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.

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.

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.

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.

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.

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.

[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.

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.

[Comparison of postprandial insulin and fasting insulin on the evaluation of cardiovascular risk factors].

OBJECTIVE: To study the feasibility of using postprandial insulin (2hINS) and fasting insulin (FINS) on evaluation of insulin resistance, comparison was conducted between 2hINS and FINS on evaluation of cardiovascular risk factors. METHODS: A survey were conducted among individuals in the community in May 2008 and data of routine clinical examination were collected. All subjects were investigated and received 75 g oral glucose tolerance test (OGTT), and fasting and OGTT2 h blood glucose as well as insulin concentrations were determined. Hyperinsulinemia was defined as a FINS or 2hINS concentration at or above the 95th percentile of the distribution among normal glucose tolerance individuals. RESULTS: 1148 individuals were investigated and insulin concentration in male was similar to female. Prevalence of 2hHINS (40.8%) in individuals with abnormal glucose metabolism was higher than FHINS (18.4%, P < 0.01). The number of metabolic risk factors in subjects with 2hHINS was similar to subjects with FHINS. After adjustment by sex, age, BMI and waist circumference, partial correlation analysis showed that the correlation between 2hINS and 2hPG (r = 0.370) was higher than that of FINS and FPG (r = 0.104); FINS was higher correlated with TG and HDL- cholesterol than 2hINS, however, 2hINS was higher correlated with diastolic blood pressure, total cholesterol and LDL-cholesterol than FINS. Logistic regression analysis showed that FHINS and 2hHINS were both the independent risk factor of metabolic syndrome, the OR (95%CI) were 5.11 (2.953 - 8.842) and 3.46 (2.109 - 5.687). CONCLUSION: 2hINS and FINS were both closely associated with cardiovascular risk factors. The correlation was inconsistent when 2hINS and FINS were related to different risk factors. The combination of 2hINS and FINS might be more helpful on evaluation of insulin resistance.

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 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.

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.

[The clinical characteristics and trend of conversion to type 2 diabetes mellitus of individuals with normal glucose tolerance-hyperinsulinemia].

OBJECTIVE: To study the outcomes and influencing factors of the conversion from normal glucose tolerance-hyperinsulinemia (NGT-HINS) to diabetes in the population of a community in Beijing. METHODS: All the subjects investigated received 75 g oral glucose tolerance test (OGTT) for diabetes screening carried out in May, 2006 and May, 2008. Data were calculated to analyze the outcomes and influencing factors of the conversion. HINS was diagnosed if fasting serum insulin≥15 mIU/L and/or 2-hour serum insulin after glucose loading≥80 mIU/L. RESULTS: The prevalence of NGT-HINS in the community in 2006 and 2008 was 5.28% and 8.67% (P<0.01) respectively and that of diabetes mellitus (DM) and impaired glucose regulation (IGR) was 3.52%, 6.56% in 2006 and 4.42%, 6.47% in 2008. The probability of the conversion from NGT-HINS to IGR and DM was 18.6% and 2.3%, being much higher than that from normal glucose tolerance-normoinsulinemia (NGT-NINS) (5.4% and 0.7%, P<0.01). However, the probability of the conversion from NGT-HINS to DM was 2.3%, which was much lower than that from IGR (26.3%, P<0.01). The reason might be that individuals with NGT-HINS had a higher waist circumference, BMI, fasting plasma glucose, 2 h plasma glucose and TG but a lower HDL-C than individuals with NGT-NINS in 2006. The HOMA ß-cell function index/HOMA insulin resistance index (HBCI/IR) of individuals with NGT-HINS was much lower than that of individuals with NGT-NINS, but much higher than that of individuals with IGR. Logistic regression analysis showed that age, TG and HBCI/IR were the major influencing factors of the conversion from NGT to glucose metabolic disorders. CONCLUSIONS: The probability of conversion from NGT to DM was increased remarkably when HINS was diagnosed. The reason might be that individuals with NGT-HINS suffered more metabolic risk factors and had a decreased ß-cell function. Therefore, individuals with NGT-HINS should be paid attention to in diabetes prevention study.

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.

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.