between the four EIs were greater than predictions based on coincidence for both self-reported and diagnosed cases (except for the overlap between diagnosed intolerance to sounds and EMFs). The results raise the question whether different types of EI share similar underlying mechanisms, or at least that the sufferers of EI share some predisposition to acquire the conditions. PMID:24029726
Palmquist, Eva; Claeson, Anna-Sara; Neely, Gregory; Stenberg, Berndt; Nordin, Steven
Salmonids are generally known to be glucose intolerant. However, previous studies have shown that growth hormone (GH) transgenic coho salmon display modified nutritional regulation of glycolysis and lipogenesis compared to non-transgenic fish, suggesting the potential for better use of glucose in GH transgenic fish. To examine this in detail, GH transgenic and non-transgenic coho salmon were subjected to glucose tolerance test and subsequent metabolic assessments. After intra-peritoneal injection of 250mg/kg glucose, we analysed post-injection kinetics of glycaemia and expression of several key target genes highly involved in glucose homeostasis in muscle and liver tissues. Our data show no significant differences in plasma glucose levels during peak hyperglycaemia (3-6h after injection), demonstrating a similar glucose tolerance between transgenic and non transgenic. However, and unrelated to the hyperglycaemic episode, GH transgenic fish return to a slightly lower basal glycaemia values 24h after injection. Correspondingly, GH transgenic fish exhibited higher mRNA levels of glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PDH) in liver, and glucose transporter (GLUT4) in muscle. These data suggest that these metabolic actors may be involved in different glucose use in GH transgenic fish, which would be expected to influence the glucose challenge response. Overall, our data demonstrate that GH transgenic coho salmon may be a pertinent animal model for further study of glucose metabolism in carnivorous fish. PMID:24486143
Panserat, Stéphane; Kamalam, Biju Sam; Fournier, Jeanne; Plagnes-Juan, Elisabeth; Woodward, Krista; Devlin, Robert H
Our case describes clinical features of two families defined by joint phenotypes: sodium oxybate intolerance and elevated serum acylcarnitines. Oxybate intolerance variably presents as either cervical dystonia or sleep-related eating disorder. Our objective is to identify biological markers which predict a poor response to sodium oxybate as a treatment for disturbed sleep. Familial inheritance pattern, genotype analysis, multiorgan system involvement, and response to treatment suggest the presence of a secondary cause of fatty oxidation defect, i.e., mitochondrial disorder. Our case report supports the possible conclusion that variance in human mitochondrial metabolism may affect sodium oxybate tolerability. Citation: Berner J. Sodium oxybate intolerance associated with familial serum acylcarnitine elevation. J Clin Sleep Med 2013;9(1):71-72. PMID:23319908
This article asks what sociological insights an analysis of food allergy and food intolerance might afford. We outline the parameters of debates around food allergy and food intolerance in the immunological, clinical and epidemiological literatures in order to identify analytic strands which might illuminate our sociological understanding of the supposed increase in both. Food allergy and food intolerance are contested and contingent terms and it is salient that the term true food allergy is replete throughout medico-scientific, epidemiological and popular discourses in order to rebuff spurious or 'nonallergic' claims of food-related symptoms. Complexity theory is introduced as a means of gaining analytic purchase on the food allergy debate. The article concludes that the use of this perspective provides a contemporary example of the 'double hermeneutic', in that the meanings and interpretations of contemporary explanations of food allergy are both permeated by, and can be made sense of, through recourse to complexity thinking. PMID:19841024
Nettleton, Sarah; Woods, Brian; Burrows, Roger; Kerr, Anne
Our case describes clinical features of two families defined by joint phenotypes: sodium oxybate intolerance and elevated serum acylcarnitines. Oxybate intolerance variably presents as either cervical dystonia or sleep-related eating disorder. Our objective is to identify biological markers which predict a poor response to sodium oxybate as a treatment for disturbed sleep. Familial inheritance pattern, genotype analysis, multiorgan system involvement, and response to treatment suggest the presence of a secondary cause of fatty oxidation defect, i.e., mitochondrial disorder. Our case report supports the possible conclusion that variance in human mitochondrial metabolism may affect sodium oxybate tolerability. PMID:23319908
Background As countries develop economically, an “epidemiological transition” occurs whereby a set of chronic diseases increasingly becomes a country’s health challenge. Against this background, this paper examines the most common conditions associated with the prevalence of diabetes in Qatar, with a specific focus on the diabetes-obesity-hypertension nexus. Methods We analyzed data from the World Health Organization’s World Health Survey conducted in the State of Qatar in 2006. The survey included demographic, anthropometric, and blood chemistry measurements. Using multivariate logistical regression analysis, we assessed the most common conditions associated with diabetes, using both objective and subjective measures of diabetes. The objective measures relied on random blood sugar tests, and the subjective measure included respondents who affirmatively answered the question on diabetes diagnosis. We repeated our analysis on respondents who had blood glucose levels high enough to be considered diabetic/glucose intolerant but did not answer affirmatively on the question of diabetes diagnosis. Results When using the objective measure of diabetes, the following conditions appeared significant: obesity (OR?=?1.5, 95% CI?=?1.2 – 1.9), higher income (OR?=?1.4, 95% CI?=?1.0 – 1.9), high cholesterol (OR?=?1.4, 95% CI?=?1.0 – 1.9), having Qatari origin (OR?=?1.3, 95% CI?=?1.0 – 1.7), and increasing systolic blood pressure (SBP) 120–139 mmHg (OR?=?1.5, 95% CI?=?1.2 – 2.0), SBP 140–159 mmHg (OR?=?2.2, 95% CI?=?1.6 – 3.1), SBP?>?160 mmHg (OR?=?3.2, 95% CI?=?2.0 – 5.3). Similar results were obtained using the subjective measure of diabetes as a dependent variable. When applied to the group of respondents that included pre-diabetics and those who did not know they were diabetic, obesity and hypertension appeared as the only statistically significant explanatory variables. Conclusion High prevalence of diabetes, hypertension, and especially obesity is documented among residents of Qatar. Further steps are required to tackle the most common conditions associated with the rising diabetes epidemic in the country, which might also pose significant fiscal challenges in the future. PMID:25170308
Background. Certain hypertension subtypes have been shown to increase the risk for cardiovascular morbidity and mortality and may be related to specific underlying genetic determinants. Inappropriate characterization of subtypes of hypertension makes efforts at elucidating the genetic contributions to the etiology of hypertension largely vapid. We report the hypertension subtypes among patients with hypertension from South-Western Nigeria. Methods. A total of 1858 subjects comprising 76% female, hypertensive, aged 18 and above were recruited into the study from two centers in Ibadan, Nigeria. Hypertension was identified using JNCVII definition and was further grouped into four subtypes: controlled hypertension (CH), isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), and systolic-diastolic hypertension (SDH). Results. Systolic-diastolic hypertension was the most prevalent. Whereas SDH (77.6% versus 73.5%) and IDH (4.9% versus 4.7%) were more prevalent among females, ISH (10.1% versus 6.2%) was higher among males (P = 0.048). Female subjects were more obese (P < 0.0001) and SDH was prevalent among the obese group. Conclusion. Gender and obesity significantly influenced the distribution of the hypertension subtypes. Characterization of hypertension by subtypes in genetic association studies could lead to identification of previously unknown genetic variants involved in the etiology of hypertension. Large-scale studies among various ethnic groups may be needed to confirm these observations. PMID:25389499
Salako, Babatunde L.; Ogunniyi, Adesola; Cooper, Richard S.
Nilotinib has significant efficacy in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) and in patients with CML-CP or CML in accelerated phase (CML-AP) after imatinib failure. We investigated the occurrence of cross-intolerance to nilotinib in imatinib-intolerant patients with CML. Only 1/75 (1%) patients with nonhematologic imatinib intolerance experienced a similar grade 3/4 adverse event (AE), and 3/75 (4%) experienced a similar persistent grade 2 nonhematologic AE on nilotinib. Only 7/40 (18%) patients with hematologic imatinib intolerance discontinued nilotinib, all because of grade 3/4 thrombocytopenia. Ninety percent of imatinib-intolerant patients with CML-CP who did not have complete hematologic response (CHR) at baseline (n = 52) achieved CHR on nilotinib. Nilotinib induced a major cytogenetic response in 66% and 41% of patients with imatinib-intolerant CML-CP and CML-AP (complete cytogenetic response in 51% and 30%), respectively. Minimal cross-intolerance was confirmed in patients with imatinib-intolerant CML. The favorable tolerability of nilotinib in patients with imatinib intolerance leads to alleviation of AE-related symptoms and significant and durable responses. In addition to its established clinical benefit in patients with newly diagnosed CML and those resistant to imatinib, nilotinib is effective and well-tolerated for long-term use in patients with imatinib intolerance. This study is registered at http://www.clinicaltrials.gov as NCT00471497 PMID:21467546
Hochhaus, Andreas; le Coutre, Philipp D.; Rosti, Gianantonio; Pinilla-Ibarz, Javier; Jabbour, Elias; Gillis, Kathryn; Woodman, Richard C.; Blakesley, Rick E.; Giles, Francis J.; Kantarjian, Hagop M.; Baccarani, Michele
The relationship between primary lactase deficiency, the amount of lactose in the diet, and symptoms of intolerance continues to be debated. Primary adult lactase deficiency is common with a worldwide occurrence of near 70%. Lactase-deficient individuals malabsorb lactose but may or may not show in- tolerance symptoms. The development of symptoms appears to depend on the dose of lactose ingested,
Dennis A. Savaiano; Michael D. Levitt
Intolerance of uncertainty (IU) is the tendency to react negatively to uncertain situations or events, and it has been found to be an important maintaining factor in a number of different anxiety disorders. It is often included as a part of cognitive behavioural interventions for anxiety disorders but its specific contribution to treatment outcome…
Hewitt, Sarah N.; Egan, Sarah; Rees, Clare
When intolerance of gays and lesbians at the University of San Diego became a problem, a group of students, staff, and faculty decided to do something about it. The result was a project called Rainbow Visibility that works on many forms to educate the campus community. (Author)
Getz, Cheryl; Kirkley, Evelyn A.
Although intolerance reaction to analgesics are not uncommon, there is still a lack of standardized procedures to diagnose the problem. We retrospectively analyzed results of scratch tests as well as oral challenges with analgesics in order to evaluate risk and diagnostic relevance of these procedures. In 1987-1992 a total of 650 patients with supposed intolerance to drugs were tested by oral challenge. Among them were 98 patients with a positive history of intolerance to non-aspirin analgesics. In 56 patients the intolerance could be verified by oral challenge. In order of decreasing frequency, the most likely agents were propyphenazone, diclofenac, metamizole, ibuprofen, carbamazepine, indomethacin, phenazone (antipyrine), and paracetamol (acteaminophen). Oral provocation showed clear dose-response relationships. For propyphenazone, the half-effective provocation dose was the same for all symptoms (cutaneous, nasal, bronchial, anaphylactoid). Scratch testing was not of diagnostic significance. Standardized test protocols starting with low dose oral challenges are suitable and helpful in minimizing the risk of severe side effects. PMID:9081936
Wiedow, O; Brasch, J; Christophers, E
b Background: Domestic violence against married women has persisted throughout Korean history. However, very little empirical research has been conducted in Korea about domestic violence, its causes, or women's responses. b Objective: To develop and test psychometrically the Korean Women's Abuse Intolerance Scale (KWAIS) to measure women's propensity or desire to leave abusive husbands in Korea. b Methods: The first
Myunghan Choi; Linda R. Phillips; Aurelio José Figueredo; Katheleen Insel; Sung-Kil Min
Orthostatic intolerance is common in astronauts after prolonged space flight. However, the "push-pull effect" in military aviators suggests that brief exposures to transitions between hypo- and hypergravity are sufficient to induce untoward autonomic cardiovascular physiology in susceptible individuals. We therefore investigated orthostatic tolerance and autonomic cardiovascular function in 16 healthy test subjects before and after a seated 2-hr parabolic flight. At the same time, we also investigated relationships between parabolic flight-induced vomiting and changes in orthostatic and autonomic cardiovascular function. After parabolic flight, 8 of 16 subjects could not tolerate a 30-min upright tilt test, compared to 2 of 16 before flight. Whereas new intolerance in non-Vomiters resembled the clinical postural tachycardia syndrome (POTS), new intolerance in Vomiters was characterized by comparatively isolated upright hypocapnia and cerebral vasoconstriction. As a group, Vomiters also had evidence for increased postflight fluctuations in efferent vagal-cardiac nerve traffic occurring independently of any superimposed change in respiration. Results suggest that syndromes of orthostatic intolerance resembling those occurring after space flight can occur after a brief (i.e., 2-hr) parabolic flight.
Schlegel, Todd T.; Brown, Troy E.; Wood, Scott J.; Benavides, Edgar W.; Bondar, Roberta L.; Stein, Flo; Moradshahi, Peyman; Harm, Deborah L.; Low, Phillip A.
LEARNING OUTCOME: To examine the impact of milk intolerance on milk consumption in older adults.Current public health policy emphasizes optimizing calcium intakes in the elderly. Fluid milk is a readily available source of calcium, but consumption may be limited by milk intolerance. Thus, the purpose of this study was to examine the impact of milk intolerance on milk consumption in
S. M. Elbon; M. A. Johnson; J. G. Fischer
The incidence of neonatal hypertension (HTN) remains low, at less than 2%, and its etiology is varied. Strict definitions of HTN in neonates are unavailable, and the decision to treat is based on opinion rather than evidence. More studies are needed to define normal blood pressure in neonates and to refine current reference values, thus permitting a better definition of HTN. Most causes of neonatal HTN, the most common of which seems to be renovascular disease, are determined by history and basic clinical investigations. Treatment is guided by clinical judgment and expert opinion, given the limited number of clinical trials. PMID:25155725
Batisky, Donald L
At least 10% of all patients with hypertension are resistant to existing therapies. These patients are at increased risk of cardiovascular events and progressive kidney disease. In the face of uncontrolled hypertension, alternative therapies are needed. A device based Baroreflex Hypertension Therapy (BHT) is being developed to treat these patients. This therapy works by electrically activating the carotid baroreflex. The
D. A. Sica; R. S. Kieval; R. C. Martin; E. D. Irwin
BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.
Shannon, J. R.; Flattem, N. L.; Jordan, J.; Jacob, G.; Black, B. K.; Biaggioni, I.; Blakely, R. D.; Robertson, D.
Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight.
Ramsdell, C. D.; Mullen, T. J.; Sundby, G. H.; Rostoft, S.; Sheynberg, N.; Aljuri, N.; Maa, M.; Mukkamala, R.; Sherman, D.; Toska, K.; Yelle, J.; Bloomfield, D.; Williams, G. H.; Cohen, R. J.
Many astronauts after being weightless in space become hypotensive and presyncopal when they assume an upright position. This phenomenon, known as orthostatic intolerance, may interfere with astronaut function during reentry and after spaceflight and may limit the ability of an astronaut to exit a landed spacecraft unaided during an emergency. Orthostatic intolerance is more pronounced after long-term spaceflight and is a major concern with respect to the extended flights expected aboard the International Space Station and for interplanetary exploration class missions, such as a human mission to Mars. Fully effective countermeasures to this problem have not yet been developed. To test the hypothesis that alpha-adrenergic stimulation might provide an effective countermeasure, we conducted a 16-day head-down-tilt bed-rest study (an analog of weightlessness) using normal human volunteers and administered the alpha(1)-agonist drug midodrine at the end of the bed-rest period. Midodrine was found to significantly ameliorate excessive decreases in blood pressure and presyncope during a provocative tilt test. We conclude that midodrine may be an effective countermeasure for the prevention of orthostatic intolerance following spaceflight. PMID:11356789
Ramsdell, C D; Mullen, T J; Sundby, G H; Rostoft, S; Sheynberg, N; Aljuri, N; Maa, M; Mukkamala, R; Sherman, D; Toska, K; Yelle, J; Bloomfield, D; Williams, G H; Cohen, R J
Effective and practical preventive procedures for postflight orthostatic intolerance are highly desirable. The current practice of attempts to expand plasma volume by ingestion of salt and fluids before reentry has proven benefits. This study evaluated alternative options using fludrocortisone (F) to expand plasma volume (PV), dextroamphetamine (Dex) to enhance norepinephrine (NE) release, and atropine (A) to reduce the effects of vagal stimulation. Seven subjects with proven post-bedrest orthostatic intolerance returned for a 7-day 6-deg head-down bedrest study. F (0.2 mg) was given at 8:00 AM and 8:00 PM the day before and 8:00 AM the day the subjects got out of bed (2 hours before standing). PV was measured before and 1 hour after the last dose of F. Dex (5 mg) and A (0.8 mg) were then taken orally 1 hour before the stand test. F expanded PV by 16 percent and caused sodium retention. Four of the 7 subjects stood for 1 hour post-bedrest and heart rate, plasma NE and plasma renin responses to standing were greatly enhanced and sustained. Although there was a narrowing of pulse pressure, the ability to overcome orthostatic intolerance with these countermeasures was largely due to vasoconstriction and sustained high heart rate.
Vernikos, J.; Dallman, M. F.; Van Loon, G.; Keil, L. C.
Objectives The development of hyperglycemia and the use of early parenteral feeding are associated with poor outcomes in critically ill patients. We therefore examined the impact of exogenous glucose administration on the integrated metabolic function of endotoxemic mice using our recently developed frequently sampled intravenous glucose tolerance test (FSIVGTT). We next extended our findings using a cecal ligation and puncture (CLP) sepsis model administered early parenteral glucose support. Methods Male C57BL/6J mice, 8-12 weeks, were instrumented with chronic indwelling arterial and venous catheters. Endotoxemia was initiated with intra-arterial lipopolysaccharide (LPS; 1 mg/kg) in the presence of saline or glucose infusion (100 µL/hr), and an FSIVGTT was performed after five hours. In a second experiment, catheterized mice underwent CLP and the impact of early parenteral glucose administration on glucose homeostasis and mortality was assessed over 24 hrs. Measurements And MAIN RESULTS: Administration of LPS alone did not impair metabolic function, whereas glucose administration alone induced an insulin sensitive state. In contrast, LPS and glucose combined caused marked glucose intolerance and insulin resistance and significantly impaired pancreatic insulin secretion. Similarly, CLP mice receiving parenteral glucose developed fulminant hyperglycemia within 18 hrs (all > 600 mg/dl) associated with increased systemic cytokine release and 40% mortality, whereas CLP alone (85 ± 2 mg/dL) or sham mice receiving parenteral glucose (113 ± 3 mg/dL) all survived and were not hyperglycemic. Despite profound hyperglycemia, plasma insulin in the CLP glucose-infused mice (3.7 ± 1.2 ng/ml) was not higher than sham glucose infused mice (2.1 ± 0.3 ng/ml). Conclusions The combination of parenteral glucose support and the systemic inflammatory response in the acute phase of sepsis induces profound insulin resistance and impairs compensatory pancreatic insulin secretion, leading to the development of fulminant hyperglycemia. PMID:23826335
Zou, Baobo; Guo, Lanping; Stefanovski, Darko; Alonso, Laura C.; Garcia-Ocana, Adolfo; O'Donnell, Christopher P.; McVerry, Bryan J.
Metabolic syndrome, characterized by obesity, hyperglycemia, dyslipidemia and hypertension, increases the risks for cardiovascular disease, diabetes and stroke. Carboxylesterase 1 (CES1) is an enzyme that hydrolyzes triglycerides and cholesterol esters, and is important for lipid metabolism. Our previous data show that over-expression of mouse hepatic CES1 lowers plasma glucose levels and improves insulin sensitivity in diabetic ob/ob mice. In the present study, we determined the physiological role of hepatic CES1 in glucose homeostasis. Hepatic CES1 expression was reduced by fasting but increased in diabetic mice. Treatment of mice with glucose induced hepatic CES1 expression. Consistent with the in vivo study, glucose stimulated CES1 promoter activity and increased acetylation of histone 3 and histone 4 in the CES1 chromatin. Knockdown of ATP-citrate lyase (ACL), an enzyme that regulates histone acetylation, abolished glucose-mediated histone acetylation in the CES1 chromatin and glucose-induced hepatic CES1 expression. Finally, knockdown of hepatic CES1 significantly increased postprandial blood glucose levels. In conclusion, the present study uncovers a novel glucose-CES1-glucose pathway which may play an important role in regulating postprandial blood glucose levels. PMID:25285996
Xu, Jiesi; Yin, Liya; Xu, Yang; Li, Yuanyuan; Zalzala, Munaf; Cheng, Gang; Zhang, Yanqiao
Although most countries state that fighting social intolerance against persons with HIV is part of their national HIV strategy, the impact of reducing intolerance on risky sexual behavior is largely unknown. In this paper, we estimate the effect of social intolerance against HIV+ persons on risky sexual behavior in rural Malawi using data from roughly 2000 respondents from the 2004 and 2006 waves of the Malawi Longitudinal Study of Families and Health (MLSFH). The effect of social intolerance on risky behavior is a priori ambiguous. On the one hand, higher social intolerance or stigma can lead people to disassociate from the stigmatized group and hence promote risky behavior. On the other hand, intolerance can be viewed as a social tax on being HIV+ and thus higher intolerance may reduce risky behavior. We find that a decrease in social intolerance is associated with a decrease in risky behavior, including fewer partners and a lower likelihood of having extra-marital relations. This effect is mainly driven by the impact of social intolerance on men. Overall the results suggests that reducing social intolerance might not only benefit the HIV positive but might also forestall the spread of HIV. PMID:24768779
Delavande, Adeline; Sampaio, Mafalda; Sood, Neeraj
Impaired fasting glucose (fasting plasma glucose 6.1 to 6.9 mmol/L [110 to 125 mg/dL]) is a common glycemic disorder which usually progress to diabetes mellitus. The relationships between impaired fasting glucose, other risk factors including blood pressure, and mortality have never been clearly investigated. We studied 63 443 consecutive men (ages 21 to 60 years), each of whom had a routine health examination with a fasting plasma glucose measurement. Men with known ischemic cardiac disease and treatment for diabetes or hypertension were excluded. Impaired fasting glucose was found in 10 773 (17.0%) of these men. Mean body mass index, serum triglyceride and cholesterol levels, and systolic, diastolic, and pulse blood pressure were significantly higher for men with impaired fasting glucose compared with those men with normal fasting glucose (fasting plasma glucose 3.9 to 6.0 mmol/L). When adjusted for confounding variables, relative risk of 8-year cardiovascular mortality associated with impaired fasting glucose was dependent on systolic blood pressure level (1.02 [95% CI: 0.62 to 1.70] when <140 mm Hg and 2.10 [95% CI: 1.16 to 3.80] between 140 and 160 mm Hg). Inversely, relative risk of 8-year cardiovascular mortality associated with moderate systolic hypertension (140 to 159 mm Hg) compared with normal systolic blood pressure (<140 mm Hg) was highly dependent on the glycemic status (2.97 [95% CI: 1.58 to 5.55] for men with impaired fasting glucose compared with 1.35 [95% CI: 0.84 to 2.18] in those with normal fasting glucose). Similar results were found concerning overall mortality. In conclusion, the presence of moderate systolic hypertension can identify subjects with impaired fasting glucose who are at risk of cardiovascular and overall mortality, and vice versa, probably through the metabolic syndrome. PMID:12364347
Henry, Patrick; Thomas, Frédérique; Benetos, Athanase; Guize, Louis
Although small size at birth is associated with hypertension and associated co-morbidities such as insulin resistance and type II diabetes mellitus, many of the animal models employed to simulate this phenomenon do not closely mimic the ontogeny of growth restriction observed clinically. While intrauterine growth restriction (IUGR) is often detected near mid-pregnancy in women and persists until term, most rodent models of IUGR employ ligation of uterine arteries for a brief period during late gestation (days 19-21 of pregnancy). We hypothesized that IUGR associated with chronic reduction in uteroplacental perfusion (RUPP) and placental ischemia during the third trimester of pregnancy in the rat alters the amniotic fluid (AF) environment and results in hypertensive offspring presenting with metabolic abnormalities such as glucose intolerance and insulin resistance. Insulin-like growth factor-1 (IGF-1), IGF-2, Na(+) concentration and oxidative stress in the AF were increased, while K(+) concentration was decreased in the RUPP compared with normal pregnant (NP) fetuses. RUPP-offspring (RUPP-O) were smaller (6.1 +/- 0.2 versus 6.7 +/- 0.2 g; P < 0.05) at birth compared with NP-offspring (NP-O) groups. At nine weeks of age, mean arterial pressure (121 +/- 3 versus 107 +/- 5 mmHg; P < 0.05), fasting insulin (0.71 +/- 0.014 versus 0.30 +/- 0.08 ng/mL; P < 0.05), glucose (4.4 +/- 0.2 versus 3.1 +/- 0.3 mmol/L; P < 0.05), leptin (3.8 +/- 0.5 versus 2.3 +/- 0.3 ng/mL; P < 0.05) and the homeostasis model assessment of insulin resistance index was greater (2.9 +/- 0.6 versus 1.0 +/- 0.3; P < 0.05) in the RUPP-O compared with the NP-O rats. These data indicate that chronic placental ischemia results in numerous alterations to the fetal environment that contributes to the development of impaired glucose metabolism, insulin resistance and hyperleptinemia in young offspring. PMID:20558843
Heltemes, Alaina; Gingery, Anne; Soldner, Emma L B; Bozadjieva, Nadejda; Jahr, Kristen N; Johnson, Britt K; Gilbert, Jeffrey S
Disruption of KSR2 in humans and mice decreases metabolic rate and induces obesity, coincident with dysregulation of glucose homeostasis. Relative to wild-type mice, ksr2(-/-) mice are small prior to weaning with normal glucose tolerance at 6 weeks of age, but demonstrate excess adiposity by 9 weeks and glucose intolerance by 12-14 weeks. Defects in AICAR tolerance, a measure of whole-body AMPK activation, are detectable only when ksr2(-/-) mice are obese. Food restriction prevents the obesity of adult ksr2(-/-) mice and normalizes glucose and AICAR sensitivity. Obesity and glucose intolerance return when ad lib feeding is restored to the diet-restricted mice, indicating that glucose dysregulation is secondary to obesity in ksr2(-/-) mice. The phenotype of C57BL/6 ksr2(-/-) mice, including obesity and obesity-related dysregulation of glucose homeostasis, recapitulates that of humans with KSR2 mutations, demonstrating the applicability of the C57BL/6 ksr2(-/-) mouse model to the study of the pathogenesis of human disease. These data implicate KSR2 as a physiological regulator of glucose metabolism during development affecting energy sensing, insulin signaling, and lipid storage, and demonstrate the value of the C57BL/6 ksr2(-/-) mouse model as a unique and relevant model system in which to develop and test therapeutic targets for the prevention and treatment of obesity, type 2 diabetes, and obesity-related metabolic disorders. PMID:24997067
Henry, MaLinda D; Costanzo-Garvey, Diane L; Klutho, Paula J; Lewis, Robert E
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
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.
Buckwheat can be used to produce a gluten free flour valuable for persons with gluten intolerance (celiac disease). Celiac disease is affecting about 0.2% of adults in Sweden. The aim of the current study is to investigate the prevalence of buckwheat allergy\\/intolerance, as well as other types of food allergies\\/intolerance, among members of a society for celiac disease patients in
Jeong-Lim Kim; Gunilla Wieslander; Dan Norblck
NASA has identified cardiovascular deconditioning as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder and the resulting orthostatic intolerance experienced by crewmembers upon their return to the 1g norm of Earth. The present study was designed to examine the feasibility of training human subjects to control their own cardiovascular responses to gravitational stimulation (i.e., a tilt table). Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), we would determine if subjects could learn to increase their own blood pressure voluntarily.
Cowings, Patricia S.; Toscano, William B.; Kamiya, Joe; Miller, Neal E.; Pickering, Thomas G.
Resistant hypertension, defined as blood pressure (BP) remaining above goal despite the use of 3 or more antihypertensive medications at maximally tolerated doses (one ideally being a diuretic) or BP that requires 4 or more agents to achieve control, occurs in a substantial proportion (>10%) of treated hypertensive patients. Refractory hypertension is a recently described subset of resistant hypertension that cannot be controlled with maximal medical therapy (?5 antihypertensive medications of different classes at maximal tolerated doses). Patients with resistant or refractory hypertension are at increased cardiovascular risk and comprise the target population for novel antihypertensive treatments. Device-based interventions, including carotid baroreceptor activation and renal denervation, reduce sympathetic nervous system activity and have effectively reduced BP in early clinical trials of resistant hypertension. Renal denervation interrupts afferent and efferent renal nerve signaling by delivering radiofrequency energy, other forms of energy, or norepinephrine-depleting pharmaceuticals through catheters in the renal arteries. Renal denervation has the advantage of not requiring general anesthesia, surgical intervention, or device implantation and has been evaluated extensively in observational proof-of-principle studies and larger randomized controlled trials. It has been shown to be safe and effective in reducing clinic BP, indices of sympathetic nervous system activity, and a variety of hypertension-related comorbidities. These include impaired glucose metabolism/insulin resistance, end-stage renal disease, obstructive sleep apnea, cardiac hypertrophy, heart failure, and cardiac arrhythmias. This article reviews the strengths, limitations, and future applications of novel device-based treatment, particularly renal denervation, for resistant hypertension and its comorbidities. PMID:25028641
Judd, Eric K; Oparil, Suzanne
In a titrated dose cross-over trial of debrisoquine and methyldopa in 38 hypertensive patients neither drug was superior in lowering supine or standing diastolic pressure with a minimum of side effects. Methyldopa caused significantly greater reduction of supine (P<0·001) and standing (P<0·02) systolic pressure but caused intolerable side effects in two patients. Tiredness was the most characteristic and troublesome side effect with methyldopa and postural hypotension was prominent in patients while on debrisoquine. PMID:5539179
Heffernan, A.; Carty, A.; O'Malley, K.; Bugler, J.
Fifty children consecutively attending a clinic for coeliac disease co-operated in a trial; 10 found to have flat mucosa were excluded. Forty children of mean age 9.8 years, whose duodenal or jejunal mucosa had returned to normal or near normal appearance after a mean of 5.8 years on gluten-free diets, were put back on normal diets. In 37, mucosal occurred in a mean of 16.9 months (four to 74 months). Four of the 37 had serial biopsies, in which mucosal enzymes (particularly lactase) fell and interepithelial lymphocyte counts rose before the mucosal morphology was regarded as definitely 'coeliac'. Three children had normal mucosal appearance after 58 to 73 months on normal diets, one of whom showed temporary mucosal abnormalities, another having occasionally low enzymes, in both suggesting underlying gluten sensitivity. Lactase suppression and raised IEL counts appear to be sensitive indicators of gluten intolerance. In our experience, a diagnosis of coeliac disease based on severe mucosal damage and a satisfactory response to a gluten-free but milk-containing diet implies a very strong likelihood of permanent or prolonged gluten intolerance, but with a striking variability in its expression. Images Figure PMID:428824
McNicholl, B; Egan-Mitchell, B; Fottrell, P F
Intrasexual competition among males of different species, including humans, is well documented. Among females, far less is known. Recent nonexperimental studies suggest that women are intolerant of attractive females and use indirect aggression to derogate potential rivals. In Study 1, an experimental design was used to test the evolutionary-based hypothesis that women would be intolerant of sexy women and would censure those who seem to make sex too readily available. Results provide strong empirical support for intrasexual competition among women. Using independent raters, blind to condition, we found that almost all women were rated as reacting negatively ("bitchy") to an attractive female confederate when she was dressed in a sexually provocative manner. In contrast, when she was dressed conservatively, the same confederate was barely noticed by the participants. In Study 2, an experimental design was used to assess whether the sexy female confederate from Study 1 was viewed as a sexual rival by women. Results indicated that as hypothesized, women did not want to introduce her to their boyfriend, allow him to spend time alone with her, or be friends with her. Findings from both studies are discussed in terms of evolutionary theory. PMID:21932332
Vaillancourt, Tracy; Sharma, Aanchal
Objective To examine if the non-expression of negative emotions (i.e., repressive coping) and differences in the ability to process and regulate emotions (i.e., alexithymia) is associated with idiopathic environmental intolerance (IEI). Methods The study included participants who had previously participated in a general population-based study and reported symptoms of environmental intolerance (n = 787) and patients with IEI (n = 237). The participants completed questionnaires assessing IEI, namely, a measure of repressive coping combining scores on the Marlowe–Crowne Social Desirability Scale (MCSDS) and the Taylor Manifest Anxiety Scale (TMAS), the Toronto Alexithymia Scale (TAS-20), and a negative affectivity scale (NAS). Multiple, hierarchical linear regression analyses were conducted using IEI variables as the dependent variables. Results The TMAS and MCSDS scores were independently associated with the IEI variables, but there was no evidence of a role of the repressive coping construct. While the total alexithymia score was unrelated to IEI, the TAS-20 subscale of difficulties identifying feelings (DIF) was independently associated with symptoms attributed to IEI. Negative affectivity was a strong independent predictor of the IEI variables and a mediator of the association between DIF and IEI. Conclusion Our results provide no evidence for a role of repressive coping in IEI, and our hypothesis of an association with alexithymia was only partly supported. In contrast, strong associations between IEI and negative emotional reactions, defensiveness and difficulties identifying feelings were found, suggesting a need for exploring the influence of these emotional reactions in IEI. PMID:21432559
Zachariae, Robert; Rasmussen, Alice; Johansen, Jeanne Duus; Elberling, Jesper
Hypertension and diabetes are common side effects of glucocorticoid treatment. To determine whether peroxisome proliferator–activated receptor-? (PPAR-?) mediates these sequelae, mice deficient in low-density lipoprotein receptor (Ldlr?\\/?), with (Ppara+\\/+) or without (Ppara?\\/?) PPAR-?, were treated chronically with dexamethasone. Ppara+\\/+, but not Ppara?\\/?, mice developed hyperglycemia, hyperinsulinemia and hypertension. Similar effects on glucose metabolism were seen in a different model using
Carlos Bernal-Mizrachi; Sherry Weng; Chu Feng; Brian N Finck; Russell H Knutsen; Teresa C Leone; Trey Coleman; Robert P Mecham; Daniel P Kelly; Clay F Semenkovich
Hypertension is the most common modifiable risk factor for cardiovascular disease, the leading cause of death in both men and women. The prevalence and severity of hypertension rise markedly with age, and blood pressure control becomes more difficult with aging in both genders, particularly in women. In addition, there are forms of hypertension that occur exclusively in women, e.g., hypertension related to menopause, oral contraceptive use, or pregnancy (e.g., chronic hypertension, gestational hypertension, pre-eclampsia or eclampsia). Randomized controlled trials show that antihypertensive therapy provides similar reductions in major cardiovascular events in men and women. Therefore, gender should not influence decisions on selection of blood pressure lowering therapies, except for consideration of gender-specific side effects or contraindications for use in women who are or may become pregnant. This article reviews the prevalence, awareness, treatment, and control of hypertension in women, as well as recent guidelines for management of hypertension in women. PMID:25028640
Hage, Fadi G; Mansur, Sulaf J; Xing, Dongqi; Oparil, Suzanne
The prevalence of hypertension, chronic kidney disease (CKD) and end-stage renal disease (ESRD) attributable to hypertension continues to rise worldwide. Identifying the precise prevalence of CKD attributable to hypertension is difficult owing to the absence of uniform criteria to establish a diagnosis of hypertensive nephropathy. Despite the increasing prevalence of CKD-associated hypertension, awareness of hypertension among individuals with CKD remains
Suneel Udani; Ivana Lazich; George L. Bakris
Comparison of the effects of captopril and nicardipine on insulin sensitivity and thrombotic profile in patients with hypertension and android obesity. CaptISM Study Group. Captopril Insulin Sensitivity Multicenter Study Group.
Hypertension is often related to metabolic disorders, such as android obesity, glucose intolerance, dyslipidemia, and hyperinsulinism (X syndrome). Insulin resistance (IR), described as the common link among these disorders, could contribute to an increase in coronary risk. The euglycemic insulin clamp technique has been used to show that different classes of antihypertensive agents have different effects on IR. The purpose of this multicenter study was to compare the effects of captopril to those of nicardipine on insulin profile using the oral glucose tolerance test (OGTT), a routine-feasible test. After a 1-month single-blind placebo period, 154 patients with hypertension and android obesity were randomized to 3 months of double-blind therapy with either 50 mg captopril twice daily (n = 77) or 50 mg nicardipine twice daily n = 77). An OGTT with an assay of insulin was performed before and after active treatment. Lipid parameters, Factor VII (F VII), fibrinogen, plasminogen activator inhibitor 1 (PAI-1), and insulin-like growth factor I (IGF-I) were measured at the same time. After 3 months of treatment, the changes from baseline in mean +/- SD values for the insulin area under the curve (AUC) were -24.8 +/- 107.4 microIU x h/mL (-15.2%) for captopril v 6.1 +/- 98.6 microIU x h/mL (4.8%) for nicardipine (P = .072). Changes in peak insulin values were -18.3 +/- 86.2 microIU/mL (-14%) for captopril v 6.7 +/- 79.4 microIU/mL (6.6%) for nicardipine (P = .070).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7986464
Raccah, D; Pettenuzzo-Mollo, M; Provendier, O; Boucher, L; Cozic, J A; Gorlier, R; Huin, P; Sicard, J; Vague, P
OBJECTIVE The induction of hepatic glucose 6-phosphatase (G6pc) by glucose presents a paradox of glucose-induced glucose intolerance. We tested whether glucose regulation of liver gene expression is geared toward intracellular homeostasis. RESEARCH DESIGN AND METHODS The effect of glucose-induced accumulation of phosphorylated intermediates on expression of glucokinase (Gck) and its regulator Gckr was determined in hepatocytes. Cell ATP and uric acid production were measured as indices of cell phosphate homeostasis. RESULTS Accumulation of phosphorylated intermediates in hepatocytes incubated at elevated glucose induced rapid and inverse changes in Gck (repression) and Gckr (induction) mRNA concomitantly with induction of G6pc, but had slower effects on the Gckr-to-Gck protein ratio. Dynamic metabolic labeling in mice and liver proteome analysis confirmed that Gckr and Gck are low-turnover proteins. Involvement of Max-like protein X in glucose-mediated Gck-repression was confirmed by chromatin immunoprecipitation analysis. Elevation of the Gck-to-Gckr ratio in hepatocytes was associated with glucose-dependent ATP depletion and elevated urate production confirming compromised phosphate homeostasis. CONCLUSIONS The lowering by glucose of the Gck-to-Gckr ratio provides a potential explanation for the impaired hepatic glucose uptake in diabetes. Elevated uric acid production at an elevated Gck-to-Gckr ratio supports a role for glucose regulation of gene expression in hepatic phosphate homeostasis. PMID:22013014
Arden, Catherine; Petrie, John L.; Tudhope, Susan J.; Al-Oanzi, Ziad; Claydon, Amy J.; Beynon, Robert J.; Towle, Howard C.; Agius, Loranne
The past 2 decades have seen a considerable global increase in cardiovascular disease, with hypertension remaining by far the most common. More than one-third of adults in Africa are hypertensive; as in the urban populations of most developing countries. Being a condition that occurs with relatively few symptoms, hypertension remains underdetected in many countries; especially in developing countries where routine screening at any point of health care is grossly underutilized. Because hypertension is directly related to cardiovascular disease, this has led to hypertension being the leading cause of adverse cardiovascular outcomes, as a result of patients living, often unknowingly, with uncontrolled hypertension for prolonged periods of time. In Africa, hypertension is the leading cause of heart failure; whereas at global levels, hypertension is responsible for more than half of deaths from stroke, just less than half of deaths from coronary artery disease, and for more than one-tenth of all global deaths. In this review, we discuss the escalating occurrence of hypertension in developing countries, before exploring the strengths and weaknesses of different measures to control hypertension, and the challenges of adopting these measures in developing countries. On a broad level, these include steps to curb the ripple effect of urbanization on the health and disease profile of developing societies, and suggestions to improve loopholes in various aspects of health care delivery that affect surveillance and management of hypertension. Furthermore, we consider how the industrial sectors' contributions toward the burden of hypertension can also be the source of the solution. PMID:24786443
Tibazarwa, Kemi B; Damasceno, Albertino A
This paper summarizes the key aspects of the problem of estimating the economic burden of hypertension and hypertension-related disease, the use of economic models, and the opportunities for containing the costs. More information is needed on the population-attributable risk of hypertension in various countries, which is indispensable to estimate the part of hypertension in the burden of stroke and heart disease. The population and high-risk approaches to hypertension control also have economic consequences, which may vary in different societies and must be assessed to ensure proper allocation of resources. Cost-containment can be achieved by more selective diagnostic investigations and by opting for cheaper drugs, though the choice of treatment is difficult owing to uncertainties in the quality-of-life estimates. PMID:7554012
Reduced telomere length and impaired telomerase activity have been linked to several diseases associated with senescence and aging. However, a causal link to metabolic disorders and in particular diabetes mellitus is pending. We here show that young adult mice which are deficient for the Terc subunit of telomerase exhibit impaired glucose tolerance. This is caused by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets, while body fat content, energy expenditure and insulin sensitivity were found to be unaltered. The impaired secretion capacity for insulin is due to reduced islet size which is linked to an impaired replication capacity of insulin-producing beta-cells in Terc-deficient mice. Taken together, telomerase deficiency and hence short telomeres impair replicative capacity of pancreatic beta-cells to cause impaired insulin secretion and glucose intolerance, mechanistically defining diabetes mellitus as an aging-associated disorder. PMID:20876939
Kuhlow, Doreen; Florian, Simone; von Figura, Guido; Weimer, Sandra; Schulz, Nadja; Petzke, Klaus J.; Zarse, Kim; Pfeiffer, Andreas F.H; Rudolph, K. Lenhard; Ristow, Michael
Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM. Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure. SLEEP 2013;36(10):1483-1490. PMID:24082307
Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.
Discomfort intolerance, defined as an individual difference in the capacity to tolerate unpleasant bodily sensations, is a construct recently posited as a risk factor for panic and anxiety psychopathology. The present report used a biological challenge procedure to evaluate whether discomfort intolerance predicts fearful responding beyond the…
Schmidt, Norman B.; Richey, J. Anthony; Cromer, Kiara R.; Buckner, Julia D.
Intolerance of uncertainty (IU) is related to anxiety, depression, worry, and anxiety sensitivity. Precedent IU measures were criticized for psychometric instability and redundancy; alternative measures include the novel 45-item measure (Intolerance of Uncertainty Index; IUI). The IUI was developed in French with 2 parts, assessing general…
Carleton, R. Nicholas; Gosselin, Patrick; Asmundson, Gordon J. G.
The purpose of this study was to explore the relationships among chronic worry, perceived racial stress, and intolerance of uncertainty in a sample of adults who racially identify as Black. Intolerance of uncertainty has been associated with worry and generalized anxiety disorder in predominantly White samples. Given that racial stress is likely…
Rucker, LaTanya S.; West, Lindsey M.; Roemer, Lizabeth
In the national study of health and growth parents' responses to a self completed questionnaire were used to categorise children according to their experience of food intolerance. The heights of the children in each group were then compared. Useful responses to the questions on food intolerance were received for 6813 (85%) children in the sample and measurements of height obtained
Charles E Price; Roberto J Rona; Susan Chinn
The spectacular criminal case of a nurse who because of killing seven old patients in an intensive care ward had been sentenced to jail for 11 years is shown as example of radical thinking in the face of intolerability of serious illness and age. The deficit model of age is on the one hand justly criticized and called invalid, on the other hand negative aspects of age may not be concealed in the face of hedonistic principles of the present epoch. There is no doubt about the monstrosity of the case of the guilty nurse but it may be exemplary for a frequent defensive behaviour against the phenomena of age. If this is right this singular case may be characteristic of common thinking on the unbearable presumption of age. Self defense turning into aggressivity because of foreseeing the own fate of hopeless illness in moribund aged would then have to be seen as a socially significant attitude. PMID:1869232
Session MP1 includes short reports on: (1) Orthostatic Tests after 42 Days of Simulated Weightlessness; (2) Effects of 12 Days Exposure to Simulated Microgravity on Central Circulatory Hemodynamics in the Rhesus Monkey; (3) Increased Sensitivity and Resetting of Baroflex Control of Exercise Heart Rate After Prolonged Bed-Rest; (4) Complex Cardiovascular Dynamics and Deconditioning During Head-down Bed Rest; (5) The Cardiovascular Effects of 6 Hours of Head-down Tilt Upon Athletes and Non-athletes; (6) Individual Susceptibility to Post-spaceflight Orthostatic Intolerance: Contributions of Gender-related and Microgravity-related Factors; (7) Cassiopee Mission 1996: Comparison of Cardiovascular Alteration after Short and Long-term Spaceflights; (8) Cerebral and Femoral Flow Response to LBNP during 6 Month MIR Spaceflights (93-95); and (9) Cerebrovascular Changes due to Spaceflight and Postflight Presyncope.
Hereditary fructose intolerance (HFI) symptoms develop at first introduction of fruit during weaning. We report on an infant with suspected HFI who presented with repeated episodes of vomiting and hypotension after ingestion of fruit-containing meals. The first episode occurred at age 4 months. Despite negative genetic testing for HFI, strict avoidance of fruit ingestion resulted in lack of recurrence of symptoms. Oral-fructose-tolerance testing conducted with an apple mousse did not determine hypoglycemia or fructosuria but caused severe hypotension. Allergy evaluations were negative, and the history was diagnostic for fruit-induced food protein-induced enterocolitis syndrome. Because this non-immunoglobulin E-mediated gastrointestinal food hypersensitivity manifests as profuse, repetitive vomiting, often with diarrhea, leading to acute dehydration and lethargy, it may be misinterpreted as HFI. We advise pediatricians to consider food protein-induced enterocolitis syndrome in the differential diagnosis when there is a suspicion of HFI. PMID:25002667
Fiocchi, Alessandro; Dionisi-Vici, Carlo; Cotugno, Giovanna; Koch, Pierluigi; Dahdah, Lamia
Sympathicotonic orthostatic intolerance (hypotension, tachycardia, or both) is associated with normal or excessive orthostatic increases in plasma norepinephrine concentration and is reversible by the inflation of a military anti-shock trouser suit enveloping the lower limbs and abdomen. These facts suggest that one possible mechanism of the disorder might be a defect in alpha-adrenergic receptor or postreceptor responsiveness of the veins or arterioles. We have investigated in 11 patients and 15 healthy controls the blood pressure and heart rate responses to increasing rates of intravenous norepinephrine infusion (1 to 16 micrograms/min), the dorsal hand vein contractile responses to increasing rates of norepinephrine infusion (1 to 256 ng/min) with a linear variable differential transformer, and the platelet alpha 2-adrenergic receptor densities and dissociation constants. No statistically significant difference in any of these parameters was found between the normal subjects and nine of the 11 patients with orthostatic intolerance. The venous contractile response to norepinephrine was excessive in one patient and was virtually absent in another. Because supersensitivity of the hand veins to norepinephrine suggests up-regulation of alpha 2-receptors resulting from postganglionic autonomic insufficiency, this finding in one patient with sympathicotonic orthostatic hypotension might have been caused by venous denervation. The venous unresponsiveness to norepinephrine in the other patient presumably resulted from a defect in the venous receptors or smooth muscle function. It is evident that norepinephrine responsiveness and the innervation of the arterioles and hand veins was normal in the other nine patients, in whom the defect must have been mediated by some other mechanism. PMID:2160509
Miller, J W; Streeten, D H
Background:A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E4 (LTE4) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B4 (LTB4) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of
F Gaber; K Daham; A Higashi; N Higashi; A Gülich; I Delin; A James; M Skedinger; P Gyllfors; M Nord; S-E Dahlén; M Kumlin; B Dahlén
Objective: The rate of resistant hypertension in China is unknown. This is an analysis of resistant hypertension based on Hypertension Optimal Treatment Study in China. Methods: The study was conducted in 148 cities in mainland China from April 2001 to February 2002, which included 54?590 hypertensive patients (?18 years of age), and used a five-step treatment programme. Patients not achieving blood pressure (BP) target (<140/90?mmHg) within 2 weeks received preplanned additional drugs. Resistant hypertension was defined in the participants with uncontrolled hypertension after 2 weeks of treatment on Step 5. Results: The rate of resistant hypertension was 1.9%. Patients with resistant hypertension were characterized by following features: higher male percentage (65.6 vs. 60.2%); younger age (59.51?±?13.02 vs. 61.76?±?12.27 years); higher BMI (24.8?±?3.5 vs. 24.0?±?3.4?kg/m2); longer disease course; higher fasting blood glucose (6.60?±?2.69 vs. 5.99?±?2.12?mmol/l); higher total cholesterol (5.67?±?1.63 vs. 5.32?±?1.24?mmol/l); higher triglycerides (2.15?±?1.32 vs. 1.96?±?1.09?mmol/l); and higher percentage of grade 3 hypertension (71.1 vs. 27.2%) (all P?0.001). Patients with resistant hypertension also had a higher rate of metabolic syndrome (45.9 vs. 35.4%), diabetes mellitus (25.5 vs. 14.7%) and history of myocardial infarction (4.7 vs. 3.3%) or stroke (17.0 vs. 11.6%) (P?0.001). Multivariate analyses revealed an association of resistant hypertension with younger age, higher BP, BMI, longer disease course, higher fasting blood glucose and total cholesterol (P?0.05). Conclusion: Resistant hypertension in Chinese patients is associated with overweight/obesity, higher BP and metabolic syndrome. The rate of resistant hypertension in China, however, is much lower than previously reported. Another intriguing characteristic is the association of resistant hypertension with younger age. PMID:24172239
Ma, Wenjun; Zhang, Yuqing
B-cell translocation gene 2 (BTG2) is a member of an emerging gene family that is involved in cellular functions. In this study, we demonstrate that BTG2 regulates glucose homeostasis via upregulation of Nur77 in diabetic mice. Hepatic BTG2 gene expression was elevated by fasting and forskolin. Overexpression of Btg2 increased the expression of hepatic gluconeogenic genes and blood glucose output and subsequently impaired glucose and insulin tolerance. Upregulation of the transcriptional activity of Nur77, gluconeogenic genes, and glucose production by forskolin was observed by Btg2 transduction, but not in Btg2 knockdown. BTG2-stimulated glucose production and glucose-6-phosphatase promoter activity were attenuated by dominant-negative Nur77. Coimmunoprecipitation and chromatin immunoprecipitation assays showed that BTG2 induced Nur77 occupancy on the glucose-6-phosphatase promoter via a physical interaction. Btg2 gene expression was increased in streptozotocin-treated and db/db mice. Finally, impairment of glucose homeostasis, such as the increase of blood glucose, glucose intolerance, and insulin intolerance, was elevated in diabetic mice, whereas this phenomenon was abolished in knockdown of Btg2. Together, these data suggest that BTG2 participates in the regulation of hepatic glucose homeostasis, which means that BTG2 might serve as a potential therapeutic target for combating metabolic dysfunction. PMID:24647738
Kim, Yong Deuk; Kim, Sun-Gyun; Hwang, Seung-Lark; Choi, Hueng-Sik; Bae, Jae-Hoon; Song, Dae-Kyu; Im, Seung-Soon
The goal of this study was to investigate the prevalence of diabetes mellitus and impaired glucose tolerance in the adult population of Catalonia and study their association with obesity, central obesity, hypertension and smoking habit. A random sample of 3839 subjects aged 30–89 years participated in this cross-sectional study: 2214 subjects underwent a health examination with oral glucose tolerance test
Conxa Castell; Ricard Tresserras; Jaume Serra; Albert Goday; Gonçal Lloveras; Llu??s Salleras
Large prospective epidemiologic studies have shown that long-term use of oral contraceptives containing estrogen induce an increase in blood pressure and sharply increase the risk of hypertension. Susceptibility to the hypertensive effects of oral contraceptives is heightened where risk factors such as age, family history of hypertension, preexisting or occult renal disease, parity and obesity exist. Hypertension among pill users usually develops within the first 6 months of usage and occasionally is delayed for as long as 6 years. Anitihypertensive therapy is seldom needed as the hypertension that developes is generally mild and uncomplicated, and rapidly reverses when the pills are discontinued. However, a small percentage of patients develop severe, even life-threatening hypertension and the hypertensive effects are felt long after the pills are discontinued. Cases of malignant hypertension and irreversible renal failure requiring maintenance hemodialysis, bilateral nephrectomy, and renal transplantation have occurred following administration of oral contraceptive pills. The mechanism by which oral pills induce hypertension in susceptible women is not known and needs further research. Before oral contraceptives are prescribed, physicians should take a careful history and perform a detailed physicial examination with special attention to the cardiovascular system. Multiple blood pressure measurements should be made and routine laboratory studies including urinalysis, blood urea and nitrogen and serum creatinine should be performed. It is preferable to start with a relatively low (50 mcg) estrogenic content preparation. Patients who develop hypertension (diastolic pressure, 90 mm Hg) on oral contraceptives should stop taking the pills immediately, and should be considered to have estrogen-induced hypertension. They should never again receive estrogen-containing oral pills, although they can try pills containing only progestogen. There is no contraindication to pregnancy in these patients, as most women who become hypertensive on oral pills go on to have normotensive pregnancies. Pregnancy in women who are susceptible to essential hypertension however should be treated as high risk. PMID:12263383
The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology
Alan R. Saltiel; C. Ronald Kahn
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 ?-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
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
Essential hypertension is a widespread multifactorial pathology which is probably controlled by numerous genes. Twenty to forty percent of hypertension may be genetically determined. In this review, polymorphism of three group of candidate genes is analyzed. Products of these genes are most likely involved in hypertension development. These are the genes controlling the renin-angiotensin system, ionic channels, and nitric oxide system and NO-synthase. PMID:10495944
Chistiakov, D A; Turakulov, R I
A contemporary approach to hypertension and prevention are covered in this article. It contains important information for\\u000a clinicians, such as hypertension management, metabolic syndrome issues, lifestyle behavioral management, nutrient issues,\\u000a weight loss treatments (ie, medications and surgical procedures) the role of physical activity, and pharmacologic treatment. The Dietary Approaches\\u000a to Stop Hypertension (DASH) trial eating plan is discussed at length,
Elise Zimmerman; Judith Wylie-Rosett
Hypertension is a major independent risk factor for cardiovascular disease. In alcohol-consuming populations, the amount of\\u000a alcohol consumption has significant impact on blood pressure values, the prevalence of hypertension, and cardiovascular as\\u000a well as all-cause mortality. In this review, we focus on the connection between alcohol consumption and hypertension, and\\u000a discuss the consequences on cardiovascular risk.
Michael Huntgeburth; Henrik ten Freyhaus; Stephan Rosenkranz
Endocrine causes of hypertension are rare in children and screening for endocrine hypertension in children should be carried out only after ruling out renal and renovascular causes. Excess levels and/or action of mineralocorticoids associated with low renin levels lead to childhood hypertension and this can be caused by various conditions which are discussed in detail in the article. Childhood pheochromocytomas are being increasingly diagnosed because of the improved application of genetic testing for familial syndromes associated with pheochromocytomas. Adolescents with polycystic ovarian syndrome (PCOS) can also have hypertension associated with their obese phenotype. PMID:22145140
Today, hypertension is considered endemic throughout the world. The number of individuals with high blood pressure and the increasing risk, morbidity and mortality caused by hypertension despite modern therapy do not decrease sufficiently. Hypertension has become a public health issue. Prevention and effective care require integrated datasets about many features, clinical presentation and therapy of patients with hypertension. The lack of this database in Hungary prompted the development of the registry which could help to provide population-based data for analysis. Data collection and processing was initiated by the Hungarian Society of Hypertension in 2002. Data recording into the Hungarian Hypertension Registry was performed four times (2002, 2005, 2007, 2011) and the registry currently contains data obtained from 108,473 patients. Analysis of these data indicates that 80% of the patients belong to the high or very high cardiovascular risk group. The registry provides data on cardiovascular risk of the hypertensive populations and the effectiveness of antihypertensive therapy in Hungary. Based on international experience and preliminary analysis of data from the Hungarian Hypertension Registry, establishment of hypertension registry may support the effectiveness of public health programs. A further step would be needed for proper data management control and the application of professional principles of evidence-based guidelines in the everyday practice. PMID:24796784
Kiss, István; Kékes, Ede
Physiology in Medicine review article A clearer understanding of the pathogenesis of hypertension will probably lead to more highly targeted therapies and to greater reduction in hypertension-related cardiovascular disease morbidity than can be achieved with current empirical treatment. Hypertension clusters in families and results from a complex interaction of genetic and environmental factors. Endothelial dysfunction, increased vascular reactivity, and vascular remodeling may be causes, rather than consequences, of blood pressure elevation; increased vascular stiffness contributes to isolated systolic hypertension in the elderly.
MD Suzanne Oparil (University of Alabama at Birmingham Department of Medicine); MD M. Amin Zaman (University of Alabama at Birmingham Dept. of Medicine, Division of Cardiovascular Diseases); MD David A Calhoun (University of Alabama at Birmingham Dept. of Medicine, Division of Cardiovascular Disease)
SUMMARY The molecular mechanisms linking the stress of un- folded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study, enforced expres- sion of a translation initiation factor 2a (eIF2a)-spe- cific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(aP)-dependent arm of the ER unfolded protein response in liver
Seiichi Oyadomari; Heather P. Harding; Yuhong Zhang; Miho Oyadomari; David Ron
Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal. PMID:24084738
Morton, Gregory J; Matsen, Miles E; Bracy, Deanna P; Meek, Thomas H; Nguyen, Hong T; Stefanovski, Darko; Bergman, Richard N; Wasserman, David H; Schwartz, Michael W
Feed intolerance in the setting of critical illness is associated with higher morbidity and mortality, and thus requires promptly and effective treatment. Prokinetic agents are currently considered as the first-line therapy given issues relating to parenteral nutrition and post-pyloric placement. Currently, the agents of choice are erythromycin and metoclopramide, either alone or in combination, which are highly effective with relatively low incidence of cardiac, hemodynamic or neurological adverse effects. Diarrhea, however, can occur in up to 49% of patients who are treated with the dual prokinetic therapy, which is not associated with Clostridium difficile infection and settled soon after the cessation of the drugs. Hence, the use of prokinetic therapy over a long period or for prophylactic purpose must be avoided, and the indication for ongoing use of the drug(s) must be reviewed frequently. Second line therapy, such as total parenteral nutrition and post-pyloric feeding, must be considered once adverse effects relating the prokinetic therapy develop. PMID:25133043
Nguyen, Nam Q
Plasma plasminogen activator inhibitor type 1 (PAI-1) and tissue plasminogen activator (tPA) antigens and activities were measured in 28 patients with hypertension and 12 normal controls. Steady state plasma glucose (SSPG) concentrations were also determined after an infusion of somatostatin, insulin and glucose. Patients with hypertension were further subdivided into two groups: insulin resistance (SSPG > 190 mg/dL, n = 14) and no insulin resistance (SSPG < 190 mg/dL, n = 14). As compared to normal controls, hypertensive patients, either with or without insulin resistance, had a significant (P < .005) increases in PAI-1 activity (18.6 +/- 1.3 upsilon 8.1 +/- 0.8 IU/mL), PAI-1 antigen (31.1 +/- 2.0 upsilon 12.7 +/- 0.9 ng/mL) and tPA antigen (15.5 +/- 0.9 upsilon 8.8 +/- 0.9 ng/mL), and significant decrease in tPA activity (0.43 +/- 0.05 upsilon 1.02 +/- 0.16 IU/mL) than normotensive controls. Furthermore, hypertensive patients with insulin resistance had significantly higher PAI-1 activity (22.0 +/- 2.2 upsilon 15.3 +/- 0.8 IU/mL, P = .006) and tPA antigen (17.4 +/- 1.2 upsilon 13.6 +/- 1.3 ng/mL, P = .02) than did hypertensive patients without insulin resistance. However, PAI-1 antigen was insignificantly higher (34.1 +/- 2.9 upsilon 28.1 +/- 2.4 ng/mL, P = .06) and tPA activity insignificantly lower (0.42 +/- 0.08 upsilon 0.43 +/- 0.08 IU/mL, P = .47) in hypertensive patients with insulin resistance than in those without insulin resistance. In addition, PAI-1 activity and tPA antigen were significantly correlated with blood pressure, SSPG, triglyceride, HDL-cholesterol and integrated glucose response to an oral load of 75 g glucose. Thus, patients with hypertension have impaired fibrinolytic activity due to increased PAI-1 when compared to normotensive controls, and the magnitude of this fibrinolytic defect is greater in hypertensive patients who have insulin resistance. Insulin resistance with associated metabolic abnormalities may be one of the causes for impaired fibrinolysis in hypertension. PMID:8735180
Jeng, J R; Sheu, W H; Jeng, C Y; Huang, S H; Shieh, S M
Food intolerance in irritable bowel syndrome (IBS) is increasingly being recognized, with patients convinced that diet plays a role in symptom induction. Evidence is building to implicate fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) in the onset of abdominal pain, bloating, wind and altered bowel habit through their fermentation and osmotic effects. Hypersensitivity to normal levels of luminal distension is known to occur in patients with IBS, with consideration of food chemical intolerance likely to answer many questions about this physiological process. This paper summarizes the evidence and application of the most common approaches to managing food intolerance in IBS: the low-FODMAP diet, the elimination diet for food chemical sensitivity and others including possible noncoeliac gluten intolerance. PMID:22778791
Barrett, Jacqueline S; Gibson, Peter R
Severe malnutrition (< 65% ideal body weight [IBW]) is associated with reduced insulin secretion, decreased receptor affinity, and glucose intolerance. To characterize the abnormality of mild malnutrition in terms of insulin action, both the insulin sensitivity index and insulin secretion were measured in 15 underweight and 15 normal-weight volunteers. Ten patients had localized squamous cell carcinomas of the head and
John A. Tayek; Savita Manglik; Elliot Abemayor
Hypertension remains disproportionately high among Filipinos compared to other racial and ethnic minority populations, and little research on cardiovascular disease risk factors has been conducted among Filipino immigrants in the Northeastern part of the United States. To determine hypertension prevalence and risk factors among Filipino Americans in the New York City area, blood pressure and other clinical measurements were taken from a sample of Filipino Americans during 119 community health screenings conducted between 2006 and 2010. Additional socio-demographic and health-related characteristics were also collected via a cross-sectional survey. A total of 1,028 Filipino immigrants completed the survey and had clinical readings collected. Bivariate analyses and logistic regression were performed in order to predict and assess risk factors for hypertension among our sample. Fifty-three percent of individuals were hypertensive, and half of hypertensive individuals were uninsured. Logistic regression indicated that older age, male gender, living in the United States for over 5 years, a BMI greater than 23.0 kg/m2, an elevated glucose reading, a family history of hypertension, and fair or poor self-reported health status were predictors of hypertension. There is a great need to develop more effective community-based interventions in the Filipino community to address cardiovascular health disparities. PMID:23553685
Islam, Nadia Shilpi; Aguilar, David E.; Wyatt, Laura C.; Tandon, S. Darius; Abesamis-Mendoza, Noilyn; Nur, Potri Ranka Manis Queano; Rago-Adia, Josephine; Ileto, Benjamin; Rey, Mariano J.; Trinh-Shevrin, Chau
A nonlinear scheme was used for the analysis of variability in the heart beat interval [R-R interval (RRI)] data to differentiate heat-intolerant humans from the heat tolerant. All subjects studied had previously suffered exertional heatstroke. Core temperature (Tre ) and electrocardiogram data from 11 heat-tolerant (HT) and 6 heat-intolerant (HIT) males were studied, the grouping being based on the distinguishing
Partha Pratim Kanjilal; Richard R. Gonzalez; Daniel Sender Moran
BACKGROUND: The baroreflex normally serves to buffer blood pressure against excessive rise or fall. Baroreflex failure occurs when afferent baroreceptive nerves or their central connections become impaired. In baroreflex failure, there is loss of buffering ability, and wide excursions of pressure and heart rate occur. Such excursions may derive from endogenous factors such as stress or drowsiness, which result in quite high and quite low pressures, respectively. They may also derive from exogenous factors such as drugs or environmental influences. METHODS AND RESULTS: Impairment of the baroreflex may produce an unusually broad spectrum of clinical presentations; with acute baroreflex failure, a hypertensive crisis is the most common presentation. Over succeeding days to weeks, or in the absence of an acute event, volatile hypertension with periods of hypotension occurs and may continue for many years, usually with some attenuation of pressor surges and greater prominence of depressor valleys during long-term follow-up. With incomplete loss of baroreflex afferents, a mild syndrome of orthostatic tachycardia or orthostatic intolerance may appear. Finally, if the baroreflex failure occurs without concomitant destruction of the parasympathetic efferent vagal fibers, a resting state may lead to malignant vagotonia with severe bradycardia and hypotension and episodes of sinus arrest. CONCLUSIONS: Although baroreflex failure is not the most common cause of the above conditions, correct differentiation from other cardiovascular disorders is important, because therapy of baroreflex failure requires specific strategies, which may lead to successful control.
Ketch, Terry; Biaggioni, Italo; Robertson, RoseMarie; Robertson, David
Substantial evidence from epidemiological data supports a link between obesity and hypertension. However, the relationship between the two disorders is not straightforward and most likely represents an interaction of demographic, genetic, hormonal, renal, and hemodynamic factors. Age, race, and sex also modulate the strength of the association between obesity and hypertension. Hyperinsulinemia, which is characteristic of obesity, can contribute to
Nasser Mikhail; Michael S. Golub; Michael L. Tuck
Epithelia serve as barriers among various compartments in the body. Transepithelial transport of glucose across the barrier epithelial layer is mediated by membrane proteins called glucose transporters. Two types of glucose transporters have been identified: Na(+)-dependent glucose cotransporters (SGLT family), and facilitated-diffusion glucose transporters (GLUT family). These transporters play important roles in the sugar absorption in the intestinal epithelium, sugar reabsorption in the kidney tubule cells, and transfer of glucose across the blood-tissue barriers. In addition to glucose transporters, connexins of gap junctions mediate the transfer of glucose in the double-epithelial cell layer found in the ciliary body and the rat placenta. Polarized localization of transporters and connexins is the structural basis of the vectorial transfer of sugars across the barrier epithelial cell layers. Various techniques of molecular and cell biology have been applied to elucidate the molecular mechanism of such polarized localization. PMID:9844339
The annotated bibliography contains 905 citations. About 90 percent of the articles annotated pertain to glucose analytical methodology and the other 10 percent consists of clinical articles which pertain to the glucose tolerance test and normal values. T...
A. M. Polk, C. Lewis, N. Radin, N. M. Richardson
... Hormones made in the body called insulin and glucagon help control blood glucose levels. See also: Glucose ... such as propranolol) Corticosteroids (such as prednisone) Estrogens Glucagon Isoniazid Lithium Oral contraceptives (birth control pills) Phenothiazines ...
Background. The incidence of hypertension in the Western countries is continuously increasing in the elderly population and remains the leading cause of cardiovascular and morbidity. Methods. we analysed some significant clinical trials in order to present the relevant findings on those hypertensive population. Results. Several studies (SYST-EUR, HYVET, CONVINCE, VALUE, etc.) have demonstrated the benefits of treatment (nitrendipine, hydrochrotiazyde, perindopril, indapamide, verapamil, or valsartan) in aged hypertensive patients not only concerning blood pressure values but also the other important risk factors. Conclusion. Hypertension is the most prevalent cardiovascular disorder in the Western countries, and the relevance of receiving pharmacological treatment of hypertension in aged patients is crucial; in addition, the results suggest that combination therapy—nitrendipine plus enalapril—could have more benefits than those observed with the use of nitrendipine alone. PMID:21876789
Gil-Extremera, Blas; Cia-Gomez, Pedro
Hypertensive disorders of pregnancy represent the second commonest cause of direct maternal death and complicate an estimated 5-10 % of pregnancies. Classification systems aim to separate hypertension similar to that seen outside pregnancy (chronic and gestational hypertension) from the potentially fatal pregnancy-specific conditions. Preeclampsia, HELLP syndrome, and eclampsia represent increasing severities of this disease spectrum. The American College of Obstetricians and Gynecologists' 2013 guidelines no longer require proteinuria as a diagnostic criterion, because of its variable appearance in the disease spectrum. The cause involves inadequate cytotrophoblastic invasion of the myometrium, resulting in placental hypoperfusion and diffuse maternal endothelial dysfunction. Changes in angiogenic and antiangiogentic peptide profiles precede the onset of clinical preeclampsia. Women with preeclampsia should be closely monitored and receive magnesium sulfate intravenously if severe features, HELLP syndrome, or eclampsia occur. Definitive therapy is delivery of the fetus. Hypertension in pregnancy increases future maternal risk of hypertension and cardiovascular disorders. PMID:24477794
Vest, Amanda R; Cho, Leslie S
Objectives: We and others showed that migraineurs are at increased risk of subclinical and clinical ischemic brain lesions. Migraineurs also have a higher prevalence of frequent syncope and orthostatic intolerance, symptoms that are associated with transient reductions in cerebral blood flow. In this study, we assessed whether these autonomic symptoms may contribute to the increased risk of brain lesions in migraine. Methods: Migraineurs (n = 291) and controls (n = 140) from the population-based, cross-sectional CAMERA (Cerebral Abnormalities in Migraine, an Epidemiologic Risk Analysis) cohort (aged 30–60 years, and free of other neurologic symptoms) underwent 1) brain MRI scan, and 2) structured telephone interview including questions on frequent syncope (?5/lifetime) and orthostatic intolerance. Results: Frequent syncope (odds ratio [OR] = 2.7; 95% confidence interval: 1.3–5.5) and orthostatic intolerance (OR = 2.0 [1.1–3.6]) were independent risk factors for high load of deep white matter lesions. Effects were strongest in women and similar in migraineurs and controls. Migraine diagnosis did not mediate or moderate these associations. Individuals with orthostatic intolerance had higher prevalence of high periventricular white matter lesion load (OR = 1.9 [1.1–3.5]). Syncope and orthostatic intolerance were not related to subclinical infarcts or infratentorial lesions. Conclusions: Frequent syncope, orthostatic intolerance, and migraine independently increase the risk of white matter lesions, particularly in females. PMID:23616159
Thijs, Roland D.; Ferrari, Michel D.; Launer, Lenore J.; van Buchem, Mark A.; van Dijk, J. Gert
In 2011, the importance of hypertension and diabetes mellitus as the two main risk factors responsible for the development of cardiovascular disease became clear, as did their significance as major public health issues. Compared with previous years, in which publication of the results of large clinical trials dominated scientific progress, in the last year, the focus has shifted to evidence that novel mechanisms associated with blood pressure, glucose metabolism and diabetes can influence cardiovascular disease. Of particular importance were clinical trials in the area of renal dysfunction, such as the SHARP and ROADMAP trials. PMID:22269836
Cordero, Alberto; Lekuona, Iñaki; Galve, Enrique; Mazón, Pilar
Glucose is named after a Greek word meaning sugar or sweet. One of the most important compounds to life, glucose was first discovered by Andreas Marggraf in 1747. The structure for glucose was first discovered by Emil Fischer during the late 19th century and early 20th century. Glucose is found in all life forms and is used as a means of storing energy. When it polymerizes, it forms cellulose, which comprises plant structures.
Transglutaminase type 2 (TG2) has been reported to be a candidate gene for maturity onset diabetes of the young (MODY) because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2?/?) mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS). Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT) and TG2?/? littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs) and insulin tolerance tests (ITTs) were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2R579A), which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes. PMID:23717413
Iismaa, Siiri E.; Aplin, Mark; Holman, Sara; Yiu, Ting W.; Jackson, Kristy; Burchfield, James G.; Mitchell, Christopher J.; O'Reilly, Liam; Davenport, Aimee; Cantley, James; Schmitz-Peiffer, Carsten; Biden, Trevor J.; Cooney, Gregory J.; Graham, Robert M.
Insulin secretion from pancreatic islet ?-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach in 1999 as the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelin is produced predominantly in the stomach and to a lesser extent in the intestine, pancreas and brain. Ghrelin, initially identified as a potent stimulator of GH release and feeding, has been shown to suppress glucose-induced insulin release. This insulinostatic action is mediated by G?i2 subtype of GTP-binding proteins and delayed outward K(+) (Kv) channels. Interestingly, ghrelin is produced in pancreatic islets. The ghrelin originating from islets restricts insulin release and thereby upwardly regulates the systemic glucose level. Furthermore, blockade or elimination of ghrelin enhances insulin release, which can ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the insulinostatic action of ghrelin, its signal transduction mechanisms in islet ?-cells, ghrelin's status as an islet hormone, physiological roles of ghrelin in regulating systemic insulin levels and glycaemia, and therapeutic potential of the ghrelin-GHS-R system as the target to treat type 2 diabetes. PMID:25200304
Yada, T; Damdindorj, B; Rita, R S; Kurashina, T; Ando, A; Taguchi, M; Koizumi, M; Sone, H; Nakata, M; Kakei, M; Dezaki, K
Hyperinsulinemia and insulin resistance are commonly observed in essential hypertension, which is part of the metabolic syndrome. The aim of this study was to examine whether insulin secretion abnormalities or alterations in insulin sensitivity and glucose tolerance are also present in healthy men, offspring of patients with essential hypertension. Twelve young (27 +/- 3.6 years), lean normotensive offspring were compared with 14 age-, sex-, and body mass index (BMI)-matched controls without a family history of hypertension, diabetes mellitus, and coronary heart disease. We studied glucose tolerance, insulin secretion, and sensitivity using 10-hour hyperglycemic and 10-hour hyperinsulinemic-euglycemic clamps (HIC). Glucose tolerance was comparable in the offspring and controls. However, the offspring had higher insulin and C-peptide levels during the hyperglycemic clamp (HGC) compared with controls (P <.05). There was no difference in the early phase of insulin secretion between the groups. The insulin sensitivity index (glucose infusion rate/serum insulin) was significantly lower in the offspring during both clamps. Moreover, the offspring had higher systolic (P <.001) and diastolic (P <.001) blood pressure and had higher serum cholesterol (P <.01) and triglyceride (P <.05) levels. Apparently healthy, young, lean individuals with a genetic predisposition to essential hypertension and with normal glucose tolerance had higher insulin secretion and lower insulin sensitivity than controls. These abnormalities, together with higher blood pressure and altered lipid metabolism, may play a role in the development of hypertension and an increased risk of cardiovascular morbidity and mortality in these individuals. PMID:15045694
Vlasáková, Zuzana; Pelikánová, Terezie; Karasová, Ludmila; Skibová, Jelena
Sixty newly diagnosed adult patients with mild to moderate essential hypertension were assessed to determine their cardiovascular risk factor profiles. Detailed history and physical examinations were done. Resting 12-lead ECG was done and serum levels of uric acid, fasting cholesterol, and fasting glucose were determined. Twenty nine patients had hypertension and two or more cardiovascular risk factors. The most prevalent cardiovascular risk factors other than hypertension were electro-cardiovascular left ventricular hypertrophy (31.7%), obesity (28.3%) and hypercholesterolaemia (28.3%). About a half of these patients (48.3%) can be classified as high risk hypertensives. This calls for aggressive management of cardiovascular risk factors as a whole and not just hypertension alone if we are to reduce incidence of hypertensive complications. PMID:8033770
Yonga, G O; Ogola, E N; Juma, F D
The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).
Serrador, J. M.; Shoemaker, J. K.; Brown, T. E.; Kassam, M. S.; Bondar, R. L.; Schlegel, T. T.
Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetically predisposition. Symptoms occur upon exposure to prolamin from wheat, rye, barley and related grain. The pathogenesis of celiac disease has not yet been sufficiently elucidated but is being considered as an autoimmune process. At its core are the deamidation of prolamin fragments, the building of specific antibodies and the activation of cytotoxic T-cells. The immunological inflammatory process is accompanied by structural damages of the enterocytes (villous atrophy, colonization and crypt hyperplasia). The symptoms and their extent depend on the type of the celiac disease; classic and non-classic forms are being distinguished (atypical, oligosymptomatic, latent and silent celiac disease). Characteristics of the classic presentation are malabsorption syndrome and intestinal symptoms such as mushy diarrhea and abdominal distension. The diagnosis of celiac disease is based on four pillars: Anamnesis and clinical presentation, serological evidence of coeliac specific antibodies (IgA-t-TG; IgA-EmA), small intestine biopsy and improvement of symptoms after institution of a gluten-free diet. The basis of the therapy is a lifelong gluten-free diet, i. e. wheat, rye, barley, spelt, green-core, faro-wheat, kamuth and conventional oats as well as food items obtained therefrom. Small amounts of up to 50 mg gluten per day are usually tolerated by most patients; amounts of > or = 100 mg/day lead mostly to symptoms. Gluten-free foods contain < or = 20 ppm or 20 mg/kg (Sign: symbol of the 'crossed ear' or label 'gluten-free'). At the beginning of the therapy the fat and lactose intake may need to be reduced; also the supplementation of single micronutrients (fat-soluble vitamins, folic acid, B12, iron, and calcium) may be required. Alternative therapies are being developed but have not yet been clinically tested. PMID:24266248
Ströhle, Alexander; Wolters, Maike; Hahn, Andreas
OBJECTIVE: Gluten intolerance is an immune-mediated enteropathy associated with gluten-containing foods in genetically susceptible patients. The typical form mainly affecting children shows failure to thrive and/or gastrointestinal symptoms. The adult form is less typical, presenting vague gastrointestinal symptoms, iron deficiency (with or without anemia) or nonspecific serum chemistry abnormalities. The present study aims to analyze clinical and biochemical differences of celiac disease (CD) according to sex and age. PATIENTS AND METHODS: The present study reviewed clinical and biochemical features of patients with suspected CD admitted to the Hospital General of Móstoles (Madrid, Spain) between July 2001 and June 2005. Two hundred fifty-two patients were analyzed, in whom intestinal biopsy was performed due to clinical and/or biochemical abnormalities suggestive of CD. One hundred seventy-eight asymptomatic relatives of the affected patients were also included. Overall, 125 patients showed diagnostic features of CD in the intestinal biopsy. RESULTS: The results confirmed higher prevalence of typical forms of CD in children (67% in children compared with only 14.3% in adults). CD seemed to be more frequent in adult women than in men (ratio of women to men 4:1), but it is worth noting that men diagnosed were most often referred with a typical clinical picture, so atypical forms of the disease in men may have been underdiagnosed. CONCLUSIONS: CD shows atypical features in adults, and physicians must include this disorder in the differential diagnosis of adults with iron deficiency or slight hypertransaminasemia. Increased awareness of the disease and extensive availability of accurate serological tests will lead to improved diagnosis of this disorder, both in children and adults. PMID:17111054
Llorente-Alonso, MJ; Fernandez-Acenero, MJ; Sebastian, M
Perioperative hypertension is commonly encountered in patients that undergo surgery. While attempts have been made to standardize the method to characterize the intraoperative hemodynamics, these methods still vary widely. In addition, there is a lack of consensus concerning treatment thresholds and appropriate therapeutic targets, making absolute recommendations about treatment difficult. Nevertheless, perioperative hypertension requires careful management. When treatment is necessary, therapy should be individualized for the patient. This paper reviews the pharmacologic agents and strategies commonly used in the management of perioperative hypertension. PMID:18827911
Varon, Joseph; Marik, Paul E
6 degrees head-down tilt bed rest experiment for 6 days was conducted at Nihon University Itabashi Hospital for 10 male athletes. In order to observe the orthostatic intolerance due to six days head-down tilt bed rest, 70 degrees head up tilt tests were performed before and after the head-down tilt. Two types of orthostatic intolerance were distinguished by the time course of their cardiovascular responses. One was vagotonia type and the other was brain anemia type. The latter type was commonly seen among astronauts after space flight due to the lack of plasma volume. As this volume change is considered to be initiated by some fluid loss from the lower extremities, analysis was made to clarify the relation between the leg volume change and the types of orthostatic intolerance. Nakayama proposed a Heart Rate Controllability Index, which is calculated from the initiate leg volume change and heart rate increase in head up tilt, for an indicator of the orthostatic intolerability. The index was applied to the subjects of six days head-down tilt above mentioned. For the subjects who showed a sign of presyncopy, the index values were higher or lower than that of the rest subjects who showed no sign of presyncopy. In order to evaluate the validity of the index, another experiment was conducted to induce an orthostatic intolerance by a different way of loading. The same types of orthostatic intolerance were observed and the index value hit high in the brain anemia type of orthostatic intolerance, while the vagotonia type showed relatively lower values than the normal group.
Yajima, Kazuyoshi; Miyamoto, Akira; Ito, Masao; Mano, Takaichi; Nakayama, Kiyoshi
The portal hypertension is responsible for many of the manifestations of liver cirrhosis. Some of these complications are the direct consequences of portal hypertension, such as gastrointestinal bleeding from ruptured gastroesophageal varices and from portal hypertensive gastropathy and colopathy, ascites and hepatorenal syndrome, and hypersplenism. In other complications, portal hypertension plays a key role, although it is not the only pathophysiological factor in their development. These include spontaneous bacterial peritonitis, hepatic encephalopathy, cirrhotic cardiomyopathy, hepatopulmonary syndrome, and portopulmonary hypertension. PMID:23024865
Al-Busafi, Said A.; McNabb-Baltar, Julia; Farag, Amanda; Hilzenrat, Nir
Softshell turtles (Apalone spinifera) were submerged at 3 degrees C in anoxic or normoxic water. Periodically, blood PO(2), PCO(2), pH, plasma [Cl(-)], [Na(+)], [K(+)], total Ca, total Mg, lactate, glucose, and osmolality were measured; hematocrit and body mass determined; and blood [HCO(3)(-)] calculated. On day 14 of anoxic submergence, five of eight softshell turtles were dead, one died immediately after removal, and the remaining two showed no signs of life other than a heartbeat. After 11 days of submergence in anoxic water, blood pH fell from 7.923 to 7.281 and lactate increased to 62.1 mM. Plasma [HCO(3)(-)] was titrated from 34.57 mM to 4.53 mM. Plasma [Cl(-)] fell, but [K(+)] and total Ca and Mg increased. In normoxic submergence, turtles survived over 150 days and no lactate accumulated. A respiratory alkalosis developed (pH-8.195, PCO(2)-5.49 after 10 days) early and persisted throughout; no other variables changed in normoxic submergence. Softshell turtles are very capable of extrapulmonary extraction of O(2), but are an anoxia-intolerant species of turtle forcing them to utilize hibernacula that are unlikely to become hypoxic or anoxic (e.g., large lakes and rivers). PMID:12687397
Reese, S A; Jackson, D C; Ultsch, G R
... Pregnancy-induced hypertension (PIH), also called toxemia or preeclampsia: This condition can cause serious problems for both ... delivery for my baby? Source NHBPEP Report on High Blood Pressure in Pregnancy: A Summary for Family Physicians by MA Zamorski, ...
BACKGROUNDNasal provocation tests with lysine-aspirin have recently been introduced for assessment of aspirin intolerant asthma. A study was undertaken to evaluate the usefulness of acoustic rhinometry, a new non-invasive technique, in the diagnosis of aspirin intolerant asthma\\/rhinitis.METHODSFifteen patients with aspirin intolerant asthma\\/rhinitis (nine women, mean (SD) age 54.7 (14) years), eight patients with aspirin tolerant asthma\\/rhinitis (three women, mean (SD)
J Casadevall; P-J Ventura; J Mullol; C Picado
Pregnancy is a normal physiological state characterized by numerous hemodynamic changes. These hemodynamic changes, although\\u000a necessary for a normal pregnancy, pose a special problem in the presence of portal hypertension. In North America, cirrhosis\\u000a of the liver is the most common cause of portal hypertension. Although rare, the occurrence of pregnancy is not altogether\\u000a unknown in this population. This is
Bimaljit Sandhu; Arun J. Sanyal
Among 1800 referred hypertensive patients, 181 had recumbent diastolic blood pressures (DBP) below 90 mm Hg and standing DBP above 90 mm Hg. Orthostatic increments in DBP were greater in these orthostatic hypertensive patients than in 181 persistently hypertensive patients and 134 normotensive subjects. In 12 patients with orthostatic hypertension, the orthostatic fall in cardiac output (27.3 +/- 2.9%, measured by a respiratory method) was double that in 8 normotensive subjects (13.3 +/- 3.7%, p less than 0.01). An inflated pressure suit over the pelvis and lower limbs prevented the excessive fall in cardiac output and significantly reduced (p less than 0.02) the excessive rise in standing DBP in orthostatic hypertensive patients. Gravitational pooling of blood in the legs and reduction of blood in the head was measured by external gamma counting of autologous erythrocytes labeled with sodium pertechnetate Tc 99m through ports in fixed positions over the leg and the temple. Orthostatic intravascular pooling was significantly greater (p less than 0.01) in orthostatic hypertensive subjects than in normotensive subjects, and the magnitudes of orthostatic pooling and orthostatic increases in DBP were closely correlated (r = +0.85). Plasma norepinephrine concentrations were similar in recumbency and after sustained handgrip exercise, but significantly greater (p less than 0.01) after 5 to 60 mins of standing in orthostatic hypertensive subjects than in normotensive subjects. Our results indicate that orthostatic hypertension is common and that its mechanism in representative patients involves excessive orthostatic blood pooling, which results in decreased venous return, decreased cardiac output, increased sympathetic stimulation (presumably through low-pressure cardiopulmonary receptors), and excessive arteriolar, but not venular, constriction. PMID:3980066
Streeten, D H; Auchincloss, J H; Anderson, G H; Richardson, R L; Thomas, F D; Miller, J W
Pulmonary arterial hypertension is a serious disease with significant morbidity and mortality. While it can occur idiopathically, it is more commonly associated with other cardiac or lung diseases. While most of the available therapies were tested in adult populations, and most therapies in children remain off-label, new reports and randomized trials are emerging that inform the treatment of pediatric populations. This review discusses currently available therapies for pediatric pulmonary hypertension, their biologic rationales, and evidence for their clinical effectiveness. PMID:23036248
Steinhorn, Robin H.
Cyclosporine (CsA) and sirolimus (SRL) have been associated with undesirable side effects, including posttransplantation diabetes and hyperlipidemia, but the molecular mechanisms underlying these effects remain to be elucidated. Animal studies focusing on clinically relevant doses are advised. This study sought to compare the metabolic effects on isolated rat adipocytes treated with either CsA or SRL ex vivo and after long-term in vivo treatment in Wistar rats. We assessed the ex vivo effects of CsA (0.5-30 ?mol/L) and SRL (1-250 ?mol/L) on insulin-stimulated (14)C-glucose uptake in epididymal adipocytes (n = 6-9). In parallel, rats (n = 12) were treated with either vehicle, CsA (5 mg/kg/d) or SRL (1 mg/kg/d) for either 3 or 9 weeks. At the end of the treatment, glucose tolerance test (GTT) and insulin-stimulated (14)C-glucose uptake as well as biochemical parameters were analyzed. A significant reduction in the insulin-stimulated glucose uptake over basal was observed among isolated adipocytes, whether exposed ex vivo or in vivo to CsA or SRL treatment. Furthermore, the SRL group showed significantly lighter fat pads and smaller adipocytes at 3 weeks with a smaller gain in body weight throughout the study compared with either the vehicle or CsA cohorts. Glucose intolerance was observed after a GTT, at the end of the treatment with either drug. Additionally, at 9 weeks serum triglycerides were increased by CsA compared with vehicle or SRL treatment. Interestingly, although SRL-treated animals presented higher fed and fasted insulin levels compared with either group, suggesting insulin resistance, the CsA group presented lower fed and fasted insulin values, suggesting a defect in insulin secretion at 9 weeks. These results suggested that either ex vivo treatment of fat cells or in vivo treatment of rats with CsA or SRL impaired insulin-stimulated glucose uptake by adipocytes. Both drugs caused glucose intolerance, which altogether could be responsible for the development of posttransplantation diabetes. PMID:23622647
Lopes, P; Fuhrmann, A; Sereno, J; Pereira, M J; Nunes, P; Pedro, J; Melão, A; Reis, F; Carvalho, E
The present study demonstrates that glabridin, a prenylated isoflavone in licorice, stimulates glucose uptake through the adenosine monophosphate-activated protein kinase (AMPK) pathway in L6 myotubes. Treatment with glabridin for 4h induced glucose uptake in a dose-dependent manner accompanied by the translocation of glucose transporter type 4 (GLUT4) to the plasma membrane. Glabridin needed at least 4h to increase glucose uptake, while it significantly decreased glycogen and increased lactic acid within 15 min. Pharmacological inhibition of AMPK by Compound C suppressed the glabridin-induced glucose uptake, whereas phosphoinositide 3-kinase and Akt inhibition by LY294002 and Akt1/2 inhibitor, respectively, did not. Furthermore, glabridin induced AMPK phosphorylation, and siRNA for AMPK completely abolished glabridin-induced glucose uptake. We confirmed that glabridin-rich licorice extract prevent glucose intolerance accompanied by the AMPK-dependent GLUT4 translocation in the plasma membrane of mice skeletal muscle. These results indicate that glabridin may possess a therapeutic effect on metabolic disorders, such as diabetes and hyperglycemia, by modulating glucose metabolism through AMPK in skeletal muscle cells. PMID:24953974
Sawada, Keisuke; Yamashita, Yoko; Zhang, Tianshun; Nakagawa, Kaku; Ashida, Hitoshi
A novel holographic sensor system capable of detecting dynamic changes in glucose concentration has been developed. The hologram is recorded within a bio-compatible hydrogel matrix containing phenylboronic acid derivatives. On binding glucose, the colour of the hologram red-shifts to longer wavelengths as the hydrogel expands and this colour change is used to quantify glucose concentration. However, phenylboronic acids are non-selective
Satyamoorthy Kabilan; Alexander J. Marshall; Felicity K. Sartain; Mei-Ching Lee; Abid Hussain; Xiaoping Yang; Jeff Blyth; Njeri Karangu; Karen James; Jimmy Zeng; Dawn Smith; Angelika Domschke; Christopher R. Lowe
This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of (/sup 14/C)glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1.
Brondsted, H.E.; Gjedde, A.
We examined whether reductions in body fat stores and insulin resistance in Syrian hamsters induced by bromocriptine are associated with reductions in daily norepinephrine (NE) and serotonin activities as indicated by their extracellular metabolite levels in the ventromedial hypothalamus (VMH). High levels of these monoamines within the VMH have been suspected to induce obesity and insulin resistance. Microdialysate samples from
Shuqin Luo; Albert H. Meier; Anthony H. Cincotta
The effect of 3 h standing, followed by a period of head-up tilt (HUT) on physiological response (orthostatic tolerance, blood pressure and heart rate), as well as on plasma vasopressin (PVP) and renin activity (PRA) were studied in 13 dehydrated (to 2.4 pct loss of body weight) subjects. Seven subjects showed signs of orthostatic intolerance (INT), manifested by sweating, pallor, nausea and dizziness. Prior to these symptoms, the INT subjects exhibited lower systolic (SP) and pulse (PP) pressures, and an elevated PRA, compared to the tolerant (TOL) subjects. HUT has aggravated increases of RPA in the INT subjects and caused an increase, higher than in TOL subjects, in PVP, while rehydration has greatly attenuated the PVP response to the HUT and decreased the PRA response. It is concluded that dehydration, together with measurements of SP, PP and PRA, may serve as a means of predicting orthostatic intolerance and may provide a physiological model for studying the causes of intolerance.
Harrison, M. H.; Kravik, S. E.; Geelen, G.; Keil, L.; Greenleaf, J. E.
Orthostatic intolerance is a common problem for inbound space travelers. There is usually tachycardia on standing but blood pressure may be normal, low or, rarely, elevated. This condition is analogous to the orthostatic intolerance that occurs on Earth in individuals with orthostatic tachycardia, palpitations, mitral valve prolapse, and light-headedness. Our studies during the Neurolab mission indicated that sympathetic nerve traffic is raised in microgravity and that plasma norepinephrine is higher than baseline supine levels but lower than baseline upright levels. A subgroup of patients with familial orthostatic intolerance differ from inbound space travelers in that they have an alanine-to-to-proline mutation at amino acid position 457 in their norepinephrine transporter gene. This leads to poor clearance of norepinephrine from synapses, with consequent raised heart rate. Clinical features of these syndromes are presented.
Robertson, D.; Shannon, J. R.; Biaggioni, I.; Ertl, A. C.; Diedrich, A.; Carson, R.; Furlan, R.; Jacob, G.; Jordan, J.
Lack of confirmation of symptoms attributed to electromagnetic fields (EMF) and triggered by EMF exposure has highlighted the role of individual factors. Prior observations indicate intolerance to other types of environmental exposures among persons with electromagnetic hypersensitivity (EHS). This study assessed differences in odor and noise intolerance between persons with EHS and healthy controls by use of subscales and global measures of the Chemical Sensitivity Scale (CSS) and the Noise Sensitivity Scale (NSS). The EHS group scored significantly higher than the controls on all CSS and NSS scales. Correlation coefficients between CSS and NSS scores ranged from 0.60 to 0.65 across measures. The findings suggest an association between EHS and odor and noise intolerance, encouraging further investigation of individual factors for understanding EMF-related symptoms. PMID:25166918
Nordin, Steven; Neely, Gregory; Olsson, David; Sandström, Monica
Lack of confirmation of symptoms attributed to electromagnetic fields (EMF) and triggered by EMF exposure has highlighted the role of individual factors. Prior observations indicate intolerance to other types of environmental exposures among persons with electromagnetic hypersensitivity (EHS). This study assessed differences in odor and noise intolerance between persons with EHS and healthy controls by use of subscales and global measures of the Chemical Sensitivity Scale (CSS) and the Noise Sensitivity Scale (NSS). The EHS group scored significantly higher than the controls on all CSS and NSS scales. Correlation coefficients between CSS and NSS scores ranged from 0.60 to 0.65 across measures. The findings suggest an association between EHS and odor and noise intolerance, encouraging further investigation of individual factors for understanding EMF-related symptoms. PMID:25166918
Nordin, Steven; Neely, Gregory; Olsson, David; Sandstrom, Monica
Type 2 diabetes mellitus (T2DM) and hypertension represent two common conditions worldwide. Their frequent association with cardiovascular diseases makes management of hypertensive patients with T2DM an important clinical priority. Carvedilol and renal denervation are two promising choices to reduce plasma glucose levels and blood pressure in hypertensive patients with T2DM to reduce future complications and improve clinical outcomes and prognosis. Pathophysiological mechanisms of both options are under investigation, but one of the most accepted is an attenuation in sympathetic nervous system activity which lowers blood pressure and improves insulin sensitivity. Choice of these therapeutic approaches should be individualized based on specific characteristics of each patient. Further investigations are needed to determine when to consider their use in clinical practice. PMID:25126399
Castro Torres, Yaniel; Katholi, Richard E
Type 2 diabetes (noninsulin-dependent diabetes mellitus) develops from a pre-diabetic condition that is characterized by insulin resistance and glucose intolerance, and is exacerbated by obesity. In this study, we compared the ability of over-the-counter analgesic drugs (OTCAD) [acetaminophen (APAP); ibuprofen (IBU); naproxen (NAP); aspirin (ASA)], to protect against the development of a pre-diabetic state in mice fed a high fat
Eric L. Kendig; Scott N. Schneider; Deborah J. Clegg; Mary Beth Genter; Howard G. Shertzer
Background Lactose intolerance is a common complication of diarrhoea in infants with malnutrition and a cause of treatment failure. A combination of nutritional injury and infectious insults in severe protein energy malnutrition reduces the capacity of the intestinal mucosa to produce lactase enzyme necessary for the digestion of lactose. The standard management of severe malnutrition involves nutritional rehabilitation with lactose-based high energy formula milk. However, some of these children may be lactose intolerant, possibly contributing to the high rate of unfavorable treatment outcomes. This study was therefore designed to establish the prevalence of lactose intolerance and associated factors in this population. Methods A descriptive cross sectional study involving 196 severely malnourished children with diarrhoea aged 3-60 months was done in Mwanamugimu Nutrition Unit (MNU), Mulago hospital between October 2006 and February 2007. Results During the study period, 196 severely malnourished children with diarrhoea were recruited, 50 (25.5%) of whom had evidence of lactose intolerance (stool reducing substance ? 1 + [0.5%] and stool pH < 5.5) and it occurred more commonly in children with kwashiorkor 27/75 (36.0%) than marasmic-kwashiorkor 6/25 (24.0%) and marasmus 17/96 (17.7%). Oedematous malnutrition (p = 0.032), perianal skin erosion (p = 0.044), high mean stool frequency (p = < 0.001) and having ?2 diarrhoea episodes in the previous 3 months (p = 0.007) were the independent predictors of lactose intolerance. Other factors that were significantly associated with lactose intolerance on bi-variate analysis included: young age of 3-12 months; lack of up to-date immunization; persistent diarrhoea; vomiting; dehydration, and abdominal distension. Exclusive breastfeeding for less than 4 months and worsening of diarrhoea on initiation of therapeutic milk were the other factors. Conclusions The prevalence of lactose intolerance in this study setting of 25.5% is relatively high. Routine screening by stool pH and reducing substances should be performed especially in the severely malnourished children with diarrhoea presenting with oedematous malnutrition, perianal skin erosion, higher mean stool frequency and having had ?2 diarrhoea episodes in the previous 3 months. Use of lactose-free diets such as yoghurt should be considered for children found to have evidence of lactose intolerance and whose response on standard therapeutic milk formula is poor. PMID:20459633
Hypertensive disorders in pregnancy are one of the leading causes of maternal death in the world and one of the major causes of perinatal mortality. The incidence of hypertensive disorders in pregnancy is 8%-15%. Significant changes of biochemical parameters in cases of hypertensive disorders in pregnancy are increased levels of blood glucose, urea, creatinine, uric acid (hyperuricemia), transaminases, and LDH. The most increased is the level of proteinuria. Bad laboratory results and the intensification of clinical signs, with multiorgan dysfunction, are indications for termination of pregnancy. PMID:22616581
Kocijancic, Dusica Maksimilijan; Plesinac, Snezana; Plecas, Darko; Aksam, Slavica; Kocijancic, Aleksandar
Essential hypertension is a "disease of civilization" but has a clear genetic component. From an evolutionary perspective, persistence in the human genome of elements capable of raising blood pressure presupposes their adaptive significance. Recently, two hypotheses that explicitly appeal to selectionist arguments, the "slavery" and "thrifty gene" theories, have been forwarded. We find neither completely successful, and we advance an alternative explanation of the adaptive importance of genes responsible for hypertension. We propose that blood pressure rises during childhood and adolescence to subserve homeostatic needs of the organism. Specifically, we contend that blood pressure is a flexible element in the repertoire of renal homeostatic mechanisms serving to match renal function to growth. The effect of modern diet and lifestyle on human growth stimulates earlier and more vigorous development, straining biologically necessary relationships between renal and general somatic growth and requiring compensation via homeostatic mechanisms preserved during evolution. Prime among such mechanisms is blood pressure, which rises as a compensation to maintain renal function in the face of greater growth. Since virtually all members of acculturated societies share in the modern lifestyle, the demands imposed by accelerated growth and development result in a populational shift to higher blood pressures, with a consequent increase in the prevalence of hypertension. We propose that hypertension is the product of maladaptation of highly genetically conserved mechanisms subserving important biological homeostatic needs. Elucidation of the mechanisms underlying hypertension will require approaches that examine the developmental processes linking growth to blood pressure. PMID:8039837
Weder, A B; Schork, N J
Background Obstructive sleep apnea syndrome (OSAS) is strongly associated with the increasing prevalence of cerebrovascular events and metabolic syndrome. A growing number of studies have shown OSAS is an independent factor for insulin resistance, glucose intolerance and type2 diabetes. However, relationship of OSAS with dysglycemia is complex and still remains poorly understood. Glucose transporter 4 (GLUT4) gene is Human and rodents’ main glucose transporter sensitive to insulin, and therefore confirmation of candidate gene polymorphisms and association with OSAS is needed. Aim of our study was to assess whether GLUT4 gene polymorphisms are associated with OSAS. Methods Patients hospitalized at People’s Hospital of Xinjiang were selected from January to December 2010. A total of 568 Han subjects who possibly exist OSAS base on a history and physical examination were completed the polysomnography, 412of whom (72.5%) were diagnosed with OSAS, and 156 individuals were confirmed without OSAS (27.5%). 96 severe OSAS patients chosen from OSAS were used for DNA sequencing in functional domain. Blood samples were collected from all subjects and genotyping was performed on DNA extracted from blood cells. Results We performed GLUT4 genome sequencing, found 4 mutated sites. And finally selected three mutated sites such as rs5415, rs4517 and rs5435, according to principle of linkage disequilibrium (r 2 > 0.8) and minimum gene allele frequency > 5%. All SNPs satisfied HEW (P > 0.05). Our study demonstrated a significant association of GLUT4 SNPrs5417 allele with OSAS, compared with controls (P < 0.05). Haplotype H1 (TCC) and H3 (CCC) defined as SNPrs5415, rs4517 and rs5435 are marginally associated with OSAS (P < 0.05). Frequencies of C haplotype of rs5417 in OSAS were higher than in controls. After adjustment for confounding factors, (AC + AA) genotype significantly reduces prevalence of OSAS, compared with CC genotype. Level of awake blood oxygen and lowest blood oxygen of (AA + AC) genotype was significantly superior to those of CC genotype. Conclusions Our study demonstrates GLUT4 gene SNPrs5417 is associated with OSAS in hypertensive population. Carriers of AA + AC have less prevalence of obstructive sleep apnea syndrome than that of CC carriers. PMID:24410986
Chewing of Qat leaves which contain amphetamine alkaloids is a traditional drug practice in the horn of Africa. Cathine and cathinone are responsible for the desired psychogenic (suppression of hunger, mind stimulation, euphoria) and sympathicomimetic effects. In this study, we monitored seven volunteers during a traditional qat ritual. An increase in systolic and diastolic pressure was observed in three patients including one presenting predisposing chronic arterial hypertension. Peak pressure was observed approximately seven hours after beginning the ritual. The three patients presenting pressure changes were not significantly different from the four unaffected patients with regard to age or duration of qat use. These findings suggest that qat use by untreated hypertensive patients who react strongly to vasoconstrictive effects can lead to hypertension and resulting cardiovascular complications. PMID:10088104
Mion, G; Oberti, M; Ali, A W
Low grade inflammation may have a key role in the pathogenesis of hypertension and cardiovascular disease. Several studies showed that both innate and adaptive immune systems may be involved, being T cells the most important players. Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes may be crucial for blood pressure elevation and related organ damage development. In the presence of a mild elevation of blood pressure, neo-antigens are produced. Activated Th1 cells may then contribute to the persistent elevation of blood pressure by affecting vasculature, kidney and perivascular fat. On the other hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role, being their activity crucial for the maintenance of cardiovascular homeostasis. Indeed, Tregs were demonstrated to be able to protect from blood pressure elevation and from the development of organ damage, including micro and macrovascular alterations, in different animal models of genetic or experimental hypertension. In the vasculature, inflammation leads to vascular remodeling through cytokine activity, smooth muscle cell proliferation and oxidative stress. It is also known that a consistent part of ischemia-reperfusion-induced acute kidney injury is mediated by inflammatory infiltration and that Treg cell infusion have a protective role. Also the central nervous system has an important role in the maintenance of cardiovascular homeostasis. In conclusion, hypertension development involves chronic inflammatory process. Knowledge of cellular and molecular players in the progression of hypertension has dramatically improved in the last decade, by assessing the central role of innate and adaptive immunity cells and proinflammatory cytokines driving the development of target organ damage. The new concept of role of immunity, especially implicating T lymphocytes, will eventually allow discovery of new therapeutic targets that may improve outcomes in hypertension and cardiovascular or renal disease in humans and uncover an entirely novel approach in the treatment of hypertension and vascular disease. PMID:24446309
De Ciuceis, Carolina; Rossini, Claudia; La Boria, Elisa; Porteri, Enzo; Petroboni, Beatrice; Gavazzi, Alice; Sarkar, Annamaria; Rosei, Enrico Agabiti; Rizzoni, Damiano
Hypertension is a serious risk factor for myocardial infarction, heart failure, vascular disease, stroke, and renal failure.\\u000a Hypertension affects 50 million Americans with a prevalence rate of 25–30% in the adult Caucasian population. The incidence\\u000a of hypertension and complications resulting from hypertension are even greater in the African-American population. The renin-angiotensin\\u000a system plays an important role in the regulation of
Introduction Contradictory results have been reported on the relationship between orthostatic hypotension (OH) and mild cognitive impairment (MCI). Objective To study the incidence of MCI and dementia and their relationship to OH and subclinical OH with orthostatic symptoms (orthostatic intolerance). Study design and setting This study used a prospective general population cohort design and was based on data from the Swedish Good Aging in Skåne study (GÅS-SNAC), they were studied 6 years after baseline of the present study, with the same study protocol at baseline and at follow-up. The study sample comprised 1,480 randomly invited subjects aged 60 to 93 years, and had a participation rate of 82% at follow-up. OH test included assessment of blood pressure and symptoms of OH. Results The 6-year incidence of MCI was 8%, increasing from 12.1 to 40.5 per 1,000 person-years for men and 6.9 to 16.9 per 1,000 person-years for women aged 60 to >80 years. The corresponding 6-year incidence of dementia was 8%. Orthostatic intolerance during uprising was related to risk for MCI at follow-up (odds ratio [OR] =1.84 [1.20–2.80][95% CI]), adjusted for age and education independently of blood pressure during testing. After stratification for hypertension (HT), the corresponding age-adjusted OR for MCI in the non-HT group was 1.71 (1.10–2.31) and 1.76 (1.11–2.13) in the HT group. Among controls, the proportion of those with OH was 16%; those with MCI 24%; and those with dementia 31% (age-adjusted OR 1.93 [1.19–3.14]). Conclusion Not only OH, but also symptoms of OH, seem to be a risk factor for cognitive decline and should be considered in the management of blood pressure among the elderly population.
Elmståhl, Sölve; Widerström, Elisabet
Introduction: Patients may fail oral overactive bladder therapies due to either poor drug efficacy or intolerability. We determined if the success of sacral neuromodulation varies if performed secondary to lack of anticholinergic efficacy versus drug intolerability. Methods: A retrospective review was performed on 152 patients undergoing staged sacral neuromodulation from 2004 to 2010 for refractory idiopathic detrusor overactivity with or without urge incontinence. Outcomes following sacral neuromodulation trials were compared based on the primary indication for anticholinergic failure: lack of drug efficacy versus intolerable side effects. Results: Overall, successful sacral neuromodulation trials were reported in 70% (106/152) of patients. Successful outcomes were noted in 70% (89/128) and 71% (17/24) of patients with poor anti-cholinergic efficacy and drug intolerability, respectively (p = NS). Conclusions: We found no significant difference in outcome success in patients undergoing sacral neuromodulation trials for refractory detrusor overactivity due to lack of anticholinergic efficacy versus intolerability. PMID:23069697
Davis, Tanya; Makovey, Iryna; Guralnick, Michael L.; O'Connor, R. Corey
Hypertension in pregnancy is an emerging sex-specific risk factor for cardiovascular disease and may lead to more severe hypertension after pregnancy. The objectives of this study were to investigate the frequency of pregnancy-related hypertension among patients referred to a hypertension clinic and its association with the severity of hypertension and evidence of end-organ damage. In this cross-sectional study, women with hypertension were submitted to a systematic clinical evaluation. The occurrence of pregnancy-related hypertension was investigated by questionnaire. The association between pregnancy-related hypertension and severity of hypertension (stage 2 according to Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII)) and end-organ damage was assessed in a logistic regression model. The mean age, systolic and diastolic blood pressure and body mass index (BMI) of the 768 women examined were 51.6+/-12.7 years, 158.2+/-26.6 mm Hg, 93.8+/-14.3 mm Hg and 29.4+/-5.6 kg/m(2), respectively. The proportion of women with pregnancy-related hypertension was 32.9%. It was significantly associated with hypertension at stage 2 (OR: 1.60, 95% CI: 1.14-2.24; P=0.01) after controlling for confounders. The occurrence of a pregnancy-related hypertension was not associated with evidence of optic fundi abnormalities, left ventricular hypertrophy or abnormalities in kidney function. In conclusion, pregnancy-related hypertension is frequent in women referred to a hypertension clinic, and is associated with severe hypertension but not with evidence of end-organ damage. PMID:19020534
Moreira, L B; Gus, M; Nunes, G; Gonçalves, C B C; Martins, J; Wiehe, M; Fuchs, F D
Background: Type 2 diabetes is characterized by glucose intolerance and insulin resistance. Obesity is the leading cause of type 2 diabetes. Growing evidence suggests that chronic exposure to inorganic arsenic (iAs) also produces symptoms consistent with diabetes. Thus, iAs exposure may further increase the risk of diabetes in obese individuals. Objectives: Our goal was to characterize diabetogenic effects of iAs exposure and high-fat diet (HFD) in weaned C57BL/6 mice. Methods: Mice were fed HFD or low-fat diet (LFD) while exposed to iAs in drinking water (25 or 50 ppm As) for 20 weeks; control HFD and LFD mice drank deionized water. Body mass and adiposity were monitored throughout the study. We measured glucose and insulin levels in fasting blood and in blood collected during oral glucose tolerance tests (OGTT) to evaluate the diabetogenic effects of the treatment. Results: Control mice fed HFD accumulated more fat, had higher fasting blood glucose, and were more insulin resistant than were control LFD mice. However, these diabetes indicators decreased with iAs intake in a dose-dependent manner. OGTT showed impaired glucose tolerance for both control and iAs-treated HFD mice compared with respective LFD mice. Notably, glucose intolerance was more pronounced in HFD mice treated with iAs despite a significant decrease in adiposity, fasting blood glucose, and insulin resistance. Conclusions: Our data suggest that iAs exposure acts synergistically with HFD-induced obesity in producing glucose intolerance. However, mechanisms of the diabetogenic effects of iAs exposure may differ from the mechanisms associated with the obesity-induced type 2 diabetes. PMID:21592922
Paul, David S.; Walton, Felecia S.; Saunders, R. Jesse
Catch-up growth, a risk factor for type 2 diabetes, is characterized by hyperinsulinemia and accelerated body fat recovery. Using a rat model of semistarvation-refeeding that exhibits catch-up fat, we previously reported that during refeeding on a low-fat diet, glucose tolerance is normal but insulin-dependent glucose utilization is decreased in skeletal muscle and increased in adipose tissue, where de novo lipogenic capacity is concomitantly enhanced. Here we report that isocaloric refeeding on a high-fat (HF) diet blunts the enhanced in vivo insulin-dependent glucose utilization for de novo lipogenesis (DNL) in adipose tissue. These are shown to be early events of catch-up growth that are independent of hyperphagia and precede the development of overt adipocyte hypertrophy, adipose tissue inflammation, or defective insulin signaling. These results suggest a role for enhanced DNL as a glucose sink in regulating glycemia during catch-up growth, which is blunted by exposure to an HF diet, thereby contributing, together with skeletal muscle insulin resistance, to the development of glucose intolerance. Our findings are presented as an extension of the Randle cycle hypothesis, whereby the suppression of DNL constitutes a mechanism by which dietary lipids antagonize glucose utilization for storage as triglycerides in adipose tissue, thereby impairing glucose homeostasis during catch-up growth. PMID:22961086
Marcelino, Helena; Veyrat-Durebex, Christelle; Summermatter, Serge; Sarafian, Delphine; Miles-Chan, Jennifer; Arsenijevic, Denis; Zani, Fabio; Montani, Jean-Pierre; Seydoux, Josiane; Solinas, Giovanni; Rohner-Jeanrenaud, Francoise; Dulloo, Abdul G.
Uroguanylin is a gastrointestinal hormone primarily involved in fluid and electrolyte handling. It has recently been reported that prouroguanylin, secreted postprandially, is converted to uroguanylin in the brain and activates the receptor guanylate cyclase-C (GC-C) to reduce food intake and prevent obesity. We tested central nervous system administration of two GC-C agonists and found no significant reduction of food intake. We also carefully phenotyped mice lacking the GC-C receptor and found them to have normal body weight, adiposity, and glucose tolerance. Interestingly, uroguanylin knockout mice had a small but significant increase in body weight and adiposity that was accompanied by glucose intolerance. Our data indicate that the modest effects of uroguanylin on energy and glucose homeostasis are not mediated by central GC-C receptors. PMID:24898144
Begg, Denovan P; Steinbrecher, Kris A; Mul, Joram D; Chambers, Adam P; Kohli, Rohit; Haller, April; Cohen, Mitchell B; Woods, Stephen C; Seeley, Randy J
This gene on chromosome 2 codes for the enzyme lactase. This enzyme enables infants to break down lactose, the main sugar in milk. In people who are lactose tolerant, the gene remains active throughout their lives. In most people who are lactose intolerant, the gene is turned off after infancy, making the digestion of dairy products difficult and painful.
We report on a female patient affected by galactosemia in whom the diagnosis was obscured by the concomitant presence of manifestations suggesting a cow’s milk intolerance. This case exemplifies the problems in reaching a correct diagnosis in patients with metabolic diseases. PMID:22992216
This study investigates the negative reactions of Dutch viewers to the content of television programs. The results show that a vast majority is sometimes irritated by TV programs, that a somewhat smaller majority is sometimes shocked by the programs, and that one fifth of the viewing population consider certain programs to be intolerable. The most frequently mentioned genres are games,
Ard Heuvelman; Allerd Peeters
A study of institutional responses to incidents of intolerance on college and university campuses was conducted. A questionnaire was sent to the deans of student affairs and student newspaper editors at 128 four-year colleges and universities; and interviews were conducted with administrators, students, faculty, and staff from 58 institutions, 11…
People for the American Way, Washington, DC.
This study examined the factor structure of the English version of the Intolerance of Uncertainty Scale (IUS; French version: M. H. Freeston, J. Rheaume, H. Letarte, M. J. Dugas, & R. Ladouceur, 1994; English version: K. Buhr & M. J. Dugas, 2002) using a substantially larger sample than has been used in previous studies. Nonclinical undergraduate…
Sexton, Kathryn A.; Dugas, Michel J.
In young infants the clinical and investigative features of coeliac disease (CD) may be mimicked by other conditions such as cow's milk intolerance or secondary disaccharidase deficiency. It is therefore especially important to confirm a diagnosis of CD by later gluten challenge in such infants. Sixteen children in whom the diagnosis of CD had been made before the age of
C J Rolles; M Anderson; A S McNeish
Abstract Submission for ESPGHAN Update 2012 Immunology including Food Allergy and Intolerance this abstract previously been presented or published?: No Objectives and Study: Allergy afflicts one third signs that a child may be at risk of developing allergies. Methods: To this end, we recruited a cohort
Postflight orthostatic intolerance was identified as a serious biomedical problem associated with long duration exposure to microgravity in space. High priority was given to the development of countermeasures for this disorder which are both effective and practical. A considerable body of clinical research demonstrated that people can be taught to increase their own blood pressure voluntarily and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The present pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, Autogenic-Feedback Training (AFT), three men and two women participated in four to nine (15-30 training sessions). At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures that the subjects made, ranged between 20 and 5O mmHg under both supine and 45 deg head-up tilt conditions. These findings suggest that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Further, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.
Cowings, Patricia S.; Toscano, William B.; Miller, Neil E.; Pickering, Thomas G.; Shapiro, David
Postflight orthostatic intolerance has been identified as a serious biomedical problem associated with long-duration exposure to microgravity in space. High priority has been given to the development of countermeasures for this disorder that are both effective and practical. A considerable body of clinical research has demonstrated that people can be taught to increase their own blood pressure voluntarily, and that this is an effective treatment for chronic orthostatic intolerance in paralyzed patients. The current pilot study was designed to examine the feasibility of adding training in control of blood pressure to an existing preflight training program designed to facilitate astronaut adaptation to microgravity. Using an operant conditioning procedure, autogenic-feedback training (AFT), three men and two women participated in four to nine training (15-30-minute) sessions. At the end of training, the average increase in systolic and diastolic pressure, as well as mean arterial pressures, that the subjects made ranged between 20 and 50 mm Hg under both supine and 45 deg head-up tilt conditions. These findings indicate that AFT may be a useful alternative treatment or supplement to existing approaches for preventing postflight orthostatic intolerance. Furthermore, the use of operant conditioning methods for training cardiovascular responses may contribute to the general understanding of the mechanisms of orthostatic intolerance.
Cowings, P. S.; Toscano, W. B.; Miller, N. E.; Pickering, T. G.; Shapiro, D.; Stevenson, J.; Maloney, S.; Knapp, J.
This article explores some of the unresolved tensions between `universalistic' and `relativistic' approaches in the establishment of standards and strategies designed to prevent or overcome the abuse of children's capacity to work. Global standards (on children's rights, on unacceptable or intolerable forms of children's work, etc.) require universal notions of (ideal, normal or `tolerable') childhood, while cultural relativism stresses the
Marked Exacerbation of Orthostatic Intolerance After Long- vs. Short-Duration Spaceflight-duration spaceflight is about 20%. How- ever, the incidence after long-duration spaceflight was unknown. The purpose-duration (129Â190 days) spaceflights and compared these data with data obtained during stand tests before
Even after short spaceflights, most astronauts experience at least some postflight reduction of orthostatic tolerance; this problem is severe in some subjects. The mechanisms leading to postflight orthostatic intolerance are not well-established, but have traditionally been thought to include the following: changes in leg hemodynamics, alterations in baroreceptor reflex gain, decreases in exercise tolerance and aerobic fitness, hypovolemia, and altered
B. J Yates; I. A Kerman
The link between religion and political tolerance in the United States, which has focused predominantly on Christianity, is replete with unfavorable images. Often, religious adherents (largely Evangelicals or the Christian right) are characterized as uneducated, poor, and white, suggesting that members of these groups may act in an intolerant…
Eisenstein, Marie A.; Clark, April K.
The Dietary Approaches to Stop Hypertension (DASH) trial showed that a diet rich in fruits, vegetables, low-fat dairy products with reduced total and saturated fat, cholesterol, and sugar-sweetened products effectively lowers blood pressure in individuals with prehypertension and stage I hypertension. Limited evidence is available on the safety and efficacy of the DASH eating pattern in special patient populations that were excluded from the trial. Caution should be exercised before initiating the DASH diet in patients with chronic kidney disease, chronic liver disease, and those who are prescribed renin-angiotensin-aldosterone system antagonist, but these conditions are not strict contraindications to DASH. Modifications to the DASH diet may be necessary to facilitate its use in patients with chronic heart failure, uncontrolled diabetes mellitus type II, lactose intolerance, and celiac disease. In general, the DASH diet can be adopted by most patient populations and initiated simultaneously with medication therapy and other lifestyle interventions. PMID:22846984
Tyson, Crystal C; Nwankwo, Chinazo; Lin, Pao-Hwa; Svetkey, Laura P
Post space flight orthostatic intolerance among Space Shuttle crew members following exposure to extended periods of microgravity has been of significant concern to the safety of the shuttle program. Following the Challenger accident, flight crews were required to wear launch and entry suits (LES). It was noted that overall, there appeared to be a higher degree of orthostatic intolerance among the post-Challenger crews (approaching 30%). It was hypothesized that the increased heat load incurred when wearing the LES, contributed to an increased degree of orthostatic intolerance, possibly mediated through increased peripheral vasodilatation triggered by the heat load. The use of liquid cooling garments (LCG) beneath the launch and entry suits was gradually implemented among flight crews in an attempt to decrease heat load, increase crew comfort, and hopefully improve orthostatic tolerance during reentry and landing. The hypothesis that the use of the LCG during reentry and landing would decrease the degree of orthostasis has not been previously tested. Operational stand-tests were performed pre and post flight to assess crewmember's cardiovascular system's ability to respond to gravitational stress. Stand test and debrief information were collected and databased for 27 space shuttle missions. 63 crewpersons wearing the LCG, and 70 crewpersons not wearing the LCG were entered into the database for analysis. Of 17 crewmembers who exhibited pre-syncopal symptoms at the R+O analysis, 15 were not wearing the LCG. This corresponds to a 21% rate of postflight orthostatic intolerance among those without the LCG, and a 3% rate for those wearing LCG. There were differences in these individual's average post-flight maximal systolic blood pressure, and lower minimal Systolic Blood pressures in those without LCG. Though other factors, such as type of fluid loading, and exercise have improved concurrently with LCG introduction, from this data analysis, it appears that LCG usage provided a significant degree of protection from post-flight orthostatic intolerance.
Billica, Roger; Kraft, Daniel
A prospective randomised trial was carried out to see whether paranormal healing by laying on of hands might reduce blood pressure in essential hypertension and whether such an effect might be due to a paranormal, psychological, or placebo factor. Patients were randomised to three treatment groups: paranormal healing by laying on of hands (n=40), paranormal healing at a distance (n=37),
Jaap J Beutler; Johannes T M Attevelt; Sybo A Schouten; Joop A J Faber; Evert J Dorhout Mees; Gijsbert G Geijskes
Systemic hypertension is a major risk factor for cardiovascular disease and is present in 69% of patients with a first myocardial infarction, in 77% of patients with a first stroke, in 74% of patients with chronic heart failure, and in 60% of patients with peripheral arterial disease. Double-blind, randomized, placebo-controlled trials have found that antihypertensive drug therapy reduces cardiovascular events in patients aged younger than 80 years and in patients aged 80 years and older in the Hypertension in the Very Elderly Trial. Although the optimal blood pressure treatment goal has not been determined, existing epidemiologic and clinical trial data suggest that a reasonable therapeutic blood pressure goal should be <140/90 mm Hg in patients younger than 80 years and a systolic blood pressure of 140-145 mm Hg if tolerated in patients aged 80 years and older. Non-pharmacologic lifestyle measures should be encouraged both to prevent development of hypertension and as adjunctive therapy in patients with hypertension. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers, calcium channel blockers, and diuretics have all reduced cardiovascular events in randomized trials. The choice of specific drugs depends on efficacy, tolerability, presence of specific comorbidities, and cost. PMID:22937486
Aronow, Wilbert S
Since children as young as seven years old can suffer from hypertension, all children should have blood pressure checked during physical examinations. Guidelines for testing children's blood pressure are presented along with suggestions about what schools and parents can do to help deal with the problem. (PP)
"Hypertension Alert," a 1979-80 blood pressure screening-awareness project of the Yonkers, New York Public Schools, is described. Data is analyzed in tables for ethnic composition, and range of blood pressure readings for the high school, junior high school, and elementary school students tested. (Author/JMK)
Sailors, Emma Lou
Endocrine hypertension is the most common cause of secondary hypertension affecting ~3 % of the population, with primary hyperaldosteronism and pheochromocytoma being the principal conditions. Both diseases share an increased cardiovascular risk in comparison with essential hypertension patients (at the same blood pressure level). This augmented cardiovascular risk as well as the availability of specific treatment emphasize the importance of timely and correct diagnosis. Primary hyperaldosteronism, representing one tenth of hypertensive patients, is an under-diagnosed disease partly because of difficult diagnostic steps and absence of standard criteria. Recently, the description of somatic mutations in KCNJ5 gene in Conn adenomas had precipitated a resurgence of research activity to understand the pathophysiology of this common disease. Research had confirmed the role of these mutations in aldosterone hypersecretion; however, its role in adenoma formation is still to be elucidated. Elsewhere, much remains to be done in order to understand the pathogenesis of bilateral idiopathic hyperaldosteronism, the other common subtype of primary hyperaldosteronism. In pheochromocytoma, the revolution of genetics has led to major advances in the characterization of this rare disease. It is now clear that up to 50 % of patients with pheochromocytoma have a genetic abnormality and that different pheochromocytomas segregate into two clusters with distinct genotypes, signal transduction pathways and expression of biomarkers (phenotype). This continuing progress has huge effects on patient's management and follow-up. In this article we will shed light on the recent developments in both diseases with emphasis on their role in patient care. PMID:23089379
Al-Salameh, A; Cohen, R; Chanson, P; Plouin, P F
AT1 Receptors vasoconstriction Na Retention BP & end organ damage Drugs used to block RAS renin;Pablo Ortiz: Trafficking of the Na/K/2 Cl cotransporter and changes caused by hypertension AVP c: Mechanism by which Ac-SDKP prevents end organ damage and identifying its receptor #12;Suresh Palaniyandi
\\u000a Sleep disordered breathing (SDB) encompasses all forms of respiratory disorders specific to sleep (1). There is a spectrum of SDB ranging from mild to severe with the most severe form being obstructive sleep apnea (OSA) (2). In adults, OSA has been linked to cardiovascular disease, specifically hypertension (HTN) (3). The association between systemic HTN and OSA is well documented in
Alisa A. Acosta
Antihypertensive treatment, by lowering blood pressure and correcting functional and/or structural abnormalities of the arterial wall, may prevent the arterial damage due to the accelerated ageing process. The objective of the present study was to determine, using a cross-sectional approach, whether arterial distensibility of patients whose blood pressure had been normalized for several months by antihypertensive treatment, was significantly higher than that of untreated hypertensive patients. The properties of the vessel wall of the common carotid artery (CCA) were studied non-invasively, using an original pulsed ultrasound echo-tracking system based on Doppler shift, during a study comparing 46 normotensive subjects and 81 age-matched hypertensive patients. The latter group included 25 patients well controlled by antihypertensive treatment for at least 3 months and 56 untreated hypertensives. The three groups did not differ with respect to age, total and high-density lipoprotein cholesterol, blood glucose and smoking. In each group, there were significant relationships between age and CCA dimensional and functional data, including end-diastolic diameter, absolute and relative stroke changes in diameter and Peterson modulus, indicating a widening of the CCA with advancing age and a decrease in its buffering function. When compared with untreated hypertensives, well controlled hypertensives had significantly lower blood pressure and Peterson elastic modulus according to age. However, although blood pressure of well controlled hypertensives was not significantly different from that of normotensive subjects, their arterial distensibility remained altered compared with that of normotensive subjects (significant increase in Peterson elastic modulus). These results suggest that long-term antihypertensive treatment may not fully reverse arterial lesions due to the hypertensive disease. PMID:1658137
Arcaro, G; Laurent, S; Jondeau, G; Hoeks, A P; Safar, M E
The economic aspects of hypertension are critical to modern medicine. The medical, economic, and human costs of untreated and inadequately controlled hypertension are enormous. Hypertension is distributed unequally and with iniquity in different countries and regions of the world. Treatment of hypertension requires an investment over many years to prolong disease-free quality years of life. The high prevalence and high cost of the disease impacts on the microeconomics and macroeconomics of countries and regions. The criteria used for inclusion in clinical guidelines for hypertension impact on the cost and cost/utility of diagnosis or treatment. PMID:19124418
Alcocer, Luis; Cueto, Liliana
Glucocorticoid excess frequently results in obesity, insu- lin resistance, glucose intolerance, and hypertension in the regulation of adipocyte gene expression. Key words: glucocorticoids, adipogenesis, adipocytes Introduction. Tissue sensitivity to glucocorticoids is regulated by the expression of glucocorticoid receptor (GR)1
Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.
Ingrahm, Lonnie O. (Gainesville, FL); Snoep, Jacob L. (Groede, NL); Arfman, Nico (Delft, NL)
Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index (DIOGTT) that is a measure of pancreatic ?-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity (SI OGTT) was calculated using a novel multiple-regression model derived from insulin sensitivity measured by hyperinsulinemic euglycemic clamp as the independent variable. We also validated the novel SI OGTT in n = 40 subjects from an independent data set. Plasma C-peptide responses during OGTT were used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P < 0.0001) and that insulin sensitivity was lowest in subjects with impaired glucose tolerance and type 2 diabetes. GSISOGTT demonstrated a significant inverse relationship with SI OGTT. GSISOGTT was lowest in normal glucose-tolerant subjects and greatest in those with impaired glucose tolerance. DIOGTT was sequentially lower with advancing glucose intolerance. We hereby derive and validate a novel OGTT-derived measurement of insulin sensitivity across the entire glucose tolerance continuum and demonstrate that ?-cell compensation for changing insulin sensitivity can be readily calculated from clinical variables collected during OGTT. PMID:25184989
Solomon, Thomas P J; Malin, Steven K; Karstoft, Kristian; Knudsen, Sine H; Haus, Jacob M; Laye, Matthew J; Pedersen, Maria; Pedersen, Bente K; Kirwan, John P
Although glucose is metabolically the most important carbohydrate in almost all living organisms, still little is known about the evolution of the hormonal control of cellular glucose uptake. In this study, we identify Phe-Met-Arg-Phe-amide (FMRFa), also known as molluscan cardioexcitatory tetrapeptide, as a glucose-lowering hormone in the snail Helix aspersa. FMRFa belongs to an evolutionarily conserved neuropeptide family and is involved in the neuron-to-muscle signal transmission in the snail digestive system. This study shows that, beyond this function, FMRFa also has glucose-lowering activity. We found neuronal transcription of genes encoding FMRFa and its receptor and moreover the hemolymph FMRFa levels were peaking at metabolically active periods of the snails. In turn, hypometabolism of the dormant periods was associated with abolished FMRFa production. In the absence of FMRFa, the midintestinal gland ("hepatopancreas") cells were deficient in their glucose uptake, contributing to the development of glucose intolerance. Exogenous FMRFa restored the absorption of hemolymph glucose by the midintestinal gland cells and improved glucose tolerance in dormant snails. We show that FMRFa was released to the hemolymph in response to glucose challenge. FMRFa-containing nerve terminals reach the interstitial sinusoids between the chondroid cells in the artery walls. We propose that, in addition to the known sites of possible FMRFa secretion, these perivascular sinusoids serve as neurohemal organs and allow FMRFa release. This study suggests that in evolution, not only the insulin-like peptides have adopted the ability to increase cellular glucose uptake and can act as hypoglycemic hormones. PMID:25096715
R?szer, Tamás; Kiss-Tóth, Eva D
In a double-blind, crossover study mildly hypertensive men were given placebo, atenolol (50 and 100 mg 3 times a day), and propranolol (40 and 80 mg 3 times a day), each for 1 wk. Changes in blood pressure, heart rate, arterial blood gases, electrolytes, glucose, lactate, and plasma renin activity (PRA) during bicycle exercise with step-wise increases in work load
Frans H H Leenen; Cees H M Coenen; Maria Zonderland; Anton H J Maas
The impact of insulin sensitivity, casual blood pressure and 24-h ambulatory blood pressure on endothelial function was studied in treated hypertensive subjects. Flow-mediated dilatation of the brachial artery after reperfusion was used to determine endothelial function. Insulin sensitivity indices were obtained by using the homeostasis model assessment, after 75 g Dextrose oral glucose tolerance tests (Matsuda index) and the euglycemic
T Konrad; S Franke; F Schneider; F Bär; G Vetter; K Winkler
Patients with chronic kidney disease are often insulin resistant and glucose intolerant--abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end-stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analog, changes glucose tolerance in earlier stages of chronic kidney disease. In a crossover design, 22 nondiabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose of 100-125 mg/dl were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in nondiabetic patients with stage 3-4 chronic kidney disease. PMID:22913981
de Boer, Ian H; Sachs, Michael; Hoofnagle, Andrew N; Utzschneider, Kristina M; Kahn, Steven E; Kestenbaum, Bryan; Himmelfarb, Jonathan
Chemerin is an adipose-derived signaling protein (adipokine) that regulates adipocyte differentiation and function, immune function, metabolism, and glucose homeostasis through activation of chemokine-like receptor 1 (CMKLR1). A second chemerin receptor, G protein-coupled receptor 1 (GPR1) in mammals, binds chemerin with an affinity similar to CMKLR1; however, the function of GPR1 in mammals is essentially unknown. Herein, we report that expression of murine Gpr1 mRNA is high in brown adipose tissue and white adipose tissue (WAT) and skeletal muscle. In contrast to chemerin (Rarres2) and Cmklr1, Gpr1 expression predominates in the non-adipocyte stromal vascular fraction of WAT. Heterozygous and homozygous Gpr1-knockout mice fed on a high-fat diet developed more severe glucose intolerance than WT mice despite having no difference in body weight, adiposity, or energy expenditure. Moreover, mice lacking Gpr1 exhibited reduced glucose-stimulated insulin levels and elevated glucose levels in a pyruvate tolerance test. This study is the first, to our knowledge, to report the effects of Gpr1 deficiency on adiposity, energy balance, and glucose homeostasis in vivo. Moreover, these novel results demonstrate that GPR1 is an active chemerin receptor that contributes to the regulation of glucose homeostasis during obesity. PMID:24895415
Rourke, Jillian L; Muruganandan, Shanmugam; Dranse, Helen J; McMullen, Nichole M; Sinal, Christopher J
Patients with chronic kidney disease are often insulin resistant and glucose intolerant; abnormalities that promote cardiovascular disease. Administration of 1,25-dihydroxyvitamin D (calcitriol) has improved glucose metabolism in patients with end stage renal disease. We conducted a randomized, placebo-controlled clinical trial to test whether paricalcitol, a 1,25-dihydroxyvitamin D analogue, changes glucose tolerance in earlier stages of chronic kidney disease. In a cross-over design, 22 non-diabetic patients with estimated glomerular filtration rates of stage 3-4 chronic kidney disease and fasting plasma glucose 100-125 mg/dL were given daily oral paricalcitol for 8 weeks and matching placebo for 8 weeks, separated by an 8-week washout period. The order of interventions was random and blinded to both participants and investigators. Paricalcitol significantly reduced serum concentrations of parathyroid hormone, 1,25-dihydroxyvitamin D, and 25-hydroxyvitamin D while significantly increasing serum concentrations of fibroblast growth factor-23 and 24,25-dihydroxyvitamin D. Paricalcitol, however, had no significant effect on glucose tolerance (the primary outcome measure), insulin sensitivity, beta-cell insulin response, plasma free fatty acid suppression, or urinary F2-isoprostane excretion. Thus, despite substantial effects on vitamin D metabolism, paricalcitol did not improve glucose metabolism in non-diabetic patients with stage 3-4 chronic kidney disease. PMID:22913981
de Boer, Ian H.; Sachs, Michael; Hoofnagle, Andrew N.; Utzschneider, Kristina M.; Kahn, Steven E.; Kestenbaum, Bryan; Himmelfarb, Jonathan
This review aims to clarify novel concepts regarding the clinical and laboratory aspects of white-coat hypertension (WCHT). Recent studies on the clinical and biological implications of WCHT were compared with existing knowledge. Studies were included if the WCHT patients were defined according to the 2013 European Society of Hypertension guidelines, i.e., an office blood pressure (BP) of ? 140/90 mmHg, a home BP of ? 135/85 mmHg, and a mean 24-h ambulatory BP of ? 130/80 mmHg. WCHT studies published since 2000 were selected, although a few studies performed before 2000 were used for comparative purposes. True WCHT was defined as normal ABPM and home BP readings, and partial WCHT was defined as an abnormality in one of these two readings. The reported prevalence of WCHT was 15%-45%. The incidence of WCHT tended to be higher in females and in non-smokers. Compared with normotensive (NT) patients, WCHT was associated with a higher left ventricular mass index, higher lipid levels, impaired fasting glucose, and decreased arterial compliance. The circadian rhythm in WCHT patients was more variable than in NT patient’s, with a higher pulse pressure and non-dipping characteristics. Compared with sustained hypertension patients, WCHT patients have a better 10-year prognosis; compared with NT patients, WCHT patients have a similar stroke risk, but receive more frequent drug treatment. There are conflicting results regarding WCHT and markers of endothelial damage, oxidative stress and inflammation, and the data imply that WCHT patients may have a worse prognosis. Nitric oxide levels are lower, and oxidative stress parameters are higher in WCHT patients than in NT patients, whereas the antioxidant capacity is lower in WCHT patients than in NT patients. Clinicians should be aware of the risk factors associated with WCHT and patients should be closely monitored especially to identify target organ damage and metabolic syndrome. PMID:25332913
Sipahioglu, Nurver Turfaner; Sipahioglu, Fikret
AbstractObjectives: To investigate and quantify the extent to which variations in guidelines influence assessment of control of hypertension.Design: Cross sectional study. Selected patients had hypertension assessed as controlled or uncontrolled with guidelines from New Zealand, Canada, the United States, Britain, and the World Health Organisation.Setting: 18 general practices in Oxfordshire.Subjects: 876 patients with diagnosed hypertension and taking antihypertensive drugs.Main outcome
T P Fahey; T J Peters
The controversial effects of dietary fiber on symptoms in functional gastrointestinal disorders are summarized. Studies concerning adverse reaction to foods are mentioned and the possible role of food allergy and food intolerances, especially pseudoallergic reactions to biogenes amines, in symptom provocation is discussed. The known effects of lactose deficiency and fructose malabsorption are reviewed. The FODMAP concept (fermentable oligo-, di-, monosaccharides and polyols) is presented in more detail and recent studies on pathophysiological effects of FODMAP constituents and of therapeutic effects of a low FODMAP diet on symptoms in patients with irritable bowel syndrome are discussed. Finally, studies on the new disorder non-celiac gluten sensitivity (NCGS) are summarized and the state of the discussion whether wheat intolerance is due to gluten or the grains is given. PMID:25390215
We compared the microbiological and chemical composition of dental plaque from subjects with hereditary fructose intolerance who restrict their dietary sugar intake with that of control subjects who do not. The two groups showed no significant differences in chemical composition of plaque: the mean protein, carbohydrate, calcium, magnesium, and phosphate contents were similar. Dental plaque from both groups contained similar numbers of total colony-forming units per microgram of plaque protein, and Streptococcus sanguis, an indigenous nonpathogen, was isolated with equal frequency from plaque samples of both groups. However, potentially odontopathic Streptococcus mutans and Lactobacillus were isolated three to four times more frequently from plaque samples of control subjects than from plaque samples of subjects with hereditary fructose intolerance. Clearly, diet (sucrose in particular) influences the colonization and multiplication of specific cariogenic organisms in dental plaque. PMID:7399699
Hoover, C I; Newbrun, E; Mettraux, G; Graf, H
The clinical and laboratory features of 68 children with food intolerance or food allergy are reviewed. Young children were affected the most with 79% first experiencing symptoms before age 1 year. Forty-eight (70%) children presented with gastrointestinal symptoms (vomiting, diarrhoea, colic, abdominal pain, failure to thrive), 16 (24%) children with skin manifestations (eczema, urticaria, angioneurotic oedema, other rashes), and 4 (6%) children with wheeze. Twenty-one children had failed to thrive before diagnosis. A single food (most commonly cows' milk) was concerned in 28 (41%) cases. Forty (59%) children had multiple food intolerance or allergy; eggs, cows' milk, and wheat were the most common. Diagnosis was based on observing the effect of food withdrawal and of subsequent rechallenge. In many children food withdrawal will mean the use of an elimination diet which requires careful supervision by a dietician. Laboratory investigations were often unhelpful in suggesting or confirming the diagnosis. PMID:7138062
Minford, A M; MacDonald, A; Littlewood, J M
Celiac disease (CD) is a gluten-dependent immune-mediated disease with a prevalence in the general population estimated between 0.3% and 1.2%. Large-scale epidemiological studies have shown that only 10-20% of cases of CD are identified on the basis of clinical findings and that laboratory tests are crucial to identify subjects with subtle or atypical symptoms. The correct choice and clinical use of these diagnostic tools may enable accurate diagnosis and early recognition of silent CD cases. In this review, we have considered some relevant aspects related to the laboratory diagnosis of CD and, more extensively, of gluten intolerance, such as the best combination of tests for early and accurate diagnosis, the diagnostic role of new tests for detecting antibodies against neoepitopes produced by the transglutaminase-gliadin complex, the forms of non-celiac gluten intolerance (gluten sensitivity), and the use and significance of measuring cytokines in CD. PMID:21181303
Bizzaro, N; Tozzoli, R; Villalta, D; Fabris, M; Tonutti, E
Frustration intolerance beliefs are central to the theory and practice of Rational Emotive Behavior Therapy. However, there\\u000a has been little investigation of the content of these beliefs, and empirical evidence linking specific beliefs to distinct\\u000a psychological problems is sparse. To redress this, the Frustration–Discomfort Scale has been developed as a multidimensional\\u000a measure. This was used to explore the relationship between
Genetic differences in HLA phenotypes were studied in coeliac disease to investigate why some patients do not react with mucosal damage after gluten challenge. Forty five children with coeliac disease and 16 with transitory gluten intolerance were typed; 76 subjects served as controls. HLA phenotypes in children with coeliac disease had significantly higher proportions of DR3\\/X and DR5\\/7 than controls
R Meuli; W J Pichler; H Gaze; M J Lentze
PURPOSE This pilot study aimed to determine whether raw milk reduces lactose malabsorption and/or lactose intolerance symptoms relative to pasteurized milk. METHODS We performed a crossover trial involving 16 adults with self-reported lactose intolerance and lactose malabsorption confirmed by hydrogen (H2) breath testing. Participants underwent 3, 8-day milk phases (raw vs 2 controls: pasteurized, soy) in randomized order separated by 1-week washout periods. On days 1 and 8 of each phase, milk consumption was 473 mL (16 oz); on days 2 to 7, milk dosage increased daily by 118 mL (4 oz), beginning with 118 mL (4 oz) on day 2 and reaching 710 mL (24 oz) on day 7. Outcomes were area under the breath H2 curve (AUC ?H2) and self-reported symptom severity (visual analog scales: flatulence/gas, audible bowel sounds, abdominal cramping, diarrhea). RESULTS AUC ?H2 (mean ± standard error of the mean) was higher for raw vs pasteurized on day 1 (113 ± 21 vs 71 ± 12 ppm·min·10?2, respectively, P = .01) but not day 8 (72 ± 14 vs 74 ± 15 ppm·min·10?2, respectively, P = .9). Symptom severities were not different for raw vs pasteurized on day 7 with the highest dosage (P >.7). AUC ?H2 and symptom severities were higher for both dairy milks compared with soy milk. CONCLUSIONS Raw milk failed to reduce lactose malabsorption or lactose intolerance symptoms compared with pasteurized milk among adults positive for lactose malabsorption. These results do not support widespread anecdotal claims that raw milk reduces the symptoms of lactose intolerance. PMID:24615309
Mummah, Sarah; Oelrich, Beibei; Hope, Jessica; Vu, Quyen; Gardner, Christopher D.
Background: Aspirin-intolerant asthma (AIA) is a clinical syndrome characterized by acute bronchoconstriction following the ingestion of aspirin. Solute carrier family 22, member 2 (SLC22A2), also known as organic cation transporter 2 (OCT2), is predominantly expressed in the luminal membrane of airway epithelial cells and has been shown to mediate the transport of prostaglandins on the cyclooxygenase pathway which is regulated
Tae-Joon Park; Jeong-Hyun Kim; Joon-Seol Bae; Byung-Lae Park; Hyun Sub Cheong; Ji-Yong Chun; Jin-Sol Lee; Jason Yongha Kim; Charisse Flerida Pasaje; Sang Heon Cho; Soo-Taek Uh; Mi-Kyeong Kim; Inseon S. Choi; In Song Koh; Choon-Sik Park; Hyoung Doo Shin
Several studies have been conducted to examine whether the construct of intolerance of uncertainty (IU) (Dugas, Gagnon, Ladouceur,\\u000a & Freeston, Behaviour Research and Therapy, 36, 215–226, 1998b) meets formal criteria as a cognitive vulnerability for excessive and uncontrollable worry. Cognitive models\\u000a of anxiety suggest that vulnerability is manifest in the manner in which individuals process information. As such, cognitive\\u000a bias
Naomi Koerner; Michel J. Dugas
An effective treatment for children with refractory nephrotic syndrome (NS), especially in those with cyclosporine (CsA)-resistant\\u000a or CsA-intolerant NS, has yet to be established. Recently, the efficacy of multidrug therapy consisting of tacrolimus (Tac),\\u000a mycophenolate mofetil (MMF) in combination with prednisolone (PDN) in adult patients with refractory NS has been reported.\\u000a We successfully treated 14 consecutive children with refractory CsA-resistant
Tomomi Aizawa-Yashiro; Kazushi Tsuruga; Shojiro Watanabe; Eishin Oki; Etsuro Ito; Hiroshi Tanaka
Background\\/Aims: This report summarizes the data gathered in four prospective studies of intravenous iron sucrose therapy administered to iron-deficient hemodialysis patients with a history of intolerance to other parenteral iron preparations. Methods: A total of 130 iron dextran- and\\/or sodium ferric gluconate-sensitive patients received intravenous iron sucrose therapy to correct iron deficiency, and\\/or maintain body iron stores. A history of
Chaim Charytan; Michael H. Schwenk; Mourhege M. Al-Saloum; Bruce S. Spinowitz
Objective: To discuss the management and resolution of suckling intolerance in a 6-month-old infant. Clinical Features: A 6-month-old boy with a 412-month history of aversion to suckling was evaluated in a chiropractic office. Static and motion palpation and observation detected an abnormal inward dishing at the occipitoparietal junction, as well as upper cervical (C1-C2) asymmetry and fixation. These indicated the
David P. Holtrop
Portal hypertension, a major hallmark of cirrhosis, is defined as a portal pressure gradient exceeding 5 mm Hg. In portal hypertension, porto-systemic collaterals decompress the portal circulation and give rise to varices. Successful management of portal hypertension and its complications requires knowledge of the underlying pathophysiology, the pertinent anatomy, and the natural history of the collateral circulation, particularly the gastroesophageal varices. PMID:18387376
Toubia, Nagib; Sanyal, Arun J
We conducted this study to observe evidence of portal hypertension in children with visceral leishmaniasis (VL). Eighty-eight\\u000a consecutive cases (50 male) of VL were subjected to ultrasonography. Those with evidence of portal hypertension also underwent\\u000a upper gastrointestinal endoscopy and liver biopsy. Eight patients had portal hypertension as evidenced by dilated caliber\\u000a of portal and splenic veins. Two patients had periportal,
Rajniti Prasad; Utpal Kant Singh; O. P. Mishra; B. P. Jaiswal; Sunil Muthusami
Changes in the epidemiology of pulmonary arterial hypertension (PAH) have resulted from changes in classification schemes and an increased emphasis on diagnosis because of the availability of effective therapies. The terms primary pulmonary hypertension and secondary pulmonary hypertension are considered inappropriate, confusing, and should not be used. Recent registries of patients with PAH have provided improved data regarding prognosis in the era of advanced therapies. PMID:24267294
Taichman, Darren B; Mandel, Jess
We examined whether the altered orthostatic tolerance following 14 days of head-down tilt bed rest (HDBR) was related to inadequate sympathetic outflow or to excessive reductions in cardiac output during a 10- to 15-min head-up tilt (HUT) test. Heart rate, blood pressure (BP, Finapres), muscle sympathetic nerve activity (MSNA, microneurography), and stroke volume blood velocity (SVV, Doppler ultrasound) were assessed during supine 30 degrees (5 min) and 60 degrees (5-10 min) HUT positions in 15 individuals who successfully completed the pre-HDBR test without evidence of orthostatic intolerance. Subjects were classified as being orthostatically tolerant (OT, n = 9) or intolerant (OI, n = 6) following the post-HDBR test. MSNA, BP, and SVV during supine and HUT postures were not altered in the OT group. Hypotension during 60 degrees HUT in the post-bed rest test for the OI group (P < 0.05) was associated with a blunted increase in MSNA (P < 0.05). SVV was reduced following HDBR in the OI group (main effect of HDBR, P < 0.02). The data support the hypothesis that bed rest-induced orthostatic intolerance is related to an inadequate increase in sympathetic discharge that cannot compensate for a greater postural reduction in stroke volume.
Shoemaker, J. K.; Hogeman, C. S.; Sinoway, L. I.
Prolonged exposure to microgravity results in cardiovascular deconditioning which is marked by orthostatic intolerance in the returning astronauts and recovering bed-ridden patients. Recent studies conducted in our laboratories at University of California, Irvine have revealed marked elevation of nitric oxide (NO) production in the kidney, heart, brain, and systemic arteries coupled with significant reduction of NO production in the cerebral arteries of microgravity-adapted animals. We have further demonstrated that the observed alteration of NO metabolism is primarily responsible for the associated cardiovascular deconditioning. Recovery from acute spinal cord injury (SCI) is frequently complicated by orthostatic intolerance that is due to the combined effects of the disruption of efferent sympathetic pathway and cardiovascular deconditioning occasioned by prolonged confinement to bed. In this presentation, I will review the nature of altered NO metabolism and its role in the pathogenesis of microgravity-induced cardiovascular deconditioning. The possible relevance of the new findings to orthostatic intolerance in patients with acute SCI and its potential therapeutic implications will be discussed.
Vaziri, N. D.; Purdy, R. E. (Principal Investigator)
Feed intolerance in the setting of critical illness should be treated promptly given its adverse impact on morbidity and mortality. The technical difficulty of postpyloric feeding tube placement and the morbidities associated with parenteral nutrition prevent these approaches being considered as first-line nutrition. Prokinetic agents are currently the mainstay of therapy for feed intolerance in the critically ill. Current information is limited but suggests that erythromycin or metoclopramide (alone or in combination) are effective in the management of feed intolerance in the critically ill and not associated with significant cardiac, haemodynamic or neurological adverse effects. However, diarrhoea is a very common gastrointestinal side effect, and can occur in up to 49% of patients who receive both erythromycin and metoclopramide. Fortunately, the diarrhoea associated with prokinetic treatments has not been linked to Clostridium difficile infection and settles soon after the drugs are ceased. Therefore, prolonged or prophylactic use of prokinetics should be avoided. If diarrhoea occurs, the drugs should be stopped immediately. To minimize avoidable adverse effects the ongoing need for prokinetic drugs in these patient should be reviewed daily. PMID:25083212
Yi Mei, Swee Lin Chen
Antihistamines are commonly used to treat allergic disease, such as allergic rhinitis, urticaria, and angioedema. Although several previous reports describe hypersensitivity to antihistamines such as cetirizine and hydroxyzine, documented cases of chlorpheniramine hypersensitivity are extremely rare. Here, we report the case of a 45-year-old Korean woman who presented with urticaria after ingesting a cold medication. Over the previous 5 years, she had also experienced a food allergy to crab and shrimp, allergic rhinitis, and repeated urticaria after ingesting cold medication. Provocation with aspirin elicited generalized urticaria. Intravenous chlorpheniramine and methylprednisolone was injected for symptom control, but in fact appeared to aggravate urticaria. A second round of skin and provocation tests for chlorpheniramine and methylprednisolone showed positive results only for chlorpheniramine. She was diagnosed with aspirin intolerance and chlorpheniramine hypersensitivity, and was instructed to avoid these drugs. To date, this is the second of only two cases of chlorpheniramine-induced type I hypersensitivity with aspirin intolerance. Although the relationship between aspirin intolerance and chlorpheniramine-induced type I hypersensitivity is unclear, physicians should be aware of the possibility of urticaria or other allergic reactions in response to antihistamines. PMID:21217928
Kim, Min-Hye; Lee, Sang-Min; Lee, So-Hee; Kwon, Hyouk-Soo; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Kim, You-Young
Numerous molecular abnormalities have been described in pulmonary arterial hypertension (PAH), complicating the translation of candidate therapies to patients because, typically, 1 treatment addresses only 1 abnormality. The realization that in addition to pulmonary artery vascular cells, other tissues and cells are involved in the syndrome of PAH (eg, immune cells, right ventricular cardiomyocytes, skeletal muscle) further complicates the identification of optimal therapeutic targets. Here, we describe a metabolic theory that proposes that many apparently unrelated molecular abnormalities in PAH do have a common denominator; they either cause or promote a mitochondrial suppression (inhibition of glucose oxidation) in pulmonary vascular cells; in turn, the signaling downstream from this mitochondrial suppression can also explain numerous molecular events previously not connected. This integration of signals upstream and downstream of mitochondria has similarities to cancer and can explain many features of the PAH vascular phenotype, including proliferation and apoptosis resistance. This suppression of glucose oxidation (with secondary upregulation of glycolysis) also underlies the abnormalities in extrapulmonary tissues, suggesting a global metabolic disturbance. The metabolic theory places mitochondria at the center stage for our understanding of PAH pathogenesis and for the development of novel diagnostic and therapeutic tools. Current PAH therapies are each addressing 1 abnormality (eg, upregulation of endothelin-1) and were not developed specifically for PAH but for systemic vascular diseases. Compared with the available therapies, mitochondria-targeting therapies have the advantage of addressing multiple molecular abnormalities simultaneously (thus being potentially more effective) and achieving higher specificity because they address PAH-specific biology. PMID:24951764
Paulin, Roxane; Michelakis, Evangelos D
Background Intestinal nutrient absorptive capacity shows a circadian rhythm synchronized with eating patterns. Studies have shown that disrupting these normally coordinated rhythms, e.g. with shift work, may contribute to metabolic disease. While circadian expression of many nutrient transporters has been studied in health, their rhythms in obesity and metabolic disorders is not known. We studied the circadian expression and function of intestinal glucose transporter SGLT1, a major glucose transporter, in a rodent model of obesity and diabetes. Methods We compared obese Zucker Diabetic Fatty (ZDF) rats to lean ZDF littermates. Temporal feeding patterns were assessed, then rats were harvested at Zeitgeber (ZT, ZT0=7am) 3, 9, or 15 to measure insulin resistance, SGLT1 (Sodium glucose co-transporter type 1) mRNA expression and intestinal glucose absorption capacity. Known regulators of SGLT1 expression (intestinal sweet taste receptor T1R2/3; clock genes) were also measured to elucidate underlying mechanisms. Results Both ZDF groups exhibited altered circadian food intake. Obese ZDF rats lost circadian rhythmicity of SGLT1 mRNA expression and functional activity. Lean ZDF rats had glucose levels less than half of the obese rats but were still hyperglycemic. Rhythmicity of mRNA expression was maintained but that of functional glucose uptake was blunted. Circadian rhythms of intestinal clock genes were maintained in both groups while there was no discernible rhythm of intestinal glucose transporter gene GLUT2 expression or of the T1R2 component of the sweet taste receptor in either group. In summary, lean and obese ZDF rats exhibited similar disruptions in circadian feeding pattern. Glucose intolerance was evident in lean rats, but only obese ZDF rats further developed diabetes and exhibited disrupted circadian rhythmicity of both SGLT1 mRNA expression and functional activity. Conclusions Our findings suggest that disrupted circadian feeding rhythms contribute to glucose intolerance, but additional factors (genetics, changes in nutrient sensing/ transport) are needed to lead to full diabetes. PMID:23633155
Bhutta, Hina Y.; Deelman, Tara E.; Ashley, Stanley W.; Rhoads, David B.; Tavakkoli, Ali
Eprosartan is an angiotensin II receptor antagonist (angiotensin II receptor blocker [ARB]) used in the treatment of hypertension. In large, randomized trials, eprosartan (with or without hydrochlorothiazide [HCTZ]) demonstrated superior antihypertensive efficacy to that of placebo and, when administered at comparable dosage regimens, had similar blood pressure-lowering effects to enalapril. Eprosartan was generally well tolerated in clinical trials and had a lower incidence of persistent dry cough than enalapril. Eprosartan has a neutral effect on metabolic parameters, such as serum lipid levels and glucose homeostasis, and a low propensity for pharmacokinetic drug interactions. The use of eprosartan or other ARBs in combination with HCTZ tends to reverse the potassium loss associated with thiazide diuretics. Independent of its antihypertensive effects, eprosartan was associated with improved clinical outcomes (primary composite endpoint of all causes of mortality and all cardiovascular and cerebrovascular events, including all recurrent events) compared with nitrendipine in a randomized, secondary prevention trial in hypertensive patients with previous cerebrovascular events (MOSES trial). Eprosartan also reduced blood pressure and was associated with a modest improvement in cognitive function in a large observational study in patients > or =50 years of age with newly diagnosed hypertension (OSCAR study). In both of these trials, additional antihypertensive therapy, such as HCTZ, was permitted. Therefore, eprosartan is a useful treatment option in the management of a broad range of patients with hypertension, and its use with HCTZ provides a rational combination regimen. PMID:19911859
Plosker, Greg L
Background Arterial hypertension and dyslipidemia are modifiable cardiovascular risk factors. The multiplicative effect of these risk factors may worsen the atherogenic index of an individual. The objective of this study was to determine the pattern and prevalence of dyslipidemia in newly presenting Nigerians with arterial hypertension, as well as determine some of its correlates. Methods This cross-sectional study compared 115 newly presenting, age- and sex-matched individuals with arterial hypertension with 115 normotensive individuals. Fasting lipids, total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose were estimated. Results Patients with arterial hypertension had higher body mass index (t=7.64; P=0.000), TC (t=2.95; P=0.006), and HDL-C (t=?5.18; P=0.000). The most common dyslipidemia was low HDL-C, found in both the hypertensive (44.3%) and normotensive (20.9%) patients. The prevalence of dyslipidemia in hypertensives and controls was 64% and 39%, respectively. In hypertensive patients, TC correlated positively to diastolic blood pressure (r=0.218; P=0.0019). Other positive correlates include LDL-C and age (r=0.217; P=0.020) and fasting plasma glucose (r=0.202; P=0.030) and body mass index (r=0.209; P=0.025). Among normotensive controls, TC correlated positively with LDL-C (r=0.63; P=0.000) but correlated negatively with tri glycerides (r=?0.30; P=0.001). Conclusion Lipid abnormalities are common in newly presenting Nigerians with arterial hypertension. Screening of these risk factors, promotion of healthy lifestyle, and the institution of therapy is desirable to reduce their multiplicative effects. PMID:24348044
Adamu, Umar G; Okuku, George A; Oladele, Clement O; Abdullahi, Aisha; Oduh, Joanah I; Fasae, Abidemi J
Approximately 20% of Space Shuttle astronauts became presyncopal during operational stand and 80deg head-up tilt tests, and the prevalence of orthostatic intolerance increases after longer missions. Greater than 60% of the US astronauts participating in Mir and early International Space Station missions experienced presyncope during post-flight tilt tests, perhaps related to limitations of the exercise hardware that prevented high intensity exercise training until later ISS missions. The objective of this study was to determine whether an intense resistive and aerobic exercise countermeasure program designed to prevent cardiovascular and musculoskeletal deconditioning during 70 d of bed rest (BR), a space flight analog, would protect against post-BR orthostatic intolerance. METHODS Twenty-six subjects were randomly assigned to one of three groups: non-exercise controls (n=11) or one of two exercise groups (ExA, n=8; ExB, n=7). Both ExA and ExB groups performed the same resistive and aerobic exercise countermeasures during BR, but one exercise group received testosterone supplementation while the other received a placebo during BR in a double-blinded fashion. On 3 d/wk, subjects performed lower body resistive exercise and 30 min of continuous aerobic exercise (=75% max heart rate). On the other 3 d/wk, subjects performed only highintensity, interval-style aerobic exercise. Orthostatic intolerance was assessed using a 15-min 80? head-up tilt test performed 2 d (BR-2) before and on the last day of BR (BR70). Plasma volume was measured using carbon monoxide rebreathing on BR-3 and before rising on the first recovery day (BR+0). The code for the exercise groups has not been broken, and results are reported here without group identification. RESULTS Only one subject became presyncopal during tilt testing on BR-2, but 7 of 11 (63%) controls, 3 of 8 (38%) ExA, and 4 of 7 (57%) ExB subjects were presyncopal on BR70. Survival analysis of post-BR tilt tests revealed no differences (p=0.77) between groups. Plasma volume (absolute or relative to body mass index) decreased (p<0.001) from pre to post-BR, with no differences between groups. CONCLUSIONS These preliminary results corroborate previous reports that the performance of a vigorous exercise countermeasure protocol during BR, even with testosterone supplementation, does not protect against orthostatic intolerance or plasma volume loss. Preventing post-BR orthostatic intolerance may require additional countermeasures, such as orthostatic stress during BR or end-of-BR fluid infusion.
Platts, Steven H.; Stenger, Michael B.; Ploutz-Snyder, Lori L.; Lee, Stuart M. C.
Hypertension is an important risk factor for cardiovascular disease and there is increasing evidence that inflammation and abnormal immune responses are involved in the pathogenesis of hypertension. However, the data on the association between specific cytokine concentrations and hypertension are inconsistent. We have evaluated the association between 12 cytokines/growth factors and the presence of different degrees of hypertension, comparing these concentrations to values in a healthy group of subjects. The concentrations of interleukin (IL)-1?, -1?, -2, -4, -6, -8, -10, tumor necrosis factor (TNF-?), interferon-? (IFN-?), monocyte chemoattractant protein (MCP-1), epidermal growth factor, and vascular endothelial growth factor were measured in 155 hypertensive patients and 148 healthy subjects, using EV-3513 cytokine biochip arrays, a competitive chemiluminescence immunoassay. Univariate and multivariate analyses were used to evaluate the association of specific cytokines and growth factors with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertensive subjects had higher serum concentrations of IL-1?, -2, -8, vascular endothelial growth factor, IFN-?, TNF-?, MCP-1, and epidermal growth factor; and lower concentrations of anti-inflammatory cytokine, IL-10 (P < .05), compared with the healthy individuals. The serum concentrations of IL-4, -6, and -1? did not differ between the hypertensive subjects and control group. Univariate and multivariate analyses revealed that IL-1? and IFN-? were independent predictors of a high SBP, while IFN-?, IL-1?, TNF-?, and MCP-1 remained statistically significant for DBP after correction for age, gender, Body mass index, smoking, fasting blood glucose, and triglycerides. There was a significant association between the concentrations of several cytokines and hypertension. These associations may either be related to common underlying factors that cause hypertension and may also be proinflammatory or because these inflammatory cytokines might directly be involved in the etiology of hypertension. PMID:25224864
Mirhafez, Seyed Reza; Mohebati, Mohsen; Feiz Disfani, Mahboobeh; Saberi Karimian, Maryam; Ebrahimi, Mahmoud; Avan, Amir; Eslami, Saied; Pasdar, Alireza; Rooki, Hassan; Esmaeili, Habibollah; Ferns, Gordon A; Ghayour-Mobarhan, Majid
Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)
Langseth, Lillian; Dowd, Judith
Introduction Cardiovascular morbidity and mortality is a major and still unresolved threat to patients with reduced glucose tolerance and Type 2 diabetes mellitus. In epidemiological studies, in non-diabetic subjects, post-prandial glycaemia is positively associated with the risk of diabetes, hypertension and cardiovascular events. If this epidemiological association is causal, Acarbose, which reduces post-prandial blood glucose concentrations, should result in a decrease
T. Kaiser; P. T. Sawicki
A family showing brachydactyly associated with hypertension is reported. The number and location of the involved bones are quite different from the other cases with brachydactyly reported in the literature. Additionally, all our patients have high blood pressure. We believe that the disorder reported here represents a hitherto undescribed entity. It is thought that both hypertension and brachydactyly are transmitted
N. Bilginturan; S. Zileli; S. Karacadag; T. Pirnar
While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…
Trott, Daniel W.; Harrison, David G.
Being overweight or obese has become highly prevalent in Western countries and are rapidly reaching epidemic proportions in the developing world. Obesity-related disorders, such as hypertension and diabetes, are also increasing at an alarming rate. The relationship between obesity, hypertension and insulin resistance is well recognised, but the molecular mechanisms involved remain relatively poorly understood. Adipose tissue plays a key
A. M. Sharma; V. T. Chetty
Importance Individuals with psoriasis are shown to have an elevated risk of hypertension, and anti-hypertensive medications, especially beta-blockers, have been linked to psoriasis development. However, the association of prior existing hypertension and anti-hypertensive medications with risk of incident psoriasis has not been accessed using prospective data. Objective To evaluate the association of hypertension and anti-hypertensive medications with risk of psoriasis based on data from the Nurses’ Health Study (NHS). Design Prospective cohort study (1996–2008). Setting Nurses’ Health Study. Participants A total of 77,728 U.S. women who provided biennially updated data on hypertension and anti-hypertensive medications. Main Outcome and Measure Physician-diagnosed psoriasis. Results We documented a total of 843 incident psoriasis cases during 1,066,339 person-years of follow-up. Compared to normotensive women, women with hypertension duration more than 6 years were at a higher risk of developing psoriasis [HR=1.27, 95% confidence interval (CI), 1.03–1.57]. In stratified analysis, the risk of psoriasis was higher among hypertensive women without medication [HR=1.49, 95% CI, 1.15–1.92] and among hypertensive women with current medication [HR=1.31, 95% CI, 1.10–1.55] when compared to normotensive participants without medication. Compared to women who never used beta-blockers, the multivariate HRs for psoriasis were 1.11 (95% CI, 0.82–1.51) for women who regularly used 1–2 years, 1.06 (95% CI, 0.79–1.40) for 3–5 years, and 1.39 (95% CI, 1.11–1.73) for 6 or more years (P for trend=0.009). There was no association between other individual anti-hypertensive drugs and risk of psoriasis. Conclusions Long-term hypertensive status is associated with an increased risk of psoriasis. Long-term regular use of beta-blockers may also increase the risk of psoriasis. PMID:24990147
Wu, Shaowei; Han, Jiali; Li, Wen-Qing; Qureshi, Abrar A.
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by pulmonary vasoconstriction, pulmonary arterial remodeling, abnormal angiogenesis and impaired right ventricular function. Despite progress in pharmacological therapy, there is still no cure for PAH. The peptide apelin and the G-protein coupled apelin receptor (APLNR) are expressed in several tissues throughout the organism. Apelin is localized in vascular endothelial cells while the APLNR is localized in both endothelial and smooth muscle cells in vessels and in the heart. Apelin is regulated by hypoxia inducible factor -1? and bone morphogenetic protein receptor-2. Patients with PAH have lower levels of plasma-apelin, and decreased apelin expression in pulmonary endothelial cells. Apelin has therefore been proposed as a potential biomarker for PAH. Furthermore, apelin plays a role in angiogenesis and regulates endothelial and smooth muscle cell apoptosis and proliferation complementary and opposite to vascular endothelial growth factor. In the systemic circulation, apelin modulates endothelial nitric oxide synthase (eNOS) expression, induces eNOS-dependent vasodilatation, counteracts angiotensin-II mediated vasoconstriction, and has positive inotropic and cardioprotective effects. Apelin attenuates vasoconstriction in isolated rat pulmonary arteries, and chronic treatment with apelin attenuates the development of pulmonary hypertension in animal models. The existing literature thus renders APLNR an interesting potential new therapeutic target for PH. PMID:22140623
Andersen, Charlotte U.; Hilberg, Ole; Mellemkjær, Søren; Nielsen-Kudsk, Jens E.; Simonsen, U.
Type 2 diabetes mellitus (T2DM) is characterized by the inability of the pancreatic ?-cells to secrete enough insulin to meet the demands of the body. Therefore, research of potential therapeutic approaches to treat T2DM has focused on increasing insulin output from ?-cells or improving systemic sensitivity to circulating insulin. In this study, we examined the role of the A(1) receptor in glucose homeostasis with the use of A(1) receptor knockout mice (A(1)R(-/-)). A(1)R(-/-) mice exhibited superior glucose tolerance compared with wild-type controls. However, glucose-stimulated insulin release, insulin sensitivity, weight gain, and food intake were comparable between the two genotypes. Following a glucose challenge, plasma glucagon levels in wild-type controls decreased, but this was not observed in A(1)R(-/-) mice. In addition, pancreas perfusion with oscillatory glucose levels of 10-min intervals produced a regular pattern of pulsatile insulin release with a 10-min cycling period in wild-type controls and 5 min in A(1)R(-/-) mice. When the mice were fed a high-fat diet (HFD), both genotypes exhibited impaired glucose tolerance and insulin resistance. Increased insulin release was observed in HFD-fed mice in both genotypes, but increased glucagon release was observed only in HFD-fed A(1)R(-/-) mice. In addition, the regular patterns of insulin release following oscillatory glucose perfusion were abolished in HFD-fed mice in both genotypes. In conclusion, A(1) receptors in the pancreas are involved in regulating the temporal patterns of insulin release, which could have implications in the development of glucose intolerance seen in T2DM. PMID:22550063
Yang, Gary K; Fredholm, Bertil B; Kieffer, Timothy J; Kwok, Yin Nam
The metabolism of glucose was examined in several clinical isolates of Neisseria gonorrhoeae. Radiorespirometric studies revealed that growing cells metabolized glucose by a combination on the Entner-Doudoroff and pentose phosphate pathways. A portion of the glyceraldehyde-3-phosphate formed via the Entner-Doudoroff pathway was recycled by conversion to glucose-6-phosphate. Subsequent catabolism of this glucose-6-phosphate by either the Entner-Doudoroff or pentose phosphate pathways yielded CO2 from the original C6 of glucose. Enzyme analyses confirmed the presence of all enzymes of the Entner-Doudoroff, pentose phosphate, and Embden-Meyerhof-Parnas pathways. There was always a high specific activity of glucose-6-phosphate dehydrogenase (EC 18.104.22.168) relative to that of 6-phosphogluconate dehydrogenase (EC 22.214.171.124). The glucose-6-phosphate dehydrogenase utilized either nicotinamide adenine dinucleotide phosphate or nicotinamide adenine dinucleotide as electron acceptor. Acetate was the only detectable nongaseous end product of glucose metabolism. Following the disappearance of glucose, acetate was metabolized by the tricarboxylic acid cycle as evidenced by the preferential oxidation of [1-14C]acetate over that of [2-14C]acetate. When an aerobically grown log-phase culture was subjected to anaerobic conditions, lactate and acetate were formed from glucose. Radiorespirometric studies showed that under these conditions, glucose was dissimilated entirely by the Entner-Doudoroff pathway. Further studies determined that this anaerobic dissimilation of glucose was not growth dependent. PMID:4156358
Morse, Stephen A.; Stein, Stefanie; Hines, James
EMBO open Anchored phosphatases modulate glucose homeostasis Simon A Hinke1 , Manuel F Navedo2 principally controls glucose homeostasis. Nutrient-induced exocytosis of insulin granules from pancreatic b signalling events that facilitate insulin secretion and glucose homeostasis may be set by AKAP150 associated
Scott, John D.
Hypertensive patients often have an unfavorable lipid and glucose profile. The main goal of dietary treatment for these patients is to achieve adequate control of blood pressure and reducing cardiovascular morbidity and mortality. The aim of this study was to evaluate whether the Brazilian Dietary Approach to Break Hypertension (BRADA) based on Dietary Approaches to Stop Hypertension but with both low sodium and glycemic index foods could reduce lipid and glycemic profiles in hypertensive patients who were seeing primary health care providers in a low-income region of Brazil. A randomized study of 206 individuals were followed up for the duration of 6 months. The experimental group received orientation and planned monthly menus from the BRADA diet. In the control group, counseling was based on standard care and mainly focused on salt intake reduction. Differences in all biochemical parameters were compared at the baseline and at the 6-month follow-up period. The mean age was 60.1 (±12.9) years old, and 156 subjects (119 females) completed the study. An intention-to-treat analysis showed that both groups reduced fasting plasma glucose, glycated hemoglobin, total cholesterol, and low-density lipoprotein cholesterol concentrations; however, statistically significant between-group differences were found for these parameters. The mean difference in fasting glucose was -7.0 (P < .01), -0.2 for HbA1c (P < .01), -28.6 for TC (P < .01), and -23.8 for LDL-c (P < .01) for the experimental group compared with the control group. This study showed the efficacy of the BRADA diet to treat hypertension on biochemical parameters tested in a primary health care service setting. PMID:25172379
Lima, Sílvia T R M; Souza, Bárbara S N; França, Ana K T; Salgado, João V; Salgado-Filho, Natalino; Sichieri, Rosely
The food contaminant bisphenol A (BPA) is pointed out as a risk factor in development of food allergy and food intolerance, two adverse food reactions increasing worldwide. We evaluated the consequences of perinatal exposure to low doses of BPA on immune-specific response to the food antigen ovalbumin (OVA) at adulthood. Perinatal exposure to BPA (0.5, 5, or 50 ?g/kg/d) from 15th day of gravidity to pups weaning resulted in an increase of anti-OVA IgG titers at all BPA dosages in OVA-tolerized rats, and at 5 ?g/kg/d in OVA-immunized rats compared to control rats treated with vehicle. In BPA-treated and OVA-tolerized rats, increased anti-OVA IgG titers were associated with higher IFN? secretion by the spleen. This result is in accordance with the increase of activated CD4(+)CD44(high)CD62L(low) T lymphocytes observed in spleen of BPA-exposed rats compared to controls. Finally, when BPA-treated OVA-tolerized rats were orally challenged with OVA, colonic inflammation occurred, with neutrophil infiltration, increased IFN?, and decreased TGF?. We show that perinatal exposure to BPA altered oral tolerance and immunization to dietary antigens (OVA). In summary, the naive immune system of neonate is vulnerable to low doses of BPA that trigger food intolerance later in life.-Menard, S., Guzylack-Piriou, L., Leveque, M., Braniste, V., Lencina, C., Naturel, M., Moussa, L., Sekkal, S., Harkat, C., Gaultier, E., Theodorou, V., Houdeau, E. Food intolerance at adulthood after perinatal exposure to the endocrine disruptor bisphenol A. PMID:25085925
Menard, Sandrine; Guzylack-Piriou, Laurence; Leveque, Mathilde; Braniste, Viorica; Lencina, Corinne; Naturel, Manon; Moussa, Lara; Sekkal, Soraya; Harkat, Cherryl; Gaultier, Eric; Theodorou, Vassilia; Houdeau, Eric
OBJECTIVE: The incidence of postflight orthostatic intolerance after short-duration spaceflight is about 20%. However, the incidence after long-duration spaceflight was unknown. The purpose of this study was to test the hypothesis that orthostatic intolerance is more severe after long-duration than after short-duration flight. METHODS: We performed tilt tests on six astronauts before and after long-duration (129-190 days) spaceflights and compared these data with data obtained during stand tests before and after previous short-duration missions. RESULTS: Five of the six astronauts studied became presyncopal during tilt testing after long-duration flights. Only one had become presyncopal during stand testing after short-duration flights. We also compared the long-duration flight tilt test data to tilt test data from 20 different astronauts who flew on the short-duration Shuttle missions that delivered and recovered the astronauts to and from the Mir Space Station. Five of these 20 astronauts became presyncopal on landing day. Heart rate responses to tilt were no different between astronauts on long-duration flights and astronauts on short-duration flights, but long-duration subjects had lower stroke volumes and cardiac outputs than short-duration presyncopal subjects, suggesting a possible decrease in cardiac contractile function. One subject had subnormal norepinephrine release with upright posture after the long flight but not after the short flight. Plasma volume losses were not greater after long flights. CONCLUSION: Long-duration spaceflight markedly increases orthostatic intolerance, probably with multiple contributing factors.
Meck, J. V.; Reyes, C. J.; Perez, S. A.; Goldberger, A. L.; Ziegler, M. G.
The prevalence of type 2 diabetes mellitus (T2DM) has increased dramatically in the United States over the past 20 years. The American Diabetes Association recommends regular exercise and maintenance of healthy body weight as important in prevention of T2DM, and exercise is also a cornerstone of treatment regimens for persons already diagnosed with T2DM. T2DM most commonly develops via progressive insulin resistance, a state that has been shown to be caused through several pathways, three of which are discussed in this review. First, the accumulation of lipid intermediates in skeletal muscle under conditions of sustained energy surplus can impair insulin signaling downstream of insulin binding to its receptor. Second, several inflammatory mediators have been shown to negatively affect insulin signaling and gene expression of glucose transporters. Third, oxidative stress induces insulin resistance by creating an environment that interferes with insulin signaling in several ways. Exercise can improve insulin sensitivity by opposing each of these three mechanisms of insulin resistance, as well as providing an avenue for muscle glucose uptake that bypasses insulin, and as such, has the capacity to serve as an important preventative measure. Furthermore, in persons with T2DM, the capacity of muscle contraction to stimulate glucose uptake in a manner that is independent of insulin establishes exercise as a powerful "medicine" in its treatment. Exercise, therefore, serves an important role in prevention and treatment of T2DM. PMID:25034542
Aims Whether patients with hypertensive preclinical cardiovascular disease (CVD) are at higher risk of incident diabetes has never been studied. Methods and results We assessed incident diabetes in 4176 hypertensive non-diabetic patients (age 58.7 ± 8.9 years, 58% male) with ?1 year follow-up (median: 3.57 years; inter-quartile range: 2.04–7.25). Left ventricular (LV) hypertrophy (LVH) was defined as LV mass index (LVMi) ?51 g/m2.7. Carotid atherosclerosis (CA) was defined as intima-media thickness >1.5 mm. During follow-up, diabetes developed in 393 patients (9.4%), more frequently in those with than without initial LVH or CA (odds ratio = 1.97 and 1.67, respectively; both P < 0.0001). In the Cox regression, the presence of either initial LVH or CA was associated with higher hazard of diabetes [hazards ratio (HR) = 1.30 and 1.38, respectively; both P = 0.03], independently of the type and number of anti-hypertensive medications, initial systolic blood pressure (P < 0.001), body mass index, fasting glucose, family history of diabetes (all P < 0.0001), and therapy with ?-blockers. The presence of one of the, or both, markers of preclinical CVD increased the chance of incident diabetes by 63 or 64%, respectively (both P < 0.002), independently of significant confounders, a result that was confirmed (HR = 1.70 or 1.93, respectively; both P < 0.0001) using ATPIII metabolic syndrome (HR = 2.73; P < 0.0001) in the Cox model. Conclusion Initial LVH and CA are significant predictors of new onset diabetes in a large population of treated hypertensive patients, independently of initial metabolic profile, anti-hypertensive therapy, and other significant covariates. This sequence may be attributable to risk factors common to preclinical CVD and diabetes, but a vascular origin of diabetes cannot be excluded. PMID:23882068
Izzo, Raffaele; de Simone, Giovanni; Trimarco, Valentina; Gerdts, Eva; Giudice, Renata; Vaccaro, Olga; De Luca, Nicola; Trimarco, Bruno
The paper presents the course of pregnancy delivery and early postpartum period in a 23-year-old woman with lysinuric protein intolerance (LPI). The pregnancy was uneventful and resulted in a caesarean birth to a healthy baby at 37 weeks gestation. Nevertheless, the course of pregnancy in women with LPI is associated with a significantly increased risk of serious complications, including acute hyperammonemia, preeclampsia and postpartum bleeding, as well as fetus intrauterine growth retardation. In many cases, intensive metabolic monitoring and a proper diet with protein limitation and appropriate amino acids supplementation may significantly reduce the risk for both the mother and the newborn. PMID:24032281
Miko?ajek-Bedner, Wioletta; Torbé, Andrzej; Kwiatkowski, Sebastian; Michalczyk, Micha?; Gizewska, Maria; Rokicki, Dariusz; Rzepka, Rafa?; Konstanty-Kurkiewicz, Violetta; Doma?ski, Maciej; Czajka, Ryszard
ABSTRACT: Asthma is characterized by chronic airway inflammation,resulting from overproduction of pro-inflammatory mediators, such as leukotrienes (LT). The authors questioned,the biosynthetic capacity of asthmatic,patients for lipoxins (LX) and 15-epimer lipoxins (15-epi-LX), endogenous regulators of inflammatory respon- ses that inhibit pro-inflammatory,events. Levels of LXA4, 15-epi-LXA4 and LTC4 were determined in 14 clinically cha- racterized aspirin-intolerant asthmatics (AIA), 11 aspirin-tolerant asthmatics (ATA)
M. Sanak; B. D. Levy; C. b. Clish; N. Chiang; K. Gronert; L. Mastalerz; C. n. Serhan; A. Szczeklik
Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human norepinephrine (NE) transporter variants, as well as in diagnostic and therapeutic applications, relating to a human NE transporter polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human NE transporter with regard to the human NE transporter polymorphism, for example, in the context of diagnosing and treating NE transport impairments, and disorders associated with NE transport impairments, such as orthostatic intolerance.
Robertson, David (Inventor); Blakely, Randy D. (Inventor)
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ? 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ? 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2–3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments. PMID:23829793
Over the past two decades, there has been a notable rise in the use of antipsychotic drugs, as they are used to treat an increasing number of neuropsychiatric disorders. This rise has been led predominantly by greater use of the second generation antipsychotic (SGA) drugs, which have a low incidence of neurological side-effects. However, many SGAs cause metabolic dysregulation, including glucose intolerance and insulin resistance, thus increasing the risk of cardiometabolic disorders. The metabolic effects of the novel SGA lurasidone, which was approved by the Food and Drug Administration in 2010, remain largely unknown. As rodent models accurately predict the metabolic effects of SGAs in humans, the aim of the present study was to use sophisticated animal models of glucose tolerance and insulin resistance to measure the metabolic effects of lurasidone. In parallel, we compared the SGA olanzapine, which has established metabolic effects. Adult female rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (10.0 mg/kg, s.c.) and subjected to the glucose tolerance test (GTT). Separate groups of rats were treated with vehicle, lurasidone (0.2, 0.8 or 2.0 mg/kg, s.c.) or olanzapine (1.5 and 15 mg/kg, s.c.) and tested for insulin resistance with the hyperinsulinemic-euglycemic clamp (HIEC). Compared to vehicle treated animals, lurasidone caused mild glucose intolerance in the GTT with a single dose, but there was no effect on insulin resistance in the GTT, measured by HOMA-IR. The HIEC also confirmed no effect of lurasidone on insulin resistance. In contrast, olanzapine demonstrated dose-dependent and potent glucose intolerance, and insulin resistance in both tests. Thus, in preclinical models, lurasidone demonstrates mild metabolic liability compared to existing SGAs such as olanzapine. However, confirmation of these effects in humans with equivalent tests should be confirmed. PMID:25254366
Wu, Claire; Yuen, Jessica; Boyda, Heidi N.; Procyshyn, Ric M.; Wang, Cathy K.; Asiri, Yahya I.; Pang, Catherine C. Y.; Honer, William G.; Barr, Alasdair M.
Accurate diagnosis of pulmonary arterial hypertension can be challenging and often requires a high index of clinical suspicion. Use of a variety of noninvasive tests can help define the population of patients in whom invasive cardiac catheterization should be pursued. An understanding of the historical, physical exam, electrocardiographic, radiographic, and echocardiographic clues in the diagnosis is important. A ventilation-perfusion scan and careful assessment for left-to-right shunting are mandatory to avoid missing reasons for pulmonary hypertension that may require nonpharmacologic management. Right heart, and sometimes concomitant left heart, catheterization is required to establish the diagnosis and distinguish pulmonary arterial from pulmonary venous hypertension. PMID:24267297
Forfia, Paul R; Trow, Terence K
Arjunolic acid (AA) obtained from plants of the Combretaceae family has shown anti-diabetic effects. Here, we analyzed whether the diabetogenic effects of dexamethasone (DEX) treatment on glucose homeostasis may be prevented or attenuated by the concomitant administration of AA. Adult Wistar rats were assigned to the following groups: vehicle-treated (Ctl), DEX-treated (1 mg/kg body weight intraperitoneally for 5 days) (Dex), AA-treated (30 mg/kg body weight by oral gavage twice per day) (Aa), AA treatment previous to and concomitant to DEX treatment (AaDex), and AA treatment after initiation of DEX treatment (DexAa). AA administration significantly ameliorated (AaDex) (P > 0.05), but did not attenuate (DexAa), the glucose intolerance induced by DEX treatment. AA did not prevent or attenuate the elevation in hepatic glycogen and triacylglycerol content caused by DEX treatment. All DEX-treated rats exhibited hepatic steatosis that seemed to be more pronounced when associated with AA treatment given for a prolonged period (AaDex). Markers of liver function and oxidative stress were not significantly altered among the groups. Therefore, AA administered for a prolonged period partially prevents the glucose intolerance induced by DEX treatment, but it fails to produce this beneficial effect when given after initiation of GC treatment. Since AA may promote further hepatic steatosis when co-administered with GCs, care is required when considering this phytochemical as a hypoglycemiant and/or insulin-sensitizing agent. PMID:25345246
Gonçalves-Neto, Luiz M; Ferreira, Francielle B D; Souza, Luiz; dos Santos, Cristiane; Boschero, Antonio C; Facundo, Valdir A; Santos, Adair R S; Nunes, Everson A; Rafacho, Alex
Objective To investigate the correlation between maternal leptin levels and 100 gram oral glucose test (OGTT) results as well as the correlation between leptin levels and the development of gestational diabetes mellitus (GDM) and glucose intolerance during pregnancy. Material and Method: 104 subjects with gestational weeks ranging from 24 to 32 weeks who had increased 50 gr OGTT values (>140) were included in this study. After the screening test, 100 gr OGTT was administered to the subjects. Sixty cases were selected from these subjects; twenty patients with one abnormal test result were identified as “glucose intolerant” group (Group 1), 20 patients with two abnormal test values were diagnosed with GDM (Group 2) and 20 patients with normal test results constituted the control group. The serum leptin levels of the groups were measured with enzyme linked immunosorbent assay (ELISA). Results The serum leptin level was 8.4±5.1 ng/ml for group 1, 9.1±5.3 ng/ml for group 2 and 6.3±4.6 ng/ml for the control group. Although serum leptin levels for group 1 and 2 was observed to be higher than the control group, the result was not statistically significant (p>0.05). This result did not change after adjusting for body mass index (BMI). Conclusion There is no statistically significant difference between leptin levels among three groups. PMID:24591860
Sengul, Ozlem Baykara; Mungan, Tamer; Erdemoglu, Evrim; Islamoglu, Goksel; K?yak, Nuran
Fetal glucose metabolism depends on additive effects of fetal plasma glucose and insulin. Glucose-stimulated insulin secretion increases over gestation, is down-regulated by constant hyperglycemia, but enhanced by pulsatile hyperglycemia. Insulin production is diminished in fetuses with intrauterine growth restriction (IUGR) by inhibition of pancreatic ?-cell replication, but not by mechanisms that regulate insulin production or secretion, while the opposite occurs with hypoglycemia alone, despite its common occurrence in IUGR. Chronic hyperglycemia down-regulates glucose tolerance and insulin sensitivity with decreased expression of skeletal muscle and hepatic Glut 1 and 4 glucose transporters, while chronic hypoglycemia up-regulates these transporters. The opposite occurs for signal transduction proteins that regulate amino acid synthesis into protein. These results demonstrate the mixed phenotype of the IUGR fetus with enhanced glucose utilization capacity, but diminished protein synthesis and growth. Such adaptations might underlie childhood and adult metabolic disorders of insulin resistance, obesity, and diabetes mellitus. PMID:18528484
Hay, William W
Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. PMID:23017736
Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.
This study investigated associations between heat intolerance, as determined by performance on a heat tolerance test (HTT), and anthropometric measurements (body surface-to-mass ratio, percent body fat, body mass index, and waist circumference) and cardiorespiratory fitness (maximal oxygen uptake [VO2max]). Relationships between predictive variables and specific physiological measurements recorded during the HTT were examined. A total of 34 male and 12 female participants, recruited from the military community, underwent anthropometric measurements, a maximal aerobic exercise test, and a standardized HTT, which consisted of walking on a treadmill at 5 km/h at 2% grade for 120 minutes at 40°C and 40% relative humidity. VO2max negatively correlated with maximum core temperature (r = -0.30, p < 0.05) and heart rate (HR) (r = -0.48, p < 0.01) although percent body fat showed a positive correlation with maximum HR (r = 0.36, p < 0.05). VO2max was the only independent attribute that significantly influenced both the maximum HR and core temperature attained during HTT. Logistic regression analyses indicated that VO2max was the only independent parameter (OR = 0.89, p = 0.026) that significantly contributed to overall HTT performance. Low cardiorespiratory fitness was associated with heat intolerance, as defined by HTT performance, and can be addressed as a preventative measure for exertional heat illness. This study provides further evidence that the HTT can be an effective tool for assessment of thermoregulatory patterns. PMID:25373064
Lisman, Peter; Kazman, Josh B; O'Connor, Francis G; Heled, Yuval; Deuster, Patricia A
The incidence of postflight orthostatic intolerance following short-duration spaceflight is about 20%. However, the incidence following long-duration spaceflight is unknown. We performed tilt tests on six astronauts before and after their long-duration (129 - 190 days) spaceflights and compared these data to those obtained during stand tests before and after their previous short-duration missions and also to tilt test data from 20 different short-duration (8 - 16 days) flight astronauts. Five of these six became presyncopal during tilt testing after long-duration flights: only one had become presyncopal during stand testing after short-duration flights. Five of the twenty astronauts who flew on other short-duration flights, became presyncopal during upright tilt on landing day. Long-duration presyncopal subjects had lower stroke volumes, lower cardiac outputs and higher peripheral vascular resistance than short-duration presyncopal subjects, but their heart rate responses were not different. One subject had subnormal norepinephrine release with upright posture after a long but not short flight. Plasma volume losses were not greater after long flights. Long-duration spaceflight markedly increases orthostatic intolerance, probably related to altered autonomic function.
Fritsch-Yelle, Janice M.; Reyes, Carlos; Perez, Sondra A.; Goldberger, Ary L.; Ziegler, Michael G.; Paloski, William H. (Technical Monitor)
Microgravity imposes adaptive changes in the human body. This review focuses on the changes in baroreflex function produced by actual spaceflight, or by experimental models that simulate microgravity, e.g., bed rest. We will analyze separately studies involving baroreflexes arising from carotid sinus and aortic arch afferents ("high-pressure baroreceptors"), and cardiopulmonary afferents ("low-pressure receptors"). Studies from unrelated laboratories using different techniques have concluded that actual or simulated exposure to microgravity reduces baroreflex function arising from carotid sinus afferents ("carotic-cardiac baroreflex"). The techniques used to study the carotid-cardiac baroreflex, using neck suction and compression to simulate changes in blood pressure, have been extensively validated. In contrast, it is more difficult to selectively study aortic arch or cardiopulmonary baroreceptors. Nonetheless, studies that have examined these baroreceptors suggest that microgravity produces the opposite effect, ie, an increase in the gain of aortic arch and cardiopulmonary baroreflexes. Furthermore, most studies have focus on instantaneous changes in heart rate, which almost exclusively examines the vagal limb of the baroreflex. In comparison, there is limited information about the effect of microgravity on sympathetic function. A substantial proportion of subjects exposed to microgravity develop transient orthostatic intolerance. It has been proposed that alterations in baroreflex function play a role in the orthostatic intolerance induced by microgravity. The evidence in favor and against this hypothesis is reviewed.
Ertl, A. C.; Diedrich, A.; Biaggioni, I.; Robertson, D. (Principal Investigator)
This paper reviews food allergy and intolerance in dogs and cats. Adverse reactions to ingested food components can affect many systems and can produce signs involving the skin, gastrointestinal tract, respiratory tract and central nervous system, and these clinical signs are reviewed. Most basic food ingredients have the potential to induce an allergic response, although most reactions are caused by proteins. In particular, dogs and cats can become sensitive to cow's milk, beef, fish or cereal. Food allergy and intolerance is rare in dogs and cats, although the incidence in practice is difficult to establish. Clinical signs are quite variable, depending on the individual response, although the major clinical sign is pruritus. Diagnosis can be difficult, as there is no single test available to help the clinician to confirm or refute the presence of food sensitivity. Diagnosis is based on dietary investigation in the form of elimination diets and test meals. Elimination diets for dogs include lamb, chicken, rabbit, horse meat and fish as sources of protein, with rice or potatoes. Successful elimination diets for cats include lamb, chicken, rabbit or venison, with rice. Improvement in clinical signs while on the elimination diet is suggestive of food allergy. The diagnosis should be confirmed by feeding the original diet, with the development of clinical signs within 7 to 14 days of feeding. PMID:7848179
Wills, J; Harvey, R
Non-nucleoside reverse transcriptase inhibitors and enfuvirtide are ineffective against HIV-2 replication. These considerations may have particular significance in the formulation of second-line or salvage regimens for HIV-2 infection when resistance or toxicity precludes the use of protease inhibitors (PIs) or specific nucleoside analogues. We describe a case of a treatment-experienced patient with important limitations in therapeutic options dictated by the presence of HIV-2 infection, severe HIV nephropathy (requiring haemodialysis), intolerance to PIs and clinical contraindications to the use of some nucleoside analogues (anaemia, pancreatic toxicity and high cardiovascular risk). A three-drug regimen based on raltegravir, tenofovir disoproxil fumarate and lamivudine was given, with no major toxicity, good immunological response and complete viral suppression. Our case indicates that regimens based on integrase inhibitors could represent an effective alternative in PI-resistant or PI-intolerant patients with HIV-2, and that tenofovir disoproxil fumarate may be used in patients with end-stage renal disease requiring haemodialysis who cannot take other nucleoside analogues because of treatment-limiting adverse effects. PMID:21344955
Francisci, Daniela; Martinelli, Laura; Weimer, Liliana E; Zazzi, Maurizio; Floridia, Marco; Masini, Giulia; Baldelli, Franco
When a population is engaged in successive prisoner's dilemmas, indirect reciprocity through reputation fosters cooperation through the emergence of moral and action rules. A simplified model has recently been proposed where individuals choose between helping others or not and are judged good or bad for it by the rest of the population. The reputation so acquired will condition future actions. In this model, eight strategies (referred to as "leading eight") enforce a high level of cooperation, generate high payoffs, and are therefore resistant to invasions by other strategies. Here we show that, by assigning each individual one of two labels that peers can distinguish (e.g., political ideas, religion, and skin color) and allowing moral and action rules to depend on the label, intolerant behaviors can emerge within minorities under sufficient economic stress. We analyze the sets of conditions where this can happen and also discuss the circumstances under which tolerance can be restored. Our results agree with empirical observations that correlate intolerance and economic stress and predict a correlation between the degree of tolerance of a population and its composition and ethical stance. PMID:25215779
Martinez-Vaquero, Luis A; Cuesta, José A
When a population is engaged in successive prisoner's dilemmas, indirect reciprocity through reputation fosters cooperation through the emergence of moral and action rules. A simplified model has recently been proposed where individuals choose between helping others or not and are judged good or bad for it by the rest of the population. The reputation so acquired will condition future actions. In this model, eight strategies (referred to as "leading eight") enforce a high level of cooperation, generate high payoffs, and are therefore resistant to invasions by other strategies. Here we show that, by assigning each individual one of two labels that peers can distinguish (e.g., political ideas, religion, and skin color) and allowing moral and action rules to depend on the label, intolerant behaviors can emerge within minorities under sufficient economic stress. We analyze the sets of conditions where this can happen and also discuss the circumstances under which tolerance can be restored. Our results agree with empirical observations that correlate intolerance and economic stress and predict a correlation between the degree of tolerance of a population and its composition and ethical stance.
Martinez-Vaquero, Luis A.; Cuesta, José A.
The prevalence of celiac disease is about 1% in the population and is growing due to the wide use of immunological methods of diagnosis. In recent years, in-depth research of the celiac disease has led not only to an increase in the number of patients with celiac disease, but also to the emergence of a broad spectrum of diseases associated with the ingestion of gluten. In this regard, a new pathology, known as "gluten intolerance or gluten sensitivity", attracted special attention of researchers. Studies in recent years have established that patients with this pathology may have both gastrointestinal symptoms and extraintestinal manifestations. Examinations of such patients usually do not find histological changes of the mucous membrane of the small intestine and autoimmune antibodies (to tissue transglutaminase (tTG) and endomysial (EMA)); however an increased level of gliadin antibodies (AGA) is often observed. Allergy to gluten is also absent. A gluten-free diet for such patients, like in case of the celiac disease, leads to the disappearance of clinical symptoms. Exact criteria for the diagnosis of this nosology have not been identified so far, but most researchers believe that prevalence of "gluten intolerance" is much higher than that of celiac disease. PMID:22830230
Sabel'nikova, E A
... with idiopathic intracranial hypertension include blockage of the brain’s venous drainage (dural sinus thrombosis), renal disease, head injuries, Lyme disease, lupus, acute sinusitis, measles, blood clotting disorders, ...
Men have higher blood pressure than women through much of life regardless of race and ethnicity. This is a robust and highly conserved sex difference that it is also observed across species including dogs, rats, mice and chickens and it is found in induced, genetic and transgenic animal models of hypertension. Not only do the differences between the ovarian and testicular hormonal milieu contribute to this sexual dimorphism in blood pressure, the sex chromosomes also play a role in and of themselves. This review primarily focuses on epidemiological studies of blood pressure in men and women and experimental models of hypertension in both sexes. Gaps in current knowledge regarding what underlie male-female differences in blood pressure control are discussed. Elucidating the mechanisms underlying sex differences in hypertension may lead to the development of anti-hypertensives tailored to one's sex and ultimately to improved therapeutic strategies for treating this disease and preventing its devastating consequences. PMID:22417477
Background and Objectives Although the association between single nucleotide polymorphisms (SNPs) of Serine/Threonine Kinase 39 (STK39) and hypertension has been reported, the prior studies have been inconsistent. The aim of this study is to evaluate the association between rs3754777 and rs6749447, the two SNPs of STK39, and hypertension and other cardiovascular risk factors in Koreans, residing in the Republic of Korea. Subjects and Methods We included 238 hypertensive patients and 260 controls. The associations between genotype and haplotype combination and hypertension were examined. In addition, possible SNP-related differences in the adjusted blood pressure and other cardiovascular risk factors were analyzed. Results There was no significant association between the two SNPs and hypertension. However, the carriers of AA genotype of rs3754777 showed lower blood glucose and cholesterol levels, particularly in females. Genotype of rs6749447 was associated with the waist circumference, triglyceride, and high density lipoprotein-cholesterol levels, only in gender-stratified analysis. The effects of haplotype combinations on risk factors were compatible with genotype effects of each SNP. Conclusion Associations between the two SNPs of STK39, rs3754777 and rs6749447, and hypertension were not significant. However, the two SNPs showed genotype-related differences in blood glucose, lipids, and waist circumference, especially in women. Further studies are needed to clarify the effect of STK39 variants in these cardiovascular risk factors. PMID:23408757
Shin, Dong-Jik; Park, Sungha; Jang, Yangsoo
Genetic and behavioral factors do not fully explain the development of hypertension, and there is increasing evidence suggesting\\u000a that psychosocial factors may also play an important role. Exposure to chronic stress has been hypothesized as a risk factor\\u000a for hypertension, and occupational stress, stressful aspects of the social environment, and low socioeconomic status have\\u000a each been studied extensively. The study
Tanya M. Spruill
Hypertension in the term or preterm neonate may be seen in up to 2% of all infants cared for in the modern neonatal intensive\\u000a care unit. Although the definition of hypertension in this age group has not been completely standardized, recent studies\\u000a have provided new normative data that may be used to facilitate identification of such infants. Common causes of
Joseph T. Flynn
Elevated blood pressure is present in more than 60% of patients with acute stroke. Moderate to severe hypertension affects stroke outcomes, yet the optimal management has been a gray area in the care of such patients. Although new data are changing the approach, particularly for hemorrhagic events, significant questions remain. This article presents the latest evidence on hypertension in the setting of ischemic and hemorrhagic stroke and highlights management considerations that are relevant to emergency medicine. PMID:24731431
Miller, Joseph; Kinni, Harish; Lewandowski, Christopher; Nowak, Richard; Levy, Phillip
Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30-60 min and 60-120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats. PMID:18398501
Ndong, Moussa; Uehara, Mariko; Katsumata, Shin-Ichi; Suzuki, Kazuharu
Forkhead transcription factors FoxO1/3/4 have pleiotrophic functions including anti-oxidative stress and metabolism. With regard to glucose metabolism, most studies have been focused on FoxO1. To further investigate their hepatic functions, we generated liver-specific FoxO1/3/4 knockout mice (LTKO) and examined their collective impacts on glucose homeostasis under physiological and pathological conditions. As compared to wild-type mice, LTKO mice had lower blood glucose levels under both fasting and non-fasting conditions and they manifested better glucose and pyruvate tolerance on regular chow diet. After challenged by a high-fat diet, wild-type mice developed type 2 diabetes, but LTKO mice remained euglycemic and insulin-sensitive. To understand the underlying mechanisms, we examined the roles of SIRT6 (Sirtuin 6) and Gck (glucokinase) in the FoxO-mediated glucose metabolism. Interestingly, ectopic expression of SIRT6 in the liver only reduced gluconeogenesis in wild-type but not LTKO mice whereas knockdown of Gck caused glucose intolerance in both wild-type and LTKO mice. The data suggest that both decreased gluconeogenesis and increased glycolysis may contribute to the overall glucose phenotype in the LTKO mice. Collectively, FoxO1/3/4 transcription factors play important roles in hepatic glucose homeostasis. PMID:24015318
Xiong, Xiwen; Tao, Rongya; DePinho, Ronald A; Dong, X Charlie
Consumption of whole-grain and sourdough breads is associated with improved glucose homeostasis. We examined the impact of commercial breads on biomarkers of glucose homeostasis in subjects at risk for glucose intolerance. In a randomized, crossover study, overweight or obese males ingested 11-grain, sprouted-grain, 12-grain, sourdough, or white bread on different occasions, matched for available carbohydrate (50?g) in part 1 (n = 12) and bread mass (107?g) in part 2 (n = 11), and blood glucose, insulin and glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) were determined for 3?h. In part 1, glucose response for sprouted-grain was lower than 11-grain, sourdough, and white breads. Insulin area under the curve (AUC) for sourdough and white was lower than 11-grain and sprouted-grain breads. GLP-1 response to sourdough was lower than all breads. In part 2, glucose and insulin AUC for sourdough was greater than 11-grain, sprouted-grain, and 12-grain breads. Sprouted-grain bread improved glycemia by lowering glucose response and increasing GLP-1 response. In overweight and obese men, the glycemic response to sprouted grain bread was reduced in both parts 1 and 2 while the other whole-grain test breads did not improve metabolic responses in the acute postprandial state. PMID:22474577
Mofidi, Anita; Ferraro, Zachary M.; Stewart, Katherine A.; Tulk, Hilary M. F.; Robinson, Lindsay E.; Duncan, Alison M.; Graham, Terry E.
Catecholamine secretory traits were significantly heritable, as were stress-induced blood pressure changes. Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis. In the tyrosine hyroxylase promoter, significant associations were found for urinary catecholamine excretion and for blood pressure response to stress. TH promoter haplotype 2 (TGGG) showed pleiotropy, increasing both norepinephrine excretion and blood pressure during stress. In hypertension, 2 independent case-control studies (1,266 subjects with 53% women and 927 subjects with 24% women) replicated the effect of C-824T in the determination of blood pressure. Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in the storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive kidney disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed such regulatory regions as the proximal promoter and 3'-UTR. In chromaffin cell-transfected CHGA 3'-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3'-UTR displayed statistical associations with hypertension and hypertensive end stage renal disease. Therefore, I would like to review the common genetic variation in TH and CHGA as a cause of inter-individual variation in sympathetic activity, and ultimately blood pressure and hypertensive kidney disease. PMID:23946762
Kang, Sun Woo
An optoelectronic apparatus has been invented as a noninvasive means of measuring the concentration of glucose in the human body. The apparatus performs polarimetric and interferometric measurements of the human eye to acquire data from which the concentration of glucose in the aqueous humor can be computed. Because of the importance of the concentration of glucose in human health, there could be a large potential market for instruments based on this apparatus.
Ansari, Rafat R.; Rovati, Luigi L.
1. The effect of insulin (0.5, 10 and 50 munits/ml of perfusate) on glucose uptake and disposal in skeletal muscle was studied in the isolated perfused hindquarter of obese (fa/fa) and lean (Fa/Fa) Zucker rats and Osborne-Mendel rats. 2. A concentration of 0.5 munit of insulin/ml induced a significant increase in glucose uptake (approx. 2.5 mumol/min per 30 g of muscle) in lean Zucker rats and in Osborne-Mendel rats, and 10 munits of insulin/ml caused a further increase to approx. 6 mumol/min per 30 g of muscle; but 50 munits of insulin/ml had no additional stimulatory effect. In contrast, in obese Zucker rats only 10 and 50 munits of insulin/ml had a stimulatory effect on glucose uptake, the magnitude of which was decreased by 50-70% when compared with either lean control group. Since under no experimental condition tested was an accumulation of free glucose in muscle-cell water observed, the data suggest an impairment of insulin-stimulated glucose transport across the muscle-cell membrane in obese Zucker rats. 3. The intracellular disposal of glucose in skeletal muscle of obese Zucker rats was also insulin-insensitive: even at insulin concentrations that clearly stimulated glucose uptake, no effect of insulin on lactate oxidation (nor an inhibitory effect on alanine release) was observed; [14C]glucose incorporation into skeletal-muscle lipids was stimulated by 50 munits of insulin/ml, but the rate was still only 10% of that observed in lean Zucker rats. 4. The data indicate that the skeletal muscle of obese Zucker rats is insulin-resistant with respect to both glucose-transport mechanisms and intracellular pathways of glucose metabolism, such as lactate oxidation. The excessive degree of insulin-insensitivity in skeletal muscle of obese Zucker rats may represent a causal factor in the development of the glucose intolerance in this species. PMID:454379
Kemmer, F W; Berger, M; Herberg, L; Gries, F A; Wirdeier, A; Becker, K
The effect of zinc deficiency on glucose tolerance was investigated using intragastric force-feeding to obviate decreased food intake and altered eating patterns. Three groups of weanling male Sprague-Dawley rats were fed a purified powdered zinc-deficient diet: zinc-deficient ad libitum fed animals (ZDA); zinc-replete gavage force-fed controls (ZRF) fed the zinc-deficient diet in water with zinc (25 ppm); zinc-deficient gavage force-fed animals (ZDF) fed the zinc-deficient diet in distilled water. A fourth group of zinc-supplemented rats fed the diet ad libitum was included to determine caloric intake for ZDF and ZRF gavage fed groups. After 8 days of feeding, the zinc concentration in the serum and pancreas were lower in both zinc-deficient groups, but the difference was much greater in the ZDF rats than in the ZDA. The ZDF group had impaired glucose tolerance curves, yet blood insulin and glucagon levels were normal. The ZDA group had normal glucose tolerance with low insulin levels compared to the ZRF group. The islet cell morphology among the three dietary groups were similar. These results suggest that the glucose intolerance observed in ZDF rats is not due to altered blood insulin and glucagon levels but rather to peripheral resistance to insulin action.
Park, J.H.Y.; Grandjean, C.J.; Hart, M.H.; Erdman, S.H.; Pour, P.; Vanderhoof, J.A.
Formal assessment of the risk of pre-eclampsia should be made early in pregnancy and antenatal care planned accordingly. Recommendations will emerge by the end of this year in a consensus statement (PRECOG guidelines) prepared by clinicians and the lay organisation Action on Pre-eclampsia (APEC) www.apec.org.uk. Some hospitals complement clinical risk assessment with Doppler screening of uterine artery waveforms in mid-pregnancy. Severe pre-eclampsia often takes an explosive course, evolving over a period of hours. Recognition may, therefore, not be amenable to intermittent blood pressure recording and urine testing, but requires women reporting relevant symptoms and GPs being sensitive to the possible significance of complaints such as vomiting and epigastric pain. Severe hypertension demands urgent antihypertensive treatment in hospital. Magnesium sulphate now has an accepted role in the prevention of eclampsia. Possible prevention of pre-eclampsia by antioxidant therapy is the subject of a clinical trial. Low-dose aspirin has a modest but beneficial effect in high-risk women. Delivery remains the definitive treatment for pre-eclampsia, but there may be initial deterioration after birth, especially in the HELLP syndrome. PMID:15491015
Meher, Shireen; Neilson, Jim
Resistance to insulin-media ted glucose disposal has been previously shown to be increased in association with obesity, high blood pressure, and non-insulin-dependent dia- betes mellitus. We initiated the present study to quantify the separate effects of hypertension and non-insulin-dependent diabetes mellitus on insulin resistance in both nonobese and obese subjects. To accomplish this, 88 subjects were divided into the following
Pierre Maheux; Jorgen Jeppesen; Wayne H.-H. Sheu; Clarie B. Hollenbeck; Cynthia Clinkingbeard; Michael S. Greenfield; Yii-Der Ida Chen; Gerald M. Reaven
BackgroundAlthough basic research has implicated abnormal glucose metabolism in the pathogenesis of hypertension (HTN), epidemiologic studies are limited.MethodsWe assessed whether baseline hemoglobin A1c (HbA1c) was pros