Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Background: Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients. Methods: Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher. Conclusion MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

BACKGROUND AND AIM: Remnant cholesterol (remnant-C) mediates the progression of major adverse cardiovascular events. It is unclear whether remnant-C, and particularly cumulative exposure to remnant-C, is associated with nonalcoholic fatty liver disease (NAFLD). This study aimed to explore whether remnant-C, not only baseline but cumulative exposure, can be used to independently evaluate the risk of NAFLD. METHODS: This study included 1 cohort totaling 21,958 subjects without NAFLD at baseline who underwent at least 2 repeated health checkups and 1 sub-cohort totaling 2,649 subjects restricted to those individuals with at least 4 examinations and no history of NAFLD until Exam 3. Cumulative remnant-C was calculated as a timeweighted model for each examination multiplied by the time between the 2 examinations divided the whole duration. Cox regression models were performed to estimate the association between baseline and cumulative exposure to remnant-C and incident NAFLD. RESULTS: After multivariable adjustment, compared with the quintile 1 of baseline remnant-C, individuals with higher quintiles demonstrated significantly higher risks for NAFLD (hazard ratio [HR] 1.48, 95%CI 1.31-1.67 for quintile 2; HR 2.07, 95%CI 1.85-2.33 for quintile 3; HR 2.55, 95%CI 2.27-2.88 for quintile 4). Similarly, high cumulative remnant-C quintiles were significantly associated with higher risks for NAFLD (HR 3.43, 95%CI 1.95-6.05 for quintile 2; HR 4.25, 95%CI 2.44-7.40 for quintile 3; HR 6.29, 95%CI 3.59-10.99 for quintile 4), compared with the quintile 1. CONCLUSION Elevated levels of baseline and cumulative remnant-C were independently associated with incident NAFLD. Monitoring immediate levels and longitudinal trends of remnant-C may need to be emphasized in adults as part of NAFLD prevention strategy.
Adult ; Humans ; Cohort Studies ; Non-alcoholic Fatty Liver Disease/etiology* ; Cholesterol ; Proportional Hazards Models ; Risk Factors

Objective:To analyze the association between visceral fat area (VFA) and fatty liver based on quantitative CT (QCT) in people receiving health examination with normal body mass index (BMI).Methods:A cross-sectional study. A total of 1 305 physical examiners who underwent chest CT and QCT examination in the Department of Health Management of Henan Provincial People′s Hospital from January to December 2021 were retrospectively selected as subjects. The physical components at the central level of the lumbar two cone were measured with QCT, including subcutaneous fat area (SFA), VFA and liver fat content (LFC). And the metabolic indexes, such as blood lipids and blood glucose, were collected. The t-test and χ2 test were used to analyze the correlation between the detection rate of fatty live and LFCr and age and gender. According to level of VFA (<100 cm 2, 100-150 cm 2 and≥150 cm 2), the subjects were divided into three groups, and one-way ANOVA and χ2 test were used in comparison between groups. Multiple linear regression was used to analyze the correlation between VFA and metabolic indexes and LFC. Results:Of the 1 305 subjects, there were 634 males and 671 females. The detection rate of fatty liver in normal BMI population was 65.67%, and it was 72.71% and 59.02% respectively in men and women ( χ2=27.12, P<0.001), and the detection rate of fatty liver and LFC increased with age (both P<0.05). With the increase of VFA, the age, BMI, SFA, LFC, total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), alanine aminotransferase (ALT), blood uric acid and prevalence of fatty liver increased (all P<0.05), and the low-density lipoprotein cholesterol (HDL-C) decreased ( P<0.001). Multiple linear regression analysis showed that after adjustment for age factors, regardless of male or female, LFC was independently positively related with VFA, BMI, and ALT (male β=0.206, 0.145, 0.174, female β=0.194, 0.150, 0.184; all P<0.05). FBG was positively correlated with male independently ( β=0.134; P<0.001). The indicators related to female independently were TC, TG, and blood uric acid ( β=-0.121, 0.145, 0.141, all P<0.05) Conclusion:In the population receiving health examination with normal BMI, the VFA measured by QCT technique is closely related to fatty liver.

Objective:To investigate whether long non-coding RNA(lncRNA) AW112010 can improve insulin resistance in aging adipocytes through the miR-204/POU2F2 signaling pathway.Methods:In vivo experiment: C57BL/6 mice were divided into young control group(4 months old) and aging model group(18 months old) based on body weight. The expression levels of AW112010, miR-204-5p, POU2F2, aging related indicators(p16, p21), and insulin signaling pathway genes [insulin receptor(INSR), insulin receptor substrate 1(IRS1), phosphatidylinositol kinase(PI3K), protein kinase B(AKT)] in epididymal adipose tissue were detected using real-time fluorescence quantitative PCR(RT-qPCR) and Western blotting. In vitro experiment: Using adriamycin(ADR) to induce 3T3-L1 aging adipocyte model, β-gal staining was used to observe cellular senescence, and miR-204 inhibitor and miR-204 mimic small interfering RNA were successfully constructed and transfected into 3T3-L1 adipocytes. Results:RT-qPCR and Western blot results showed that compared with the young group, the expression of AW112010 in the adipose tissue of aging mice was increased, while the expression of miR-204-5p was decreased. The expressions of POU2F2, p16, and p21 in the adipose tissue of aging mice were increased, while the expressions of INSR, IRS1, PI3K, GLUT4 mRNA and protein were decreased. The β-gal stainging results showed that the number of 3T3-L1 senescent adipocytes induced by ADR was significantly increased, and the expression levels of AW112010, POU2F2, p16, and p21 in ADR-induced senescent adipocytes were increased compared with the control group, while the expression levels of miR-204-5p, INSR, IRS1, PI3K, GLUT4 were decreased, and remaining glucose in the culture medium was increased. Compared with control, overexpression of miR-204 resulted in decreased expressions of aging indicators p16, p21, and target gene POU2F2 while the expressions of INSR and GLUT4 were increased.Conclusion:Upregulation of lncRNA AW112010 in adipocytes of aging mice may induce insulin resistance by targeting miR-204-5p/POU2F2/IRS1.

Objective:To determine the incidence of adrenal incidentalomas(AIs) in patients with diabetes mellitus and the metabolism profiles.Methods:A total of 615 hospitalized patients with diabetes mellitus in the Department of Endocrinology and Metabolism of Peking University People′s Hospital from March 2020 to May 2021 were retrospectively included in this study. AIs were screened by unenhanced chest computed tomography(CT) retrospectively and subsequently confirmed by multiplanar reconstruction. Participants′ physical indicators, metabolic profiles, and adrenal function parameters were collected. Unpaired t test, Mann-Whitney U test, and Chi-Square test were adopted to compare the metabolism profiles between diabetes mellitus patients with or without AIs. Regression models were used to estimate the correlations between AIs and the metabolism profiles such as blood glucose, blood lipids, blood pressure, and the adrenal function parameters.Results:Twenty-seven out of 615 participants were detected with AIs(4.4%). Patients with AIs had higher body mass index, waist circumference, and hip circumference than patients without AIs [(29.4±5.1)kg/m 2vs(26.8±3.8)kg/m 2,P=0.018; (102.3±11.7)cm vs(95.8±10.3)cm, P=0.002; (107.3±10.1)cm vs(101.4±7.6)cm, P=0.008]. The levels of serum uric acid and urinary albumin/creatinine ratio were also significantly increased in patients with AIs [(409.6±118.1)μmol/L vs(357.4±100.6)μmol/L, P=0.009; 21.25(7.49, 180.24)mg/g vs 8.60(4.71, 34.56)mg/g, P=0.010]. Besides, individuals with AIs were also associated with a higher risk of co-existing hypertension( P=0.045). Conclusion:The incidence of AIs in patients with diabetes is 4.4%. The presence of AIs in patients with diabetes may associated with increased risk of obesity and hypertension.

OBJECTIVE To explore the mechanism of steam-processed Polygonatum sibiricum polysaccharides(SPSP) in prophylaxis and treatment of mice with blood deficiency syndrome(BDS) by RNA sequencing(RNA-seq) technology. METHODS The mice were randomly divided into five groups(10 mice in each group), namely normal group, model group, SPSP groups(0.1, 0.4 g·kg−1), Danggui Buxue oral liquid(DOL) group. BDS model was induced in mice by acetylphenyl-hydrazine and cyclophosphamide. Blood routine, body weight and body temperature were tested after a consecutive administration for 14 d. The differential expressed genes(DEGs) related to anti-BDS by SPSP were screened through the transcriptome sequencing of the hepatic tissue in BDS mice. Functional annotation and enrichment analysis were performed to screen out the gene expression signaling pathways related to the treatment of SPSP on BDS mice. Quantitative polymerase chain reaction(qPCR) was used to verify the experiment. RESULTS Compared with the model group, SPSP(0.4 g·kg−1) could elevate the blood routine indexes such as red blood cell, white blood cell, hemoglobin, platelet, mean corpuscular hemoglobin concen-tration(P<0.01), and reverse the body weight and body temperature to normal(P<0.01 or P<0.05). The result of transcriptomic analysis showed that the underlying mechanism was mainly related to hematopoietic cell line, retinol metabolism, steroid hormone biosynthesis, platelet activation, B cell receptor signaling pathway, and leukocyte transendothelial migration, etc. The result of qPCR showed that SPSP(0.4 g·kg−1) could elevate the expression of JAK1, STAT1 and GATA1 mRNA (P<0.01 or P<0.05). CONCLUSION SPSP has therapeutic effects on BDS. The key DEGs in the treatment of BDS by SPSP are mainly related to the restoration of hematopoietic function, regulation of hormone and immune function. The mechanism of SPSP on treatment of BDS might be the regulation of JAK1/STAT1 signaling pathway.

Objective:Insulin resistance(IR)is closely associated with atherosclerosis and adverse cardiovascular events.The triglyceride-glucose(TyG)index is an effective indicator for assessing IR.This study aims to explore the relationship between the TyG index and the risk of arterial stiffness progression. Methods:This retrospective cohort study included adults who had undergone at least 2 health examinations with arteriosclerosis testing at the Health Management Medical Center of the Third Xiangya Hospital,Central South University,between January 2012 and December 2022.Clinical data were collected.The TyG index was calculated using the formula of ln(triglyceridesxfasting blood glucose/2).The baseline TyG index was assessed as both a continuous variable and as a quartile-based categorical variable.The progression of arteriosclerosis was evaluated by the annual change rate of brachial-ankle pulse wave velocity(baPWV)and the new onset of increased arterial stiffness.Linear regression model and Cox proportional hazard model were used to explore whether the TyG index is an independent risk factor for arterial stiffness progression.Subgroup analyses were performed based on age,gender,body mass index(BMI),and the presence of type 2 diabetes,hypertension,or hyperlipidemia to determine the characteristics of the association between the TyG index and arterial stiffness progression. Results:A total of 4 971 participants were included,with a follow-up period of(3.01±1.98)years.During follow-up,the annual baPWV change rate was(24.94±81.15)cm/s,and 278 cases of new onset of increased aterial stiffness were recorded.After fully adjusting for confounding factors,the baseline TyG index was independently positively correlated with both the annual baPWV change rate(β=17.5,95％CI 9.00 to 25.94,P＜0.001)and the risk of new onset of increased aterial stiffness[hazard ratio(HR)=1.43,95％CI 1.18 to 1.74,P＜0.001]when the TyG index was treated as a continuous variable.When treated as a categorical variable,higher TyG index quartiles were associated with progressively higher baPWV change rates and new onset of increased arterial stiffness(all P＜0.055).In subgroups of participants aged ≥45 years,males,BMI＜28 kg/m2,those with or without hypertension,and those without type 2 diabetes or hyperlipidemia,the baseline TyG index(both continuous and categorical)was significantly associated with new onset of increased arterial stiffness(all P＜0.05),with no significant interactions observed across subgroups(all P＞0.05). Conclusion:The TyG index is independently associated with an increased risk of arterial stiffness progression and may serve as a useful indicator for assessing arterial stiffness progression risk in health check-up populations.