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.

Change of vitamin D status and all-cause mortality among Chinese older adults: a population-based cohort study.

BACKGROUND: The association of vitamin D with all-cause mortality remains controversial and longitudinal evidence exploring the potential effects of change in vitamin D status is limited in the oldest old (aged ≥ 80 years old). We aimed to study the relationship between vitamin D change and all-cause mortality among older Chinese adults including the oldest old. METHODS: The data of Chinese Longitudinal and Health Longevity Study in 2012 and 2014 wave was used for baseline data. Mortality was assessed in the subsequent 2018 survey waves. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% confidence interval (CI) of all-cause mortality related to vitamin D change, including maintaining deficiency or no deficiency, deficiency to no deficiency, and no deficiency to deficiency, using below 50 nmol/L as definition of deficiency. RESULTS: The mean age of the total 1362 participants was 84.4 ± 12.1(60-113) years. The prevalence of vitamin D deficiency was 67.5% and 68.4% in 2012 and 2014 wave respectively, and significantly differed by sex and age at baseline. Cox regression showed that participants with deficiency to no deficiency and maintaining no deficiency of vitamin D status had decreased HR for all-cause mortality, compared to the maintaining deficiency group. The HRs for mortality were 0.70(95%CI: 0.50-0.96, p = 0.028) and 0.47(95%CI: 0.33-0.68, p < 0.001) respectively in the adjusted model. Also, females and the oldest old had a greatest reduction in mortality risk. And no significant difference in mortality in the no deficiency to deficiency group. CONCLUSIONS: Not only maintaining no deficiency, but also the change from deficiency to no deficiency of vitamin D status were associated with lower risk of all-cause mortality, especially in the female and oldest-old participants initially with low vitamin D level.

Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.

Testosterone is essential for spermatogenesis and the maintenance of secondary sexual characteristics in males. An important transcription factor, LIM-homeobox gene 9 (Lhx9) is indispensable for testis development and testosterone production; however, post-translational modifications of Lhx9 are largely unknown. Here, for the first time to our knowledge, we demonstrate that the level of Lhx9 protein increases in human chorionic gonadotropin-exposed Leydig cells and can be polyubiquitylated. We found that Smad ubiquitylation regulatory factor 1 (Smurf1), an E3 ubiquitin ligase, targets Lhx9 for ubiquitin-mediated proteasome degradation, thereby negatively modulating its function. Increasing Smurf1 decreases the level of Lhx9 and inhibits the Lhx9 transactivation capacity of steroidogenic factor 1 [nuclear receptor subfamily 5, group A, member 1 (NR5A1)]. In contrast, the depletion of Smurf1 leads to increased expression of Lhx9 protein and enhances testosterone biosynthesis-related gene transcripts [NR5A1, steroidogenic acute regulatory protein, CYP17A1, hydroxy-δ-5-steroid dehydrogenase, hydroxy-δ-5-steroid dehydrogenase isomerase 6, and hydroxysteroid (17-ß) dehydrogenase 3] and testosterone production in Leydig cells. Furthermore, we found that Smurf1 knockout mice exhibit higher levels of Lhx9 protein and steroidogenesis, which leads to increased serum testosterone concentration. These findings reveal that Smurf1 promotes Lhx9 ubiquitylation and is involved in testosterone production in Leydig cells directly. Our results provide new insights into the molecular events that play a role in the homeostasis of testosterone levels and may provide a new target for testosterone regulation.-Hu, F., Zhu, Q., Sun, B., Cui, C., Li, C., Zhang, L. Smad ubiquitylation regulatory factor 1 promotes LIM-homeobox gene 9 degradation and represses testosterone production in Leydig cells.

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.

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.

Metabolic diseases and sex hormone levels affect differently in the development of cardiovascular and cerebrovascular diseases in elderly males.

OBJECTIVE: This single-centre cross-sectional study aimed to investigate the metabolic and gonadal risk factors of vascular diseases in elderly males. METHODS: After screening, 337 subjects aged 60-90 were found to be qualified. Odds ratios (ORs) in cross-table analyses and exp(B) in logistic regression analyses were used to evaluate the vascular risk of dependent factors. R(2) of logistic regression equation was used to estimate the goodness-of-fit of vascular diseases logistic regression models. RESULTS: Hypertension increased the risk of cardiovascular disease (CAVD) in elderly men approximately 3-fold. The number of metabolic diseases also correlated with incremental risks of CAVD; presence of one abnormality approximately increases the risk approximately 62%. Cerebrovascular disease (CEVD) development was closely associated with both metabolic syndrome and sex hormone levels; their explanation effects of single action and combined action were 13.2%, 12.55% and 28.5%. C-peptide might be the underlying mechanism of the metabolic syndrome's effect on CEVD. C-peptide = 2.43 U/L and FE(2) = 0.66 were the tangent points in receiver operating characteristic (ROC) analyses. CONCLUSIONS: Metabolic diseases and sex hormones play different roles in the development of CAVD and CEVD, the methods for vascular protection in elderly men should be promoted differently according to the their risks of CAVD and CEVD.

Adipose stromal-vascular fraction-derived paracrine factors regulate adipogenesis.

Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to metabolic disease. Therefore, the adipogenic potential of different fat depots was investigated and found to be higher in subcutaneous compared with visceral stromal-vascular fraction (SVF), which contains adipocyte precursor cells. This increased differentiation capacity was not due to elevated numbers of Lin-Sca1+CD29+CD34+Pref1+ precursor cells, as the number of preadipocytes was higher in visceral than in subcutaneous SVF. The secreted heat-sensitive factors from the SVF inhibited adipocyte differentiation more in visceral than in subcutaneous SVF. In order to explore secreted proteins that potentially inhibit differentiation, the secretome of murine SVF was analyzed by mass spectrometry, which resulted in the identification of 113 secreted proteins with an overlap of 42 % between subcutaneous and visceral SVF. Comparison of the mRNA expression in SVF from both depots revealed 16 transcripts that were significantly expressed more in visceral than in subcutaneous SVF. A functional differentiation screen identified seven potential inhibitory candidates: biglycan, decorin, bone morphogenic protein 1, epidermal growth factor-containing fibulin-like extracellular matrix protein 2, elastin microfibril interfacer 1, matrix gla protein, and Sparc-like 1. For further verification, murine recombinant decorin or Sparc-like 1 was added to the media during the differentiation process leading to a dose-dependent decrease in adipogenesis. Further analysis will be necessary to assess the impact of the other candidates on adipocyte differentiation.

MiR-199a is overexpressed in plasma of type 2 diabetes patients which contributes to type 2 diabetes by targeting GLUT4.

Decreased GLUT4 expression and impaired GLUT4 cell membrane translocation are involved in type 2 diabetes mellitus (T2DM) pathogenesis so the factors impacting GLUT4 expression may be associated with T2DM. In this study, we identified four miRNAs: miR-31, miR-93, miR-146a, and miR-199a which suppress GLUT4 expression in HEK293T cells. Subsequently, we determined expression of these four miRNAs in plasma samples of T2DM patients, T2DM susceptible individuals, and healthy controls and found miR-199a was overexpressed in patients' plasma compared with healthy control. Because the miR-199a binding site in GLUT4 3'UTR is highly conserved among vertebrates, we detected the glucose uptake in rat L6 myoblast cells through gain- and loss-of-function of miR-199a. We found that miR-199a can repress glucose uptake in L6 cells, which was rescued by GLUT4 overexpression. These results indicate that T2DM patients may have a high level miR-199a that reduce GLUT4 expression and contribute to the insulin resistance. Hence, miR-199a may be a novel biomarker for risk estimation and classification in T2DM patients.

[Relationship between metabolic diseases and all-cause and cardiovascular disease death in elderly male diabetics during a 10-year follow-up].

OBJECTIVE: To explore the relationship between metabolic diseases and death from all causes and cardiovascular diseases (CVD) in elderly male diabetics. METHODS: A total of 681 elderly male diabetics were recruited from June 1997 to June 1999 and followed up for 10 years. All underwent regular check-ups in PLA General Hospital each year. The Cox proportional hazards model was applied to the multivariate survival analysis for all-cause and CVD mortality. And the cumulative survival rates were calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates. RESULTS: During a 10-year follow-up, 208 subjects died, including 70 deaths from CVD. Multivariate Cox regression analysis showed that age [relative risk (RR) = 1.099, 95% confidence interval (CI)1.076-1.123], pulse pressure (RR = 1.009, 95%CI 1.001-1.017) , elevated postprandial glucose level (RR = 1.115, 95%CI 1.075-1.157) and lower triglyceride (RR = 0.683, 95%CI 0.539-0.865) and high-density lipoprotein cholesterol (RR = 0.444, 95%CI 0.257-0.766) increased the risks of all-cause mortality while age (RR = 1.112, 95%CI 1.070-1.155) , elevated postprandial glucose level (RR = 1.278, 95%CI 1.170-1.396) and systolic blood pressure (RR = 1.013, 95%CI 1.002-1.024) increased the risks of CVD mortality. The cumulative survival rates from CVD mortality in diabetics with metabolic syndrome were significantly lower compared with those with diabetes only (P < 0.01) . CONCLUSION: CVD remains a main cause of death for Chinese elderly male diabetics. Advanced age and elevated postprandial glucose level are risk factors of all-cause and CVD mortality. Diabetes mellitus with concurrent hypertension or metabolic syndrome is associated with an increased risk of CVD death.

[Relationship between metabolic diseases and all-cause and cardiovascular death in an elderly male population during a 15-year follow-up].

OBJECTIVE: To explore the relationship between metabolic diseases and death from all causes, cardiovascular diseases (CVD) in an elderly male population. METHODS: A cohort of 1 447 elderly males was followed up for 15 years from 1996 to 2011. All of them received annual check-ups at our hospital. The Cox proportional hazard model was applied to multivariate survival analysis for all-cause and CVD mortality. And the cumulative survival rates were calculated by Kaplan-Meier method and log-rank test was used to compare the survival rates. RESULTS: During a 15-year follow-up, 639 subjects died, including 186 deaths from cardiovascular causes. Multivariate Cox regression analysis showed that age [relative risk (RR) = 1.131, 95% confidence interval (CI) 1.114-1.148], impaired glucose metabolism (RR = 1.344, 95% CI 1.139-1.585), hypertension (RR = 1.241, 95% CI 1.055-1.460) , elevated fasting glucose level (RR = 1.101, 95% CI 1.031-1.177) and lower body mass index (BMI) (RR = 0.968, 95% CI 0.943-0.993) increased the risks of all-cause mortality while age (RR = 1.119, 95% CI 1.086-1.153) , impaired glucose metabolism (RR = 1.856, 95% CI 1.386-2.458) and hypertension (RR = 1.699, 95% CI 1.242-2.324) elevated the risks of CVD mortality. The cumulative survival rates from all-cause and CVD mortality in impaired glucose regulation and diabetes group were significantly lower than those in normal glucose tolerance group (P < 0.01) . However, no difference existed between impaired glucose regulation (IGR) and diabetes groups. The cumulative survival rates from all-cause and CVD mortality significantly decreased in cases of impaired glucose metabolism and hypertension (P < 0.01) . The cumulative survival rates from all-cause mortality in low BMI group were significantly lower than those in normal and high BMI groups (P < 0.05) . A substantially higher risk of all-cause and CVD mortality was present in those with 2 or more metabolic disorders versus those with 0-1 metabolic disorder (P < 0.01). CONCLUSIONS: Malignant tumor and CVD are the main cause of death for Chinese elderly male population. Advanced age, impaired glucose metabolism, hypertension and 2 or more concurrent metabolic disorders are risk factors of all-cause and CVD mortality. And underweight is associated with an increased risk of death in elders.

[Mortality risks of type 2 diabetes mellitus among elderly patients: a 17-year cohort study].

OBJECTIVE: To explore the mortality risks of elders with and without type 2 diabetes mellitus (T2DM) during a fellow-up period of 17 years. METHODS: The subjects were elderly patients (>60 years old) undergoing annual health examinations at our hospital. And the incidence and risk factors were analyzed by Kaplan-Meier method and COX's proportional hazard. RESULTS: A total of 2 142 subjects were divided into T2DM group (DM, n = 746) and non-T2DM group (N-DM, n = 1 396). During a 17-year follow-up, the mortality rate of all causes was 50.9% in DM group versus 32.45% in N-DM group (P < 0.01). The major mortality causes were malignant tumor, respiratory disease and cardiovascular disease. Kaplan-Meier analysis revealed that the accumulative mortality of all causes and cardiovascular with DM was significantly above that of N-DM. The independent mortality risk factors of elders was T2DM (P < 0.01, HR = 1.36, 95% CI: 1.192-1.558) and cardiovascular disease (P < 0.01, HR = 3.26, 95% CI: 2.887-3.690) based upon the COX's proportional hazard analysis. CONCLUSION: Type 2 diabetes mellitus is an independent risk factor for elders with increased mortality risk.

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.

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

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.

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.

[Risks of type 2 diabetes mellitus and impaired glucose regulation among elderly patients with essential hypertension: a 10-years cohort study].

OBJECTIVE: To explore the incidence of type 2 diabetes mellitus (T2DM) and impaired glucose regulation (IGR) among elderly patients with and without hypertension during a follow-up period of 10 years. METHODS: The subjects were elderly patients (> 60 years old) undergoing annual health examinations at our hospital. And the previously diagnosed T2DM and IGR patients were excluded. And the incidence and risk factors were analyzed by Kaplan-Meier method and COX's proportional hazard. RESULTS: Among a total of 1136 subjects, 582 were enrolled. They were divided into essential hypertension group (HT, n = 384) and non-essential hypertension group (NHT, n = 198) (including new-onset 67 subjects). During a 10-year follow-up, the incidence of new-onset diabetes was 27.6% in HT group and 18.7% in NHT group (HR = 1.48; 95%CI: (1.07 - 2.04), P < 0.05). And the incidence density of T2DM were 33.8‰ and 20.6‰ respectively in two groups. There was no difference in the prevalence of IGR among HT and NHT groups and no difference was found in the prevalence of T2DM or IGR among new-onset HT and NHT groups. The independent risk factors of T2DM was dyslipidemia (HR = 1.459; 95%CI: 1.027 - 2.072, P < 0.05) and hypertension (HR = 1.516; 95%CI: 1.039 - 2.212, P < 0.05) based upon the COX's proportional hazard analysis. Dyslipidemia (HR = 1.545; 95%CI: 1.087 - 2.195, P < 0.05) and hypertension (HR = 1.524; 95%CI: 1.044 - 2.224, P < 0.05) were also independent risk factors of abnormal glycometabolism (T2DM and IGR). Kaplan-Meier analysis indicated that the accumulative incidence of DM and abnormal glycometabolism was different between the HT and NHT groups. CONCLUSION: The DM risk is 1.516 folds higher in elderly patients with HT than in those without. According to multivariate analysis, hypertension and dyslipidemia are independent risk factors of T2DM and abnormal glycometabolism (T2DM and IGR).

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.

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.

One-hour plasma glucose concentration can identify elderly Chinese male subjects at high risk for future type 2 diabetes mellitus: A 20-year retrospective and prospective study.

AIM: There have been few reports regarding the association between 1 h-PG concentration and type 2 diabetes mellitus (T2DM) in the elderly. This study was performed to assess the efficacy of 1 h-PG and 2 h-PG values in predicting future risk of T2DM in elderly. METHODS: The study population consisted of 928 male volunteers ≥ 55 years old without diabetes who were involved in a retrospective-prospective cohort study over 20 years with a baseline fasting plasma glucose (FPG) and OGTT that included measurement of 1 h-PG and 2 h-PG. The predictive capabilities of FPG and 1 h-PG, 2 h-PG values obtained during OGTT alone and added to a clinical prediction model consisting of traditional diabetes risk factors were assessed. RESULTS: Overall, 577 of all the 928 study participants (62%) developed T2DM over the 20-year follow-up. 1 h-PG and 2 h-PG values predicted T2DM and remained independent predictors of T2DM after adjusting for various traditional risk factors [HR = 1.269 (95% CI = 1.214-1.327), P < 0.001; HR = 1.269 (95% CI = 1.179-1.366), P < 0.001, respectively]. C-statistics for 1-h PG (C-statistics 0.794 [95% CI 0.765-0.823]) was significantly greater than that for 2-h PG (C-statistic 0.747 [95% CI 0.716-0.779]) in models adjusting for various traditional risk factors. 1 h-PG had the greatest area under the ROC curve (AUC, 0.766), which was greater than that of 2 h-PG (0.719). CONCLUSIONS: 1 h-PG is useful as a predictor of future development of T2DM independently of traditional risk factors in an elderly Chinese male population.

Higher Prevalence of Non-thyroidal-Illness Syndrome in Elderly Male Patients With Active Helicobacter pylori Infection.

Objective: It is currently unclear whether the Helicobacter pylori (H. pylori) infection leads to associated alterations in thyroid functions and thyroidal illnesses. This study aims to analyse this relationship in an elderly male cohort over a five-year period. Design: A case retrospective study. Methods: A longitudinal study was designed to collect subjects (≥65 years old) receiving both a thyroid examination and H. pylori infection status determined by 13C-urea breath test in 2013 at our unit. Subjects were followed every 1 to 2 years until December 2017 for laboratory results, visits to outpatient clinics/emergency departments etc. Blood tests and thyroid ultrasonography were performed to determine thyroid function and morphology. Results: 356 male subjects with mean age 78.5 ± 9.8 years were included. Active H. pylori infection was positive in 88 subjects (24.7%). Thyroid function tests and ultrasonography showed similar patterns between H. pylori positive and negative groups. Non-thyroidal-illness syndrome (NTIS) was diagnosed in 30/210 (14%) patients who experienced acute illnesses and hospitalization over five-year follow-up. Notably, NTIS demonstrated significantly higher prevalence in the H. pylori positive group compared to the negative group (17.1 vs. 5.6%, P = 0.001). Multivariate analysis showed that when age, APACHE II score and hemoglobin levels were adjusted, H. pylori status still has significant interrelationship with NTIS (OR = 3.497, P = 0.003). Conclusions: There is a positive association between chronic active H. pylori infection and NTIS prevalence in this elderly male cohort. Further studies are needed to elucidate the role of H. pylori infection on NTIS in elderly male patients.

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.