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.

Hepatic conversion of acetyl-CoA to acetate plays crucial roles in energy stress.

Accumulating evidence indicates that acetate is increased under energy stress conditions such as those that occur in diabetes mellitus and prolonged starvation. However, how and where acetate is produced and the nature of its biological significance are largely unknown. We observed overproduction of acetate to concentrations comparable to those of ketone bodies in patients and mice with diabetes or starvation. Mechanistically, ACOT12 and ACOT8 are dramatically upregulated in the liver to convert free fatty acid-derived acetyl-CoA to acetate and CoA. This conversion not only provides a large amount of acetate, which preferentially fuels the brain rather than muscle, but also recycles CoA, which is required for sustained fatty acid oxidation and ketogenesis. We suggest that acetate is an emerging novel 'ketone body' that may be used as a parameter to evaluate the progression of energy stress.

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.

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.].

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.

Single-cell transcriptomics of hepatic stellate cells uncover crucial pathways and key regulators involved in non-alcoholic steatohepatitis.

Background: Fibrosis is an important pathological process in the development of non-alcoholic steatohepatitis (NASH), and the activation of hepatic stellate cell (HSC) is a central event in liver fibrosis. However, the transcriptomic change of activated HSCs (aHSCs) and resting HSCs (rHSCs) in NASH patients has not been assessed. This study aimed to identify transcriptomic signature of HSCs during the development of NASH and the underlying key functional pathways. Methods: NASH-associated transcriptomic change of HSCs was defined by single-cell RNA-sequencing (scRNA-seq) analysis, and those top upregulated genes were identified as NASH-associated transcriptomic signatures. Those functional pathways involved in the NASH-associated transcriptomic change of aHSCs were explored by weighted gene co-expression network analysis (WGCNA) and functional enrichment analyses. Key regulators were explored by upstream regulator analysis and transcription factor enrichment analysis. Results: scRNA-seq analysis identified numerous differentially expressed genes in both rHSCs and aHSCs between NASH patients and healthy controls. Both scRNA-seq analysis and in-vivo experiments showed the existence of rHSCs (mainly expressing a-SMA) in the normal liver and the increased aHSCs (mainly expressing collagen 1) in the fibrosis liver tissues. NASH-associated transcriptomic signature of rHSC (NASHrHSCsignature) and NASH-associated transcriptomic signature of aHSC (NASHaHSCsignature) were identified. WGCNA revealed the main pathways correlated with the transcriptomic change of aHSCs. Several key upstream regulators and transcription factors for determining the functional change of aHSCs in NASH were identified. Conclusion: This study developed a useful transcriptomic signature with the potential in assessing fibrosis severity in the development of NASH. This study also identified the main pathways in the activation of HSCs during the development of NASH.

Risk Factors for Glycemic Control in Hospitalized Patients with Type 2 Diabetes Receiving Continuous Subcutaneous Insulin Infusion Therapy.

INTRODUCTION: Patients with diabetes are confronted with numerous obstacles to achieve adequate glycemic control during hospitalization. The aim of this study was to explore the risk factors associated with glycemic control in hospitalized patients with type 2 diabetes mellitus (T2DM) treated with continuous subcutaneous insulin infusion (CSII). METHODS: This cross-sectional study included 5223 patients hospitalized with T2DM in a tertiary hospital in Xiamen (China) between January 2017 and December 2019. All patients were managed according to established protocols for glycemic monitoring and insulin pump treatment regimens. Demographic information and clinical profiles were collected from electronic health records. Multiple linear regression analysis was used to identify the risk factors associated with glycemic control. RESULTS: Among the 5223 hospitalized patients with T2DM receiving CSII therapy, 55.2% achieved their ideal blood glucose level (3.9-10.0 mmol/L), 44.5% experienced hyperglycemia (> 10.0 mmol/L), and 0.3% experienced hypoglycemia (< 3.9 mmol/L) during their hospitalization. Multivariate analyses showed that among inpatients with T2DM, older age, male gender, higher low-density lipoprotein-cholesterol (LDL-C) level, lower C-peptide (C-P) level, lower body mass index (BMI), longer duration of diabetes, previous insulin prescriptions, nephropathy, and retinopathy were factors more likely to be associated with a blood glucose level in the hyperglycemic range (P < 0.05). We also observed that among hospitalized patients with T2DM, those with lower BMI, lower C-P, lower LDL-C, longer disease duration, and previous insulin prescriptions were more likely to correlate with a higher proportion of hypoglycemia range (all P < 0.05). CONCLUSION: Older age, male gender, lower BMI, lower C-P, higher LDL-C, previous insulin prescriptions, longer duration of diabetes, nephropathy, and retinopathy may be risk factors for a higher proportion of hyperglycemic events in hospitalized patients with T2DM under CSII therapy. Furthermore, lower BMI, lower C-P, lower LDL-C, longer duration of diabetes, and previous insulin prescriptions were found to be important factors for a higher proportion of hypoglycemic events. Evaluating the clinical features, comorbidities, and complications of hospitalized patients is essential to achieve reasonable glycemic control.

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.

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.

Hypoglycemia unawareness identified by continuous glucose monitoring system is frequent in outpatients with type 2 diabetes without receiving intensive therapeutic interventions.

BACKGROUND: Patients with diabetes are prone to asymptomatic hypoglycemia (AH) due to diminished ability to perceive the onset of hypoglycemia. However, the actual prevalence and influencing factors of AH in outpatients with type 2 diabetes (T2DM) have not been well investigated. METHODS: A total of 351 outpatients with T2DM underwent glucose monitoring by continuous glucose monitoring system (CGMS) for consecutive 72 h without changing their lifestyle and treatment regimens. Hypoglycemia is defined as a blood glucose level less than 3.9 mmol/L, which was further divided into Level 1 hypoglycemia (blood glucose 3.0-3.9 mmol/L) and Level 2 hypoglycemia (blood glucose < 3.0 mmol/L). Univariate and multivariate logistic regression analyses were used to determine the possible risk factors of AH. RESULTS: In all 351 subjects studied, 137 outpatients (39.0%) were captured AH events, in which Level 1 AH and Level 2 AH accounted for 61.3% and 38.7%, respectively. 85 (62.0%) of the AH patients experienced nocturnal asymptomatic hypoglycemia (NAH) and 25 (18.2%) exclusively NAH. Multivariate logistic regression analysis demonstrated that patients with younger age, lower hemoglobin A1c (HbA1c), and higher systolic blood pressure (SBP) levels were associated with increased risk of AH. While after further grading of AH, male sex and Dipeptidylpeptidase-4 inhibitors (DPP4i) regime were shown to be associated with lower risk of Level 2 AH. CONCLUSIONS: Hypoglycemia unawareness could be frequently observed at either daytime or nighttime, although NAH was more common, in outpatients with T2DM. Relative relax HbA1c targets should be considered for patients who are prone to AH.

Sex-Specific Associations Between Low Muscle Mass and Glucose Fluctuations in Patients With Type 2 Diabetes Mellitus.

Objective: Studies have shown that sex differences in lean mass, concentrations of sex hormones, and lifestyles influence cle health and glucose metabolism. We evaluated the sex-specific association between low muscle mass and glucose fluctuations in hospitalized patients with type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) therapy. Methods: A total of 1084 participants were included. Body composition was determined by dual-energy X-ray absorptiometry. Intraday blood glucose fluctuation was estimated by the Largest amplitude of glycemic excursions (LAGE) and standard deviation of blood glucose (SDBG). Results: The prevalence of low muscle mass was higher in males than in females (p<0.001). There was a significant sex-specific interaction between the status of low muscle mass and glucose fluctuations (LAGE and SDBG) (p for interaction=0.025 and 0.036 for SDBG and LAGE, respectively). Among males, low muscle mass was significantly associated with a higher LAGE and SDBG (difference in LAGE: 2.26 [95% CI: 1.01 to 3.51], p < 0.001; difference in SDBG: 0.45 [95% CI: 0.25 to 0.65], p < 0.001) after adjustment for HbA1c, diabetes duration, hyperlipidemia, diabetic peripheral neuropathy, diabetic nephropathy, and cardiovascular disease. These associations remained significant after further adjustment for age and C-peptide. Among females, low muscle mass was not associated with LAGE or SDBG after adjustment for all covariates. Conclusion: The prevalence of low muscle mass was higher in males than in females. Low muscle mass was significantly associated with higher LAGE and SDBG among males, but not females.

Hepatokine Fetuin B expression is regulated by leptin-STAT3 signalling and associated with leptin in obesity.

Obesity is an expanding global public health problem and a leading cause of metabolic disorders. The hepatokine Fetuin B participates in regulating insulin resistance, glucose metabolism and liver steatosis. However, the mechanism underlying Fetuin B activation remains unclear. Our previous population-based study demonstrated a significant association between serum Fetuin B and body fat mass in an obese population, which indicates its potential in mediating obesity-related metabolic disorders. In the present study, we further revealed a significant correlation between Fetuin B and leptin, the classic adipokine released by expanding adipose tissue, in this obese population. Consistently, elevated Fetuin B and leptin levels were confirmed in diet-induced obese mice. Furthermore, an in vitro study demonstrated that the leptin signalling pathway directly activated the transcription and expression of Fetuin B in primary hepatocytes and AML12 cells in a STAT3-dependent manner. STAT3 binds to the response elements on FetuB promoter to directly activate FetuB transcription. Finally, the mediating effect of Fetuin B in insulin resistance induced by leptin was confirmed according to mediation analysis in this obese population. Therefore, our study identifies leptin-STAT3 as an upstream signalling pathway that activates Fetuin B and provides new insights into the pathogenic mechanisms of obesity-related metabolic disorders.

Largest Amplitude of Glycemic Excursion Calculating from Self-Monitoring Blood Glucose Predicted the Episodes of Nocturnal Asymptomatic Hypoglycemia Detecting by Continuous Glucose Monitoring in Outpatients with Type 2 Diabetes.

Aims: Nocturnal asymptomatic hypoglycemia (NAH) is a serious complication of diabetes, but it is difficult to be detected clinically. This study was conducted to determine the largest amplitude of glycemic excursion (LAGE) to predict the episodes of NAH in outpatients with type 2 diabetes. Methods: Data were obtained from 313 outpatients with type 2 diabetes. All subjects received continuous glucose monitoring (CGM) for consecutive 72 hours. The episodes of NAH and glycemic variability indices (glucose standard deviation [SD], mean amplitude of plasma glucose excursion [MAGE], mean blood glucose [MBG]) were accessed via CGM. LAGE was calculated from self-monitoring blood glucose (SMBG). Results: A total of 76 people (24.3%) had NAH. Compared to patients without NAH, patients with NAH showed higher levels of glucose SD (2.4 ± 0.9 mmol/L vs 1.7 ± 0.9 mmol/L, p <0.001), MAGE (5.2 ± 2.1 mmol/L vs 3.7 ± 2.0, p<0.001) and LAGE (4.6 ± 2.3 mmol/L vs 3.8 ± 1.9 mmol/L, p=0.007), and lower level of MBG (7.5 ± 1.5 mmol/L vs 8.4 ± 2.2 mmol/L, p=0.002). LAGE was significantly associated with the incidence of NAH and time below rang (TBR) in model 1 [NAH: 1.189 (1.027-1.378), p=0.021; TBR: 0.008 (0.002-0.014), p=0.013] with adjustment for age, BMI, sex, work, hyperlipidemia, complication and medication, and in model 2 [NAH: 1.177 (1.013-1.367), p=0.033; TBR: 0.008 (0.002-0.014), p=0.012] after adjusting for diabetes duration based on model 1, as well as in model 3 [NAH: 1.244 (1.057-1.464), p=0.009; TBR: 0.009 (0.002-0.016), p=0.007] with further adjustment for HbA1c based on model 2. In addition, no significant interactions were found between LAGE and sex, age, HbA1c, duration of diabetes, BMI and insulin therapy on the risk of NAH. The receiver operator characteristic (ROC) curve shows the ideal cutoff value of LAGE for the prediction of NAH was 3.48 mmol/L with 66.7% sensitivity, 50% specificity and 0.587 (95% CI: 0.509-0.665) of area under the ROC curve. Conclusions: High glycemic variability is strongly associated with the risk of NAH. The LAGE based on SMBG could be an independent predictor of NAH for outpatients with type 2 diabetes, and LAGE greater than 3.48 mmol/L could act as a warning alarm for high risk of NAH in daily life.

Breastfeeding on childhood obesity in children were large-for-gestational age: retrospective study from birth to 4 years.

Our aim was to assess effects of breast-feeding (BF) in the association between large-for-gestational age (LGA) and body mass index (BMI) trajectories on childhood overweight from 1 to 4 years old. A total of 1649 healthcare records of mother-child pairs had detailed records of feeding practices and were included in this retrospective cohort study. Data were available in Medical Birth Registry of Xiamen between January 2011 and March 2018. Linear and logistic regression models were used to access the difference between BF and no-BF group. For offspring were LGA and BF was significantly associated with a lower BMI Z-score from 1 to 4 years old after adjustment confounders in Model 1 to 3 [difference in BMI Z-score in Model 1: estimated ß: -0.07 [95%CI: -0.13 to -0.01]; Model 2: estimated ß: -0.07 (-0.13 to -0.004); Model 3: estimated ß: -0.06 (-0.12 to -0.001); P = 0.0221, 0.0371, 0.0471]. A significantly lower risk of childhood overweight was observed in Model 1 [odd ratio (OR): 0.85 (95%CI, 0.73 to 1.00)], P = 0.0475) with adjustment for maternal pre-pregnancy BMI. Furthermore, Model 2 and Model 3 showed LGA-BF infants had a lower risk for childhood overweight then LGA-no-BF infants [OR: 0.87 and 0.87 (95%CI, 0.73 to 1.03; 0.74 to 1.03)], however, there was no statistical significance (P = 0.1099, and 0.1125)]. BF is inversely related to BMI Z-score and risk for overweight in children were LGA from 1 to 4 years old. Adjustment for maternal pre-pregnancy BMI, the protective association between BF and childhood overweight was more significant.

Cross-comparative metabolomics reveal sex-age specific metabolic fingerprints and metabolic interactions in acute myocardial infarction.

The elucidation of metabolic perturbations and gender-age-specific metabolic characteristics associated with acute myocardial infarction (AMI) is essential for clinical risk stratification and disease management. A comprehensive cross-comparative metabolomics analysis was performed on the sera from 445 healthy controls, 347 AMI patients without cardiovascular disease (CVD), 79 AMI with CVD (AMICVD) patients including 27 deaths. Machine-learning-based integrated biomarker profiling and global network analysis were used to create a multi-biomarker for distinguishing the different AMI outcomes. The changes of most metabolites were dependent on AMI, but gender and age also give additional contributions to the changes of histidine, malonate, O-acetyl-glycoprotein and trimethylamine N-oxide. The altered metabolic pathways included gut dysbiosis, increased amino acid metabolism, glucose metabolism and ketone metabolism, and inactivation of tricarboxylic acid cycle. Enhanced histidine metabolism and microbiota dysbiosis may be one of the key factors during the developing of AMI into AMICVD. For the differential diagnosis of AMI events, three sets of specific multi-biomarkers provided relatively high accuracy with the areas under the curve more than 0.8 and hazard ratio more than 1 in the discovery set, and the results were reproduced and confirmed by the validation set. First use of cross-comparative metabolomics and machine-learning-based integrated biomarker analysis gives great capability to discriminate the different AMI outcomes. Also, the multi-biomarkers seem to be a valid and accurate auxiliary diagnosis biomarker in addition to standard stratification based on clinical parameters.

Relationship between Obstetric Mode of Delivery and Risk of Overweight/Obesity in 1- to 4-Year-Old Children.

INTRODUCTION: Childhood obesity is an important public health problem, which may lead to increased risk of obesity in adulthood. The relationship between the incidence of obesity and the mode of delivery is not clear. Cesarean section (CS) may be one of the risk factors of obesity in children. We investigated the relationship between the mode of delivery of pregnant women and the risk of overweight/obesity in children of all ages from 1 to 4 years. METHODS: Registered in the maternal and child registration system of Xiamen city, newborns born between January 2011 and December 2012 were followed up to 4 years old. RESULTS: 9,964 cases were included in the study, of which 3,462 cases (34.7%) were cesarean deliveries. From 1 to 4 years of age, BMI Z-scores and the risk for overweight/obesity of children delivered by CS were higher than by the vagina. Longitudinal analysis of anthropometric outcomes assessed during study visits in 1- to 4-year-old offspring exposed to CS showed that after adjustment for kinds of effect factors, the changes in BMI Z-scores were 0.04 (95% CI: 0.01-0.09, p = 0.003), significantly higher than vaginal delivery, and the risk incidence of overweight/obesity by increased 8% in CS offspring; OR = 1.08 (1.01-1.21, p< 0.05). CONCLUSION: The mode of cesarean delivery is related to the risk of overweight and obesity in children aged 1-4 years. When pregnant women choose cesarean delivery without medical indications, they should be concerned that their offspring may have a higher risk of obesity.