Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

BACKGROUND: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN: Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING: 38 community health centers in Xiamen, China. PATIENTS: 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION: Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS: Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS: During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION: There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION: Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE: Xiamen Municipal Health Commission.

Identifying a distinct fibrosis subset of NAFLD via molecular profiling and the involvement of profibrotic macrophages.

BACKGROUND: There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. METHODS: To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. RESULTS: The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-ß signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. CONCLUSION: Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

Age-specific effects on adverse pregnancy outcomes vary by maternal characteristics: a population-based retrospective study in Xiamen, China.

BACKGROUND: Advanced maternal age (AMA; ≥35 years) is considered to be a major risk factor for adverse pregnancy outcomes. Along with the global trend of delayed childbearing, and in particular, the implementation of China's second and third-child policy leading to a dramatic increase of AMA in recent years, the association between maternal age and pregnancy outcomes requires more investigation. METHODS: A population-based retrospective study was performed. Data were derived from the Medical Birth Registry of Xiamen from 2011 to 2018. Univariate and multivariate logistic regression was used to evaluate the effects of maternal age on pregnancy outcomes. RESULTS: A total of 63,137 women categorized into different age groups (< 25 years, 25-29 years, 30-34 years, and ≥ 35 years) were included in this study. Compared with the mothers aged 25-29 years, the univariate regression analysis showed that mothers aged < 25 years had lower risks of gestational diabetes mellitus (GDM) and cesarean. AMA was associated with higher risks of GDM, hypertension, cesarean, preterm birth, low-birth weight (LBW), large-for-gestational-age (LGA), macrosomia, and stillbirth (all P < 0.01). After adjustment for potential confounding factors, increased risks of GDM, hypertension, cesarean, preterm birth, and LBW remained significantly associated with AMA (all P < 0.05), whereas AMA mothers showed a lower risk of macrosomia than their younger counterparts. Additionally, no significant differences were detected in terms of Apgar score < 7. CONCLUSION: AMA was associated with adverse pregnancy outcomes including increased risks of GDM, hypertension, cesarean, preterm birth, and LBW. This study confirmed the relationship between AMA and certain adverse maternal and fetal outcomes and emphasizes the necessity for women to be cautious about the age at which they become pregnant.

The correlation between triiodothyronine and the severity of liver fibrosis.

BACKGROUND: The severity of liver fibrosis is an important predictor of death in patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). However, there is still no definite conclusion on the relationship between triiodothyronine (T3) and the severity of liver fibrosis. Thus, the aim of this study was to analyze the correlation between T3 level and the severity of liver fibrosis. METHODS: We performed a cross-sectional study of 2072 T2DM patients with normal thyroid function from January 2017 to January 2020. NAFLD fibrosis score (NFS), Fibrosis index based on the 4 factors (FIB-4) and BARD score (BARD) were used to assess the severity of fibrosis in T2DM patients, and linear regression analyses were used to determine the factors independently associated with liver fibrosis. Further experiments were performed to assess the impact of low T3 on fibrosis progression in mice model and explore possible mechanisms. RESULTS: Free triiodothyronine (fT3) levels had significantly inverse correlations with NFS and FIB-4, and BARD in T2DM patients (P < 0.05). In multiple linear regression analyses, decreased fT3 level was an independent risk factor for the severity of liver fibrosis of T2DM patients (P < 0.01). Findings from in-vivo experiment using mice model proved that hypothyroidism mice had more severe of liver fibrosis than those mice with normal thyroid function. We also found that T3 could inhibit the profibrotic TREM2+CD9+ macrophage, which had been identified an important player in the progression of liver fibrosis. CONCLUSION: The findings from this study proved an inverse correlation between T3 level and the severity of liver fibrosis, and lower fT3 level within the normal range was an independent risk factor for severe liver fibrosis.

Metabolic Interactions and Differences between Coronary Heart Disease and Diabetes Mellitus: A Pilot Study on Biomarker Determination and Pathogenesis.

Comprehensive understanding of plasma metabotype of diabetes mellitus (DM), coronary heart disease (CHD), and especially diabetes mellitus with coronary heart disease (CHDDM) is still lacking. In this work, the plasma metabolic differences and links of DM, CHD, and CHDDM patients were investigated by the strategy of comparative metabolomics based on 1H NMR spectroscopy combined with network analysis for revealing their metabolic differences. A total of 17 metabolites are related to three diseases, among which valine, alanine, leucine, isoleucine, and N-acetyl-glycoprotein are positively correlated with CHD and CHDDM (odds ratios (OR) > 1). The trimethylamine oxide, glycerol, lactose, indoleacetate, and scyllo-inositol are closely related to the development of DM to CHDDM (OR > 1), and indoleactate (OR: 1.06, 95% confidence interval (CI): 1.01-1.12) and lactose (OR: 2.46, 95% CI: 1.67-3.25) are particularly prominent in CHDDM. We identified three multi-biomarkers types that were significantly associated with glycosylated hemoglobin (HbA1C) at baseline. All diseases demonstrated dysregulated glycolysis/gluconeogenesis and amino acid biosynthesis pathway. In addition, enrichment in tryptophan metabolism observed in CHDDM, enrichment in inositol phosphate metabolism observed in DM, and the metabolites related to microbiota metabolism were dysregulated in both DM and CHDDM. The comparative metabolomics strategy of multi-diseases offers a new perspective in disease-specific markers and pathogenic pathways.

Comparative effectiveness of team-based care with a clinical decision support system versus team-based care alone on cardiovascular risk reduction among patients with diabetes: Rationale and design of the D4C trial.

BACKGROUND: Diabetes has become a major public health challenge worldwide, especially in low- and middle-income countries (LMICs). Uncontrolled hyperglycemia, hypertension, and dyslipidemia major risk factors for all-cause mortality and cardiovascular disease (CVD) are common in patients with diabetes in China. We propose to compare the effectiveness of team-based care plus a clinical decision support system (CDSS) with team-based care alone on glycemic, blood pressure (BP), and lipid control, and clinical CVD reduction among patients with type-2 diabetes and at high risk for CVD. METHODS: The Diabetes Complication Control in Community Clinics (D4C) study is a cluster-randomized trial conducted among 38 community health centers in Xiamen City, China. Nineteen clinics have been randomly assigned to team-based care plus CDSS and 19 to team-based care alone. Team-based care includes primary care providers, health coaches, and diabetes specialists working collaboratively with patients to achieve shared treatment goals for CVD risk factor reduction. The CDSS integrates guideline-based treatment algorithms for glycemic, BP, and lipid control, along with a patient's medical history and insurance policy, to recommend treatment and follow-up plans. In phase 1, the co-primary outcomes are mean reduction in glycated hemoglobin (HbA1c), systolic BP (SBP), and low-density lipoprotein (LDL)-cholesterol over 18 months, and the proportion of patients with controlled HbA1c, SBP, and LDL-cholesterol at 18 months' between the 2 comparison groups. In phase 2, the primary outcome is the difference in major CVD incidence (non-fatal stroke, non-fatal myocardial infarction, hospitalized heart failure, and CVD mortality) between the 2 comparison groups. Mean reduction in HbA1c, SBP, and LDL-cholesterol levels will be simultaneously modeled for a single overall treatment effect. CONCLUSION: The D4C trial will generate evidence on whether a CDSS will further reduce the CVD burden among patients with diabetes beyond team-based care at community clinics. If proven effective, this implementation strategy could be scaled up within primary care settings in China and other LMICs to reduce CVD incidence and mortality among patients with diabetes.

Benefits and harms of hemithyroidectomy, total or near-total thyroidectomy in 1-4 cm differentiated thyroid cancer.

OBJECTIVE: For 1-4 cm differentiated thyroid cancer (DTC), current ATA guideline recommended hemithyroidectomy (HT) as an acceptable alternative initial procedure to total or near-total thyroidectomy (TT). The aim of this study was to evaluate benefits and harms of HT, TT in 1-4 cm DTC. DESIGN: Retrospective cohort study. PATIENTS: DTC patients aged 18 years or older who underwent initial thyroidectomy in a tertiary medical centre were included from January 2008 to July 2018. MEASUREMENTS: The structural persistent/recurrent disease, reoperation rates and surgical complications were compared using Cox proportional regression and logistic regression. Propensity score matching was performed to adjust for related clinicopathological variables. RESULTS: Among 1824 DTC patients, 795 patients sized 1-4 cm were included. A total of 286 patients underwent HT and 509 patients underwent TT. In the matched analysis, no significant difference in disease-free survival (DFS) between HT and TT was observed during the median follow-up period of 56.5 months (hazard ratio [HR] 0.86; 95% CI, 0.37-2.00; p = .733). The difference in DFS between two groups was consistent regardless of age, sex, tumour size, follow-up duration. Meanwhile, HT was associated with a decreased risk of surgical complications (odds ratio [OR] 0.47, 95% CI 0.31-0.71, p < .001), as well as lower proportion of levothyroxine replacement (p = .007). Two cases in HT group received reoperation. Further multivariate analysis showed surgical procedure was not associated with structural persistence/recurrence (HR 0.68; 95%CI, 0.29-1.58, p = .367). CONCLUSIONS: For patients with 1-4 cm DTC without clinical evidence of lymph node metastasis or extrathyroidal extension, HT was associated with lower risk of surgical complications than TT while provided similar benefits as TT.

Using real-world data to estimate the changing trends in the prevalence and incidence of type 2 diabetes mellitus in Xiamen of China from 2014 to 2019.

BACKGROUND: The prevalence of diabetes is increasing worldwide. Our study aimed to estimate the changing trends in the prevalence and incidence of diagnosed type 2 diabetes mellitus (T2DM) among Xiamen residents and the floating population using real-world data. METHOD: We used real-world data from the System of Xiamen Citizens Health Information from 2014 to 2019 to estimate the changing trends in the prevalence and incidence of diagnosed T2DM. The System included the diagnosis of diabetes and the prescription of hypoglycemic drugs. Prevalent cases of T2DM were individuals who were diagnosed with T2DM and/or using hypoglycemic drugs. Incident cases were individuals with diagnosed T2DM and/or using hypoglycemic drugs in 2014 or 2019 who had not been diagnosed and/or did not use hypoglycemic drugs in the past. RESULTS: In 2014 and 2019, the prevalence of T2DM in Xiamen was 4.04 and 4.84%, respectively. In 2014 and 2019, the incidence rate of T2DM in Xiamen was 14.1 per 1000 person-year and 15.0 per 1000 person-year, respectively. There was a significant increase in both the prevalence (Prevalence difference: 0.80, 95%CI 0.76-0.83%, P < 0.001) and the incidence of T2DM (Incidence difference: 0.9, 95%CI 0.7-1.1, P < 0.001). in Xiamen. The prevalence and incidence of T2DM in people aged 18-39 increased significantly (P < 0.001), while the prevalence and incidence of T2DM in people aged 40-69 reduced significantly (P < 0.001). CONCLUSIONS: There was a significant increase in the prevalence and incidence of T2DM in Xiamen from 2014 to 2019 especially among those with younger age.

Sex-specific associations between prenatal antibiotics exposure and offspring's body mass index.

OBJECTIVE: Animal studies and epidemiological studies have shown that there is potential sex-specific sensitivity to the intrauterine environment in relation to the developmental programming of obesity. The objective of this study was to assess the sex-specific association between prenatal antibiotics exposure and body mass index (BMI) in offspring from 1 to 4 years. METHODS: A total of 10,163 mother-child pairs from the Medical Birth Registry in Xiamen, China, were included in this prospective cohort study. Data on prenatal antibiotics exposure were collected from the prescription database. RESULTS: A total of 4909 (48.3%) offspring had prenatal antibiotics exposure. The associations between prenatal antibiotics exposure and offspring's BMI were significantly different among female offspring and male offspring (P for interaction: 0.034 at 1 year of age; 0.033 at 2 years of age; 0.020 at 3 years of age; and 0.021 at 4 years of age). In female offspring, prenatal antibiotic use was significantly associated with a higher BMI Z-score from 1 to 4 years old (difference in BMI Z-score: 0.11 [95% CI: 0.05-0.17] at 1 years of age; 0.10 [95% CI: 0.05-0.16] at 2 years of age; 0.14 [95% CI: 0.09-0.21] at 3 years of age; and 0.13 [95% CI: 0.07-0.19] at 4 years of age) after adjustment for confounder. Prenatal antibiotics use was not associated with offspring BMI Z-score from 1 to 4 years in male offspring. CONCLUSIONS: The association of prenatal antibiotics exposure and BMI Z-score from 1 to 4 years old may differ by sex of offspring.

MATERNAL GESTATIONAL DIABETES MELLITUS AND OFFSPRING BODY MASS INDEX FROM 1 TO 4 YEARS.

Objective: Using the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria to diagnose gestational diabetes mellitus (GDM), the association between GDM and offspring body mass index (BMI) gains in early childhood in China remains unclear. We aimed to assess the association between GDM diagnosed by the IADPSG criteria and BMI gain and the risk for overweight/obesity in offspring from 1 to 4 years. Methods: This prospective cohort study was based on the healthcare records data from the Medical Birth Registry in Xiamen, China. We included 10,412 mother-child pairs tested for GDM using IADPSG criteria. Results: A total of 1,786 (17.2%) offspring were exposed to GDM. The offspring exposed to GDM had higher mean BMI Z-score (difference, 0.07; 95% confidence interval [CI], 0.02 to 0.12) and risk for overweight/obesity (odds ratio [OR], 1.22; 95% CI, 1.06 to 1.40) compared to those unexposed to GDM from 1 to 4 years of age. However, after adjustment for maternal pre-pregnancy BMI (Model 2), these associations attenuated towards the null (difference in BMI Z-score, 0.02; 95% CI, -0.03 to 0.07; OR for overweight/obesity, 1.09; 95% CI, 0.95 to 1.25). Conclusion: The associations between GDM diagnosed using IADPSG criteria and BMI Z-score and the risk for overweight/obesity in offspring at the age of 1 to 4 years were largely explained by maternal pre-pregnancy BMI. Reducing the prevalence of childhood overweight and obesity in China should focus on maternal weight status before pregnancy, in addition to glycemia during pregnancy. Abbreviations: BMI = body mass index; CI = confidence interval; GDM = gestational diabetes mellitus; IADPSG = International Association of Diabetes and Pregnancy Study Groups; LGA = large for gestational age; MBRX = Medical Birth Registry in Xiamen; OGTT = oral glucose tolerance test; OR = odds ratio.

Age at menarche and risk of gestational diabetes mellitus: a population-based study in Xiamen, China.

BACKGROUND: It has been reported that earlier age at menarche is associated with a higher risk for type 2 diabetes mellitus. However, the relationship between age at menarche and gestational diabetes mellitus is inconsistent across studies. We hypothesized that an earlier age at menarche would predict the gestational diabetes mellitus risk. METHODS: This was a population-based, retrospective cohort study of 70,041 women aged 18 to 53 years old, conducted between 2011 and 2018. The subjects were recruited from the Medical Birth Registry in Xiamen, China. Age at menarche was categorized as 8-12, 13, 14, 15, 16-19 years old. Logistic regression analysis and spline analysis was used to assess the risk of the menarche age group for gestational diabetes mellitus. Linear regression analysis was performed to evaluate independent associations between age at menarche and fasting plasma glucose and blood glucose 1 hour and 2 hours after a 75-g of glucose load between 24 and 28 weeks' gestation. RESULTS: The overall prevalence of GDM was 17.6%. After adjustment for family history of diabetes, earlier age at menarche (8-12, and 13 years old) was associated with increased odds for GDM (OR, 1.08; 95% CI, 1.02-1.15, and OR, 1.07; 95% CI, 1.03-1.14, respectively) compared with average age at menarche (14 years old). With further adjustment for pre-pregnancy body mass index, blood pressure, educational level, age at delivery, and hepatitis B surface antigen status, this association was attenuated (OR, 0.93, and OR, 1.02, respectively). Multivariable-adjusted spline regression models showed a linear dose-response association between age at menarche and GDM (P for nonlinearity, 0.203; P for linearity, 0.006). On linear regression analysis, earlier age at menarche was significantly associated with increased blood glucose one and 2 hours after a glucose load but not with the fasting plasma glucose. CONCLUSIONS: As expected, early age at menarche was found to be associated with an increased risk of gestational diabetes mellitus. However, this association may be mediated by potential confounding factors other than age. An additional finding was that earlier menarche was significantly related with elevated pregnancy glucose concentrations after a glucose load.

Effects of Prepregnancy Body Mass Index, Weight Gain, and Gestational Diabetes Mellitus on Pregnancy Outcomes: A Population-Based Study in Xiamen, China, 2011-2018.

BACKGROUND: It is unclear that how prepregnancy body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) affect pregnancy outcomes in -China. Thus, we explored how BMI, GWG, and GDM affect the risks of adverse pregnancy outcomes. METHODS: We performed a retrospective, population-based study included all births in Xiamen, China, 2011-2018. Demographic data and pregnancy outcomes of 73,498 women were acquired from the Medical Birth Registry of Xiamen. Women were categorized into groups on prepregnancy BMI and GWG in order to assess the risk of pregnancy outcomes. Multivariable logistic regression was performed to evaluate risk factors. RESULTS: Overall, 6,982 (9.37%) women were obese, and 8,874 (12.07%) women were overweight. Obese women are more vulnerable to cesarean delivery, preterm birth, large-for-gestational age (LGA), and macrosomia (crude OR [cOR] 2.00, 1.89-2.12; 1.35, 1.20-1.51; 2.12, 1.99-2.26; 2.53, 2.25-2.86, respectively, adjusted ORs 1.73, 1.62-1.84; 1.25, 1.10-1.42; 2.03, 1.90-2.18; 2.77, 2.44-3.16, respectively). Similar results were observed in overweight women (cORs 1.49, 1.42-1.57; 1.02, 0.91-1.15; 1.60, 1.50-1.70; 2.01, 1.78-2.26, respectively). Furthermore, women who gain weight in excessive group were 1.43, 2.06, and 2.16 times to deliver cesarean, LGA, and macrosomia, respectively. Additionally, GDM women were easily subjected to cesarean section, preterm birth, LGA, low birth weight, and macrosamia (cORs 1.52, 1.55, 1.52, 1.37, 1.27, respectively). CONCLUSIONS: Obesity prior to pregnancy, excessive GWG, and GDM were all associated with increased odds of cesarean, LGA, and macrosomia. Blood glucose and weight control before and during pregnancy are needed that may reduce the complications of pregnancy.

Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study.

BACKGROUND: There is no evidence available on the association of Fetuin-B with chronic kidney disease (CKD), and mechanisms linking nonalcoholic fatty liver disease (NAFLD) to CKD are not fully understood. We aimed to explore the independent associations and potential mechanisms of Fetuin-B and NAFLD with CKD. METHODS: A cross-sectional study of 1,072 Chinese adults who underwent serum Fetuin-B test and hepatic ultrasonography scanning was conducted in Xiamen, China. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 and/or the presence of albuminuria. RESULTS: Subjects with CKD showed significantly higher prevalence of NAFLD (69.5 vs. 57.2%, p < 0.001) and serum Fetuin-B levels (4.32 ± 1.45 vs. 4.05 ± 1.36 µg/mL, p = 0.007) than their controls. Increased serum Fetuin-B was also significantly associated with increased levels of fasting insulin and homeostasis model assessment - insulin resistance (both p values < 0.05). NAFLD and higher serum Fetuin-B were significantly associated with increased risk of CKD, and the unadjusted ORs (95% CIs) were 1.701 (1.256-2.303, p = 0.001) and 1.213 (1.053-1.399, p = 0.008, per SD increase of Fetuin-B), respectively. With adjustment for potential confounding factors, including metabolic/insulin resistance syndrome, NAFLD but not serum Fetuin-B was still significantly associated with increased risk of CKD, and the adjusted ORs (95% CIs) were 1.820 (1.327-2.496, p < 0.001) and 1.116 (0.959-1.298, p = 0.153, per SD increase of Fetuin-B), respectively. CONCLUSIONS: Fetuin-B might link NAFLD to CKD via inducing insulin resistance, and NAFLD contributes independently to the pathogenesis of CKD via multiple mechanisms besides of metabolic/insulin resistance syndrome.

Non-ossifying fibroma with a pathologic fracture in a 12-year-old girl with tricho-rhino-phalangeal syndrome: a case report.

BACKGROUND: Tricho-rhino-phalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterized by distinctive craniofacial and skeletal abnormalities, while non-ossifying fibroma (NOF) is a common benign bone tumour in children and adolescents. To date, no case of TRPS coexisting with NOF has been reported. This report presents a 12-year-old girl who had the characteristic features of tricho-rhino-phalangeal syndrome and non-ossifying fibroma with a fibula fracture. CASE PRESENTATION: A 12-year-old girl was admitted to the Department of Endocrinology and Diabetes for evaluation of brachydactyly and a right fibula fracture. Clinical examination revealed sparse scalp hair, a characteristic bulbous pear-shaped nose, and brachydactyly with significant shortening of the fourth metatarsal. Neither intellectual disability nor multiple exostoses were observed. Radiography of both hands showed brachydactyly and cone-shaped epiphyses of the middle phalanges of the digits of both hands with deviation of the phalangeal axis. Genetic analysis of TRPS1 identified a heterozygous germline sequence variant (p.Ala932Thr) in exon 6 in the girl and her father. Approximately 1 month before being admitted to our department, the girl experienced a minor fall and suffered a fracture of the proximal fibula in the right lower limb. The pathological cytological diagnosis of the osteolytic lesion was NOF. Ten months following the surgery, the lesion on the proximal fibula of the girl disappeared. CONCLUSIONS: In conclusion, the present study is the first to report a rare case of NOF with a pathologic fracture in the fibula of a girl with TRPS. The identification of a missense mutation, (p.Ala932Thr), in exon 6 of TRPS1 in this kindred further suggested that the patient had type I TRPS and indicated that mutations in this exon may be correlated with more pronounced features of the syndrome. Radiological techniques and genetic analysis played key roles in the definitive diagnosis.

Fetuin-B links nonalcoholic fatty liver disease to type 2 diabetes via inducing insulin resistance: Association and path analyses.

OBJECTIVE: Laboratory models suggested that Fetuin-B impaired insulin action in myotubes and hepatocytes and caused glucose intolerance in mice. We aimed to explore the independent associations and pathways among serum Fetuin-B, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). METHODS: A cross-sectional study of 1318 obese adults who underwent serum Fetuin-B test and hepatic ultrasonography scanning was conducted in Xiamen, China. Multivariable logistic regression was used to calculate adjusted odds ratio (OR) and 95% confidence intervals (CI) of serum Fetuin-B level and NAFLD for T2D in different models with adjustment for potential confounders. Structural equation modeling (SEM) was used to examine the paths among NAFLD, serum Fetuin-B, metabolic/insulin resistance syndrome and T2D. RESULTS: Subjects with T2D or NAFLD showed significantly increased serum Fetuin-B levels compared to their controls (4.25 ±â€¯1.35 vs. 4.08 ±â€¯1.38 µg/ml for diabetes; and 4.26 ±â€¯1.41 vs. 4.07 ±â€¯1.33 µg/ml for NAFLD; both p-values < 0.05). NAFLD and higher serum Fetuin-B were significantly associated with higher risk of T2D with adjustment for sociodemographic and lifestyle habits; and the adjusted ORs (95%CIs) were 2.90 (2.17-3.87, p < 0.001) and 1.16 (1.01-1.32, p = 0.032), respectively. With further adjustment for metabolic/insulin resistance syndrome (BMI, systolic and diastolic BP, triglyceride, total cholesterol, HDL- and LDL-cholesterol, HOMA-IR and serum uric acid), NAFLD but not serum Fetuin-B was significantly associated with increased risk of T2D (ORs (95%CIs): 1.58 (1.12-2.21, p = 0.009) and 1.07 (0.92-1.23, p = 0.384), respectively). A one pathway model by using SEM fitted well (χ2 = 497.92, p < 0.001; CFI = 0.965; TLI = 0.926; and RMSEA = 0.097) and showed that NAFLD increased serum Fetuin-B and elevated Fetuin-B increased fasting insulin level, which in turn induced insulin resistance and T2D. Besides, NAFLD increased the risk of T2D directly in addition to its indirect effects of inducing metabolic/insulin resistance syndrome which in turn increased the risk of T2D. CONCLUSIONS: Fetuin-B links NAFLD to T2D via inducing insulin resistance, and NAFLD contributes to the pathogenesis of T2D via multiple mechanisms.

Elevated circulating irisin is associated with lower risk of insulin resistance: association and path analyses of obese Chinese adults.

BACKGROUND: Evidence on the role of irisin in insulin resistance is limited and controversial, and pathways between them remain unknown. We aimed to examine the independent effects of circulating irisin and different adiposity measurements, as well as their potential interactions, on insulin resistance. We also aimed to explore possible pathways among circulating irisin, adiposity, glucose and insulin levels and insulin resistance. METHODS: A cross-sectional study of 1,115 community- living obese Chinese adults, with data collection on clinical characteristics, glucose and lipid metabolic parameters and circulating irisin levels. RESULTS: Among the 1,115 subjects, 667 (59.8 %) were identified as insulin-resistance, and showed significantly decreased serum irisin than their controls (log-transformed irisin: 1.19 ± 2.34 v.s. 1.46 ± 2.05 ng/ml, p = 0.042). With adjustment for potential confounders, elevated circulating irisin was significantly associated with reduced risk of insulin resistance, with adjusted odds ratio per standard deviation increase of irisin of 0.871 (0.765-0.991, p = 0.036). As for different adiposity measurements, body fat percentage, but neither BMI nor waist, was significantly associated with increased risk of insulin resistance (OR: 1.152 (1.041-1.275), p = 0.006). No significant interaction effect between serum irisin and adiposity on insulin resistance was found. A one pathway model about the relationship between serum irisin and insulin resistance fits well (χ (2) = 44.09, p < 0.001; CFI-0.994; TLI =0.986; and RMSEA = 0.067), and shows that elevated circulating irisin might improve insulin resistance indirectly through lowering fasting insulin levels (standardized path coefficient = -0.046, p = 0.032). CONCLUSIONS: Elevated circulating irisin is associated with lower risk of insulin resistance indirectly through lowering fasting insulin.

Dietary Intakes of Women with Gestational Diabetes Mellitus and Pregnancy Outcomes: A Prospective Observational Study.

Purpose: Nutrient intake for pregnant women with gestational diabetes mellitus (GDM) is important to ensure satisfactory birth outcomes. This study aims to explore the dietary profiles of patients with GDM, compare the results with the Chinese dietary guidelines or Dietary Reference Intakes (DRIs) from China and investigate the relationship between maternal dietary intake and pregnancy outcomes. Patients and Methods: A total of 221 patients with GDM in the second trimester were included in the cohort. Dietary intake data were collected using a 24-hour recall method for three consecutive days. The pregnancy outcomes of these participants were subsequently monitored. Both univariate logistic regression and multivariate logistic regression analyses were conducted to explore the associations between dietary intake variables or general characteristics variables and adverse pregnancy outcomes. Results: Participants with adverse pregnancy outcomes showed a lower intake of iodine and vitamin D, a lower percentage of dietary energy intake from carbohydrates and a higher percentage of dietary energy intake from fats, compared to participants without adverse pregnancy outcomes. The gestational weight gain and family history of diabetes were associated with an increased risk of adverse pregnancy outcomes. Conversely, regular exercise, the intake of iodine and Vitamin D, and the percentage of dietary energy intake from carbohydrates were associated with a decreased risk. Conclusion: The daily diet of pregnant women with GDM in China did not meet the dietary guidelines or DRIs. The low intake of Vitamin D and iodine, the low dietary carbohydrate ratio, family history of diabetes, lack of exercise, and high gestational weight gain were associated with increased risk of adverse pregnancy outcomes in pregnant women with GDM.

Interleukin-6 promotes visceral adipose tissue accumulation during aging via inhibiting fat lipolysis.

BACKGROUND: Age-related visceral obesity could contribute to the development of cardiometabolic complications. The pathogenesis of visceral fat mass accumulation during the aging process remains complex and largely unknown. Interleukin-6 (IL-6) has emerged as one of the prominent inflammaging markers which are elevated in circulation during aging. However, the precise role of IL-6 in regulating age-related visceral adipose tissue accumulation remains uncertain. RESULTS: A cross-sectional study including 77 older adults (≥65 years of age) was initially conducted. There was a significant positive association between serum IL-6 levels and visceral fat mass. We subsequently validated a modest but significant elevation in serum IL-6 levels in aged mice. Furthermore, we demonstrated that compared to wildtype control, IL-6 deficiency (IL-6 KO) significantly attenuated the accumulation of visceral adipose tissue during aging. Further metabolic characterization suggested that IL-6 deficiency resulted in improved lipid metabolism parameters and energy expenditure in aged mice. Moreover, histological examinations of adipose depots revealed that the absence of IL-6 ameliorated adipocyte hypertrophy in visceral adipose tissue of aged mice. Mechanically, the ablation of IL-6 could promote the PKA-mediated lipolysis and consequently mitigate lipid accumulation in adipose tissue in aged mice. CONCLUSION: Our findings identify a detrimental role of IL-6 during the aging process by promoting visceral adipose tissue accumulation through inhibition of lipolysis. Therefore, strategies aimed at preventing or reducing IL-6 levels may potentially ameliorate age-related obesity and improve metabolism during aging.

Integration of metabolomics and network pharmacology for enhancing mechanism understanding and medication combination recommendation for diabetes mellitus and diabetic nephropathy.

With the increasing prevalence of diabetes mellitus (DM) and diabetic nephropathy (DN), effective treatment is particularly important for the recovery of patients. However, the currently approved drugs are usually tailored to clinical symptoms and no mechanism-targeted drugs are available. In this study, the combination of metabolomics and network pharmacology was applied to provide reasonable medication combination regimens to meet the different clinical needs for the targeted treatment of DM and DN. An NMR-based metabolomic strategy was applied to identify the potential urinary biomarkers of DM or/and DN, while network pharmacology was used to identify the therapy targets of DM and DN by intersecting the targets of diseases and currently approved drugs. According to the enriched signaling pathways using the potential biomarkers and the therapy targets, the specific medication combinations were recommended for the specific clinical demands in terms of hypoglycemic, hypertensive, and/or lipid-lowering. For DM, 17 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 34 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension, and hypoglycemia, hypertension, and lipid-lowering were administered. For DN, 22 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 21 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension were proposed. Molecular docking was used to verify the binding ability, docking sites, and structure of the drug molecules to target proteins. Moreover, an integrated biological information network of the drug-target-metabolite-signaling pathways was constructed to provide insights into the underlined mechanism of DM and DN as well as clinical combination therapy.

Corrigendum: Role of aerobic exercise in ameliorating NASH: Insights into the hepatic thyroid hormone signaling and circulating thyroid hormones.

[This corrects the article DOI: 10.3389/fendo.2022.1075986.].