[Retracted] Liraglutide protects renal mesangial cells against hyperglycemia­mediated mitochondrial apoptosis by activating the ERK­Yap signaling pathway and upregulating Sirt3 expression.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the TUNEL assay data shown in Fig. 1C on p. 2853 and Fig. 5H on p. 2857 were strikingly similar to data that had already been published in different form in different articles written by different authors at different research institutes, or were submitted for publication at around the same time (a number of of which have now been retracted). Owing to the fact that the contentious data in the above article had already been published, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 19: 2849­2860, 2019; DOI: 10.3892/mmr.2019.9946].

Astragalus polysaccharides attenuate rat aortic endothelial senescence via regulation of the SIRT-1/p53 signaling pathway.

BACKGROUND: Astragalus polysaccharides (APS) have been verified to have antioxidative and antiaging activities in the mouse liver and brain. However, the effect of APS on aortic endothelial senescence in old rats and its underlying mechanism are currently unclear. Here, we aimed to elucidate the effects of APS on rat aortic endothelial oxidative stress and senescence in vitro and in vivo and investigate the potential molecular targets. METHODS: Twenty-month-old natural aging male rats were treated with APS (200 mg/kg, 400 mg/kg, 800 mg/kg daily) for 3 months. Serum parameters were tested using corresponding assay kits. Aortic morphology was observed by staining with hematoxylin and eosin (H&E) and Verhoeff Van Gieson (VVG). Aging-related protein levels were evaluated using immunofluorescence and western blot analysis. Primary rat aortic endothelial cells (RAECs) were isolated by tissue explant method. RAEC mitochondrial function was evaluated by the mitochondrial membrane potential (MMP) measured with the fluorescent lipophilic cationic dye JC­1. Intracellular total antioxidant capacity (T-AOC) was detected by a commercial kit. Cellular senescence was assessed using senescence-associated-ß-galactosidase (SA-ß-Gal) staining. RESULTS: Treatment of APS for three months was found to lessen aortic wall thickness, renovate vascular elastic tissue, improve vascular endothelial function, and reduce oxidative stress levels in 20-month-old rats. Primary mechanism analysis showed that APS treatment enhanced Sirtuin 1 (SIRT-1) protein expression and decreased the levels of the aging marker proteins p53, p21 and p16 in rat aortic tissue. Furthermore, APS abated hydrogen peroxide (H2O2)-induced cell senescence and restored H2O2-induced impairment of the MMP and T-AOC in RAECs. Similarly, APS increased SIRT-1 and decreased p53, p21 and p16 protein levels in senescent RAECs isolated from old rats. Knockdown of SIRT-1 diminished the protective effect of APS against H2O2-induced RAEC senescence and T-AOC loss, increased the levels of the downstream proteins p53 and p21, and abolished the inhibitory effect of APS on the expression of these proteins in RAECs. CONCLUSION: APS may reduce rat aortic endothelial oxidative stress and senescence via the SIRT-1/p53 signaling pathway.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

The role of TyG index in predicting the incidence of diabetes in Chinese elderly men: a 20-year retrospective study.

Background: The triglyceride glucose index (TyG index) has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of diabetes. However, few studies have reported the association between the TyG index and diabetes in the elderly population. Accordingly, this study aimed to investigate the association between the TyG index and diabetes progression in elderly Chinese. Methods: Baseline medical history, fasting plasma glucose (FPG), glucose levels during the oral glucose tolerance test (OGTT) after 1-hour (1h-PG) and 2-hour (2h-PG), and triglyceride (TG) were obtained from a cohort of 862 elderly (aged ≥ 60 years) Chinese in the Beijing urban area between 1998 and 1999. A follow-up visit was conducted between 1998 and 2019 to assess incident diabetes. TyG index was calculated by the following formula ln[TG (mg/dL) × FPG (mg(dL)/2]. The predictive values of TyG index, lipids, and glucose levels during OGTT were assessed alone and also in a clinical prediction model comprising traditional risk factors using concordance index (C-index). Areas under the receiver operating characteristics curves (AUC) and 95% CIs were calculated. Results: After 20 years of follow-up, there were 544 cases of incident type 2 diabetes mellitus (63.1% of incidence). The multivariable HRs (95% CI) for TyG index, FPG, 1h-PG and 2h-PG, high-density lipoprotein-cholesterol (HDL-c), and TG were 1.525 (1.290-1.804), 1.350 (1.181-1.544), 1.337 (1.282-1.395), 1.401 (1.327-1.480), 0.505 (0.375-0.681), and 1.120 (1.053-1.192), respectively. The corresponding C-index were 0.623, 0.617, 0.704, 0.694, 0.631, and 0.610, respectively. The AUC (95% CI) for the TyG index, FPG, 1h-PG, 2h-PG, HDL-c, and TG were 0.608 (0.569-0.647), 0.587 (0.548-0.625), 0.766 (0.734-0.797), 0.713 (0.679-0.747), 0.397 (0.358-0.435), and 0.588 (0.549-0.628). The AUC of the TyG index was higher than that of TG but did not differ with FPG and HDL-c. In addition, the AUCs of 1h-PG and 2h-PG were higher than that of the TyG index. Conclusions: Elevated TyG index is independently correlated with an increased risk of incident diabetes in the elderly male population, but it is not superior to OGTT 1h-PG and 2h-PG in predicting the risk of diabetes.

Analysis of clinical features and 7-year all-cause mortality in older male patients with non-thyroidal illness syndrome on general wards.

PURPOSE: Older patients with non-thyroidal illness syndrome (NTIS) have a poor prognosis. However, there are few studies on the association of NTIS and mortality among older inpatients on general wards. In a 7-year retrospective observational study, we aimed to investigate the clinical features of NTIS and the association of NTIS and all-cause mortality in older inpatients. METHODS: A total of 959 older male inpatients whose average age was 86.3 ± 8.1 years were enrolled and divided into the NTIS group and non-NTIS group. Cox models were performed to explore the association of thyroid hormone level and mortality. RESULTS: Patients had more respiratory disease and chronic kidney disease in the NTIS than in the non-NTIS group, especially in primary nursing care, respiratory failure and haemodialysis patients; serum total protein, albumin, prealbumin, haemoglobin, uric acid and high-density lipoprotein cholesterol levels were lower, and urea nitrogen and fasting blood glucose levels were higher, in the NTIS than in the non-NTIS group. Patients in the NTIS group had a lower survival rate over 7 years follow-up (P < 0.01). A lower free T3 level was associated with all-cause mortality with a HR of 1.50 (1.36, 1.66). Lower free T4 level was associated with reduced all-cause mortality with a HR of 0.91 (0.88, 0.94) even after adjusting for confounding factors (P < 0.01). CONCLUSIONS: Among older male inpatients, the survival rate was lower in the NTIS group. A reduced free T3 level with low albumin and Hb levels was associated with all-cause mortality; moreover, a higher free T4 in the normal range may be a strong predictor for long-term mortality risk in hospitalised older male patients.

Islet function changes of post-glucose-challenge relate closely to 15 years mortality of elderly men with a history of hyperglycemia.

Aims: We aimed to investigate the relationship between islet function changes during a glucose challenge and 15-year mortality in elderly men. Methods: Elderly men who did the oral glucose tolerance test in 2005 owing to an abnormal glucose history without diabetes were included. Changes in insulin resistance and secretion were evaluated using the homeostasis model assessment (HOMA) of fast, post-load, and ratios. Comparisons between the dead and the survival groups were analyzed using the Student's t-test (continuous variables) or χ2 test (Categorical variables). Single-factor logistic regression was used to identify the possible affecting factors. Multifactorial logistic regression was used to identify the independent risk factors in total population and in the subgroups. ROC curve was used to assess the predictive ability of risk factor and to determine the cut-off value. Results: Of the 220 elderly men, 67 died according to 15-year retrospection. Age (OR = 1.243, P = 0.000), diastolic pressure (OR = 0.958, P = 0.027), and HOMA-IR (2 h/0 h) (OR = 1.040, P = 0.010) were independent risk factors for 15-year mortality. Subgroup analysis showed that HOMA-IR (2 h/0 h) was an obvious risk factor, especially for normal glucose tolerance (OR = 1.060, P = 0.030), age 60-70 years (OR = 1.068, P = 0.005), and hypertension (OR = 1.048, P = 0.013); HOMA-ß (2 h/0 h) showed some protective effects in the impaired glucose regulation subgroup (OR = 0.779, P = 0.057). HOMA-IR (2 h/0 h) cut-off value was 15. Conclusions: HOMA-IR (2 h/0 h) higher than 15 was an independent risk factor for 15-year mortality in elderly men with hyperglycemia history.

The bidirectional association of C-peptide with cardiovascular risk in nondiabetic adults and patients with newly diagnosed type 2 diabetes mellitus: a retrospective cohort study.

BACKGROUND: Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. METHODS: A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. RESULTS: Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was < 1.4 ng/mL and positive if the value was ≥ 1.4 ng/mL. These relationships remained significant after adjusting for hemoglobin A1c, insulin resistance index, and its interaction with C-peptide, even if the participants were stratified by glucose metabolism status or levels of insulin resistance index. Hazard ratios of cardiovascular events were first decreased and then increased with the increasing of baseline C-peptide levels, though these associations became unsignificant using the multivariate Cox regression model. Unlike the participants without previous T2DM, the associations of C-peptide with cardiovascular biomarkers and events were not significant in the patients with previous T2DM. CONCLUSIONS: The associations of C-peptide with cardiovascular biomarkers and events were different between the participants without previous T2DM and those with previous T2DM. The effect of C-peptide on cardiovascular risk may be bidirectional, play a benefit role at a low level, and play a harmful role at a high level in the nondiabetic adults and the patients with newly diagnosed T2DM.

One-hour plasma glucose as a long-term predictor of cardiovascular events and all-cause mortality in a Chinese older male population without diabetes: A 20-year retrospective and prospective study.

Introduction: Elevated one-hour plasma glucose (1 h-PG) during oral glucose tolerance test predicts the development of type 2 diabetes mellitus and its complications. However, to date, there have been no studies investigating the predictive values of 1 h-PG for the risk of cardiovascular diseases (CVDs) and all-cause mortality in the elderly population in China. This study aimed to evaluate and compare the effectiveness of 1 h-PG and two-hour plasma glucose (2 h-PG) to predict the risk of CVD and all-cause mortality in the Chinese elderly population. Materials and methods: This retrospective and prospective cohort study was conducted using data obtained from the Chinese People's Liberation Army General Hospital. All the non-diabetic elderly participants, who had plasma glucose measured at 0, 1, and 2 h during an OGTT (75 g glucose), were followed for 20 years. The primary outcomes were all-cause mortality, myocardial infarction, unstable angina, and stroke. Multivariate-adjusted Cox proportional hazard regression models were performed to examine the association between risk factors and outcomes and to estimate the risk of CVD and all-cause mortality based on 1 h-PG levels. Results: A total of 862 non-diabetic male individuals were included. The median age was 74.0 (25th-75th percentile: 68.0-79.0) years. There were 480 CVD events and 191 deaths during 15,527 person-years of follow-up. The adjusted hazard ratio (HR) of 1 h-PG as a continuous variable was 1.097 (95% CI 1.027-1.172; P = 0.006) for CVD events and 1.196 (95% CI 1.115-1.281; P < 0.001) for higher risk of mortality. When compared with the lowest 1 h-PG tertile, the other tertiles were associated with CVD events (HR 1.464, 95% CI 1.031-2.080; P = 0.033 and HR 1.538, 95% CI 1.092-2.166; P = 0.014, for tertile 2 and tertile 3 compared with tertile 1, respectively), and the highest 1 h-PG tertile had a significantly higher risk of mortality (HR 2.384, 95% CI 1.631-3.485; P < 0.001) after full adjustment. Compared with 1 h-PG, 2 h-PG had similar abilities to predict all-cause mortality. However, 2 h-PG was less closely associated with CVD when examined in the fully adjusted model, neither as a continuous variable nor as a categorical variable. Conversely, 1 h-PG remained an independent predictor of CVD and all-cause mortality after adjusting for various traditional risk factors. Conclusion: Patients with higher 1 h-PG had a significantly increased risk of CVD and all-cause mortality regardless of prediabetes status or development of diabetes at follow-up. The 1 h-PG level might be a better predictor of cardiovascular risk than the 2 h-PG level for the Chinese elderly population.

Implementation of five machine learning methods to predict the 52-week blood glucose level in patients with type 2 diabetes.

Objective: For the patients who are suffering from type 2 diabetes, blood glucose level could be affected by multiple factors. An accurate estimation of the trajectory of blood glucose is crucial in clinical decision making. Frequent glucose measurement serves as a good source of data to train machine learning models for prediction purposes. This study aimed at using machine learning methods to predict blood glucose for type 2 diabetic patients. We investigated various parameters influencing blood glucose, as well as determined the most effective machine learning algorithm in predicting blood glucose. Patients and methods: 273 patients were recruited in this research. Several parameters such as age, diet, family history, BMI, alcohol intake, smoking status et al were analyzed. Patients who had glycosylated hemoglobin less than 6.5% after 52 weeks were considered as having achieved glycemic control and the rest as not achieving it. Five machine learning methods (KNN algorithm, logistic regression algorithm, random forest algorithm, support vector machine, and XGBoost algorithm) were compared to evaluate their performances in prediction accuracy. R 3.6.3 and Python 3.12 were used in data analysis. Results: The statistical variables for which p< 0.05 was obtained were BMI, pulse, Na, Cl, AKP. Compared with the other four algorithms, XGBoost algorithm has the highest accuracy (Accuracy=99.54% in training set and 78.18% in testing set) and AUC values (1.0 in training set and 0.68 in testing set), thus it is recommended to be used for prediction in clinical practice. Conclusion: When it comes to future blood glucose level prediction using machine learning methods, XGBoost algorithm scores the highest in effectiveness. This algorithm could be applied to assist clinical decision making, as well as guide the lifestyle of diabetic patients, in pursuit of minimizing risks of hyperglycemic or hypoglycemic events.

Effects of a prolonged diet regimen on autophagic function in rat islets with aging.

The prevalence of type 2 diabetes increases with age-associated increased susceptibility of islet ß-cells and altered dietary patterns, in part because of insufficient compensation of ß-cell functional mass in the face of increasing insulin resistance. However, the underlying mechanisms have not been fully elucidated. In the present study, we investigated the effects of a long-term calorie-restricted (CR) or high-fat (HF) diet compared to a normal ad libitum diet on ß-cell structure-function relationships and autophagy in the islets of 3- and 24-month-old Fischer 344 rats. Aging and the HF diet decreased the ß-cell-to-islet area ratio, disorganized the islet structure, and increased the expression of senescence markers. Aging and the long-term HF diet also decreased autophagy-related proteins, which suggests compromised autophagic function. These findings were further corroborated by increased p62 accumulation and polyubiquitin aggregates observed with aging and the HF diet intervention; these are cardinal markers of attenuated autophagic function. It is important to note that the 24-month-old rats maintained on the CR diet closely mimicked the 3-month-old rats, which indicates that a long-term CR diet can delay islet aging and prevent the decline in the autophagic function of islets during the aging process. Taken together, our results indicate an autophagy-dependent mechanism responsible for islet function in older people or those with altered dietary patterns and lay the foundations for future research leading to novel therapeutic strategies for treating diabetes.

The Predictive Effect of Health Examination in the Incidence of Diabetes Mellitus in Chinese Adults: A Population-Based Cohort Study.

BACKGROUND: The incidence of diabetes mellitus (DM) was increasing in recent years, and it is important to screen those nondiabetic populations through health examination to detect the potential risk factors for DM. We aimed to find the predictive effect of health examination on DM. METHODS: We used the public database from Rich Healthcare Group of China to evaluate the potential predictive effect of health examination in the onset of DM. The colinear regression was used for estimating the relationship between the dynamics of the health examination index and the incident year of DM. The time-dependent ROC was used to calculate the best cutoff in predicting DM in the follow-up year. The Kaplan-Meier method and Cox regression were used to evaluate the HR of related health examination. RESULTS: A total of 211,833 participant medical records were included in our study, with 4,172 participants diagnosing as DM in the following years (among 2-7 years). All the initial health examination was significantly different in participants' final diagnosing as DM to those without DM. We found a negative correlation between the incidence of years of DM and the average initial FPG (r = -0.1862, P < 0.001). Moreover, the initial FPG had a strong predictive effect in predicting the future incidence of DM (AUC = 0.961), and the cutoff was 5.21 mmol/L. Participants with a higher initial FPG (>5.21 mmol/L) had a 2.73-fold chance to develop as DM in follow-up (95%CI = 2.65-2.81, P < 0.001). CONCLUSION: Initial FPG had a good predictive effect for detecting DM. The FPG should be controlled less than 5.21 mmol/L.

Association of the Ratio of Triglycerides to High-Density Lipoprotein Cholesterol Levels with the Risk of Type 2 Diabetes: A Retrospective Cohort Study in Beijing.

BACKGROUND: Previous studies have shown that the ratio of triglyceride to high-density lipoprotein cholesterol level (TG/HDL-C) is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the nonlinear relationship between TG/HDL-C and the incidence of T2DM in a Chinese population. METHODS: We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the incidence of T2DM among 7,791 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) cohort study at baseline. RESULTS: After adjusting for age, sex, body mass index, smoking status, alcohol intake, low-density lipoprotein cholesterol level, strenuous activity, education level, family histories of T2DM and tumors, and the presence of hypertension, tumor, stroke, and coronary heart disease, we showed that TG/HDL-C was positively associated with the incidence of T2DM at the 4-year follow-up (OR = 1.49, 95%CI = 1.26-1.78). TG/HDL-C and incidence of T2DM showed a nonlinear relationship; the inflection point of TG/HDL-C was 1.50. The ORs (95% CI) on the left and right sides of the inflection point were 2.50 (1.70-3.67) and 0.96 (0.67-1.37), respectively. After adjusting for age, sex, and body mass index (BMI) in the linear relationship, the OR of the incidence of T2DM was 1.60 (95%CI = 1.37-1.87). When the TG/HDL-C was less than 1.50 or greater than 1.76, the ORs (95% CI) were 2.41 (1.82-3.18) or 0.81 (0.53-1.25), respectively. Subgroup analysis showed no relationships of T2DM incidence with sex, BMI, family history of T2DM, or TG/HDL-C. CONCLUSION: TG/HDL-C is positively associated with diabetes risk. In our study, with each increasing quintile, the risk of T2DM after 4 years was 1.60 or 1.49 depending on the variables adjusted. In addition, our cohort study showed a nonlinear relationship between TG/HDL-C and T2DM incidence, with an inflection point of 1.76 or 1.50, depending on the variables adjusted. When the TG/HDL was less than 1.50, the ORs (95% CI) were 2.41 (1.82-3.18) and 2.50 (1.70-3.67). When the TG/HDL-C was greater than 1.76 or 1.50, there was no significant difference in the change in OR.

Association Between Triglyceride-Glucose Index and the Risk of Type 2 Diabetes Mellitus in an Older Chinese Population Aged Over 75 Years.

Background: The association between the triglyceride-glucose (TyG) index and type 2 diabetes mellitus (T2DM) in older adults has not been fully understood. This research aims to explore the association between the TyG index and the incidence of T2DM in an older Chinese population aged over 75 years. Methods: This longitudinal analysis study was performed based on a database from a health check screening program in China. The participants were stratified based on the quintile ranges of the TyG index (Q1 to Q5 groups). T2DM was defined as fasting plasma glucose (FPG) ≥ 7.00 mmol/L and/or self-reported T2DM. The cumulative incidences of T2DM in various quintile groups were estimated by the Kaplan-Meier method. The Cox proportional hazard model was used to examine the independent impact of the TyG index on the risk of T2DM during the follow-up period. Subgroup analysis was performed by gender and BMI to further validate the credibility of the results. Results: During the follow-up period, a total of 231 new-onset T2DM cases were recorded among the 2,571 individuals aged over 75 years. After adjusting confounding factors, elevated TyG index independently indicated a higher risk of T2DM (HR = 1.89; 95% CI, 1.47-2.44; p < 0.01). Higher TyG index quintile groups (Q3 to Q5) also presented with a higher risk of T2DM (hazard ratio (HR) = 1.36, 1.44, and 2.12, respectively) as compared with the lowest quintile group (Q1). Subgroup analysis showed that increased TyG index led to a higher risk of T2DM with HR = 2.35 (95% CI, 1.73-3.19), 1.90 (95% CI, 1.27-2.83), 2.95 (95% CI, 1.94-4.50), and 1.72 (95% CI, 1.25-2.35) in male subgroup, female subgroup, BMI < 24 kg/m2 subgroup, and BMI ≥ 24 kg/m2 subgroup, respectively. Conclusions: Triglyceride-glucose index independently correlated with the risk of incident T2DM in Chinese adults aged over 75 years. The TyG index might be useful in monitoring T2DM in the older populations.

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice.

BACKGROUND: Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice. METHODS: Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration. RESULTS: Aging resulted in urine ca2+ excretion, a decrease in bone ca2+ content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in Runx2, osterix and Col1a1 mRNA expression and a decrease in Ctsk, MMP-9 and CAII mRNA expression in the tibia from aging mice. CONCLUSION: These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.

Glycemic control and comprehensive metabolic risk factors control in older adults with type 2 diabetes.

BACKGROUND: Older adults with type 2 diabetes are prone to multiple metabolic abnormalities. However, data from these patients on comprehensive metabolic risk factors control are limited. METHODS: The present study included 2736 older adults aged 60 to 90 years with type 2 diabetes from 114 hospitals across 22 provinces in China. Metabolic abnormalities, including hypertension, dyslipidemia, hyperuricemia, and obesity, were recorded. Comprehensive metabolic risk factors control included the control of hemoglobin A1c (HbA1c) level, blood pressure, serum lipids level, serum uric acid level, and body mass index. The target glycemic control was defined as HbA1c <7%. RESULTS: The proportion of older adults who achieved the HbA1c target was 23.0%. The glycemic control rate increased with the number of metabolic abnormalities increased. The patients who had all four metabolic abnormalities had 4.05 times (95% confidence interval: 2.16, 7.61) the odd to meet glycemic target than those with none of metabolic abnormalities. However, only 4.6% of patients met the targets for all 5 metabolic risk factors. The comprehensive rate of all 5 factors in control decreased from 13.4% to 0% with the number of metabolic abnormalities increased. CONCLUSION: The glycemic control rate and the comprehensive metabolic risk factors control rate were 23.0% and 4.6%, respectively. As the number of metabolic abnormalities increased, the number of risk factor targets achieved decreased. Our findings suggest that a strategy for comprehensive control is urgently needed in older adults with type 2 diabetes, especially in those with co-existing metabolic abnormalities.

Liraglutide protects renal mesangial cells against hyperglycemia­mediated mitochondrial apoptosis by activating the ERK­Yap signaling pathway and upregulating Sirt3 expression.

Diabetic nephropathy results from hyperglycemia­mediated renal glomerular cell death via mitochondrial apoptosis. There is an emerging requirement for novel approaches with mitochondrial protective effects that alleviate the hyperglycemia­induced loss of functional cells during diabetic renal damage. Liraglutide, a type of glucagon­like peptide­1 agonist, has been suggested to inhibit the progression of obesity and hyperglycemia. However, the contributions and mechanism of action of liraglutide on hyperglycemia­mediated cell mitochondrial apoptosis in diabetic kidneys have not been illustrated. The present study demonstrated that liraglutide may protect human renal mesangial cells (HRMCs) against hyperglycemia­induced cell death by inhibiting mitochondrial apoptosis. Liraglutide administration also maintained HRMC viability and promoted HRMC proliferation within a high glucose stress environment. Functional studies demonstrated that hyperglycemia triggered mitochondrial dysfunction, including mitochondrial potential reduction, mitochondrial permeability transition pore opening, reactive oxygen species overproduction and the activation of the mitochondrial apoptotic pathway. However, liraglutide treatment preserved mitochondrial function and prevented activation of mitochondrial apoptosis by upregulating sirtuin 3 (Sirt3) expression. Deletion of Sirt3 abrogated the protective effects of liraglutide on mitochondrial homeostasis following high glucose challenge. In addition, molecular analysis confirmed that liraglutide upregulated Sirt3 via activating the extracellular signal­regulated kinase­Yes­associated protein (ERK­Yap) signaling pathway. Inhibition of the ERK­Yap axis negated the action of liraglutide on Sirt3 activation, leading to mitochondrial injury and HRMC apoptosis. Taken together, the present study illustrated that liraglutide protected renal mesangial cells from hyperglycemia­mediated mitochondrial apoptosis by upregulating Sirt3 expression and activation of the ERK­Yap signaling pathway.

Relationship between abnormal glucose metabolism and osteoporosis in Han Chinese men over the age of 50 years.

AIM: The aim of this study was to determine the relationship between abnormal glucose metabolism and osteoporosis (OP) in Han Chinese men over the age of 50 years. PATIENTS AND METHODS: A cross-sectional study of 775 male patients aged over 50 years was performed at our hospital in 2011. The patients were divided into a normal glucose metabolism group, an impaired glucose regulation (IGR) group, and a type 2 diabetes mellitus (T2DM) group. Differences in their bone mineral densities (BMDs), OP detection rates, and indices of bone metabolism were assessed. RESULTS: After adjusting for age and body mass index (BMI), there were no significant differences in lumbar spine, femoral neck, and total hip BMD values in the three groups (P>0.05) nor in OP detection rates (P=0.19). However, there were some significant differences in bone metabolism markers between the groups after adjusting for age, BMI, and serum creatinine (Cr): 25-hydroxyvitamin D (25(OH)D) was positively correlated with the presence of abnormal glycometabolism (r=0.08; P<0.01), while ß-carboxy-terminal cross-linking telopeptide of type I collagen (ß-CTX), bone gamma-carboxyglutamic acid protein (BGP; osteocalcin [OC]), and procollagen type 1 intact N-terminal propeptide (P1NP) were negatively correlated (r=-0.13, -0.21, -0.14, respectively; P<0.01). Logistic regression analysis of the data indicated that BGP was the only bone metabolism marker significantly influenced by abnormal glucose metabolism (OR =0.96). CONCLUSION: There were no significant differences in BMD or OP detection rates between the three glycometabolism groups after adjusting for age and BMI. However, the bone metabolism marker, BGP, was significantly negatively correlated with abnormal glucose metabolism.

Impaired glucose tolerance predicts all-cause mortality among older men at high risk for cardiovascular disease in China.

AIMS: To investigate the potential association between impaired glucose tolerance (IGT) and all-cause mortality among older men at high risk for cardiovascular disease (CVD) in China. METHODS: In this prospective observational study, 460 older men aged ≥60 years were determined to have either IGT or normal glucose tolerance (NGT) based on an oral glucose tolerance test conducted between May 2005 and May 2007. IGT and NGT were diagnosed according to the 1999 WHO diagnostic criteria. All subjects were followed until March 2017. The primary outcome studied was all-cause mortality. Multivariate Cox models were used to estimate relative risk for all-cause mortality. RESULTS: During a mean follow-up of 11.2 years, forty-three (21.4%) subjects in the IGT group and twenty-nine (11.2%) subjects in the NGT group died (HR 2.05, 95% CI 1.28-3.28, P=0.003). Multivariate Cox proportional-hazards analysis demonstated that IGT was significantly associated with increased risk for all-cause mortality, composite cardiovascular outcome, nonfatal stroke and heart failure after adjusting for potential confounding factors. Logistic regression analysis showed that IGT at baseline (P<0.05) rather than incident type 2 diabetes was a risk factor of all-cause mortality. CONCLUSIONS: IGT was significantly associated with all-cause mortality in older Chinese men at high risk for CVD.

Melatonin attenuates renal fibrosis in diabetic mice by activating the AMPK/PGC1α signaling pathway and rescuing mitochondrial function.

Mitochondrial homeostasis is a highly regulated process that serves a critical role in the maintenance of renal structure and function. The growing interest in the field of mitochondrial homeostasis promises to provide more information regarding the mechanisms involved in diabetic renal fibrosis, and aid in the development of novel strategies to combat the disease. In the present study, the effects of melatonin on renal damage in mice with diabetes were evaluated and the underlying mechanisms were investigated. Cellular apoptosis was determined using TUNEL assay and western blotting. Mitochondrial function was measured using fluorescence assay and western blotting. The results indicated that diabetic renal fibrosis was associated with 5'adenosine monophosphate­activated protein kinase (AMPK) downregulation. However, melatonin administration rescued AMPK activity, reduced diabetic renal fibrosis, alleviated glomerular apoptosis and preserved kidney function. The functional experiments demonstrated that melatonin­induced AMPK activation enhanced peroxisome proliferator­activated receptor γ coactivator 1­α (PGC1α) expression, sustained mitochondrial function and blocked mitochondrial apoptosis, leading to protection of the glomerulus against glucotoxicity. However, loss of AMPK and PGC1α negated the protective effects of melatonin on mitochondrial homeostasis, glomerular survival and diabetic renal fibrosis. In summary, the present study revealed that melatonin rescued impaired mitochondrial function and reduced glomerular apoptosis in the context of diabetic renal fibrosis by activating the AMPK/PGC1α pathway.

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

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.