Yanhui Lu

The effect of age on the changes in bone mineral density and osteoporosis detection rates in Han Chinese men over the age of 50.

Abstract Objective: To examine the relationship between age and BMD at different skeletal sites and osteoporosis (OP) detection rates in Han Chinese men over 50 years and to assess the diagnostic value of the OSTA. Methods: A retrospective analysis of 1488 men over 50 was carried out and group comparisons were made. Results: BMDs at total hip and femoral neck decreased with age (p < 0.01) and were negatively correlated with age by liner correlation analysis (r = −0.36, −0.30; p all <0.05). The detection rates of OP and osteopenia were 10.08% and 43.21% respectively, which increased with age, and significantly higher among over 70 years old than under 70 individuals (47.75% versus 35.56%; 14.88% versus 1.99%; p all <0.01). The detection rate at the femoral neck was similar to the overall detection rate. Sensitivities of OSTA index at a cutoff value of −1 and −4 were 87.33% and 52.0% respectively, and the specificities were 56.20% and 87.59%. Conclusion: BMDs at femoral neck and total hip decrease with age. Detection rates of OP increase with age. Bilateral femoral neck BMD measurement can improve detection rates of OP. OSTA is a useful screening tool for OP in Han Chinese men over 50 years.

Elevated T/E2 Ratio Is Associated with an Increased Risk of Cerebrovascular Disease in Elderly Men

Objective To investigate the relationship between sex hormones and the risk of vascular disease in elderly men and to evaluate the advantages and disadvantages of testosterone replacement. Methods A total of 337 men, aged 60 to 91 years, were enrolled in this single-center, cross-sectional study, and their sex hormone levels were assessed. Linear and logistic regression analyses were utilized to compare the sex hormone levels between patients with and without vascular disease. The nonparametric K-sample test was used for inter-group comparisons. Results Aging and abnormal metabolism were both significantly associated with an increased risk of vascular diseases and changes in sex hormone levels. Primary linear and logistic regression analyses showed no significant differences in sex hormone concentrations between patients with and without vascular diseases after adjusting for age. Logistic regression with abnormal metabolism as categorical variable showed that free testosterone (FT) and free estradiol (FE2) had significant relationships with CEVD risk (P<0.05). In further regression with all metabolic continuous variables included, the testosterone/estradiol (T/E2) ratio replaced FT and FE2 (P<0.05). Trend line analyses showed that T/E2 actually had a binomial linear correlation with the risk of cerebrovascular disease; its best protective effect occurred at values of 0.13–0.15, with an OR value extremely close to those of FT and FE2 (0.23 vs. 0.24–0.25). Conclusion T/E2 balance plays a key role in the relationship between sex hormones and the risk of cerebrovascular disease. The balance between T and E2 may be more important than their absolute quantities. Extremely low T/E2 and inappropriately high T/E2 ratio can both harm the brain blood vessels. Careful consideration should be given before beginning testosterone replacement treatment, and supplementing with estrogen seems to be a good way to protect blood vessels of the brain in elderly men.

Hepatotoxicity induced by zoledronic acid in an aged woman with primary osteoporosis.

Zoledronic acid, a bisphosphonate, has been approved for treatment and prevention of osteoporosis. This case describes a 73-year-old woman with primary osteoporosis who developed transient hepatotoxicity after zoledronic acid (ZOL) treatment. Three days after ZOL infusion, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) were increased by 9.9, 8.1, and 3.7 times, respectively, compared with pretreatment values. Liver protective agents were administered. The aminotransferase returned within normal ranges 12 days post-infusion. Currently, the relationship of ZOL and liver damage is not quite clear, which cannot be explained by its pharmacokinetics. The aim of this case report is to increase the clinicians awareness of the possible adverse effect on the liver, and ZOL should be cautiously administered in patients with liver disease.

The DPP-4 inhibitor MK0626 and exercise protect islet function in early pre-diabetic kkay mice

Dipeptidyl peptidase-4 (DPP-4) inhibitor and exercise have proven to be effective treatments for diabetes. However, the effects of these interventions in compensatory hyperinsulinemia prediabetic period are unknown. The purpose of this study was to determine if these interventions have protective effects on β-cell function and preventive effects on the onset of diabetes in prediabetic kkay mice. After 2 weeks of high-fat diet feeding, we treated 7-week-old mice with a normal diet, high-fat diet, exercise training, or the DPP-4 inhibitor for 8 weeks. C57BL/6J mice served as a normal control. Kkay mice without intervention developed diabetes at week 15, but no diabetic mice were observed in the DPP-4I or exercise groups as well as the normal control group. The DPP-4I and exercise groups showed improved body weight, blood glucose level, glucose tolerance, insulin sensitivity, islet area, and islet morphology. In addition, the proportion of Ki67-positive β-cells in the treatment groups was obviously higher than that in the untreated groups. MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homolog A) expression in the treated groups increased markedly. However PDX-1 (pancreatic and duodenal homeobox-1) expression did not differ significantly among the groups. The results show that exercise and DPP-4I treatment conducted during the hyperinsulinemic prediabetic stage contribute to the maintenance of β-cell function and morphology, enhance β-cell proliferation, extend the compensatory insulin hypersecretion period, and delay disease onset. The expression of PDX-1 was not altered significantly during the early stages of diabetes. However, the reduced expression of the insulin transcription factor MafA may play an important role in the development of prediabetes.

Association between sex hormone levels and abnormal metabolism in a population of elderly Chinese men.

Abstract Objective: Low testosterone levels may be a signal of poor health. This study aimed to investigate the effects of age and abnormal metabolism on sex hormones in Chinese male. Methods: Three hundred and thirty-seven elder men were enrolled into this single-center, cross-sectional study, and their sex hormone levels and metabolic parameters were assessed. Results: Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and sex-hormone-binding globulin (SHBG) concentrations increased with age, while free testosterone index (FTI), testosterone secretion index (TSI), estradiol (E2)/SHBG and progestin (PROG) decreased. Abnormal metabolisms were related to androgen indices (TT, FT, BT, FTI, TSI, T/E2), SHBG and E2/SHBG even after adjusting by age and macrovascular disease. Obesity and overweight, hyperglycemia and dyslipidemia were the most important abnormal metabolism that related to decreased androgen indices. Including SHBG in the stepwise regression increased the explanation effect of TT and BT by 32.7% and 28.5%, respectively, and all metabolic indices were excluded. Abnormal metabolism indies (BMI and PBG) were correlated to the decrease in SHBG levels, while age and LH was positively correlated to SHBG levels. Conclusions: Age and abnormal metabolism were independently important factors associated with the sex hormone levels in elderly Chinese men, which were all mediated by SHBG.

Long-term efficacy and safety of sodium-glucose cotransporter-2 inhibitors as add-on to metformin treatment in the management of type 2 diabetes mellitus: A meta-analysis.

Background: Drug intensification is often required for patients with type 2 diabetes mellitus on stable metformin therapy. Among the potential candidates for a combination therapy, sodium-glucose transporter-2 (SGLT2) inhibitors have shown promising outcomes. This meta-analysis was performed to compare the efficacy and safety of SGLT2 inhibitors with non-SGLT2 combinations as add-on treatment to metformin. Methods: Literature search was carried out in multiple electronic databases for the acquisition of relevant randomized controlled trials (RCTs) by following a priori eligibility criteria. After the assessment of quality of the included RCTs, meta-analyses of mean differences or odds ratios (OR) were performed to achieve overall effect sizes of the changes from baseline in selected efficacy and safety endpoints reported in the individual studies. Between-studies heterogeneity was estimated with between-studies statistical heterogeneity (I2) index. Results: Six RCTs fulfilled the eligibility criteria. SGLT2 inhibitors as add-on to metformin treatment reduced % HbA1c significantly more than non-SGLT2 combinations after 52 weeks (P = .002) as well as after 104 weeks (P < .00001). Among other endpoints, SGLT2 inhibitors also reduced fasting plasma glucose levels, body weight, systolic, and diastolic blood pressures after 52 weeks and 104 weeks significantly (P < .00001) more than non-SGLT2 combinations. Incidence of hypoglycemia was significantly lower (P = .02) but incidence of suspected or confirmed genital tract infections was significantly higher (P < .00001) in SGLT2 inhibitors treated in comparison with non-SGLT2 combinations. Conclusion: As add-on to metformin treatment, SGLT2 inhibitors are found significantly more efficacious than non-SGLT2 inhibitor combinations in the management of type 2 diabetes mellitus, although, SGLT2 inhibitor therapy is associated with significantly higher incidence of suspected or confirmed genital tract infections.

Testosterone level in aging male with different glucose tolerance state and its association with osteocalcin

Abstract Objective: To investigate the relationship of testosterone and different glucose tolerance state, and its association with osteocalcin. Methods: A cross-sectional study was conducted of 1176 males aged 60–97 years who were arranged for an annual regular checkup from March to May 2012 in Chinese PLA general hospital in Beijing. Results: Individuals categorized as having prediabetes or diabetes were more likely to have lower osteocalcin, testosterone, and SHBG levels compared to those with normal glucose tolerance (p < .05 in males). In aging males, after adjusting for age, the negative association between osteocalcin and BMI, waist circumference, FPG, 2hPBG, or TG were significant. And serum TT was negatively associated with BMI, waist circumference, FPG, 2hPBG, or TG independent of age, ALP, Ca, P, VitD, and PTH. Conclusions: It showed that serum osteocalcin and TT were closely related with BMI, blood glucose, and TG, which supported the hypothesis that regulation of bone remodeling, energy metabolism, and reproduction are linked.

Effects of Stratified Vitamin D Supplementation in Middle-Aged and Elderly Individuals with Vitamin D Insufficiency

The incidence of vitamin D deficiency is high globally, and vitamin D supplementation draws particular attention. The objective of this study was to investigate the effects of stratified vitamin D supplementation in middle-aged and elderly individuals with vitamin D insufficiency in Beijing. A total of 448 subjects aged over 40 years old were selected from a community in Beijing. Among them, 100 middle-aged and elderly people with vitamin D insufficiency were randomly selected on a voluntary basis. They were further divided into control group and intervention group. The control group received health education and lifestyle guidance, and the intervention group received lifestyle guidance and vitamin D supplementation for nine months. The doses were stratified as follows: for vitamin D insufficiency, oral vitamin D3 supplement was given at 5000 IU/w; for mild vitamin D deficiency, oral vitamin D3 supplement was given at 10 000 IU/w; for severe vitamin D deficiency, oral vitamin D3 supplement was given at 15 000 IU/w. Safety evaluation was conducted after three-month treatment. The intervention group consisted of 8%, 62%, and 30% of cases who had vitamin D insufficiency, mild vitamin D deficiency, and severe vitamin D deficiency, respectively, which were similar with the control group. It showed that the blood 25(OH)D level increased significantly in the intervention group, from 14.30±4.30 ng/ml to 33.62±6.99 ng/ml (p<0.001), in contrast to insignificant change in the control group. Stratified vitamin D supplementation effectively increased the blood 25(OH)D level, as well as the number of cases with corrected vitamin D insufficiency or deficiency.

TEMPORARY REMOVAL: The glucagon-like peptide-1 analogue liraglutide promotes autophagy through the modulation of 5′-AMP-activated protein kinase in INS-1 β-cells under high glucose conditions

HighlightsGLP‐1 analogue liraglutide increases pancreatic &bgr;‐cells autophagy under high glucose conditions;.Liraglutide inhibits pancreatic &bgr;‐cells apoptosis under high glucose conditions;.Liraglutide may protect &bgr;‐cells from high glucose by enhancing cell autophagy;.Liraglutide promotes pancreatic &bgr;‐cells autophagy through the modulation of 5′‐AMP‐activated protein kinase under high glucose conditions. ABSTRACT Glucagon‐like peptide‐1 (GLP‐1) is a potent therapeutic agent for the treatment of diabetes and has been proven to protect pancreatic &bgr;‐cells from glucotoxicity; however, its mechanisms of action are not entirely understood. Autophagy is a dynamic lysosomal degradation process that can protect organisms against metabolic stress. Studies have shown that autophagy plays a protective role in the survival of pancreatic &bgr;‐cells under high glucose conditions. In the present study, we explored the role of autophagy in GLP‐1‐induced protection of pancreatic &bgr;‐cells exposed to high glucose. We demonstrated that the GLP‐1 analogue liraglutide increased autophagy in rat INS‐1 &bgr;‐cells, and inhibition of autophagy abated the anti‐apoptosis effect of liraglutide under high glucose conditions. Our results also showed that activation of 5′‐AMP‐activated protein kinase (AMPK) reduced liraglutide‐induced autophagy enhancement and inhibited liraglutide‐induced protection of INS‐1 &bgr;‐cells from high glucose. These data suggest that GLP‐1 may protect &bgr;‐cells from glucotoxicity through promoting autophagy by the modulation of AMPK. Deeper insight into the molecular mechanisms linking autophagy and GLP‐1‐induced &bgr;‐cell protection may reveal novel therapeutic targets to preserve &bgr;‐cell mass.