Clinical Characteristics and Mortality of Old and Very Old Patients Hospitalized for Hip Fracture or Acute Medical Conditions.

BACKGROUND: There is increasing interest in healthcare quality and economic implications for hip fracture patients of very old age. However, results are limited by access to comparable control groups. OBJECTIVES: We examined healthcare quality measures including mortality and length of stay (LOS) in hospital of adults aged 60-107 years undergoing hip operations, compared to an age-matched group admitted for acute general medical conditions. DESIGN: Monocentric cross-sectional study. SETTING: Ashford and St Peter's Hospitals NHS Foundation Trust, Surrey, United Kingdom. PARTICIPANTS: A total of 3972 consecutive admissions for hip operation from 1st April 2009 to 30th June 2019 (dataset-1) and 6979 for acute general medical conditions from 1st April 2019 to 29th February 2020 (dataset-2). Respective ages, mean (±standard deviation), were 83.5 years (±9.1) and 79.8 years (±9.8). MEASUREMENTS: Mortality and LOS were assessed with each group divided into five- year age bands and those ≥95 years. RESULTS: There were proportionally more (P <0.001) females admitted for hip operations (72.8%) than for acute general medical conditions (53.8%). Amongst patients admitted with general medical conditions, the frequency of the most serious recorded conditions - including congestive heart failure, stroke, and pneumonia - increased with age. Amongst patients undergoing hip operations, 5.7% died in hospital and 29.3% had a LOS ≥3 weeks. Corresponding values for acute general medical conditions were 10.4% and 11.8%. For those undergoing hip operations in all age categories, the risk of death was lower than for acute general medical group: sex-adjusted odds ratios ranged between 0.27 and 0.67, but the risk of LOS ≥3 weeks was greater: odds ratios ranged between 2.46 and 2.95. CONCLUSIONS: Compared to those admitted with acute general medical conditions, patients admitted for hip operations had a lower risk of death, but a longer hospital LOS. .

Metabolic syndrome and cardiovascular disease after haematopoietic cell transplantation (HCT) in adults: an EBMT cross-sectional non-interventional study.

Metabolic syndrome (MetS) is associated with cardiovascular disease in the general population and is also a potential cardiovascular risk factor in survivors of haematopoietic cell transplantation (HCT). We report an EBMT cross-sectional, multi-centre, non-interventional study of 453 adult HCT patients surviving a minimum of 2 years post-transplant attending routine follow-up HCT and/or late effects clinics in 9 centres. The overall prevalence of MetS was 37.5% rising to 53% in patients >50 years of age at follow-up. There were no differences in rates of MetS between autologous and allogeneic HCT survivors, nor any association with graft-versus-host disease (GvHD) or current immunosuppressant therapy. Notably, there was a significantly higher occurrence of cardiovascular events (CVE, defined as cerebrovascular accident, coronary heart disease or peripheral vascular disease) in those with MetS than in those without MetS (26.7% versus 9%, p < 0.001, OR 3.69, 95% CI 2.09-6.54, p < 0.001), and, as expected, MetS and CVE were age-related. Unexpectedly, CVE were associated with occurrence of second malignancy. Screening for and management of MetS should be integrated within routine HCT long-term follow-up care for both allogeneic and autologous HCT survivors. Further research is warranted, including randomised controlled trials of interventional strategies and mechanistic studies of cardiovascular risk in HCT survivors.

[Study on the relationship between serum vitamin D and the risk of type 2 diabetes in Harbin residents].

Objective: To analyze the relationship between serum vitamin D level and the risk of type 2 diabetes in Harbin residents. Methods: On April 2010, 24 communities in 7 districts of Harbin were selected as research sites using multi-stage stratified cluster random sampling method. A total of 9 734 residents aged 20-74 years was investigated using general questionnaire survey, dietary survey and biochemical indicators test and followed up from January 2015 to July 2016. A total of 4 721 subjects with serum vitamin D were included in the study. According to the quartile of baseline serum vitamin D, the subjects were divided into four groups, from Q1 to Q4 group. The multivariate logistic regression model was used to analyze the relationship between serum vitamin D and the risk of type 2 diabetes. A mediation analysis model was used to analyze the mediating role of insulin resistance in this risk relationship. Results: At the time of follow-up, 432 patients with type 2 diabetes were screened. The median (P(25), P(75)) age of the diabetic group and the non-diabetic group were 54 (49, 61) and 51 (43, 57) years, respectively, and males accounted for 40.5% (175 cases) and 35.5% (1 513 cases), respectively. The median (P(25), P(75)) serum vitamin D was 16.0 (13.5, 18.5) and 17.4 (14.3, 20.5) ng/ml, respectively. After relevant confounders and insulin resistance index (HOMA-IR) were adjusted, compared to the serum vitamin D level Q(1) group, the risk of diabetes was reduced by 40% in the Q(3) group with RR (95%CI) about 0.60 (0.44-0.82), while the risk of diabetes was reduced by 59% in Q(4) group with RR (95%CI) about 0.41 (0.29-0.57). Through mediation analysis, the Gutt index mediating effect representing peripheral insulin resistance was 53.8%, and the mediating effect of HOMA-IR representing hepatic insulin resistance was 6.6%. Conclusion: The risk of type 2 diabetes is low in Harbin residents with higher serum vitamin D level. Insulin resistance has a mediating effect on the relationship of vitamin D and the risk of type 2 diabetes.

[Association between dietary magnesium and the risk of type 2 diabetes in Harbin residents].

Objective: To investigate the relationship between the magnesium intake and patterns of diary and the risk of type 2 diabetes in Harbin residents. Methods: On April 2010, 24 communities in 7 districts of Harbin were selected as research sites using multi-stage stratified random cluster sampling method. A total of 9 734 residents aged 20-74 years was investigated using general questionnaire survey, dietary survey and biochemical indicators test. A total of 9 376 subjects were included in the study. Factor analysis was used to analyze dietary patterns. According to the quartile of dietary magnesium intake, the subjects were divided into four groups, from Q(1) to Q(4) group. The multivariate logistic regression model was used to analyze the relationship between dietary magnesium intake and the risk of type 2 diabetes within different dietary patterns. Results: A total of 998 subjects with type 2 diabetes were screened. The median age of the diabetic group and the non-diabetic group were 54.8 and 50.8, respectively, and the males accounted for 43.4% (2 896 cases) and 34.6% (433 cases), respectively. The magnesium intake median (P(25), P(75)) of two groups was 336.36 (257.31, 440.65) and 339.50 (264.51, 443.78) mg/d. Four dietary patterns were identified as western dietary mode, savvy dietary mode, traditional dietary mode, and staple food mode. In the western dietary model, the Q(4) group had a higher risk of type 2 diabetes than Q(1) group, with an OR (95%CI) value of 1.56 (1.06 to 2.32). However, in the savvy diet mode, compared with the Q(1) group, the risk of diabetes in the Q(4) group was lower, and the OR (95%CI) value was 0.61 (0.37 to 0.96). There was no statistically significant association between dietary magnesium intake and the risk of type 2 diabetes without considering dietary patterns (P>0.05). Conclusion: Dietary magnesium intake has a different relationship with the risk of type 2 diabetes within different dietary patterns.

Associations of BMI, waist circumference, body fat, and skeletal muscle with type 2 diabetes in adults.

AIMS: Type 2 diabetes (T2D) is known to be associated with high BMI and waist circumference (WC). These measures do not discriminate well between skeletal muscle (SM) and body fat (BF), which may have opposite influences. METHODS: We conducted a secondary analysis of population-based data from 58,128 aged 18-85 yrs from Scottish Health Surveys (2003, 2008-2011) and Health Surveys for England (2003-2006, 2008-2013), excluding pregnant women and insulin-treated diabetes. Logistic regression was used to assess associations of known T2D, and of screened HbA1c > 48 mmol/mol (> 6.5%), with sex-specific quintiles of BMI, WC, and BF% and SM% estimated by validated anthropometric equations, adjusted for age, sex, smoking, ethnicity, country, and survey year. RESULTS: As expected, ORs for having known T2D rose with quintiles of BMI (1, 1.5, 2.3, 3.1, and 6.5) and WC (1, 1.8, 2.5, 3.5, and 8.7). Compared to the lowest BF% quintile, OR for having T2D in highest BF% quintile was 11.1 (95% CI = 8.4-14.6). Compared to the highest SM% quintile, OR for having T2D in lowest SM% quintile was 2.0 (1.7-2.4). Of 72 adults with T2D/HbA1c > 6.5% in the lowest quintile of BF%, 27 (37.5%) were in quintile 1 of SM%. Similar patterns of OR were observed for having HbA1c > 6.5% in those without known T2D. CONCLUSIONS: Estimated BF% associates strongly with T2D. Low SM% also has a significant association, suggesting a neglected aspect of aetiology within T2D. These two simple measures with biological relevance, available from data collected in most health surveys, may be more useful than the purely statistical terms BMI.

Different associations between body composition and alcohol when assessed by exposure frequency or by quantitative estimates of consumption.

BACKGROUND: Alcohol intake is widely assumed to contribute to excess body fatness, especially among young men; however, the evidence is inconsistent. We have addressed this research question by investigating associations between reported alcohol consumption and body composition from large representative national surveys in a high alcohol-consuming country with a high obesity prevalence. METHODS: The present study comprised a secondary analysis of combined cross-sectional nationally representative Scottish Health Surveys (1995-2010). Reported alcohol-drinking frequency was divided into five groups: from 'nonfrequent drinking' (reference) to daily/'almost every day' among 35 837 representative adults [mean (SD) age: 42.7 (12.7) years (range 18-64 years)]. Quantitative alcohol consumption was categorised into seven groups: from '1-7 to ≥50 10 g units per week'. Regression models against measured body mass index (BMI) and waist circumference (WC) were adjusted for age, physical activity, income, smoking, deprivation category and economic status. RESULTS: Among alcohol-consuming men, heavier drinking (21-28 units per week) was associated with a higher BMI by +1.4 kg m-2 [95% confidence interval (CI) = 1.38-1.43] and higher WC by +3.4 cm (95% CI = 3.2-3.6) than drinking 1-7 units per week. However, those who reported daily drinking frequency were associated with a lower BMI by -2.45 kg m-2 (95% CI = -2.4 to -2.5) and lower WC by -3.7 cm (95% CI = -3.3 to -4.0) than those who reported less-frequent drinking. Similar associations were found for women. Most of these associations were restricted to subjects aged >30 years. Unexplained variances in BMI and WC are large. CONCLUSIONS: Quantitative alcohol consumption and frequency of consumption were positively and inversely associated, respectively, with both BMI and WC among alcohol-consuming adults. Surveys are needed that evaluate both the quantity and frequency of consumption. The lowest BMI and WC were associated with a 'Mediterranean' drinking style (i.e. relatively little, but more frequently).

Intestinal cancer progression by mutant p53 through the acquisition of invasiveness associated with complex glandular formation.

Tumor suppressor TP53 is frequently mutated in colorectal cancer (CRC), and most mutations are missense type. Although gain-of-functions by mutant p53 have been demonstrated experimentally, the precise mechanism for malignant progression in in vivo tumors remains unsolved. We generated ApcΔ716 Trp53LSL•R270H villin-CreER compound mice, in which mutant p53R270H was expressed in the intestinal epithelia upon tamoxifen treatment, and examined the intestinal tumor phenotypes and tumor-derived organoids. Mutant Trp53R270H, but not Trp53-null mutation accelerated submucosal invasion with generation of desmoplastic microenvironment. The nuclear accumulation of p53 was evident in ApcΔ716 Trp53R270H/R270H homozygous tumors like human CRC. Although p53 was distributed to the cytoplasm in ApcΔ716 Trp53+/R270H heterozygous tumors, it accumulated in the nuclei at the invasion front, suggesting a regulation mechanism for p53 localization by the microenvironment. Importantly, mutant p53 induced drastic morphological changes in the tumor organoids to complex glandular structures, which was associated with the acquisition of invasiveness. Consistently, the branching scores of human CRC that carry TP53 mutations at codon 273 significantly increased in comparison with those of TP53 wild-type tumors. Moreover, allografted ApcΔ716 Trp53R270H/R270H organoid tumors showed a malignant histology with an increased number of myofibroblasts in the stroma. These results indicate that nuclear-accumulated mutant p53R270H induces malignant progression of intestinal tumors through complex tumor gland formation and acquisition of invasiveness. Furthermore, RNA sequencing analyses revealed global gene upregulation by mutant p53R270H, which was associated with the activation of inflammatory and innate immune pathways. Accordingly, it is possible that mutant p53R270H induces CRC progression, not only by a cell intrinsic mechanism, but also by the generation or activation of the microenvironment, which may synergistically contribute to the acceleration of submucosal invasion. Therefore, the present study indicates that nuclear-accumulated mutant p53R270H is a potential therapeutic target for the treatment of advanced CRCs.

Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study.

OBJECTIVE: Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. DESIGN: Cross-sectional general population survey. SETTING: Scotland. PARTICIPANTS: 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45-64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30-59 years surveyed in 1996. MAIN MEASURES: Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. RESULTS: Regression coefficients for BMI associations between father-son (0.30) and mother-daughter (0.33) were greater than father-daughter (0.23) or mother-son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m(2). Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. CONCLUSIONS: There are modest genetic/epigenetic influences on the environmental factors behind adverse adiposity. Maternal smoking appears a specific hazard on obesity and metabolic syndrome. A possible epigenetic mechanism linking maternal smoking to obesity and metabolic syndrome in offspring is proposed. Individuals with family histories of obesity should be targeted from an early age to prevent obesity and complications.

Associations of obesity with socioeconomic and lifestyle factors in middle-aged and elderly men: European Male Aging Study (EMAS).

BACKGROUND: Social and lifestyle influences on age-related changes in body morphology are complex because lifestyle and physiological response to social stress can affect body fat differently. OBJECTIVE: In this study, we examined the associations of socioeconomic status (SES) and lifestyle factors with BMI and waist circumference (WC) in middle-aged and elderly European men. DESIGN AND SETTING: A cross-sectional study of 3319 men aged 40-79 years recruited from eight European centres. OUTCOMES: We estimated relative risk ratios (RRRs) of overweight/obesity associated with unfavourable SES and lifestyles. RESULTS: The prevalence of BMI ≥ 30 kg/m(2) or WC ≥ 102 cm rose linearly with age, except in the eighth decade when high BMI, but not high WC, declined. Among men aged 40-59 years, compared with non-smokers or most active men, centre and BMI-adjusted RRRs for having a WC between 94 and 101.9 cm increased by 1.6-fold in current smokers, 2.7-fold in least active men and maximal at 2.8-fold in least active men who smoked. Similar patterns but greater RRRs were observed for men with WC ≥ 102 cm, notably 8.4-fold greater in least active men who smoked. Compared with men in employment, those who were not in employment had increased risk of having a high WC by 1.4-fold in the 40-65 years group and by 1.3-fold in the 40-75 years group. These relationships were weaker among elderly men. CONCLUSION: Unfavourable SES and lifestyles associate with increased risk of obesity, especially in middle-aged men. The combination of inactivity and smoking was the strongest predictor of high WC, providing a focus for health promotion and prevention at an early age.

Carotenoderma in a young woman of normal body mass index with hypothalamic amenorrhoea: a 2-year follow-up case report.

Hypothalamic amenorrhoea has been shown to be associated with hypercarotenaemia, but no causal link has been established. Many people are unaware of the health implications of carotenoderma. We report on a 36-year-old woman with normal body mass index and with a history of secondary amenorrhoea for 2 years and carotenoderma for 5 years. She had a history of practising a fixed-menu diet of predominantly leafy greens, exercised intensively and had a stressful job. Blood tests confirmed the presence of hypercarotenaemia and hypogonadotrophic hypogonadism. Carotenoderma subsided after 6 months of lifestyle modification, but she remained amenorrhoeic up to 12 months later. Since then, her condition had relapsed up to the time of 2 years of follow-up. We conclude that hypercarotenaemia/carotenoderma and hypothalamic amenorrhoea are manifestations of a constrained lifestyle rather than causally linked. The presence of carotenoderma should alert public individuals and clinicians, especially in primary care, alike for signs of potential health complications including reproductive dysfunction even without weight problems.

Relationship between final height and health outcomes in adults with congenital adrenal hyperplasia: United Kingdom congenital adrenal hyperplasia adult study executive (CaHASE).

CONTEXT: Treatment of congenital adrenal hyperplasia (CAH) in childhood focuses on growth and development and adult final height (FH) is a measure of effective treatment. We hypothesized that shorter adults will have more severe underlying disease and worse health outcomes. METHODS: This was a cross-sectional analysis of 199 adults with CAH. FH and quality of life were expressed as z-scores adjusted for midparental target height or UK population height. RESULTS: FH correlated inversely with age (men, r = -0.38; women, r = -0.26, P < .01). Men and women had z-scores adjusted for midparental target height of -2 and -1, respectively, and both groups had UK population height z-scores of -1 below the UK population (P < .01). In women, FH was shorter in non-salt-wasting than salt-wasting classic CAH (P < .05) and in moderately affected genotype group B women than either more severely affected groups null and A (P < .01) or the mildest group C (P < .001). Short stature and a higher prevalence of hypertension were observed in classic CAH patients diagnosed late (after 1 y) compared with those diagnosed early and in women treated with glucocorticoid only compared with those treated with both glucocorticoids and mineralocorticoids (P < .05). FH did not associate with insulin sensitivity, lipid profile, adiposity, or quality of life. CONCLUSIONS: Adult CAH patients remain short, although height prognosis has improved over time. The shortest adults are those diagnosed late with moderate severity CAH and are at increased risk of adult hypertension; we hypothesize that these patients are exposed in childhood to high androgens and/or excessive glucocorticoids with potential programming of hypertension. Another possibility is inadequate mineralocorticoid treatment early in life in the late-diagnosed patient group. Prospective studies are now required to examine these hypotheses.

Late-onset hypogonadism and mortality in aging men.

CONTEXT: Late-onset hypogonadism (LOH) has recently been defined as a syndrome in middle-aged and elderly men reporting sexual symptoms in the presence of low T. The natural history of LOH, especially its relationship to mortality, is currently unknown. OBJECTIVE: The aim of this study was to clarify the associations between LOH, low T, and sexual symptoms with mortality in men. DESIGN, SETTING, AND PARTICIPANTS: Prospective data from the European Male Aging Study (EMAS) on 2599 community-dwelling men aged 40-79 years in eight European countries was used for this study. MAIN OUTCOME MEASURE(S): All-cause, cardiovascular, and cancer-related mortality was measured. RESULTS: One hundred forty-seven men died during a median follow-up of 4.3 years. Fifty-five men (2.1%) were identified as having LOH (31 moderate and 24 severe). After adjusting for age, center, body mass index (BMI), current smoking, and poor general health, compared with men without LOH, those with severe LOH had a 5-fold [hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.7, 11.4] higher risk of all-cause mortality. Compared with eugonadal men, the multivariable-adjusted risk of mortality was 2-fold higher in those with T less than 8 nmol/L (irrespective of symptoms; HR 2.3; 95% CI 1.2, 4.2) and 3-fold higher in those with three sexual symptoms (irrespective of serum T; compared with asymptomatic men; HR 3.2; 95% CI 1.8, 5.8). Similar risks were observed for cardiovascular mortality. CONCLUSIONS: Severe LOH is associated with substantially higher risks of all-cause and cardiovascular mortality, to which both the level of T and the presence of sexual symptoms contribute independently. Detecting low T in men presenting with sexual symptoms offers an opportunity to identify a small subgroup of aging men at particularly high risk of dying.

PPP1R1B-STARD3 chimeric fusion transcript in human gastric cancer promotes tumorigenesis through activation of PI3K/AKT signaling.

Fusion genes act as potent oncogenes, resulting from chromosomal rearrangements or abnormal transcription in many human cancers. Although multiple gastric cancer genomes have been sequenced, the driving recurrent gene fusions have not been well characterized. Here, we used paired-end transcriptome sequencing to identify novel gene fusions in 18 human gastric cancer cell lines and 18 pairs of primary human gastric cancer tissues and their adjacent normal tissues. Multiple samples revealed expression of PPP1R1B-STARD3 fusion transcript. The presence of PPP1R1B-STARD3 correlated with elevated levels of PPP1R1B mRNA. PPP1R1B-STARD3 fusion transcript was detected in 21.3% of primary human gastric cancers but not in adjacent matched normal gastric tissues. Based on reverse transcription PCR analysis of DNA, unlike other fusions described in gastric cancer, the PPP1R1B-STARD3 appears to be generated by RNA processing without chromosomal rearrangement. Overexpression of PPP1R1B-STARD3 in MKN-28 significantly increased cell proliferation and colony formation. This increased proliferation was mediated by activation of phosphatidylinositol-3-kinase (PI3K)/AKT signaling. Furthermore, expression of PPP1R1B-STARD3 fusion transcript enhanced the tumor growth of MKN-28 cells in athymic nude mice. These findings show that PPP1R1B-STARD3 fusion transcript has a key role in subsets of gastric cancers through the activation of PI3K/AKT signaling.

Obesity and weight management in the elderly: a focus on men.

The rising rate of overweight/obesity among the ever-growing ageing population is imposing massive and rapidly changing burdens of ill health. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults, mainly through its reduced impact on coronary heart disease, has often been misinterpreted that obesity is not as harmful in the elderly, who suffer a large range of disabling consequences of obesity. All medical consequences of obesity are multi-factorial and most alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. But severe obesity, e.g. BMI >40 may demand greater weight loss e.g. >15 kg to reverse type 2 diabetes. Since relatively reduced physical activity and reduced muscle mass (sarcopenic obesity) are common in the elderly, combining exercise and modest calorie restriction optimally reduces fat mass and preserves muscle mass - age presents no obstacle and reducing polypharmacy is a valuable outcome. The currently licensed drug orlistat has no age-related hazards and is effective in a low fat diet, but the risks from bariatric surgery begin to outweigh benefits above age 60. For the growing numbers of obese elderly with diabetes, the glucagon-like peptide-1 (GLP-1) receptor analogue liraglutide appears a safe way to promote and maintain substantial weight loss. Obesity and sarcopenia should be prevented from younger age and during life-transitions including retiral to improve future health outcomes and quality of life, with a focus on those in "obese families".

Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study.

OBJECTIVE: Health and lifestyle factors are associated with variations in serum testosterone levels in ageing men. However, it remains unclear how age-related changes in testosterone may be attenuated by lifestyle modifications. The objective was to investigate the longitudinal relationships between changes in health and lifestyle factors with changes in hormones of the reproductive endocrine axis in ageing men. DESIGN: A longitudinal survey of 2736 community-dwelling men aged 40-79 years at baseline recruited from eight centres across Europe. Follow-up assessment occurred mean (±S.D.) 4.4±0.3 years later. RESULTS: Paired testosterone results were available for 2395 men. Mean (±S.D.) annualised hormone changes were as follows: testosterone -0.1±0.95  nmol/l; free testosterone (FT) -3.83±16.8  pmol/l; sex hormone-binding globulin (SHBG) 0.56±2.5  nmol/l and LH 0.08±0.57  U/l. Weight loss was associated with a proportional increase, and weight gain a proportional decrease, in testosterone and SHBG. FT showed a curvilinear relationship to weight change; only those who gained or lost ≥15% of weight showed a significant change (in the same direction as testosterone). Smoking cessation was associated with a greater decline in testosterone than being a non-smoker, which was unrelated to weight change. Changes in number of comorbid conditions or physical activity were not associated with significant alterations in hypothalamic-pituitary-testicular (HPT) axis function. CONCLUSIONS: Body weight and lifestyle factors influence HPT axis function in ageing. Weight loss was associated with a rise, and weight gain a fall, in testosterone, FT and SHBG. Weight management appears to be important in maintaining circulating testosterone in ageing men, and obesity-associated changes in HPT axis hormones are reversible following weight reduction.

Epidemiological evidence against a role for C-reactive protein causing leptin resistance.

OBJECTIVE: It has been suggested that elevated levels of C-reactive protein (CRP) might interfere with leptin signalling and contribute to leptin resistance. Our aim was to assess whether plasma levels of CRP influence leptin resistance in humans, and our hypothesis was that CRP levels would modify the cross-sectional relationships between leptin and measures of adiposity. DESIGN AND METHODS: W assessed four measures of adiposity: BMI, waist circumference, fat mass and body fat (%) in 2113 British Regional Heart Study (BRHS) men (mean (s.d.) age 69 (5) years), with replication in 760 (age 69 (6) years) European Male Ageing Study (EMAS) subjects. RESULTS: IN BRHS subjects, leptin correlated with CRP (SPEARMAN'S R=0.22, P0.0001). Leptin and crp correlated with all four measures of adiposity (R VALUE RANGE: 0.22-0.57, all P<0.0001). Age-adjusted mean levels for adiposity measures increased in relation to leptin levels, but CRP level did not consistently influence the ß-coefficients of the regression lines in a CRP-stratified analysis. In BRHS subjects, the BMI vs leptin relationship demonstrated a weak statistical interaction with CRP (P=0.04). We observed no similar interaction in EMAS subjects and no significant interactions with other measures of adiposity in BRHS or EMAS cohorts. CONCLUSION: We have shown that plasma CRP has little influence on the relationship between measures of adiposity and serum leptin levels in these middle-aged and elderly male European cohorts. This study provides epidemiological evidence against CRP having a significant role in causing leptin resistance.

Glucocorticoid treatment regimen and health outcomes in adults with congenital adrenal hyperplasia.

BACKGROUND: Adults with congenital adrenal hyperplasia (CAH) are treated with a wide variety of glucocorticoid treatment regimens. OBJECTIVE, DESIGN AND METHODS: To test whether drug dose and timing of glucocorticoid treatment regimen impacts on health outcomes. This was a cross-sectional study of 196 adult CAH patients in whom treatment and health outcomes were measured. Glucocorticoid dose was converted to prednisolone dose equivalent (PreDEq) using three published formulae. Associations between the type of glucocorticoid regimen and PreDEq with specific health outcome variables were tested using partial correlation and principal components analysis (PCA). RESULTS: Patients on dexamethasone had lower androgens and ACTH but greater insulin resistance compared with those receiving hydrocortisone or prednisolone. Dexamethasone dose and once daily administration were associated with insulin resistance. Partial correlation analysis adjusted for age and sex showed PreDEq weakly correlated (r < 0·2) with blood pressure and androstenedione. Mutation severity was associated with increased PreDEq (F(3,141)  = 4·4, P < 0·01). In PCA, 3 PCs were identified that explained 62% of the total variance (r(2) ) in observed variables. Regression analysis (age and sex adjusted) confirmed that PC2, reflecting disease control (androstenedione, 17-hydroxypregesterone and testosterone), and PC3, reflecting blood pressure and mutations (systolic and diastolic blood pressure and mutation severity), related directly to PreDEq (r(2)  = 23%, P < 0·001). CONCLUSIONS: In adults with congenital adrenal hyperplasia, dexamethasone use was associated with lower androgens but greater insulin resistance, and increasing glucocorticoid dose associated with increased blood pressure, poor disease control and mutation severity.

Frailty Is Associated with Impaired Quality of Life and Falls in Middle-Aged and Older European Men.

OBJECTIVES: Adapt a measure of frailty for use in a cohort study of European men and explore relationships with age, health related quality of life and falls. DESIGN: Longitudinal cohort study. SETTING: 8 European centers. PARTICIPANTS: 3047 men aged 40-79 participating in the European Male Ageing Study (EMAS). MEASUREMENTS: Frailty was assessed using an adaptation of the Cardiovascular Health Study criteria. Health related quality of life was evaluated using the Rand Short Form-36 (SF-36) questionnaire which comprises both mental and physical component scores. Self reported falls in the preceding 12 months were recorded at 2-year follow-up. RESULTS: 78 men (2.6%) were classified as frail (≥3 criteria) and 821 (26.9%) as prefrail (1-2 criteria). The prevalence of frailty increased from 0.1% in men aged 40-49 up to 6.8% in men aged 70-79. Compared to robust men, both prefrail and frail men had lower health related quality of life. Frailty was more strongly associated with the physical than mental subscales of the SF-36. Frailty was associated with higher risk of falls OR (95% CI) 2.92 (1.52, 5.59). CONCLUSIONS: Frailty, assessed by the EMAS criteria, increased in prevalence with age and was related to poorer health related quality of life and higher risk of falls in middle-aged and older European men. These criteria may help to identify a vulnerable subset of older men.

Thyroid hormones and male sexual function.

The role of thyroid hormones in the control of erectile functioning has been only superficially investigated. The aim of the present study was to investigate the association between thyroid and erectile function in two different cohorts of subjects. The first one derives from the European Male Ageing Study (EMAS study), a multicentre survey performed on a sample of 3369 community-dwelling men aged 40-79 years (mean 60 ± 11 years). The second cohort is a consecutive series of 3203 heterosexual male patients (mean age 51.8 ± 13.0 years) attending our Andrology and Sexual Medicine Outpatient Clinic for sexual dysfunction at the University of Florence (UNIFI study). In the EMAS study all subjects were tested for thyroid-stimulating hormone (TSH) and free thyroxine (FT4). Similarly, TSH levels were checked in all patients in the UNIFI study, while FT4 only when TSH resulted outside the reference range. Overt primary hyperthyroidism (reduced TSH and elevated FT4, according to the reference range) was found in 0.3 and 0.2% of EMAS and UNIFI study respectively. In both study cohorts, suppressed TSH levels were associated with erectile dysfunction (ED). Overt hyperthyroidism was associated with an increased risk of severe erectile dysfunction (ED, hazard ratio = 14 and 16 in the EMAS and UNIFI study, respectively; both p < 0.05), after adjusting for confounding factors. These associations were confirmed in nested case-control analyses, comparing subjects with overt hyperthyroidism to age, BMI, smoking status and testosterone-matched controls. Conversely, no association between primary hypothyroidism and ED was observed. In conclusion, erectile function should be evaluated in all individuals with hyperthyroidism. Conversely, assessment of thyroid function cannot be recommended as routine practice in all ED patients.

Obesity and weight management in the elderly.

Our population is ageing, and obesity is increasing in the elderly bringing massive and rapidly changing burdens of ill health related to increased body weights and fat as well as the main drivers of poor diet and inactivity. Overweight and obesity, and a static body mass index (BMI) commonly conceal sarcopenia (gain in body fat but loss of muscle mass and functional capacity) in older people, aggravated by inactivity. A systematic computerized literature search using an iterative manipulation process of the keywords: obesity, elderly, weight loss. The following databases were accessed on 20 October 2010: Medline, Cochrane Collaboration, Ovid and Scholar Google. A large number of clinical consequences of overweight and obesity are particularly problematic for elderly individuals, including type 2 diabetes mellitus, arthritis, urinary incontinence and depression. The observation that the BMI value associated with the lowest relative mortality is slightly higher in older than in younger adults has often been misinterpreted that obesity is not as harmful in the elderly. BMI may be a less appropriate index in the elderly. All the medical consequences of obesity are multi-factorial but all are alleviated by modest, achievable weight loss (5-10 kg) with an evidence-based maintenance strategy. Since sarcopenic obesity is common in the elderly, a combination of exercise and modest calorie restriction appears to be the optimal method of reducing fat mass and preserving muscle mass. Reduction in polypharmacy is a valuable target for weight management. Age is not an obstacle to weight management interventions using moderate calorie restriction and exercise, and the currently licensed drug orlistat appears to have no age-related hazards. Overall balance of clinical outcomes has not been evaluated. In older people the risks from bariatric surgery outweigh benefits. Obesity, and specifically sarcopenic obesity, should also be prevented not only from younger age, but also during major life transitions including retirement, to improve better health outcomes and quality of life in later years, with a focus on those in 'obese families', where the main increases in obesity are located. Randomized controlled trials to determine health benefits and risks from long-term weight management in obese elderly are necessary.