Association between physical activity and mortality in patients with osteoporosis: a cohort study of NHANES.

We utilized data from the NHANES to investigate the impact of physical activity on mortality in osteoporotic patients. Our study suggests that osteoporotic patients may require higher volumes of physical activity to reduce mortality risk compared to the general population. In osteoporotic patients, the dose-response relationships between physical activity volumes and both all-cause and cardiovascular mortality were linear. In contrast, these relationships were non-linear in participants without osteoporosis. PURPOSE: To determine the impact of physical activity on mortality in osteoporotic patients. METHODS: A total of 5606 participants were included in this study, including 716 osteoporosis patients. Physical activity was assessed using standardized questionnaire. Participants were categorized into four groups: inactive (no physical activity), low active (physical activity volumes < 150 min/week), moderate active (≥ 150 min/week but < 300 min/week), and high active (≥ 300 min/week). Multivariable Cox regression models, using the inactive group as the reference and adjusted for potential confounders, were performed to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: Osteoporotic patients demonstrated higher mortality rates attributed to various causes compared to non-osteoporosis participants. Physical activity was associated with lower mortality regardless of osteoporosis status. However, Multivariable Cox regression analysis indicated that among osteoporosis patients, only those engaging in ≥ 300 min/week physical activity experienced a significant decrease in mortality (all-cause mortality, HR (95% CI) 0.453 (0.268, 0.767) and cardiovascular mortality, HR (95% CI) 0.521 (0.259, 1.049)), surpassing the threshold of 150 min observed in non-osteoporosis patients. In sensitivity analysis, or when the proportion of vigorous physical activity was included as a confounder in the multivariate Cox regression analysis, only the high active group still showed a significant reduction in mortality. No significant interactions were observed when the analysis was stratified according to age, sex, and body mass index (P for interaction > 0.05). Restricted cubic spline analysis revealed a linear relationship between physical activity volume and all-cause mortality (P < 0.01 [overall] and P = 0.470 [non-linearity]) and cardiovascular-specific mortality (P = 0.003 [overall] and P = 0.610 [non-linearity]) in patients with osteoporosis. In contrast, these relationships were non-linear in participants without osteoporosis. CONCLUSION: Patients with osteoporosis need to engage in ≥ 300 min/week physical activity to significantly reduce their mortality risk. And the higher the volume of physical activity, the lower the risk of death.

The effect of statin adherence on patients with type 2 diabetes after percutaneous coronary intervention for acute coronary syndrome.

PURPOSE: To investigate the effect of long-term statin adherence among patients with type 2 diabetes mellitus (T2DM) after percutaneous coronary intervention (PCI) for acute coronary syndrome. MAIN OUTCOME MEASURES: All-cause readmission after initial PCI intervention was defined as the main outcome of the study. Readmission for revascularization, cerebrovascular disease, and so on among the study population was analyzed as secondary outcomes. METHODS: A total of 11,172 patients with T2DM who underwent PCI for ACS were selected from the Beijing Basic Medical Insurance Database for urban employees between January 1, 2014, and December 31, 2018. Patients' long-term adherence to statin utilization was investigated during a 3-year follow-up period through survival analysis after adjusting for covariates, including outpatient medications for secondary prevention of coronary heart disease and other complications. RESULTS: Among patients, 29.7% showed a high level of adherence in terms of statin utilization after 3 years of follow-up. High statin utilization adherence was associated with a reduction in all-cause hospitalization rates compared to those with low levels of adherence (62.72% vs. 68.18%; HR, 0.85 [95% CI, 0.80-0.90], P < 0.0001). For secondary outcomes, a high level of statin adherence showed a protective effect as well: readmission rate for revascularization (49.56% vs. 53.96%, HR, 0.87 [95% CI, 0.82-0.93], P < 0.0001), readmission rate for cerebrovascular disease (6.78% vs. 10.17%, HR, 0.65 [95% CI, 0.55-0.76], P < 0.0001), and diabetes-related readmissionrate (11.05% vs. 14.81%, HR, 0.69 [95% CI, 0.61-0.79], P < 0.0001). CONCLUSION: In Beijing, long-term statin adherence among patients with T2DM after PCI is still not high, and the incidence of all-cause readmission, revascularization and cerebrovascular disease may be reduced through improving statin adherence.

Comparing the effects of twice-daily exenatide and insulin on renal function in patients with type 2 diabetes mellitus: secondary analysis of a randomized controlled trial.

This is a secondary analysis of a randomized controlled trial (RCT) on the effects of the glucagon-like peptide-1 receptor agonists exenatide and insulin aspartate 30 injection on carotid intima-media thickness. Here, we report the renal outcomes of the intervention in patients with type 2 diabetes mellitus (T2DM). Data from the RCT study was used to evaluate the effect of exenatide or insulin given for 52 weeks on estimated glomerular filtration rate (eGFR) in patients with T2DM. The primary end point was the change in the eGFR from baseline between the exenatide and insulin groups in normal versus overweight patients and patients with obesity. The secondary end point was the correlation between change in eGFR and oxidative stress, glycemic control, and dyslipidemia. There was a significant difference in eGFR between the insulin and exenatide groups at 52 weeks (p=0.0135). Within the insulin group, the eGFR remained below baseline at 52 weeks in all patients, and there was an increase in body weight in the normal group compared with the overweight patients and patients with obesity. The opposite was observed in the exenatide group. A decrease in body weight was prominent in the exenatide group at 52 weeks (p<0.05), the eGFR was below baseline in overweight patients and patients with obesity and significantly above baseline in the normal group (p<0.05). The eGFR was positively correlated to 8-oxo-7,8-dihydroguanosine in the insulin group (p<0.05) but not the exenatide group. It can be concluded that compared with insulin, exenatide may improve renal function in overweight patients and patients with obesity more than in normal-weight patients with T2DM, but a further RCT is needed to confirm this effect.

Efficacy of Exenatide Administered Twice Daily in Body Mass Index Reduction in Patients with Type 2 Diabetes Mellitus.

Background: Exenatide is a glucagon-like peptide-1 receptor agonist that can reduce body weight. This study aimed to determine the efficacy of exenatide on body mass index (BMI) reduction in patients with type 2 diabetes mellitus (T2DM) with differing baseline body weight, blood glucose, and atherosclerotic status and to determine if there is a correlation between BMI reduction and cardiometabolic indices in these patients. Methods: This retrospective cohort study used data from our randomized controlled trial. A total of 27 T2DM patients treated with combination therapy of exenatide twice daily and metformin for 52 weeks were included. The primary endpoint was a change in the BMI from the baseline to week 52. The secondary endpoint was a correlation between BMI reduction and cardiometabolic indices. Findings. The BMIs of overweight and obesity patients and those with glycated hemoglobin (HbA1c) ≥ 9% significantly decreased -1.42 ± 1.48 kg/m2(P=0.015) and -0.87 ± 0.93 kg/m2(P=0.003), respectively, at the baseline after 52 weeks of treatment. There was no reduction in BMI in patients with normal weight, HbA1c <9%, the nonatherosclerosis group, and the atherosclerosis group. The decrease in BMI was positively correlated with changes in blood glucose, high-sensitivity C-reactive protein (hsCRP), and systolic blood pressure (SBP). Conclusion: BMI scores improved after exenatide treatment for 52 weeks in T2DM patients. Weight loss was affected by baseline body weight and blood glucose level. In addition, BMI reduction from the baseline to 52 weeks was positively correlated with baseline HbA1c, hsCRP, and SBP. Trial Registration. Chinese Clinical Trial Registry (ChiCTR-1800015658).

Treatment Outcomes of Clopidogrel in Patients With ACS and Diabetes Undergoing PCI-Analysis of Beijing Municipal Medical Insurance Database.

Background and Aims: Several clinical trials have proved the efficacy of clopidogrel treatment for patients with percutaneous coronary intervention. There are few large-scale studies to identify the mortality associated with different durations of treatment of clopidogrel in patients with diabetes and ACS undergoing PCI in the Chinese population. The objective of this analysis was to determine the efficacy of long-term clopidogrel therapy (≥12 months) versus short-term use (<12 months) in Chinese patients with diabetes after PCI. Methods and Results: We used the Beijing Municipal Medical Insurance Database provided by the Beijing Municipal Medical Insurance Bureau. The Beijing Municipal Medical Insurance Database contained medical data of about 16 million people, including about 990,000 patients with diabetes and a history of taking antidiabetic medicines. Patients were divided into two groups, one group of 9,116 patients receiving consecutive clopidogrel for one year or more, and another group of 3290 patients receiving consecutive clopidogrel for less than one year. The primary outcomes of this analysis were the risk of all-cause death, myocardial infarction, and revascularization. In patients with diabetes after PCI, long-term clopidogrel treatment was associated with a reduced risk of all-cause death (HR, 0.57[95%CI, 0.49-0.67], P<0.0001), myocardial infarction (HR, 0.79[95%CI, 0.68-0.93], P=0.0035) and an increased risk of angina (HR, 1.18[95%CI, 1.10-1.27], P<0.0001]) and revascularization (HR, 1.07[95%CI, 1.01-1.13], P=0.02]). There was no significant difference in the prevalence of all-cause re-hospitalization, diabetes-related re-hospitalization, and cerebrovascular re-hospitalization. Conclusion: The present study concluded that long-term dual antiplatelet therapy including clopidogrel and aspirin could decrease the risks of all-cause death, myocardial infarction. But it could increase the risks of angina and revascularization. Further studies should interpret the cause of this question.

Impaired Mitochondrial Fusion and Oxidative Phosphorylation Triggered by High Glucose Is Mediated by Tom22 in Endothelial Cells.

Much evidence demonstrates that mitochondrial dysfunction plays a crucial role in the pathogenesis of vascular complications of diabetes. However, the signaling pathways through which hyperglycemia leads to mitochondrial dysfunction of endothelial cells are not fully understood. Here, we treated human umbilical vein endothelial cells (HUVECs) with high glucose and examined the role of translocase of mitochondrial outer membrane (Tom) 22 on mitochondrial dynamics and cellular function. Impaired Tom22 expression and protein expression of oxidative phosphorylation (OXPHOS) as well as decreased mitochondrial fusion were observed in HUVECs treated with high glucose. The deletion of Tom22 resulted in reduced mitochondrial fusion and ATP production and increased apoptosis in HUVECs. The overexpression of Tom22 restored the balance of mitochondrial dynamics and OXPHOS disrupted by high glucose. Importantly, we found that Tom22 modulates mitochondrial dynamics and OXPHOS by interacting with mitofusin (Mfn) 1. Taken together, our findings demonstrate for the first time that Tom22 is a novel regulator of both mitochondrial dynamics and bioenergetic function and contributes to cell survival following high-glucose exposure.

Associations between urinary iodine concentration, lipid profile and other cardiometabolic risk factors in adolescents: a cross-sectional, population-based analysis.

Low urinary iodine concentration (UIC) is associated with dyslipidaemia in adults but is not well characterised in adolescents. Because dyslipidaemia is a cardiovascular risk factor, identifying such an association in adolescents would allow for the prescription of appropriate measures to maintain cardiovascular health. The present study addresses this question using data in the 2001-2012 National Health and Nutrition Examination Survey for 1692 adolescents aged 12-19 years. Primary outcomes were UIC, cardiometabolic risk factors and dyslipidaemia. Data for subjects categorised by low and normal UIC and by sex were analysed by univariate and multivariate logistic regression. Treating UIC as the independent variable, physical activity level, apoB and lipid profiles differed significantly between subjects with low and normal UIC. Subjects with low UIC had a significantly greater risk of elevated total cholesterol (TC) (95 % CI 1·37, 2·81), elevated non-HDL (95 % CI 1·33, 2·76) and elevated LDL (95 % CI 1·83, 4·19) compared with those with normal UIC. Treating UIC as a dependent variable, the risk of low UIC was significantly greater in those with higher apoB (95 % CI 1·52, 19·08), elevated TC (≥4·4mmol/l) (95 % CI 1·37, 2·81) and elevated non-HDL (≥3·11mmol/l) (95 % CI 1·33, 2·76) than in those with normal UIC. These results show that male and female adolescents with low UIC tend to be at greater risk of dyslipidaemia and abnormal cardiometabolic biomarkers, though the specific abnormal parameters differed between sexes. These results may help to identify youth who would benefit from interventions to improve their cardiometabolic risk.

Novel role of SF1 in alleviating thyroid-associated ophthalmopathy through the AMPK/mTOR signaling pathway.

BACKGROUND/AIM: Thyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue. This study aims to explore whether steroidogenic factor 1 (SF1) is implicated in development of TAO through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. METHODS: Initially, we extracted orbital preadipocytes from 10 TAO patients for culture and identification. After differentiation, cells were inoculated with plasmids with overexpressed SF1, and plasmids with siRNA against SF1, respectively. Then fat content and PGE2 secretion were measured by using ELISA. The levels of SF1, Bax, Bcl-2, Caspase3, Pref-1, PPARγ, Leptin, Adiponectin, p-AMPKαThr172, p-mTORSer2448, and p-S6KThr389 were detected by RT-qPCR and western blot analysis. Cell proliferation and apoptosis were measured by EdU and flow cytometry. RESULTS: TAO patients showed reduced SF1 expression in orbital preadipocytes. Overexpression of SF1 led to inhibited expression of Bcl-2, PPARγ, Leptin, Adiponectin and p-AMPKαThr172, fat content, cell proliferation and differentiation, but increased levels of Bax, Caspase3, Pref-1, p-mTORSer2448 and p-S6KThr389, PGE2 secretion and apoptosis rate. CONCLUSION: Our result showed up-regulated SF1 may relieve TAO through suppressing cell proliferation and differentiation, but accelerating cell apoptosis by inhibiting the activation of the AMPK/mTOR signaling pathway.

Sitagliptin Protects Cardiac Function by Reducing Nitroxidative Stress and Promoting Autophagy in Zucker Diabetic Fatty (ZDF) Rats.

PURPOSE: The purpose of the study is to identify potential mechanisms involved in the cardiac protective effects of sitagliptin in Zucker diabetic fatty (ZDF) rats. METHODS AND RESULTS: Male non-diabetic lean Zucker rats (Lean) and ZDF rats treated with saline (ZDF) or sitagliptin (ZDF + sita) were used in this study. The blood pressure and lipid profiles were increased significantly in ZDF rats compared with Lean rats. ZDF + sitagliptin rats had decreased systolic blood pressure compared with ZDF rats. Sitagliptin treatment decreased total cholesterol (TC), triglycerides (TGs), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels. Ejection fraction (EF) and fractional shortening (FS) were decreased in ZDF rats, which improved with sitagliptin from 59.8% ± 3.0 and 34.5% ± 3.1 to 66.9% ± 3.4 and 40.9% ± 4.2, respectively. Moreover, the nitroxidative stress level was increased while autophagy levels were decreased in ZDF rats, which was reversed by the administration of sitagliptin. Treatment with sitagliptin or FeTMPyP improved the autophagy level in high-glucose cultured H9c2 cells by increasing autolysosome numbers from 15 ± 4 to 21 ± 3 and 22 ± 3, respectively. We detected a positive correlation between DPP-4 activity and 3-nitrotyrosine levels (r = 0.3903; P < 0.01), a negative correlation between Beclin-1 levels and DPP-4 activity (r = - 0.3335; P < 0.01), and a negative correlation between 3-nitrotyrosine and Beclin-1 levels (r = - 0.3794; P < 0.01) in coronary heart disease patients. CONCLUSIONS: Sitagliptin alleviates diabetes-induced cardiac injury by reducing nitroxidative stress and promoting autophagy. This study indicates a novel target pathway for the treatment of cardiovascular complications in type 2 diabetes mellitus.

A cross-sectional study on the associations of insulin resistance with sex hormone, abnormal lipid metabolism in T2DM and IGT patients.

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients.In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism.Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed.Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes.