Comparison of clinical characteristics and disease burden between early- and late-onset type 2 diabetes patients: a population-based cohort study.

BACKGROUND: The clinical characteristics of early-onset type 2 diabetes (T2D) patients are not fully understood. To address this gap, we conducted a cohort study to evaluate clinical characteristics and disease burden in the new-onset T2D population, especially regarding the progression of diseases. METHODS: This cohort study was conducted using a population-based database. Patients who were diagnosed with T2D were identified from the database and were classified into early- (age < 40) and late-onset (age ≥ 40) groups. A descriptive analysis was performed to compare clinical characteristics and disease burden between early- and late-onset T2D patients. The progression of disease was compared using Kaplan‒Meier analysis. RESULTS: A total of 652,290 type 2 diabetic patients were included. Of those, 21,347 were early-onset patients, and 300,676 were late-onset patients. Early-onset T2D patients had poorer glycemic control than late-onset T2D patients, especially at the onset of T2D (HbA1c: 9.3 [7.5, 10.9] for early-onset vs. 7.7 [6.8, 9.2] for late-onset, P < 0.001; random blood glucose: 10.9 [8.0, 14.3] for early-onset vs. 8.8 [6.9, 11.8] for late-onset, P < 0.001). Insulin was more often prescribed for early-onset patients (15.2%) than for late-onset patients (14.8%). Hypertension (163.0 [28.0, 611.0] days) and hyperlipidemia (114.0 [19.0, 537.0] days) progressed more rapidly among early-onset patients, while more late-onset patients developed hypertension (72.7% vs. 60.1%, P < 0.001), hyperlipidemia (65.4% vs. 51.0%, P < 0.001), cardiovascular diseases (66.0% vs. 26.7%, P < 0.001) and chronic kidney diseases (5.5% vs. 2.1%, P < 0.001) than early-onset patients. CONCLUSIONS: Our study results indicate that patients with newly diagnosed early-onset T2D had earlier comorbidities of hypertension and hyperlipidemia. Both clinical characteristics and treatment patterns suggest that the degree of metabolic disturbance is more severe in patients with early-onset type 2 diabetes. This highlights the importance of promoting healthy diets or lifestyles to prevent T2D onset in young adults.

Inhibition of NCAPG expression inactivates the Wnt/ß-catenin signal to suppresses endometrial cancer cell growth in vitro.

Endometrial cancer (EC) ranks as the most prevalent malignancy occurring in the female genital tract. Non-SMC condensin I complex subunit G (NCAPG), a mitotic associated chromosomal condensing protein, is reported to be frequently abnormally expressed in several tumors and plays a vital role in carcinogenesis. Our study aimed to explore the effect of NCAPG on cell proliferation and apoptosis in EC cells and to determine the underlying mechanism. Expression and survival data of NCAPG in EC tissues were analyzed by bioinformatics methods. Cell proliferation was evaluated by EdU and CCK-8 assays. Apoptosis was assessed by flow cytometry analysis. Expression of NCAPG, proliferating cell nuclear antigen (PCNA), Ki67, Bcl-2, Bax, active caspase-3, active ß-catenin, and c-Myc were determined by western blotting. NCAPG was highly expressed in EC tissues and cells and predicted poor survival for EC patients. NCAPG knockdown inhibited cell proliferation and induced apoptosis in EC cells. Additionally, NCAPG knockdown inactivated the Wnt/ß-catenin pathway in EC cells. Mechanistically, ß-catenin overexpression blocked the tumorigenic effects of NCAPG in EC cells. In conclusion, NCAPG silencing inhibited cell proliferation and induced apoptosis in EC cells via inhibiting the Wnt/ß-catenin pathway.

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease: A multicenter cross-sectional study in China.

BACKGROUND: This study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD). METHODS: This was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance. RESULTS: Of 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m2 was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037-8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388-4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772-9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398-6.210; P = 0.004) after the adjustments of the BMI and diabetes. CONCLUSIONS: Metabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.

[Association of choroidal thickness with diabetic retinopathy at different stages].

OBJECTIVE: To explore the association of choroidal thickness variations in type 2 diabetes mellitus (T2DM) patients with diabetic retinopathy (DR) at different stages. METHODS: A total of 161 patients with T2DM were included in this study, from October 2012 to June 2014. According to Early Treatment Diabetic Retinopathy Study (ETDRS) criteria, the patients were divided into 5 groups: non-DR without diabetic macular edema (DME) group(DR-/DME- group, 45 eyes), nonproliferative diabetic retinopathy (NPDR) without DME group(NPDR+/DME- group, 58 eyes), proliferative diabetic retinopathy (PDR) without DME group (PDR+/DME- group, 12 eyes), NPDR with DME group (NPDR+/DME+ group, 41 eyes), PDR with DME group (PDR+/DME+ group, 5 eyes). Meanwhile, 60 normal subjects were enrolled as the control group. All study subjects received optical coherence tomography enhanced depth imaging (EDI-OCT) examination to detect and compare subfoveal choroidal thickness at different stages of DR. RESULTS: Mean SFCT was (271 ± 36), (270 ± 35), (262 ± 38), (244 ± 36), (229 ± 35) µm respectively in control, DR-/DME-, NPDR+/DME-, PDR+/DME-, NPDR+/DME+ groups. The SFCTs of PDR+/DME- and NPDR+/DME+ group were statistically lower than that of control group (P=0.004, P=0.001). The SFCT of PDR+/DME- group was lower than that of DR-/DME- group (P=0.003), and there was also a significant difference of SFCT between NPDR+/DME+ and NPDR+/DME- group (P=0.001). There was linear correlation between SFCT and the logMAR best-corrected visual acuity (r=0.397, P<0.01), but the SFCT was independent of diabetic duration, fasting blood glucose, HbA1c, axial length, diastolic blood pressure (DBP) and systolic blood pressure SBP (r=-0.024, 0.159, 0.089, 0.036, 0.143, 0.057, all P>0.05). There was no significant difference of SFCT among different DME types (F=0.071, P>0.05). CONCLUSION: The SFCT decreased with increasing severity of DR. To monitor the SFCT in T2DM patients may be helpful to evaluate the severity of DR and provide a new treatment conception.

[Relationship of socioeconomic status and non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus].

OBJECTIVE: To explore the relationship between socioeconomic status (SES) and non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). METHODS: The medical records of Tianjin Third Central Hospital were retrospectively reviewed to identify patients who had been hospitalized for treatment of T2DM but without diagnosis of NAFLD between 2007 and 2012 and who had required a second hospitalization during this same period. Each patient was contacted by telephone for self-reporting of SES. Analysis was carried out with patients grouped according to SES (high vs. low) to determine association of SES with incidence of NAFLD at the second hospitalization; the relative risk (RR), attributable risk (AR) and attributable risk percent (ARP) were calculated. Furthermore, the correlation of SES with other clinical and socio-psychological variables was assessed. RESULTS: The patients in the high and low SES groups showed no significant differences at baseline. For development of NAFLD by the time of the second hospitalization, the low SES group had an RR of 2.19, an AR of 20.74%, and an ARP of 54.39%. Correlation analysis showed that SES was positively correlated with body mass index (r=-0.582) and levels of glycated hemoglobin (r=-0.421), fasting serum insulin (r=-0.570), insulin resistance (as assessed by the HOMA method) (r=-0.487), low-density lipopmtein (r=-0.396) and C-reactive protein (r=-0.353) (all P<0.05), and negatively correlated with high-density lipopmtein (r =0.539) and with the scores for physical functioning (r =0.241), general health (r=0.234), social functioning (r =0.286), emotional health (r=0.251), and mental health (r=0.215) (all P<0.05). CONCLUSION: SES is an influencing factor of NAFLD in patients with T2DM and is closely related to obesity, insulin resistance, lipid metabolic disorder, chronic inflammation and life quality in patients with NAFLD and T2DM.

Accuracy of FibroTouch in assessing liver steatosis and fibrosis in patients with metabolic-associated fatty liver disease combined with type 2 diabetes mellitus.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM) patients and can rapidly progress to steatohepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). Accurate evaluation and proper management of MAFLD can help prevent adverse liver outcomes. Here we evaluated the precision of the FibroTouch (FT) in the staging of liver steatosis and fibrosis in patients with MAFLD combined with T2DM using two indicators: controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). METHODS: Eighty-five adult MAFLD combined with T2DM patients were selected at our center from July 2016 to July 2019 and underwent liver puncture biopsy for histopathology and the FT assay simultaneously. Two blinded pathologists independently reviewed the samples. The severity of fatty liver was classified using two scoring systems: the nonalcoholic fatty liver disease activity score (NAS) and the fibrosis score. Scores were then assessed following the Pathology Working Group of the NASH Clinical Research Network of the National Institutes of Health. Similarly, the severity of nonalcoholic steatohepatitis (NASH) was classified using the European Steatosis Activity Fibrosis (SAF) system. The FT assay was applied to obtain the LSM and the CAP. FT accuracy in diagnosing steatosis and fibrosis was determined by the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUROC). RESULTS: Using biopsy analysis as the gold standard, the AUROCs and cutoff values of CAP in diagnosing liver steatosis were as follows: 0.84 (95% CI: 0.67-1.01) and 278 dB/m for S ≥ S1, 0.88 (95% CI: 0.81-0.95) and 305 dB/m for S ≥ S2, 0.89 (95% CI: 0.82-0.95) and 307 dB/m for S ≥ S3. The AUROCs and cutoff values of LSM in diagnosing liver fibrosis were as follows: 0.76 (95% CI: 0.66-0.86) for F ≥ F2, 0.81 (95% CI: 0.71-0.91) and 13.8 kPa for F ≥ F3, 0.92 (95% CI: 0.85-1.00) and 20.1 kPa for F ≥ F4. CONCLUSIONS: In patients of MAFLD with T2DM, CAP and LSM obtained by FT are highly accurate in assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.76 to 0.92.

Metabolic Disorders Combined with Noninvasive Tests to Screen Advanced Fibrosis in Nonalcoholic Fatty Liver Disease.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic disorders. This study aimed to explore the role of metabolic disorders in screening advanced fibrosis in NAFLD patients. METHODS: A total of 246 histologically-proven NAFLD patients were enrolled across 14 centers. We compared the severity of fibrosis in patients with different components of metabolic disorders. Based on standard noninvasive tests and metabolic disorders, we developed new algorithms to identify advanced fibrosis. RESULTS: Metabolic syndrome (MetS) was frequent in NAFLD patients (133/246, 54%). Patients with MetS had a higher proportion of significant fibrosis (p=0.014) and higher LSM values (9.2 kPa, vs. 7.4 kPa, p=0.002) than those without MetS. Patients with more metabolic disorders had higher fibrosis stages (p=0.017). Reduced high-density lipoprotein cholesterol (odds ratio [OR]: 2.241, 95% confidence interval [CI]: 1.004-5.002, p=0.049) and raised fasting glucose (OR: 4.500, 95% CI: 2.083-9.725, p<0.001) were significantly associated with advanced fibrosis. Using these two metabolic disorders as a screening tool, a sensitivity, specificity and accuracy of 92%, 81% and 83% was achieved, respectively. With the new algorithms combining metabolic disorders with noninvasive measurements, the number of patients requiring liver biopsy was reduced, especially in combination with the Fibrosis-4 score and metabolic disorders (36% to 17%, p<0.001). In addition, this stepwise algorithm could achieve a high accuracy (85%) and high negative predictive value (93%). CONCLUSIONS: Metabolic disorders should be taken into consideration in the diagnosis of advanced fibrosis. With further validation and investigation, new algorithms could be recommended in primary care units to spare patients from unnecessary referral and liver biopsies.

Regional difference in the susceptibility of non-alcoholic fatty liver disease in China.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a global health problem with high geographic heterogeneity. We aimed to investigate regional-specific concomitant rate of NAFLD and quantitative relationship between liver fat content (LFC) and glucose metabolism parameters in representative clinical populations from six provinces/municipalities of China. RESEARCH DESIGN AND METHODS: A total of 2420 eligible Han Chinese were enrolled consecutively from 10 clinics of obesity, diabetes and metabolic diseases located at six provinces/municipalities of China, and divided into North (Tianjin, Shandong and Heilongjiang) and South (Shanghai, Jiangsu and Henan) groups according to their geographical latitude and proximity of NAFLD concomitant rate. LFC was assessed by a quantitative ultrasound method. Multivariate regression models and analysis of covariance were used to assess the regional difference in the risk of NAFLD. RESULTS: The concomitant rate of NAFLD was 23.3%, 44.0% and 55.3% in individuals with normal glucose tolerance (NGT), pre-diabetes and diabetes, respectively. A higher concomitant rate of NAFLD was found in the participants from the North comparing with the South group, regardless of glucose metabolism status (34.7% vs 16.2% in NGT, 61.5% vs 34.7% in pre-diabetes and 67.1% vs 48.1% in diabetes). This regional difference remained significant after adjustment for age, gender, alcohol drinking, cigarette smoking, confounding metabolic parameters and liver enzymes. For any given blood glucose, participants from the North had higher LFC than those from the South group. CONCLUSIONS: Half of Han Chinese with pre-diabetes/type 2 diabetes had NAFLD, and the individuals from the North cities were more susceptible to NAFLD.

Serum glycated hemoglobin level as a predictor of atrial fibrillation: A systematic review with meta-analysis and meta-regression.

BACKGROUND AND AIM: Glycated hemoglobin (HbA1c) is a long-term measure of glucose control. Although recent studies demonstrated a potential association between HbA1c levels and the risk of atrial fibrillation (AF), the results have been inconsistent. The aim of this meta-analysis is to evaluate the utility of HbA1c level in predicting AF. METHODS: PubMed and the Cochrane Library databases were searched for relevant studies up to March 2016. Prospective cohort studies and retrospective case-control studies were included. Relative risk (RR) or odds ratio (OR) with 95% confidence intervals (CIs) of AF development were determined for different HbA1c levels. The random effect model was conducted according to the test of heterogeneity among studies. Subgroup analyses and meta-regression models were carried out to identify potential sources of heterogeneity. RESULTS: Eight prospective cohort studies with 102,006 participants and 6 retrospective case-control studies with 57,669 patients were finally included in the meta-analysis. In the primary meta-analysis, HbA1c levels were not associated with an increased risk of AF whether as a continuous (RR, 1.06; 95% CI, 0.96-1.18) or categorical variable (RR, 0.99; 95% CI, 0.83-1.18). Nevertheless, prospective studies showed about 10% increased risk of AF with elevated HbA1c levels both as a continuous (RR, 1.11; 95% CI, 1.06-1.16) and as a categorical variable (RR, 1.09; 95% CI, 1.00-1.18). In subgroup analyses, pooled results from studies with longer follow-up durations, published after 2012, aged < 63 years, with exclusion of cardiac surgery patients demonstrated an increased risk of AF for every 1% increase in HbA1c levels, while studies conducted in the United States with longer follow-up (more than 96 months), larger sample size and higher quality score (≥6) showed an increased risk of AF for higher HbA1c level as a categorical variable. CONCLUSIONS: Elevated serum HbA1c levels may be associated with an increased risk of AF, but further data are needed. Serum HbA1c levels might be considered as a potential biomarker for prediction of AF.

Non-Alcoholic Fatty Liver Disease Is a Risk Factor for the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is prevalent in individuals with type 2 diabetes mellitus (T2DM). Diabetic nephropathy (DN) is also associated with T2DM. However, little is known about the interaction between these conditions in patients with T2DM. OBJECTIVE: To examine the association between NAFLD and DN in patients with T2DM. METHODS: This retrospective study included patients seen between January 2006 and July 2014.T2DM patients were divided into two groups based on NAFLD status (with NAFLD = group A; without = group B). The cumulative incidence of DN and chronic kidney disease (CKD) staging were compared between the two groups. Liver fat content was examined in some patients. Associations among NAFLD, other factors,and DN were analyzed by the additive interaction method. RESULTS: Cumulative incidence of DN in patients from group A (58.58%) was higher than in group B (37.22%) (P = 0.005). In both groups, the number of DN patients with CKD stage 1 was greater than the number of patients with stages 2-5. Increased liver fat content was associated with increased occurrence of severe and mild albuminuria and decreased glomerular filtration rate (GFR). There were positive correlations between NAFLD and insulin resistance index (HOMA-IR), free fatty acids (FFA), tumor necrosis factor-α (TNF-α), omentin-1, visceral fat area, homocysteine (HCY), and serum uric acid (UA). CONCLUSION: NAFLD might be a risk factor for DN. Elevated liver fat content could be associated with higher DN burden.