The role of miRNAs carried by extracellular vesicles in type 2 diabetes and its complications.

Diabetes poses severe global public health problems and places heavy burdens on the medical and economic systems of society. Type 2 diabetes (T2D) accounts for 90% of these cases. Diabetes also often accompanies serious complications that threaten multiple organs such as the brain, eyes, kidneys, and the cardiovascular system. MicroRNAs (miRNAs) carried by extracellular vesicles (EV-miRNAs) are considered to mediate cross-organ and cross-cellular communication and have a vital role in the pathophysiology of T2D. They also offer promising sources of diabetes-related biomarkers and serve as effective therapeutic targets. Here, we briefly reviewed studies of EV-miRNAs in T2D and related complications. Specially, we innovatively explore the targeting nature of miRNA action due to the target specificity of vesicle binding, aiding mechanism understanding as well as the detection and treatment of diseases.

Fat Mass is Associated with Subclinical Left Ventricular Systolic Dysfunction in Patients with Type 2 Diabetes Mellitus Without Established Cardiovascular Diseases.

INTRODUCTION: Left ventricular global longitudinal strain (GLS) is considered to be the first marker of diabetes mellitus-related subclinical cardiac dysfunction, but whether it is attributable to fat mass and distribution remains uncertain. In this study, we explored whether fat mass, especially fat mass in the android area, is associated with subclinical systolic dysfunction before the onset of cardiac disease. METHODS: We conducted a single-center prospective cross-sectional study between November 2021 and August 2022 on inpatients of the Department of Endocrinology, Nanjing Drum Tower Hospital. We included 150 patients aged 18-70 years with no signs, symptoms, or history of clinical cardiac disease. Patients were evaluated with speckle tracking echocardiography and dual energy X-ray absorptiometry. The cutoff values for subclinical systolic dysfunction were set at a global longitudinal strain (GLS) < 18%. RESULTS: After adjusting for sex and age, patients with GLS < 18% had a higher mean (± standard deviation) fat mass index (8.06 ± 2.39 vs. 7.10 ± 2.09 kg/m2, p = 0.02), higher mean trunk fat mass (14.9 ± 4.9 vs. 12.8 ± 4.3 kg, p = 0.01), and higher android fat mass (2.57 ± 1.02 vs. 2.18 ± 0.86 kg, p = 0.02) than those in the GLS ≥ 18%. Partial correlation analysis showed that the fat mass index, truck fat mass, and android fat mass were negatively correlated with GLS after adjusting for sex and age (all p < 0.05). Adjusted for traditional cardiovascular metabolic factors, fat mass index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05-1.55, p = 0.02), trunk fat mass (OR 1.13, 95% CI 1.03-1.24, p = 0.01), and android fat mass (OR 1.77, 95% CI 1.16-2.82, p = 0.01) were independent risk factors for GLS < 18%. CONCLUSION: Among patients with type 2 diabetes mellitus without established clinical cardiac disease, fat mass, especially android fat mass, was associated with subclinical systolic dysfunction independently of age and sex.

Low levels of osteocalcin, but not CTX or P1NP, are associated with nonalcoholic hepatic steatosis and steatohepatitis.

AIM: The association of bone turnover with the incidence and progression of nonalcoholic fatty liver disease (NAFLD) is unclear. We aimed to evaluate serum levels of bone turnover markers in relation to NAFLD and nonalcoholic hepatic steatohepatitis (NASH). METHODS: Two cohorts were involved in our study. For the first cohort, 370 participants without NAFLD were retrospectively recruited and followed up for incident NAFLD according to ultrasound. For the second cohort, 562 subjects who underwent liver biopsy were included and grouped into non-NAFLD, non-NASH or NASH according to the NASH Clinical Research Network system. The bone turnover markers osteocalcin, C-terminal telopeptide (CTX) and N-terminal propeptide of type-1 procollagen (P1NP) were measured. RESULTS: Baseline osteocalcin was significantly lower in subjects who developed NAFLD (13.93 [11.03;16.39] versus 18.24 [15.45;22.47] ng/ml, P < 0.001), with a median of 26.4 months of follow-up. Low levels of osteocalcin, but not CTX or P1NP, was an independent predictor of incident NAFLD (OR 0.755 [95%CI 0.668; 0.855] P < 0.001). Moreover, the osteocalcin level was negatively associated with the degree of liver steatosis. Furthermore, subjects with NASH had significantly lower osteocalcin than non-NASH and non-NAFLD group (13.28 [10.49;16.59] versus 14.91 [12.45;18.09] versus 18.21 [15.04;22.05] ng/ml, all P < 0.001). A low osteocalcin level was an independent risk factor for NASH (OR for highest versus lowest quartile: 0.282 [0.147;0.543] P < 0.001). CONCLUSION: Low level of osteocalcin, but not CTX or P1NP, was associated with NAFLD and NASH, indicating its potential role as an important endocrine regulator of hepatic energy metabolism.

The association between visceral adipocyte hypertrophy and NAFLD in subjects with different degrees of adiposity.

OBJECTIVE: To investigate the association between visceral adipocyte hypertrophy and the onset and development of non-alcoholic fatty liver disease (NAFLD) in subjects with different degrees of adiposity. METHODS: Omental adipose tissue and liver biopsies were collected from obese subjects. NAFLD was defined according to the NASH Clinical Research Network scoring system. Adipocyte size was measured using pathological section analysis. Adipose tissue insulin resistance (Adipo-IR) was calculated as fasting insulin (pmol/L) × fasting free fatty acid concentration (mmol/L). RESULTS: In total, 275 obese patients were enrolled, including 158 females and 58 males with NAFLD. In females, adipocyte size was significantly larger in NAFLD participants as compared to the controls (99.37 ± 14.18 vs. 84.14 ± 12.65 [Formula: see text]m, p < 0.001). Moreover, adipocyte size was larger in females with non-alcoholic steatohepatitis (NASH) as compared to those with non-alcoholic fatty liver (NAFL) (101.45 ± 12.77 vs. 95.79 ± 15.80 [Formula: see text]m, p = 0.015). Mediation analysis showed that adipocyte size impacted the NAFLD activity score through Adipo-IR (b = 0.007 [95% bootstrap CI 0.002, 0.013]). Furthermore, the females were divided into: Q1 (BMI < 32.5 kg/m2), Q2 (BMI 32.5-35.5 kg/m2), Q3 (BMI 35.5-38.8 kg/m2) and Q4 (BMI ≥ 38.8 kg/m2) according to BMI quartiles. Omental adipocyte size was larger in NAFLD subjects in Q1-Q3, but not in Q4. No similar results were observed in males. CONCLUSION: For the first time, we reported that visceral adipocyte hypertrophy was associated with the onset and progression of NAFLD in mild to moderate adiposity but not in severe obesity, which may be mediated by adipose tissue insulin resistance.

Gender differences in the association of body composition and biopsy-proved nonalcoholic steatohepatitis.

BACKGROUND AND AIM: Body composition was associated with nonalcoholic steatohepatitis (NASH), but results were controversial probably due to gender differences. Hence, we aim to explore the association of body composition and NASH in males and females. METHODS: We conducted a cross-sectional analysis of obese subjects undergone liver biopsy. According to NASH Clinical Research Network system, subjects were categorized as Normal Control (NC), non-NASH or NASH. Body composition was accessed by dual-energy X-ray absorptiometry. RESULTS: This study enrolled 336 subjects (mean age 32.0 years, mean BMI 39.15 kg/m2, female, 64.0%). Males have lower relative muscle mass (RMM 55.21 ± 4.07%) and females have higher android to gynoid ratio (AGR, 0.82 ± 0.21) in NASH when compared with non-NASH (RMM 57.49 ± 4.75%; AGR 0.7 ± 0.15) and NC (RMM 58.69 ± 4.09%; AGR 0.66 ± 0.19, p < 0.05 for each). After adjusting for confounding factors, low RMM was the independent risk factor for NASH in males (odds ratio [OR] 0.550; 95% confidence interval [CI] 0.312-0.970), high AGR was the independent risk factor for NASH in females (OR 1.694; 95% CI 1.073-2.674). Further, RMM in males and AGR in females, respectively, was associated with liver steatosis and activity, but not with fibrosis. ROC curve revealed that the optimal cutoff value of RMM was 58.09% in males and AGR was 0.92 in females for predicting NASH. CONCLUSIONS: We firstly revealed that low RMM and high AGR were the independent risk factors for NASH in males and females, respectively, indicating that sex-specific interventions for improving body composition may reduce the risk of NASH in obese subjects.

Associations Between Obesity and Kidney Disease in Chinese Men and Women With Type 2 Diabetes: A Retrospective Cohort Study.

BACKGROUND: Our aim in this study was to explore the risk factors for kidney disease in Chinese men and women with type 2 diabetes (T2D) and to clarify the relationship between obesity and the risk of chronic kidney disease (CKD). METHODS: This retrospective study included 3,194 patients with T2D. Among 2,574 T2D patients without CKD at baseline, 753 with follow-up records of at least 12 months were included in the retrospective cohort. Logistic regression and Cox regression were used to evaluate the risk for CKD in men and women. A restricted cubic spline model was used to analyze the association of body mass index (BMI) and waist circumference (WC) with CKD risk. RESULTS: Multivariate logistic regression analysis suggested that obesity was a risk factor for T2D with CKD in men but not in women. After a median follow-up period of 2.8 years, the incidence of CKD in men with obesity was significantly higher than that in men with obesity with T2D (p=0.039), but there was no statistically significant difference between women with obesity and women without obesity with T2D (p=0.825). In the restricted cubic spline model analysis, BMI and WC were associated with CKD risk in a nonlinear fashion in males and females. The risk of CKD was higher in males with a BMI of ≥29.5 kg/m2 or a WC of ≥100 cm, whereas there was no difference observed in females. CONCLUSIONS: Obesity was strongly related to T2D with CKD in men. Male diabetes patients with obesity, especially abdominal obesity, are more likely to develop CKD.

Effects of Early Intensive Insulin Therapy on Endothelial Progenitor Cells in Patients with Newly Diagnosed Type 2 Diabetes.

AIM: This study aimed to investigate the alteration of circulating CD34+KDR+CD133+ endothelial progenitor cells (EPCs) in patients with newly diagnosed type 2 diabetes and the mechanism of the effect of early intensive insulin therapy. METHODS: In this study, 36 patients with newly diagnosed type 2 diabetes and 22 control subjects matched by age and gender were enrolled. All of the patients with diabetes received intensive insulin therapy. The number of EPCs was assessed by flow cytometry based on the expression of CD34, CD133, and kinase insert domain-containing receptor (KDR). RESULTS: Levels of circulating CD34+KDR+CD133+ EPCs were higher in patients with diabetes compared to control subjects and significantly decreased after intensive insulin therapy. Levels of vascular endothelial growth factor (VEGF), a major contributor to EPC mobilization, were significantly higher in patients with diabetes compared to control subjects, and dramatically decreased after insulin therapy. Importantly, VEGF levels correlated with number of EPCs. Moreover, compared with control subjects, pro-inflammatory cytokines and oxidative stress were significantly higher in patients with diabetes and markedly decreased after intensive insulin therapy. CONCLUSIONS: These results showed that type 2 diabetes is associated with an increase of circulating CD34+KDR+CD133+ EPCs at the onset of diabetes, indicating increased compensatory mobilization. Additionally, early intensive insulin therapy exerts a preserving effect on EPC level partly through improving inflammation status and oxidative stress, thereby implying a putative long-term beneficial effect on vascular integrity via suspending excessive EPC exhaustion. CLINICAL TRIAL NUMBER: NCT03710811.

Performance Evaluation of the Glunovo® Continuous Blood Glucose Monitoring System in Chinese Participants with Diabetes: A Multicenter, Self-Controlled Trial.

INTRODUCTION: The present study was aimed to evaluate the performance and safety of the Glunovo® real-time continuous glucose monitoring system (CGMS) in monitoring interstitial fluid glucose in adult participants with diabetes (at least 18 years old) using venous blood glucose as control. METHODS: This was a multicenter, self-controlled clinical trial, conducted in participants with diabetes from China, between March 2019 to October 2019. The CGMS was used by all the participants for a 14-day wear-in period. The real-time glucose values measured by Glunovo® CGMS were compared with venous blood glucose values measured by the Entwicklung, Konstruktion und Fertigung (EKF) blood glucose detector. The primary outcomes were the consistency rate of CGMS readings and venous blood glucose values (20/20% standard). RESULTS: A total of 78 participants (41 men, 37 women) and 156 CGMS sensors were included in the study. Among the included participants, 25 and 53 participants had type 1 and type 2 diabetes, respectively, with median age of 52.50 years (range 32-62 years). The overall agreement rate (20/20%) was 89.71% (95% CI 89.18-90.24%). It was observed that 99.08% (95% CI 98.91-99.24%) and 99.82% (95% CI 99.74-99.89%) of the measuring points fell within the A + B zones of the Clarke error grid analysis and Parkes/consensus error grid analysis, respectively. The mean absolute relative difference was 10.30% ± 4.86%. The probability of a glucose measurement falling within a range, when stratified by venous glucose measurements, ranged from 7.14% for 19.44-22.22 mmol/L to 79.21% for 4.44-6.67 mmol/L. There were 73 (41.24%) and 27 (57.45%) successful CGMS alarms for hypoglycemic and hyperglycemic events, respectively. CONCLUSION: From the results, Glunovo® CGMS had excellent accuracy and limited clinical risk compared with venous blood glucose in the range of 2.2-22.2 mmol/L over 14 days.

The Risk Factors for Diabetic Retinopathy in a Chinese Population: A Cross-Sectional Study.

AIMS: Epidemiological data on diabetic retinopathy (DR) in Chinese population is still rather scarce, and risk factors for diabetic retinopathy are inconsistent because of study designs, grading standards, and population samples. MATERIALS AND METHODS: This hospital-based retrospective study included 1052 type 2 diabetes patients. Diabetic retinopathy was diagnosed by nonmydriatic fundus photography and/or fundus examination apparatus. Logistic regression analysis was performed to evaluate the risk of diabetic retinopathy. RESULTS: A total of 352 (33.5% prevalence) subjects were diagnosed with diabetic retinopathy based on our population. The patients in the DR group not only had significantly higher hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), urinary microalbumin-creatinine ratio (ACR), and systolic blood pressure but also had higher follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels compared to those in the non-DR group. Moreover, we confirmed that diabetes duration and HbA1c are strongly associated with DR risk. We also found that serum LH was an independent risk factor in male diabetic retinopathy patients (OR = 1.086, 95% CI 1.024-1.152), and the levels of LH were significantly associated with diabetic retinopathy prevalence (P = 0.018). CONCLUSIONS: Our study strengthens the argument that diabetes duration and HbA1c are risk factors for patients with DR. Additionally; we firstly confirmed that serum LH was an independent risk factor in male diabetic retinopathy patients.

Increased circulating conjugated primary bile acids are associated with hyperandrogenism in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a common metabolic disorder with hyperandrogenism as the core pathophysiologic feature. Increased bile acids and altered bile acid pool composition have been implicated in the pathogenesis of several metabolic diseases. Thus, this study aimed to clarify the specific alterations in circulating bile acids in patients with PCOS and investigate its associations with hyperandrogenism. We recruited 37 patients with PCOS and 35 age- and BMI-matched control subjects. Serum bile acids and androgen profiles were assessed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Compared with control subjects, glycine- and taurine-conjugated primary bile acids were significantly elevated in patients with PCOS (P = 0.001 and P < 0.001). In addition, these conjugated primary bile acids were significantly and positively associated with serum concentrations of total testosterone and androstenedione in the PCOS group. In conclusion, increased circulating conjugated primary bile acids are positively associated with hyperandrogenism in women with PCOS. Further studies are warranted to explore the underlying mechanism.

Comparative effect of saxagliptin and glimepiride with a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in patients uncontrolled with metformin therapy: Results from the SPECIFY study, a 48-week, multi-centre, randomized, controlled trial.

AIMS: To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: In this 48-week, multi-centre, open-label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment. RESULTS: Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05-1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m2 . Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (-0.94% with saxagliptin vs -0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was -1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001). CONCLUSIONS: This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes.

The catalytic activity and mechanism of oxygen reduction reaction on P-doped MoS2.

With the approaching commercialization of proton exchange membrane fuel cell technology, developing active, non-precious metal oxygen reduction reaction (ORR) catalyst materials to replace currently used Pt-based catalysts is a necessary and essential requirement in order to reduce the overall system cost. Here, we report a single-atom doped molybdenum disulfide sheet (short as X-MoS2) catalyst for the ORR using a dispersion-corrected density functional theory method. Of all the eleven X-MoS2 (X = B, C, N, O; Al, Si, P; Ga, Ge, As, and Se) systems, only the phosphorus atom doped molybdenum disulfide (P-MoS2) has an O2 adsorption energy close to that of a Pt(111) surface. We have further explored the detailed ORR mechanism of P-MoS2. Along the four-electron reaction pathway, the reduction of OH to H2O is the rate-limiting step with the largest diffusion barrier of 0.79 eV.

Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome.

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); ß-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p < 0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387-4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and ß-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and ß-cell dysfunction in women with PCOS.

Subclinical hypothyroidism is not a risk factor for polycystic ovary syndrome in obese women of reproductive age.

Obese women are at high risk for polycystic ovary syndrome (PCOS). Subclinical hypothyroidism (SCH) has been associated with weight gain, insulin resistance and impaired fertility, which are also factors involved in PCOS. However, there is limited information regarding the influence of SCH on the presence of PCOS. In order to determine whether SCH increases the prevalence of PCOS, we performed a cross-sectional study in a cohort of reproductive-aged obese women. All subjects underwent anthropometric evaluation, laboratory tests and ultrasound examination. Diagnosis of PCOS was based on the Rotterdam criteria. A total of 534 obese women were included and 108 (20.2%) of them were diagnosed with SCH. Patients with SCH showed similar insulin resistance, comparable androgen levels, and higher triglycerides levels (1.7 vs. 1.5 mmol/L, p = .002) compared to those with normal thyroid status. The frequency of PCOS did not differ between the two groups (56.1% for normal thyroid function vs. 60.2% for subclinical hypothyroidism, p = .514). In logistic regression analysis, SCH was not an independent risk factor for PCOS after adjusting for confounding factors (OR = 0.984, 95% CI 0.581-1.667). For the first time, our results suggest that SCH does not increase the risk of PCOS in obese women of reproductive age.

A retrospective study on association between obesity and cardiovascular risk diseases with aging in Chinese adults.

This study aimed to investigate the prevalence of overweight and obesity and its relationship with cardiovascular risk diseases among different sex and age groups in an urban Chinese adult population. A retrospective analysis was performed on 384,061 Chinese adults aged 20 years and older in Nanjing. The age-standardized prevalence of overweight and obesity was 42.8% and 13.2% in men and 23.9% and 6.6% in women. A gradually increasing trend was observed in the prevalence of overweight and obesity from 2008 to 2016, especially in individuals aged 20~39 years. Overweight and obesity were significantly associated with increased risks of dyslipidemia, diabetes mellitus, hypertension, and hyperuricemia. Age weakened such relationship for both genders, which spiked in individuals aged 20~39 years. For men and women aged 20~39 years, the OR (95% CI) of obesity reached 4.23 (4.01-4.47) and 5.29 (4.63-6.04) for dyslipidemia, 3.70 (2.97-4.60) and 6.38 (3.86-10.55) for diabetes mellitus, 6.19 (5.76-6.64) and 9.36 (7.86-11.13) for hypertension, and 3.66 (3.45-3.88) and 6.65 (5.70-7.74) for hyperuricemia, respectively. The increasing trend in the epidemic of overweight and obesity is a risk factor for cardiovascular risk diseases in Chinese adults, especially in individuals aged 20~39 years.

Enhanced Stability of PtML/MML/WC(0001) Multilayer Alloys under Electrochemical Conditions: A First Principle Study.

A platinum (Pt) monolayer catalyst could greatly reduce the use of Pt. However, the core or subsurface transition metal could easily segregate to the surface and eventually selectively dissolve in the working conditions. In this work, a type of PtML/MML/tungsten carbide (WC) multilayer structure catalyst has been designed using the density functional theory method. The results show that the stability of W-terminated core catalysts is lower than that of the corresponding C-terminated one. More importantly, the C-terminated PtML/CoML/WC alloy could also maintain a stable Pt monolayer structure in various electrolyte solutions (e.g., perchloric acid, phosphoric acid, and alkaline solutions) and via different oxygen reduction reaction (ORR) pathways, in addition to the previously well-known precious alloy elements, such as Ru, Ir, and so forth. The segregation of the M metal will be suppressed by introducing a high electronegativity nonmetal element in the core such as C through enhanced interaction between the C and M interlayers. The improved ORR activity and the stability of C-terminated PtML/Co(Ru)ML/WC(0001) multilayer structures highlight the importance of surface chemistry of the substrate in rational design Pt monolayer catalysts.

Erythropoietin alleviates hepatic steatosis by activating SIRT1-mediated autophagy.

Erythropoietin (EPO), besides its stimulatory effect on erythropoiesis, is beneficial to insulin resistance and obesity. However, its role in hepatic steatosis remains unexplored. Activating autophagy seems a promising mechanism for improving fatty liver disease. The present study investigated the role of EPO in alleviating hepatic steatosis and sought to determine whether its function is mediated by the activation of autophagy. Here, we show that EPO decreased hepatic lipid content significantly in vivo and in vitro. Furthermore, EPO/EPO receptor (EPOR) signalling induced autophagy activation in hepatocytes as indicated by western blot assay, transmission electron microscopy, and confocal microscopy. In addition, EPO increased the co-localization of autophagosomes and cellular lipids as shown by double labelling of the autophagy marker light chain microtubule-associated protein 3 (LC3) and lipids. Importantly, suppression of autophagy by an inhibitor or small interfering RNA (siRNA) abolished the EPO-mediated alleviation hepatic steatosis in vitro. Furthermore, EPO up-regulated sirtuin 1 (SIRT1) expression, and siRNA-mediated SIRT1 silencing abrogated the EPO-induced increases in LC3 protein and deacetylation levels, thereby preventing the alleviation of hepatic steatosis. Taken together, this study revealed a new mechanism wherein EPO alleviates hepatic steatosis by activating autophagy via SIRT1-dependent deacetylation of LC3. This finding might have therapeutic value in the treatment of hepatic steatosis.

Insulin Glargine Combined with Oral Antidiabetic Drugs for Asians with Type 2 Diabetes Mellitus: A Pooled Analysis to Identify Predictors of Dose and Treatment Response.

INTRODUCTION: In Asia, patients with type 2 diabetes mellitus (T2DM) often have suboptimal glycemic control for many years prior to initiating basal insulin. Active titration of basal insulin is also required to improve glycemic outcomes. This pooled analysis was conducted to determine the impact of patient baseline covariates on the required dose of basal insulin and treatment response, for the improved management of Asian patients with T2DM. METHODS: Data on insulin-naïve Asian patients with T2DM who initiated and fully titrated insulin glargine 100 U/mL (Gla-100) for ≥ 20 weeks were pooled from seven randomized, controlled, treat-to-target trials. Covariance and multivariate linear/logistic regression analyses were applied to determine the impact of the baseline covariates on Gla-100 dose (primary outcome) and treatment response (secondary outcomes) at week 24 for patients from Asia (N = 724) and from China alone (n = 249). Based on the multivariate analysis for the primary outcome in the Asian population, a nomogram was developed. RESULTS: The dose of Gla-100 at week 24 was negatively correlated with age and positively correlated with body mass index (BMI) and fasting plasma glucose (FPG) at baseline in both Asian and Chinese populations. In both populations, higher baseline glycated hemoglobin (HbA1c) was associated with a lower reduction in HbA1c from baseline, higher HbA1c at week 24, and a lower chance of achieving HbA1c < 7% at week 24. The constructed nomogram enables calculation of the likely dose of Gla-100 required by Asian patients with T2DM to achieve HbA1c < 7% at week 24. CONCLUSIONS: Higher doses of Gla-100 are likely to be required in younger patients or patients with higher baseline BMI or FPG. The nomogram developed in this study can aid clinicians to titrate the dose of Gla-100 appropriately. Evidence in this pooled analysis also indicates that initiating basal insulin at a lower HbA1c can lead to greater glycemic control. FUNDING: Sanofi China Investment Company.

Gender and Age Differences in Lipid Profile Among Chinese Adults in Nanjing: a Retrospective Study of Over 230,000 Individuals from 2009 to 2015.

BACKGROUND: Previous national survey suggested that dyslipidemia is an increasing burden in China and more severe in urban population. In this study, we retrospectively analyzed the gender and age differences in lipids and lipoproteins in a large Chinese urban population in Nanjing city. METHODS: A total of 236, 945 adults (age ≥20 years old) who undertook a health check between 2009 and 2015 in our medical examination center were involved in the analysis. Fasting total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride (TG) were measured by standard methods. RESULTS: The age-standardized estimates of serum total cholesterol, HDL cholesterol, LDL cholesterol and triglyceride were 4.77 (4.76-4.79), 1.19 (1.18-1.19), 2.53 (2.52-2.54) and 1.74 (1.72-1.76) mmol/L in males (n=130954), and 4.79 (4.78-4.80), 1.46 (1.45-1.46), 2.44 (2.43-2.45) and 1.21 (1.19-1.22) mmol/L in females (n=105991), respectively. The prevalence of dyslipidemia was significantly elevated in females above 50 years old, and the peak prevalence of dyslipidemia in males was in the age group of 40-59 years, earlier as compared to females (peaked at 60-69 years old). In addition, an increasing secular trend was observed in LDL cholesterol levels from 2009 to 2015 in both males and females. CONCLUSIONS: Dyslipidemia is an increasing epidemic in China, characterized by a rising trend of LDL cholesterol. The gender and age differences in serum levels of lipid profile as well as prevalence of dyslipidemia suggested that the middle-age men and postmenopausal women should be the prioritized target for better control of dyslipidemia and early prevention of cardiovascular disease.