Metformin and Improvement of the Hepatic Insulin Resistance Index Independent of Anthropometric Changes

ObjectiveTo determine the change in the hepatic insulin resistance index (HIRI) after metformin treatment.MethodsIn this retrospective cohort study, Mexican mestizo patients with a body mass index (BMI) of 25 kg/m² or greater were evaluated. Participants were classified into 2 groups: patients who received metformin and patients who did not. Both groups were followed up for a median of 6 months (range. 4-10 months). The HIRI was calculated at baseline and at follow-up in both groups. We evaluated the independent effect of metformin on HIRI after adjustment for the difference in basal and final values (DELTA) of BMI, waist circumference, glucose, and insulin.ResultsA total of 71 patients were enrolled (51 [72%] female). Forty-one patients received metformin and 30 patients did not. Mean age was 36.3 ± 12.2 years and mean BMI was 42.2 ± 10.7 kg/m². After metformin treatment. HIRI significantly decreased from 38 ± 10.7 to 34.7 ± 9.5 (P = .03). In contrast. the control group had a nonsignificant increase in HIRI (37.6 ± 11.7 to 40.0 ± 14.0, P = .22). Weight significantly decreased in both groups (group 1: 114.6 ± 33.8 kg to 107.6 ± 28.9 kg, P < .01; group 2: 104.8 ± 28.5 kg to 98.9 ± 26.0 kg, P < .01). After BMI adjustment, the total metformin dosage correlated negatively with HIRI (r = –0.36, P = .03). Using a linear regression model (F = 6.0, r² = 0.37, P = .002) adjusted for DELTA BMI and DELTA waist circumference. the administration of metformin resulted in independent improvement in the HIRI level (standardized β = –0.29, t = –2.0, P = .04).ConclusionsMetformin improves HIRI independently of anthropometric changes. In persons with elevated HIRI levels, metformin may be considered among the treatment options. (Endocr Pract. 2012;18:8-16)     

Relationship of Prostate -Specific Antigen to Age and Testosterone in Men With Type 2 Diabetes Mellitus

ObjectiveTo determine whether prostate-specific antigen (PSA) concentrations in type 2 diabetic men with hypogonadotrophic hypogonadism are lower than those in eugonadal men with type 2 diabetes and whether PSA concentrations are related to plasma testosterone concentrations.MethodsIn this cross-sectional study, we measured serum total testosterone, sex hormone–binding globulin, free testosterone, PSA, hematocrit, and hemoglobin A_1c in consecutive type 2 diabetic men who presented to 2 endocrinology referral centers between January 2006 and January 2007. We collected other clinical and demographic data including age, height, weight, and ethnicity.ResultsOf 400 eligible patients, 280 men met inclusion criteria. Plasma PSA concentrations were lower in type 2 diabetic men with low free testosterone concentrations than in those with normal free testosterone concentrations (25.65 ± 2.02 ng/dL vs 31.70 ± 2.31 ng/dL, P = .011). PSA concentrations were positively related to age (r = 0.34, P < .001), total testosterone (r = 0.29, P < .001), free testosterone (r = 0.17, P = .02), and sex hormone– binding globulin (r = 0.22, P < .001) and negatively related to body mass index (r = –0.28, P < .001). In stepwise backward regression analysis, PSA concentration was predicted by age (P < .001) and free testosterone (P < .001), but not by body mass index or sex hormone–binding globulin.ConclusionsPlasma PSA concentrations are lower in type 2 diabetic men with hypogonadism than in eugonadal men with type 2 diabetes, and plasma PSA is related to age, plasma total testosterone concentrations, and free testosterone concentrations in patients with type 2 diabetes. (Endocr Pract. 2008;14:1000-1005)     

Correlation between endogenous polyamines in human cardiac tissues and clinical parameters in patients with heart failure

Polyamines contribute to several physiological and pathological processes, including cardiac hypertrophy in experimental animals. This involves an increase in ornithine decarboxylase (ODC) activity and intracellular polyamines associated with cyclic adenosine monophosphate (cAMP) increases. The aim of the study was to establish the role of these in the human heart in living patients. For this, polyamines (by high performance liquid chromatography) and the activity of ODC and N¹‐acetylpolyamine oxidases (APAO) were determined in the right atrial appendage of 17 patients undergoing extracorporeal circulation to correlate with clinical parameters. There existed enzymatic activity associated with the homeostasis of polyamines. Left atria size was positively associated with ODC (r = 0.661, P = 0.027) and negatively with APAO‐N¹‐acetylspermine (r = −0.769, P = 0.026), suggesting that increased levels of polyamines are associated with left atrial hemodynamic overload. Left ventricular ejection fraction (LVEF) and heart rate were positively associated with spermidine (r = 0.690, P = 0.003; r = 0.590, P = 0.021) and negatively with N¹‐acetylspermidine (r = −0.554, P = 0.032; r = −0.644, P = 0.018). LVEF was negatively correlated with cAMP levels (r = −0.835, P = 0.001) and with cAMP/ODC (r = −0.794, P = 0.011), cAMP/spermidine (r = −0.813, P = 0.001) and cAMP/spermine (r = −0.747, P = 0.003) ratios. Abnormal LVEF patients showed decreased ODC activity and spermidine, and increased N¹‐acetylspermidine, and cAMP. Spermine decreased in congestive heart failure patients. The trace amine isoamylamine negatively correlated with septal wall thickness (r = −0.634, P = 0.008) and was increased in cardiac heart failure. The results indicated that modifications in polyamine homeostasis might be associated with cardiac function and remodelling. Increased cAMP might have a deleterious effect on function. Further studies should confirm these findings and the involvement of polyamines in different stages of heart failure.     

Baseline blood volume identified by dynamic contrast-enhanced computed tomography as a new independent prognostic factor in metastatic renal cell carcinoma

BackgroundPreliminary data showed prognostic impact of contrast-enhanced computed tomography (DCE-CT) identified Blood Volume (BV) in patients with metastatic renal cell carcinoma (mRCC). BV as an independent prognostic factor remains to be assessed.Materials and MethodsDCE-CT identified BV was prospectively quantified in patients with mRCC receiving first line therapies, adjusted for International mRCC Database Consortium (IMDC) individual features and treatments, and associated with overall survival (OS), progression-free survival (PFS) and objective response (ORR), using Cox and logistic regression, respectively.Results105 patients with mRCC were included. Median baseline BV was 32.87 mL × 100 g⁻¹ (range 9.52 to 92.87 mL × 100 g⁻¹). BV above median was associated with IMDC favorable risk category (P = 0.004), metastasis free interval ≥ 1 year (P = 0.007), male gender (P = 0.032), normal hemoglobin (P = 0.040) and normal neutrophils (P = 0.007), whereas low BV was associated with poor risk IMDC features (P < 0.05). Patients with high vs. low baseline BV had longer PFS (12.5 vs. 5.6 months, P = 0.015) and longer OS (42.2 vs. 22.4 months, P = 0.001), respectively. In multivariate analysis high baseline BV remained independent favorable for OS (HR 0.49, 95% CI 0.30–0.78, P = 0.003) and PFS (HR 0.64; 95% CI 0.42–0.97, P = 0.036). BV as a continuous variable was also associated with OS in the multivariate analysis (HR 0.98, 95% CI 0.96–1.00, P = 0.017). The estimated concordance index (c-index) was 0.688 using IMDC score and 0.701 when BV was added.ConclusionsDCE-CT identified Blood Volume is a new, independent prognostic factor in mRCC, which may improve the prognostic accuracy of IMDC.     

Evaluation of Body Composition in Patients With and Without Adrenal Tumors and Without Overt Hypersecretory Syndromes

ObjectiveTo compare body composition between patients with autonomous cortisol secretion (ACS), those with nonfunctioning adrenal incidentalomas (NFAIs), and control subjects without adrenal tumors.MethodsA cross-sectional study was performed, incluidng the following 3 groups: patients with ACS (cortisol post–dexamethasone suppression test [DST] >1.8 μg/dL), NFAIs (cortisol post-DST ≤ 1.8 μg/dL), and patients without adrenal tumors (control group). Patients of the 3 groups were matched according to age (±5 years), sex, and body mass index (±5 kg/m²). Body composition was evaluated by bioelectrical impedance and abdominal computed tomography (CT) and urinary steroid profile by gas chromatography mass spectrometry.ResultsThis study enrolled 25 patients with ACS, 24 with NFAIs, and 24 control subjects. Based on CT images, a weak positive correlation between the serum cortisol level post-DST and subcutaneous fat area (r = 0.3, P =.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r = 0.56, P <.001; and r = 0.58, P <.001, respectively); visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r = 0.28, P =.031; and r = 0.42, P =.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r = 0.30, P =.036) and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r = 0.34, P =.014; r = 0.29, P =.042; and r = 0.31, P =.170, respectively).ConclusionThe urinary steroid profile observed in adrenal tumors, comprising a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumors.     

Gender differences in diabetes mellitus and effectson self-care activity

Background:Effective self-care, including adherence to diet, exercise, and medication regimens, is an essential component of health care for individuals with diabetes mellitus (DM).Objective:The goals of this study were to examine sex-based differences in DM and to explore the effects of gender on self-care.Methods:This study was conducted retrospectively using data from the 2001 Medical Expenditure Panel Survey (MEPS). People with DM were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code; analyses were stratified by sex. Variables included age, race/ethnicity, education, income, body mass index (BMI), number of comorbidities, physical and cognitive limitations, smoking status, and depression. Outcome measures were assessed by Short Form-12 (SF-12) Mental Component Summary (MCS) and Physical Component Summary (PCS) scores. Univariate analyses were determined using t, χ², or Fisher exact tests, as appropriate. Multivariate analyses examined associations between sex and SF-12 MCS/PCS scores adjusted for other variables.Results:A total of 1653 MEPS respondents (883 women, 770 men) with DM were identified for the current study. The women were significantly older than the men (61.2 vs 59.1 years), had less education (11.1 vs 12.0 years), and had lower incomes. Women had higher calculated BMI (31.4 vs 30.3), more comorbidities (7.8 vs 6.4), more depression, and more physical and cognitive limitations than did men. Women also scored lower than men on the SF-12 MCS and PCS (47.8 vs 49.9 and 38.2 vs 41.4, respectively). All these measures were statistically significant (P < 0.01). In multivariate analyses, physical limitations, BMI, and number of comorbidities were negatively correlated, and income and education were positively correlated, with MCS and PCS scores.Conclusions:Compared with their male counterparts, diabetic women scored lower on measuresof health status and functioning—factors that are likely to affect self-care activities. Sex-based differences should be considered when developing screening and treatment programs for people with DM.     

Hypoglycemia assessed by continuous glucose monitoring is associated with preclinical atherosclerosis in individuals with impaired glucose tolerance

Hypoglycemia is associated with increased risk of cardiovascular adverse clinical outcomes. There is evidence that impaired glucose tolerance (IGT) is associated with cardiovascular morbidity and mortality. Whether IGT individuals have asymptomatic hypoglycemia under real-life conditions that are related to early atherosclerosis is unknown. To this aim, we measured episodes of hypoglycemia during continuous interstitial glucose monitoring (CGM) and evaluated their relationship with early manifestation of vascular atherosclerosis in glucose tolerant and intolerant individuals. An oral glucose tolerance test (OGTT) was performed in 79 non-diabetic subjects. Each individual underwent continuous glucose monitoring for 72 h. Cardiovascular risk factors and ultrasound measurement of carotid intima-media thickness (IMT) were evaluated. IGT individuals had a worse cardiovascular risk profile, including higher IMT, and spent significantly more time in hypoglycemia than glucose-tolerant individuals. IMT was significantly correlated with systolic (r = 0.22; P = 0.05) and diastolic blood pressure (r = 0.28; P = 0.01), total (r = 0.26; P = 0.02) and LDL cholesterol (r = 0.27; P = 0.01), 2-h glucose (r = 0.39; P<0.0001), insulin sensitivity (r = −0.26; P = 0.03), and minutes spent in hypoglycemia (r = 0.45; P<0.0001). In univariate analyses adjusted for gender, minutes spent in hypoglycemia were significantly correlated with age (r = 0.26; P = 0.01), waist circumference (r = 0.33; P = 0.003), 2-h glucose (r = 0.58; P<0.0001), and 2-h insulin (r = 0.27; P = 0.02). In a stepwise multivariate regression analysis, the variables significantly associated with IMT were minutes spent in hypoglycemia (r² = 0.252; P<0.0001), and ISI index (r² = 0.089; P = 0.004), accounting for 34.1% of the variation. Episodes of hypoglycemia may be considered as a new potential cardiovascular risk factor for IGT individuals.     

Analysis of Sex Differences in Cancer-Specific Survival and Perioperative Mortality Following Radical Cystectomy: Results of a Large German Multicenter Study of Nearly 2500 Patients with Urothelial Carcinoma of the Bladder

BackgroundOutcome of patients with urothelial carcinoma of the bladder (UCB) varies between sexes. Although overall incidence is higher in men, cancer-specific survival (CSS) has been suggested to be lower in women. Although the former effect is attributed to greater exposure to carcinogens in men, the latter has not been elucidated.ObjectivesThe aim of the study was to identify sex-specific outcomes based on one of the largest databases of patients with UCB who underwent radical cystectomy (RC).MethodsThis retrospective multicenter series comprised 2483 patients in Stage M0 who underwent RC for UCB from 1989 to 2008; 20.4% of patients were women. The impact of sex on CSS in the entire study group and in specific subgroups was analyzed. The median follow-up time was 42 months (interquartile range, 21–79).ResultsHistopathologic criteria of pathologic tumor (pT), pathologic nodal (pN), grade, lymphovascular invasion (LVI), and associated carcinoma in situ (CIS) of the study did not differ between sexes. The percentage of female patients increased over time. Five-year CSS in female patients was significantly lower than in male patients (60% vs 66%; P = 0.005). In multivariate analysis adjusted to other covariates, tumor stage ≥pT3 (hazard ratio [HR] = 2.44; P < 0.001), positive pN status (HR = 1.91; P < 0.001), LVI (HR = 1.48; P < 0.001), lower count of lymph nodes removed (HR = 0.98; P = 0.002), older age (HR = 1.01; P < 0.001), and female gender (HR = 1.26; P = 0.011) had an independent impact on CSS. Deterioration of CSS in female patients was pronounced when LVI was present (HR = 1.57; P < 0.001) and when RC was performed in the earlier time period (HR = 2.44; P < 0.001). However, women showed significantly lower perioperative mortality (within 90 days after RC) compared with men.ConclusionsAfter RC for UCB, cancer-specific mortality was higher in female patients; this disadvantage was more pronounced in earlier time periods. In addition, worse outcome of women with verified LVI was shown to be comparable with men. These findings were suggestive of different tumor biology and potentially unequal access to timely RC in earlier time periods because of reduced awareness of UCB in women. Further studies are required to improve UCB outcome in both sexes, notably in female patients.     

Furosemide-sensitive Na+ and K+ transport and human erythrocyte volume

The relationship between cation transport and cell volume in human erythrocytes was investigated by measuring ouabain-sensitive K⁺ influx, ouabain-resistant, furosemide-sensitive K⁺ influx, and ouabain + furosemide-resistant K⁺ influx, and maximal ouabain binding in microcytic, normocytic and macrocytic red cells. A significant correlation was found between the mean corpuscular volume and furosemide-sensitive K⁺ influx normalized either to cell number (r = 0.636, P < 0.001) or to cell volume (r = 0.488, P < 0.001). No relationship was seen between mean corpuscular volume and ouabain-sensitive K⁺ influx, and the number of ouabain-binding sites per cell was only weakly correlated with mean corpuscular volume (r = 0.337, P < 0.05). A slight, negative relationship existed between mean corpuscular volume and ouabain + furosemide-resistant K⁺ influx expressed per volume of cells (r = −0.359, P < 0.01), and an apparent relationship between furosemide-sensitive K⁺ influx and mean corpuscular hemoglobin concentration (r = 0.446, P < 0.01) disappeared when microcytic samples were excluded from analysis. Furosemide-sensitive transport, including Na⁺ influx and K⁺ and Na⁺ efflux, was completely absent in microcytic cells from one patient with α-thalassemia minor. In addition, these cells exhibited a furosemide-resistant, Cl⁻-dependent K⁺ influx. Exposure of normal erythrocytes to hypotonic conditions (196 mosM) increased furosemide-sensitive K⁺ influx by a mean of 45% (P < 0.05), while exposure to hypertonic conditions (386 mosM) had no significant effect. The results indicate that furosemide-sensitive transport and cell volume are interrelated in human erythrocytes. However, the inability to fully recreate this relationship with in vitro manipulation of cell volume suggests that this relationship is established prior to red cell maturation.     

Adiponectin and leptin in African Americans

Objective: African Americans (AAs) have less visceral and more subcutaneous fat than whites, thus the relationship of adiponectin and leptin to body fat and insulin sensitivity in AA may be different from that in whites. Methods and Procedures: Sixty‐nine non‐diabetic AA (37 men and 32 women), aged 33 ± 1 year participated. The percent fat was determined by dual‐energy X‐ray absorptiometry, abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volume by computerized tomography (CT), and insulin sensitivity by homeostasis model assessment (HOMA). Results: VAT was greater in men (1,619 ± 177 cm³ vs. 1,022 ± 149 cm³; P = 0.01); women had a higher percentage of body fat (34.1 ± 1.4 vs. 24.0 ± 1.2; P < 0.0001), adiponectin (15.8 ± 1.2 μg/ml vs. 10.4 ± 0.8 μg/ml; P = 0.0004) and leptin (23.2 ± 15.8 ng/ml vs. 9.2 ± 7.2 ng/ml; P < 0.0001). SAT and HOMA did not differ because of the sex. Adiponectin negatively correlated with VAT (r = ?0.41, P < 0.05) in men, and with VAT (r = ?0.55, P < 0.01), and SAT (r = ?0.35, P < 0.05) in women. Adiponectin negatively correlated with HOMA in men (r = ?0.38, P < 0.05) and women (r = ?0.44, P < 0.05). In multiple regression, sex (P = 0.02), HOMA (P = 0.03) and VAT (P = 0.003) were significant predictors of adiponectin (adj R ² = 0.38, P < 0.0001). Leptin positively correlated with VAT, SAT, percent fat and HOMA in men (r = 0.79, r = 0.86, r = 0.89, and r = 0.53; P < 0.001) and women (r = 0.62, r = 0.75, r = 0.83, and r = 0.55; P < 0.01). In multiple regression VAT (P = 0.04), percent body fat (P < 0.0001) and sex (P = 0.01), but not HOMA were significant predictors of serum leptin (adj R ²= 0.82, P < 0.0001). Discussion: The relationship of adiponectin and leptin to body fat content and distribution in AA is dependent on sex. Although VAT and insulin sensitivity are significant determinants of adiponectin, VAT and percent body fat determine leptin.     

Analysis of Sex Differences in Preadmission Management of ST-Segment Elevation (STEMI) Myocardial Infarction

BackgroundMany reports suggest gender disparity in cardiac care as a contributor to the increased mortality among women with heart disease.ObjectiveWe sought to identify gender differences in the management of Myocardial Infarction (MI) Alert–activated ST-segment elevation myocardial infarction (STEMI) patients that may have resulted from prehospital initiation.MethodsA retrospective database was created for MI Alert STEMI patients who presented to the emergency department (ED) of an academic community hospital with 74,000 annual visits from April 2000 through December 2008. Included were patients meeting criteria for an MI Alert (an institutional clinical practice guideline designed to expedite cardiac catheterization for STEMI patients). Data points (before and after initiation of a prehospital alert protocol) were compared and used as markers of therapy: time to ECG, receiving β-blockers, and time to the catheterization laboratory (cath lab). Differences in categorical variables by patient sex were assessed using the χ² test. Medians were estimated as the measure of central tendency. Quantile regression models were used to assess differences in median times between subgroups.ResultsA total of 1231 MI Alert charts were identified and analyzed. The majority of the study population were male (70%), arrived at the ED via ambulance (60.1%), and were taking a β-blocker (67.8%) or aspirin (91.6%) at the time of the ED admission. Female patients were more likely than male patients to arrive at the ED via ambulance (65.9% vs 57.6%, respectively; P = 0.014). The median age of female patients was 68 years, whereas male patients were significantly younger (median age, 59 years; P < 0.001). The proportion of patients currently taking a β-blocker or low-dose aspirin did not vary by gender. Overall, 78.2% of the MI Alert patients arriving at the ED were MI2 (alert initiated by ED physician), and this did not vary by gender (P = 0.33). A total of 1064 MI Alert patients went to the cath lab: 766 male patients (88.9%) and 298 female patients (80.8%). Overall, the median time to cath lab arrival was 79 minutes for men and 81 minutes for women (P = 0.38). Overall, the median time to cath lab arrival significantly decreased from MI1 to MI3, (P_trend < 0.001). For prehospital-initiated alerts (MI3), the median time to cath lab arrival was the same for men and women (64 minutes; P = 1.0). For hospital-initiated alerts, time to cath lab arrival was 82 minutes for male patients and 84 minutes for female patients (P = 0.38). Prehospital activation of the process decreased the time to the cath lab by 19 minutes (P < 0.001; 95% CI, 13.2–24.8).ConclusionNo significant gender differences were apparent in the STEMI patients analyzed, whether the MI Alert was initiated in the ED or prehospital initiated. Initiating prehospital-based alerts significantly decreased the time to the cath lab.     

Nitrogen partitioning and isotopic discrimination are affected by age and dietary protein content in growing lambs

It is difficult to separate an age-dependent fall in nitrogen use efficiency (NUE; N balance/N intake) in growing ruminants from a progressively decrease in animal protein requirements over time. This study examined the effect of dietary protein content on N partitioning, digestibility and N isotopic discrimination between the animal and its diet (Δ¹⁵N_animal-diet) evaluated at two different fattening periods (early v. late). Twenty-four male Romane lambs (age: 19 ± 4.0 days; BW: 8.3 ± 1.39 kg) were equally allocated to three dietary CP treatments (15%, 17% and 20% CP on a DM basis). Lambs were reared with their mothers until weaning, thereafter housed in individual pens until slaughter (45 kg BW). During the post-weaning period, lambs were allocated twice (early fattening (30 days post-weaning) and late fattening (60 days post-weaning)) to metabolic cages for digestibility and N balance study. When diet CP content increased, the average daily gain of lambs increased (P < 0.05) while the age at slaughter decreased (P = 0.01), but no effect was observed on feed efficiency (P > 0.10). Diet CP content had limited effect on lamb carcass traits. Higher fibre digestibility was observed at the early v. late fattening period (P < 0.001). The N intake and the urinary N excretion increased when diet CP content increased (P < 0.001) and when shifting from early to late fattening period (P < 0.001). Faecal N excretion (P = 0.14) and N balance (P > 0.10) were not affected by diet CP content. Nitrogen digestibility increased (P < 0.001) as the diet CP content increased and on average it was greater at late v. early fattening period (P = 0.02). The NUE decreased (P = 0.001) as the diet CP content increased and as the lamb became older (P < 0.001). However, the age-dependent fall in NUE observed was lower at high v. low dietary CP content (CP × age interaction; P = 0.04). The Δ¹⁵N_animal-diet was positively correlated (P < 0.05) with N intake (r = 0.59), excretion of faecal N (r = 0.41), urinary N (r = 0.69) and total manure N (r = 0.64), while negatively correlated with NUE (r = −0.57). Overall, the experiment showed NUE was lower in older lambs and when lambs were fed high diet CP content, and that Δ¹⁵N_animal-diet was a useful indicator not only for NUE but also for urinary N excretion, which is a major environmental pollution factor on farm.     

The associations between socioeconomic status, allostatic load and measures of health in older Taiwanese persons: Taiwan social environment and biomarkers of aging study

Data from a national representative sample of 1023 elderly and near-elderly Taiwanese were used to explore whether allostatic load is associated with health outcomes and mediates the association between socioeconomic status and health in a non-Western population. The information collected included: demographic characteristics; allostatic load scores; socioeconomic status, measured by education and income; health behaviours; health-related variables, including self-rated health, basic activities of daily living difficulties, instrumental activities of daily living difficulties, and physical activity difficulties. The adjusted prevalent odds ratios of higher allostatic load level were 1.25 (95% CI: 1.00, 1.56) for reporting one level worse in self-rated health and 1.43 (95% CI: 1.14, 1.82) for reporting one more physical activity difficulty. There were significant associations of lower education or less income with worse self-rated health and more difficulties with physical functioning. The associations between education, income and health status are not mediated by the conventional ten-point measure of allostatic load in older Taiwanese adults.     

Determinants of Circulating 25-Hydroxyvitamin D and bone Mineral Density in Young Physicians

ObjectiveTo examine determinants of serum 25-hydroxyvitamin D [25(OH)D] and bone mineral density (BMD) in young physicians, a group not well studied previously.MethodsWe analyzed data from a questionnaire completed by young physicians as well as results of serum 25(OH)D, serum parathyroid hormone, and BMD measurements.ResultsAmong 104 study subjects, 42% were white, 46% were Asian, 12% were “other” (10 Hispanic and 2 African American subjects), and 75% were women. The mean age and body mass index (BMI) were 28.1 years and 23.0 kg/m², respectively. White subjects had a higher mean serum 25(OH)D level (27.3 ng/mL) than did Asian subjects (15.9 ng/mL) and other subjects (22.3 ng/mL) (P < .0001). White subjects tended to have higher Z-scores than Asian subjects and other subjects for the hip (P = .06), trochanter (P = .08), and lumbar spine (P = .08). The serum 25(OH)D level was negatively associated with serum parathyroid hormone (r = -0.44; P < .01) but not with BMD. The prevalence of vitamin D insufficiency [serum 25(OH)D < 30 ng/mL, 77% for the entire group] was higher (P < .01) in Asian subjects (93%) than in white subjects (61%) and other subjects (73%). Significant determinants of serum 25(OH)D included age, ethnicity, exposure to sunlight, use of vitamin D supplements, and family history of osteoporosis (P < .05 for all), and together with sex, calcium supplements, exercise, and BMI, these factors explained 49% of serum 25(OH)D level variability. Significant determinants of low BMD (osteopenia plus osteoporosis, prevalence 37.5%) included sex (P = .002) and BMI (P < .0001) but not serum 25(OH)D; Asian ethnicity reached borderline significance (P = .088). Age, sex, ethnicity, smoking, and BMI explained 20% to 30% of the Z-score variations.ConclusionIn young physicians with a healthful lifestyle, determinants of low serum 25(OH)D and BMD included modifiable risk factors. Vitamin D insufficiency and low BMD could be important contributors to future osteoporotic fractures in this population. (Endocr Pract. 2012;18:219-226)     

Vitamin D Deficiency Among Medical Residents and Its Relationship with Metabolic Indices

ObjectiveTo evaluate different elements of the cal- ciotropic system in a group of house staff physicians, comparing them with age, gender, and body mass index (BMI) matched controls.MethodsWe measured vitamin D, calcium, phosphorus, parathyroid hormone (PTH), glucose, insulin (estimating the insulin resistance index by the homeostatic model [HOMA]), and lipid levels in 20 medical residents and 20 age-, gender-, and BMI-matched controls. We looked for correlations between elements of the calciotropic system and metabolic indices.ResultsMedical residents and controls were similar in regard to gender distribution, weight, height, BMI, abdominal circumference, as well as systolic and diastolic blood pressure. No differences were found between the two groups in regard to low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, plasma insulin levels, and HOMA-IR. Vitamin D and calcium levels were significantly lower among the medical residents (P = .001 and P = .003, respectively), whereas PTH concentrations tended to be higher. We found an inverse correlation between triglyceride concentrations and vitamin D (r = −0.31, P = .04).ConclusionVitamin D deficiency among resident physicians is frequent and could have metabolic effects. Our findings highlight the consequences of the lack of sun exposure due to occupational reasons. We recommend a higher intake of vitamin D during this period. (Endocr Pract. 2013;19:59-63)     

Depression,Sex and Gender Roles in Older Adult Populations: The International Mobility in Aging Study (IMIAS)

Objectives

To assess the associations between gender roles and depression in older men and women and whether gender roles are independent risk factors for depression.

Methods

International cross-sectional study of adults between 65 and 74 years old (n = 1,967). Depression was defined by a score of 16 or over in the Center for Epidemiologic Studies Depression Scale (CES-D). A validated 12-item Bem Sex Role Inventory (BSRI) was used to classify participants in gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using research site medians of femininity and masculinity as cut-off points. Poisson regressions were fitted to estimate the prevalence ratios (PR) of depression for each gender role compared to the masculine role, adjusting for sex, sufficiency of income, education, marital status, self-rated health, and chronic conditions.

Results

Among men, 31.2% were androgynous, 26% were masculine, 14.4% were feminine, and 28.4% were undifferentiated; among women, the corresponding percentages were 32.7%, 14.9%, 27%, and 25.4%. Both in men and in women, depressive symptoms (CES-D≥16) were more prevalent in those endorsing the undifferentiated type, compared to masculine, feminine or androgynous groups. However, after adjusting for potential confounders, compared to the masculine group only those endorsing the androgynous role were 28% less likely to suffer from depression: PR of 0.72 (95% CI: 0.55–0.93). In fully adjusted models, prevalence rates of depression were not different from masculine participants in the two other gender groups of feminine and undifferentiated.

Conclusions

Androgynous roles were associated with lower rates of depression in older adults, independently of being a man or a woman.     

Validity and reliability of isometric,isokinetic and isoinertial modalities for the assessment of quadriceps muscle strength in patients with total knee arthroplasty

Reliability of isometric, isokinetic and isoinertial modalities for quadriceps strength evaluation, and the relation between quadriceps strength and physical function was investigated in 29 total knee arthroplasty (TKA) patients, with an average age of 63 years. Isometric maximal voluntary contraction torque, isokinetic peak torque, and isoinertial one-repetition maximum load of the involved and uninvolved quadriceps were evaluated as well as objective (walking parameters) and subjective physical function (WOMAC). Reliability was good and comparable for the isometric, isokinetic, and isoinertial strength outcomes on both sides (intraclass correlation coefficient range: 0.947–0.966; standard error of measurement range: 5.1–9.3%). Involved quadriceps strength was significantly correlated to walking speed (r range: 0.641–0.710), step length (r range: 0.685–0.820) and WOMAC function (r range: 0.575–0.663), independent from the modality (P < 0.05). Uninvolved quadriceps strength was also significantly correlated to walking speed (r range: 0.413–0.539), step length (r range: 0.514–0.608) and WOMAC function (r range: 0.374–0.554) (P < 0.05), except for WOMAC function/isokinetic peak torque (P > 0.05). In conclusion, isometric, isokinetic, and isoinertial modalities ensure valid and reliable assessment of quadriceps muscle strength in TKA patients.     

Influence of Visceral Obesity and Liver Fat on Vascular Structure and Function in Obese Subjects

Endothelial dysfunction and increased intima–media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 ± 4.3 kg/m²), we determined (i) endothelial function as flow‐mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = ?0.577, P < 0.0001 and r = ?0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r² = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r² = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.     

The relationship between phosphorylation status of focal adhesion kinases,molecular subtypes,tumour microenvironment and survival in patients with primary operable ductal breast cancer

BackgroundDespite advances in therapies to treat breast cancer, over 100,000 patients die in the UK of this disease per year, highlighting the need to develop effect predictive and prognostic markers for patients with primary operable ductal breast cancer. Therefore, the aim of the present study was to examine the relationship between membranous, cytoplasmic and nuclear expression of focal adhesion kinase (phosphorylated at Y 397, Y 861 and Y 925), molecular subtypes, tumour microenvironment and survival in patients with primary operable ductal breast cancer.MethodsFour hundred and seventy-four patients presenting between 1995 and 1998 with primary operable ductal breast cancer were included in this study. Using tissue microarrays expression of membranous, cytoplasmic and nuclear tumour cell phosphorylation of FAK at Y³⁹⁷, Y⁸⁶¹ and Y⁹²⁵ was assessed, and associations with clinicopathological characteristics, tumour microenvironment and cancer-specific survival (CSS) were examined.ResultsNo significant association was observed for ph-FAK Y⁸⁶¹ with survival at all sites. However, high expression of membranous ph-FAK Y³⁹⁷ was associated with increased tumour grade (P < .001), molecular subtypes (P < .001), increased tumour necrosis (P < .001), high Klintrup–Mäkinen grade (P < .001), increased CD138+ plasma cells (P = .031), endocrine therapy (P = .001) and poor cancer specific survival (P = .040). Similarly, high expression of nuclear ph-FAK Y³⁹⁷ was associated with decreased age (P = .042), increased CD138+ plasma cells (P = .001) and poor cancer specific survival (P = .003). Furthermore, high expression of cytoplasmic ph-FAK Y⁹²⁵ was associated with decreased tumour grade (P < .001), less involved lymph node (P = .020), molecular subtypes (P < .001), decreased tumour necrosis (P < .001), low Klintrup–Mäkinen grade (P < .001), decreased CD4+ T-cells (P = .006), decreased CD138+ plasma cells (P = .034), endocrine therapy (P < .001), chemotherapy (P = .048), and improved cancer specific survival (P = .044). On multivariate analysis, high expression of nuclear ph-FAK Y³⁹⁷ was independently associated with reduced cancer specific survival (P = .017).ConclusionThe results of the present study show that membranous and nuclear ph-FAK Y³⁹⁷ and cytoplasmic ph-FAK Y⁹²⁵ were associated with prognosis in patients with primary operable ductal breast cancer. In addition, high expression of nuclear ph-FAK Y³⁹⁷ was an independent prognostic factor in patients with primary operable ductal breast cancer and could be incorporated into clinical practice.