A prospective cohort study of multimetal exposure and risk of gestational diabetes mellitus.

The relationship between co-exposure to multiple metals and gestational diabetes mellitus (GDM) and the mechanisms involved are poorly understood. In this nested case-control study, 228 GDM cases and 456 matched controls were recruited, and biological samples were collected at 12-14 gestational weeks. The urinary concentrations of 10 metals and 8-hydroxydeoxyguanosine (8-OHdG) as well as the serum levels of malondialdehyde (MDA) and advanced glycation end products (AGEs) were determined to assess the association of metals with GDM risk and the mediating effects of oxidative stress. Urinary Ti concentration was significantly and positively associated with the risk of GDM (odds ratio [OR]:1.45, 95 % confidence interval [CI]: 1.12, 1.88), while Mn and Fe were negatively associated with GDM risk (OR: 0.67, 95 % CI: 0.50, 0.91 or OR: 0.61, 95 % CI: 0.47, 0.80, respectively). A significant negative association was observed between Mo and GDM risk, specifically in overweight and obese pregnant women. Bayesian kernel machine regression showed a significant negative joint effect of the mixture of 10 metals on GDM risk. The adjusted restricted cubic spline showed a protective role of Mn and Fe in GDM risk (P < 0.05). A significant negative association was observed between essential metals and GDM risk in quantile g-computation analysis (P < 0.05). Mediation analyses showed a mediating effect of MDA on the association between Ti and GDM risk, with a proportion of 8.7 % (P < 0.05), and significant direct and total effects on Ti, Mn, and Fe. This study identified Ti as a potential risk factor and Mn, Fe, and Mo as potential protective factors against GDM, as well as the mediating effect of lipid oxidation.

Psychological status of pregnant women during the omicron pandemic outbreak in China.

BACKGROUND: Pregnant women faced great challenges and psychological and physiological changes of varying degrees during the omicron epidemic outbreak. It is important to recognize the potential impact of these challenges on the mental health of pregnant women and to provide appropriate resources and support to mitigate their effects. METHOD: By using the convenience sampling approach, a total of 401 pregnant women from two hospitals of different grades in two cities were included in the survey. The cross-sectional survey was conducted by basic characteristics, Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), Insomnia Severity Index (ISI) and self-made questionnaire. RESULTS: Insomnia affected 207 participants (51.6%), depression affected 160 participants (39.9%) and anxiety affected 151 participants (37.7%). Moreover, pregnant women in provincial capital city were more likely to experience anxiety, depression and insomnia than those in county-level city (P < 0.01). Pregnant women's anxiety, depression and insomnia were positively correlated with the severity of COVID-19 infection (P < 0.05). However, COVID-19 infection had no appreciable impact on maternal demand for termination of pregnancy and cesarean section (P > 0.05). CONCLUSION: Pregnant women frequently suffer from anxiety disorder, depression and insomnia as a result of the omicron pandemic in China. During this period, the community and medical professionals should provide more psychological counseling, conduct health education and offer virtual prenatal care to pregnant women (particularly in the provincial capital city).

Spontaneous miscarriage and social support in predicting risks of depression and anxiety: a cohort study in UK Biobank.

BACKGROUND: It is still unclear whether social support can moderate the high risk of depression and anxiety due to spontaneous miscarriage. OBJECTIVE: This study prospectively investigated the associations of spontaneous miscarriage with risks of depression and anxiety, and evaluated the interactions between spontaneous miscarriage and the degree of social support in relation to depression and anxiety risks. STUDY DESIGN: A total of 179,000 participants from the UK Biobank with pregnancy experience and without depression or anxiety at baseline were included. Spontaneous miscarriage was defined by self-report from participants at enrollment or by International Classification of Diseases codes. The degree of social support was defined as the number of social support factors including living with a spouse or partner, participation in social activities, and confiding. Cox proportional hazards models were used to evaluate the joint association of spontaneous miscarriage and social support with the risks of depression and anxiety. RESULTS: During a median follow-up of 12.3 years, 4939 depression incidents and 5742 anxiety incidents were documented. For participants with 1, 2, and ≥3 spontaneous miscarriages, hazard ratios (95% confidence intervals) for depression were 1.10 (1.02-1.19), 1.31 (1.14-1.50), and 1.40 (1.18-1.67), respectively (P trend <.001), compared with participants without a history of spontaneous miscarriage, after adjustment for covariates. For anxiety, the hazard ratios (95% confidence intervals) were 1.07 (1.00-1.15), 1.04 (0.90-1.19), and 1.21 (1.02-1.44), respectively (P trend=.01). Moreover, we found that the risk of depression associated with a combination of spontaneous miscarriage and low degree of social support in later life was greater than the sum of the risks associated with each individual factor, indicating significant interactions on an additive scale (P interaction=.03). CONCLUSION: Spontaneous miscarriage is associated with higher risks of depression and anxiety, and the risk of depression is further increased when there is also low degree of social support.

Smoking timing, genetic susceptibility and the risk of incident type 2 diabetes: A cohort study from the UK Biobank.

AIM: To prospectively assess the association of smoking timing with the risk of type 2 diabetes (T2D) and examine whether smoking amount or genetic susceptibility might modify the relationship. MATERIALS AND METHODS: A total of 294 815 participants without diabetes from the UK Biobank, including non-smokers and smokers with data on the time from waking to first cigarette, were included. Cox proportional hazards models were used to evaluate the association between smoking timing and the risk of incident T2D. RESULTS: During a median follow-up time of 12 years, a total of 9937 incident cases of T2D were documented. Compared with non-smokers, a shorter time from waking to first cigarette was significantly associated with a higher risk of incident T2D (P for trend < .001). In the fully adjusted model, the hazard ratios (HRs) (95% confidence interval) associated with smoking timing were 1.46 (1.17-1.81) for more than 2 hours, 1.51 (1.21-1.87) for 1-2 hours, 1.58 (1.34-1.85) for 30-60 minutes, 1.86 (1.57-2.21) for 5-15 minutes and 2.01 (1.60-2.54) for less than 5 minutes. We found that even among those who reported being light smokers, those with the shortest time from waking to first cigarette had a 105% higher risk of T2D with an HR of 2.05 (1.52-2.76), which was comparable with heavy smokers. The genetic risk score for T2D did not modify this association (P-interaction = .51). CONCLUSIONS: Our findings indicate that shorter time from waking to first cigarette is significantly associated with a higher risk of incident T2D.

Psychological Status of Medical Staff in Obstetrics and Gynecology Hospitals during the Omicron Pandemic Outbreak in China.

Background: Medical staff in China faced great challenges and psychological and physiological changes of varying degrees during the omicron epidemic outbreak. It is important to recognize the potential impact of these challenges on the mental health of medical staff and to provide appropriate resources and support to mitigate their effects. Methods: A total of 354 medical staff in two obstetrics and gynecology hospitals of different grades were included in this survey using convenience sampling. The cross-sectional self-report questionnaires survey was conducted using the Basic Characteristics Questionnaire, Generalized Anxiety Disorder (GAD-7), Patient Health Questionnaire (PHQ-9), and Insomnia Severity Index (ISI). Results: There were 169 (47.7%) participants suffering from anxiety disorder. Working with fever, working in obstetrics, and working with protective clothing were the risk factors for anxiety in medical staff (p < 0.05). One hundred and ninety-six (55.4%) participants were depressed. Working with fever and working in obstetrics were the risk factors for depression in medical staff (p < 0.05). There were 117 (33.1%) participants suffering from insomnia. Working with fever, high educational level, and severe COVID-19 infection status were the risk factors for insomnia in medical staff (p < 0.05). Moreover, medical staff in a provincial hospital were more anxious and depressed than those in a county hospital. At last, there were more participants working with fever in obstetrics (p < 0.05). Conclusion: Anxiety disorder, depression, and insomnia were common among obstetrics and gynecology medical staff during the outbreak of omicron pandemic. During this period, more resources for psychological counselling should be provided to the hospital as well as more reasonable staffing arrangements, and working while having a fever is prohibited, especially in provincial hospital.

Risk factor control and incident cardiovascular disease in patients with diabetes: Sex-specific relations.

AIM: Women with diabetes are at higher risk of cardiovascular diseases (CVD) than men with diabetes; however, the sex difference in the association between the degree of risk factor control and the risk of CVD in patients with diabetes is unclear. METHODS: In total, 17 260 participants diagnosed with diabetes from the UK Biobank were included and matched with 86 300 non-diabetes controls based on age, sex and assessment centre. The main exposure was the number of risk factors within the target range, including glycated haemoglobin level <53 mol/mol (7%), blood pressure <140/90 mm/Hg, low-density lipoprotein cholesterol <100 mg/dl, non-current smoking and absence of microalbuminuria. RESULTS: During a median follow-up of 13.3 years, a total of 3338 incident CVD cases, including 2807 ischaemic heart disease and 793 strokes, were documented. A more stringent control of risk factors was significantly associated with a lower risk of incident CVD, and such an association was significantly stronger in women than men. Compared with non-diabetes participants, the diabetes-related risk of CVD appeared to be eliminated if more than three risk factors were well controlled among women and men with diabetes. Moreover, clinical biomarkers (e.g. glycated haemoglobin and blood pressure) showed greater relative importance than other factors in women, whereas socio-economic and psychological factors (e.g. education and depression) exhibited similar relative importance to clinical biomarkers in men with diabetes. CONCLUSION: Our findings highlighted the importance of raising awareness of sex differences in the management of CVD risk factors among patients with diabetes.

Maternal Height Is an Independent Risk of Adverse Outcomes in Women with Gestational Diabetes Mellitus.

INTRODUCTION: Maternal height has been shown to be associated with adverse outcomes in women with gestational diabetes mellitus (GDM). The aim of this study is to evaluate the association between maternal height and adverse outcomes stratified for gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) in women with GDM. METHODS: We conducted a retrospective study that included 2048 women diagnosed with GDM during 24-28 gestational weeks from July 1, 2017, to June 30, 2018, in Zhejiang Province, China. Demographic data, maternal characteristics and pregnancy complications were extracted from medical records. Maternal height was divided into three categories by tertiles. Chi-square was used to evaluate categorical data while one-way ANOVA was utilized to analyze continuous variables. The relationship between maternal height and adverse outcomes was examined using logistic regression. RESULTS: We found that shorter women had higher rates of low birth weight (LBW) (p = 0.003) and primary cesarean section (primary CS) (p < 0.001) while taller women had higher rates of abnormal neonatal ponderal index (p < 0.001), postpartum hemorrhage (p = 0.044) and macrosomia (p < 0.001). In taller women who had excess GWG, maternal height was positively associated with the risk of macrosomia (aOR 1.97, 95% CI 0.95-4.10). In shorter women who had inadequate GWG, maternal height was significantly associated with LBW (aOR 2.20, 95% CI 1.13-4.29) and primary CS (aOR 2.08, 95% CI 1.38-3.12). Maternal height was a protective factor of postpartum hemorrhage (aOR 0.15, 95% CI 0.03-0.72) in shorter women with excess GWG. In women with normal pre-pregnancy BMI, maternal height was positively associated with LBW (aOR 2.00, 95% CI 1.15-3.49) and primary CS (aOR 1.71, 95% CI 1.28-2.28) in shorter women while it was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women compared to average height women (aOR 0.71, 95% CI 0.55-0.92; aOR 0.66, 95% CI 0.51-0.85). CONCLUSION: The association between maternal height and adverse pregnancy outcomes varies with pre-pregnancy BMI and GWG in GDM women. Taking maternal height, pre-pregnancy BMI and GWG into account and using personalized prenatal management may reduce the risk of adverse pregnancy outcomes in GDM.

Adherence to Life's Essential 8 and incident chronic kidney disease: a prospective study of 147,988 UK Biobank participants.

BACKGROUND: The American Heart Association recently updated Life's Essential 8 (LE8) score. This amalgamation of health factors, recognized for their individual associations with chronic kidney disease (CKD) risk, provides a robust tool to assess overall cardiovascular health (CVH), which could potentially be extrapolated to predict CKD risk. OBJECTIVES: This study aimed to investigate the association between levels of CVH, as measured by the LE8 score, and risk of CKD in the UK Biobank. METHODS: A total of 147,988 participants free of CKD and cardiovascular disease from the UK Biobank were included in this prospective study. CVH levels were categorized as low (0-49), moderate (50-79), and high (80-100) using LE8 score. An adjusted Cox proportional hazard model was used to investigate the association between LE8 and CKD. The population attributable-risk (PAR) was also calculated. RESULTS: During a median follow-up of 10 y, 1936 CKD cases were documented. A higher LE8 score was associated with a significant lower risk of CKD (P < 0.001), and a linear dose-response relationship was observed. Similar patterns were also found in the associations of the LE8 behavior and biological subscale scores with CKD. Compared with participants with a low CVH category, participants with a moderate CVH were associated with a 39% lower risk of developing CKD (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.52, 0.72); and those with a high CVH had a 57% lower risk of CKD incidence (HR: 0.43; 95% CI: 0.35, 0.53) after adjustment for covariates. Among 8 distinct metrics of LE8 score, the BMI metric had the highest PAR (24.6%; 95% CI: 18.8, 30.2). Of the total CKD risk, 3.2% (95% CI: 1.4, 5.0) was attributable to inadequate or excessive sleep duration. CONCLUSIONS: High CVH, defined by LE8, is significantly associated with a lower risk of CKD. These results suggest that promoting optimal cardiovascular health may lower the burden of CKD.

BMI change during childhood, DNA methylation change at TXNIP, and glucose change during midlife.

OBJECTIVE: This study investigated whether changes in DNA methylation (DNAm) at TXNIP are associated with glycemic changes and whether such an association differs with early-life adiposity changes. METHODS: A total of 594 Bogalusa Heart Study participants who had blood DNAm measurements at two time points in midlife were included. Of them, 353 participants had at least four BMI measurements during childhood and adolescence. The incremental area under the curve was calculated as a measure of long-term trends of BMI during childhood and adolescence. RESULTS: Increase in DNAm at TXNIP was significantly associated with decrease in fasting plasma glucose (FPG) independent of covariates (p < 0.001). The study found that the strength of this relationship was significantly modified by a trend of increasing BMI during childhood and adolescence (p-interaction = 0.003). Each 1% increase in DNAm at TXNIP was associated with a 2.90- (0.77) mg/dL decrease in FPG among participants with the highest tertile of BMI incremental area under the curve and a 0.96- (0.38) mg/dL decrease among those with the middle tertile, whereas no association was observed among participants with the lowest tertile. CONCLUSIONS: These results indicate that changes in blood DNAm at TXNIP are significantly associated with changes in FPG in midlife, and this association was modified by BMI trends during childhood and adolescence.

The heterogeneous associations between gestational weight gain and adverse pregnancy outcomes in gestational diabetes mellitus according to abnormal glucose metabolism.

OBJECTIVES: The gestational weight gain (GWG) and hyperglycemia are two key factors affecting adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM). We aimed to investigate the combinatorial effect of abnormal glucose metabolism and GWG on adverse outcomes in GDM. METHODS: This retrospective cohort study included 2611 pregnant women with GDM in Women's Hospital School of Medicine Zhejiang University. Bases on the OGTT glucose levels, we categorized the GDM cohort into three subgroups: impaired fasting glucose (IFG) group, impaired glucose tolerance (IGT) group, and combined impaired glucose (IFG&IGT) group. RESULTS: Among pregnant women with IGT, insufficient GWG (IGWG) was an independent protective factor for pregnancy-induced hypertension syndrome (PIH) (aOR 0.55, 95% CI 0.32-0.95), macrosomia (0.38, 0.19-0.74) and large for gestational age (0.45, 0.32-0.62), as well as an independent risk factor for low birth weight infants (2.29, 1.24-4.22) and small for gestational age (1.94, 1.17-3.19); and excessive GWG (EGWG) was related to increased risks of PIH (1.68, 1.12-2.52), preterm delivery (1.82, 1.28-2.58), postpartum hemorrhage (1.85, 1.05-3.28), cesarean delivery (1.84, 1.38-2.46) and low body weight infants (2.36, 1.33-4.20). Moreover, EGWG was positively associated with PIH (3.27, 1.09-9.80) in the IFG group. But there were no significant associations between either IGWG or EGWG and any pregnancy outcomes in women with combined IFG&IGT. CONCLUSIONS: The relationships between GWG and adverse outcomes were modified by abnormal glucose metabolism in women with GDM. Our results suggest that more specific GWG recommendations according to their metabolic state are needed for GDM.

Association between maternal second-trimester stress and adverse pregnancy outcomes according to pre-pregnancy body mass index and gestational weight gain.

Objective: To investigate the impact of maternal second-trimester stress on pregnancy outcomes according to pre-pregnancy body mass index (BMI) and gestational weight gain (GWG). Methods: We did a prospective study in Women's Hospital, School of Medicine, Zhejiang University and included 960 pregnant women in our final analysis. Obstetric characteristics and the incidence of adverse pregnancy outcomes were examined in stressed and non-stressed women. The associations between maternal prenatal stress with adverse pregnancy outcomes were analyzed by logistic regression. Results: The incidence of premature rupture of membranes (PROM) was significantly higher in stressed pregnant women than non-stressed pregnant women (p = 0.035), whereas no significant difference in the incidence rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), primary cesarean delivery, preterm birth, macrosomia, low birth weight, fetal stress, admission into neonatal intensive care unit (NICU) or neonatal jaundice was found between two groups. Maternal second-trimester stress was an independent risk factor for the development of PROM (aOR = 1.468, 95% CI 1.037-2.079). Moreover, maternal second-trimester stress was significantly associated with PROM in pregnant women with normal pre-pregnancy BMI (aOR = 1.587, 95% CI 1.068-2.357) while no association was observed in either underweight or overweight and obese pregnant women. Meanwhile, no difference was found in the odds of PROM with maternal second-trimester stress in all GWG subgroups. Conclusion: Maternal second-trimester stress is associated with a higher risk of PROM and it is significant in pregnant women with normal pre-pregnancy BMI. Therefore, interventions to reduce stress during second-trimester of pregnancy might be essential for lowering the prevalence of PROM in pregnant women with normal pre-pregnancy BMI.

The association between maternal HbA1c and adverse outcomes in gestational diabetes.

Background: The role of HbA1c in women with gestational diabetes mellitus (GDM) is still unclear, particularly in the Asian population. Aim: To investigate the association between HbA1c levels and adverse outcomes considering maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) in women with GDM. Method: A retrospective study included 2048 women with GDM and singleton live births. Using logistic regression, the associations between HbA1c and adverse pregnancy outcomes were assessed. Result: Compared to women with HbA1c ≤ 5.0%, HbA1c was significantly associated with macrosomia (aOR 2.63,95%CI1.61,4.31), pregnancy-induced hypertension (PIH, aOR 2.56,95%CI1.57,4.19), preterm birth (aOR 1.64,95%CI 1.05,2.55), and primary Cesarean section (primary C-section, aOR1.49,95%CI1.09,2.03) in GDM women with HbA1c ≥5.5% while significantly associated with PIH (aOR 1.91,95%CI1.24,2.94) in women with HbA1c 5.1-5.4%. The associations between HbA1c and adverse outcomes varied with maternal age, pre-pregnancy BMI, and GWG. In women aged ≤29 years, there's significant association between HbA1c and primary C-section when HbA1c was 5.1-5.4% and ≥5.5%. In women aged 29-34 years and HbA1c ≥5.5%, HbA1c was significantly associated with macrosomia. In women aged ≥35 years, there's significant association between HbA1c and preterm birth when HbA1c was 5.1-5.4% and macrosomia and PIH when HbA1c ≥5.5%. In pre-pregnant normal-weight women, HbA1c was significantly associated with macrosomia, preterm birth, primary C-section, and PIH when HbA1c ≥5.5% while HbA1c was significantly associated with PIH when HbA1c was 5.1-5.4% . In pre-pregnant underweight women with HbA1c 5.1-5.4%, HbA1c was significantly associated with primary C-section. HbA1c was significantly associated with macrosomia among women with inadequate GWG or excess GWG and HbA1c≥5.5%. In women with adequate GWG, there's significant association between HbA1c and PIH when HbA1c was 5.1-5.4% and ≥5.5% . Conclusion: Conclusively, HbA1c at the time of diagnosis is significantly associated with macrosomia, preterm birth, PIH, and primary C-section in Chinese women with GDM.

Cardiovascular Health and Life Expectancy Among Adults in the United States.

BACKGROUND: Cardiovascular disease may be the main reason for stagnant growth in life expectancy in the United States since 2010. The American Heart Association recently released an updated algorithm for evaluating cardiovascular health (CVH)-Life's Essential 8 (LE8) score. We aimed to quantify the associations of CVH levels, estimated by the LE8 score, with life expectancy in a nationally representative sample of US adults. METHODS: We included 23 003 nonpregnant, noninstitutionalized participants aged 20 to 79 years who participated in the National Health and Nutrition Examination Survey from 2005 to 2018 and whose mortality was identified through linkage to the National Death Index through December 31, 2019. The overall CVH was evaluated by the LE8 score (range, 0-100), as well as the score for each component of diet, physical activity, tobacco/nicotine exposure, sleep duration, body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure. Life table method was used to estimate life expectancy by levels of the CVH. RESULTS: During a median of 7.8 years of follow-up, 1359 total deaths occurred. The estimated life expectancy at age 50 years was 27.3 years (95% CI, 26.1-28.4), 32.9 years (95% CI, 32.3-33.4), and 36.2 years (95% CI, 34.2-38.2) in participants with low (LE8 score <50), moderate (50≤ LE8 score <80), and high (LE8 score ≥80) CVH, respectively. Equivalently, participants with high CVH had an average 8.9 (95% CI, 6.2-11.5) more years of life expectancy at age 50 years compared with those with low CVH. On average, 42.6% of the gained life expectancy at age 50 years from adhering to high CVH was attributable to reduced cardiovascular disease death. Similarly significant associations of CVH with life expectancy were observed in men and women, respectively. Similarly significant associations of CVH with life expectancy were observed in White participants and Black participants but not in Mexican participants. CONCLUSIONS: Adhering to a high CVH, defined as the LE8 score, is related to a considerably increased life expectancy in US adults, but more research needs to be done in other races and ethnicities (eg, Hispanic and Asian).

Independent and Joint Associations of Age, Pre-pregnancy BMI, and Gestational Weight Gain with Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus.

INTRODUCTION: To explore the independent and combined effects of maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: A total of 2171 pregnant women with GDM attending the Women's Hospital of Zhejiang University were retrospectively included. We compared pregnancy outcomes in different age, BMI, and GWG groups after adjusting for confounding variables. RESULTS: Results showed that (1) advanced maternal age increased the risk of primary Cesarean section and hypertensive disorders of pregnancy (HDP) in normal weight; (2) independent of age and GWG, high BMI significantly increased the risk of HDP, primary Cesarean section, and macrosomia; (3) Women with excessive GWG had a higher risk of primary Cesarean section and HDP, even they were ≤ 29 years old or normal weight, respectively; (4) Pregnant women with inadequate GWG had a higher risk of preterm birth and a lower risk of macrosomia in both the 30-34 age group and the normal weight group; (5) BMI was a better predictor of HDP than GWG among women younger than 30. CONCLUSIONS: Among the GDM population, women over the age of 35, overweight and obese, or with an excessive GWG were more prone to adverse pregnancy outcomes, especially primary Cesarean delivery and HDP.

Non-coding RNAs: Role in diabetic foot and wound healing.

Diabetic foot ulcer (DFU) and poor wound healing are chronic complications in patients with diabetes. The increasing incidence of DFU has resulted in huge pressure worldwide. Diagnosing and treating this condition are therefore of great importance to control morbidity and improve prognosis. Finding new markers with potential diagnostic and therapeutic utility in DFU has gathered increasing interest. Wound healing is a process divided into three stages: Inflammation, proliferation, and regeneration. Non-coding RNAs (ncRNAs), which are small protected molecules transcribed from the genome without protein translation function, have emerged as important regulators of diabetes complications. The deregulation of ncRNAs may be linked to accelerated DFU development and delayed wound healing. Moreover, ncRNAs can be used for therapeutic purposes in diabetic wound healing. Herein, we summarize the role of microRNAs, long ncRNAs, and circular RNAs in diverse stages of DFU wound healing and their potential use as novel therapeutic targets.

Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1ß. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.

The Influence of HbA1c and Gestational Weight Gain on Pregnancy Outcomes in Pregnant Women With Gestational Diabetes Mellitus.

Background: To investigate the influence of HbA1c level and GWG on pregnancy outcomes in pregnant women with GDM. Methods: A total of 2,171 pregnant women with GDM were retrospectively included and categorized as follows: (1) normal (HbA1c <6%) and elevated (HbA1c ≥6%) HbA1c groups according to the HbA1c level in the second trimester, and (2) inadequate, appropriate, and excessive GWG groups according to the IOM guidelines. Results: In pregnant women with GDM, advanced age and high pre-pregnancy BMI were high-risk factors for elevated HbA1c. Pregnant women with elevated HbA1c had higher OGTT levels than those with normal HbA1c, and the risks of adverse pregnancy outcomes were higher (P < 0.05). The risks of primary cesarean section, hypertensive disorders during pregnancy, and macrosomia in pregnant women with excessive GWG were significantly higher than those with inadequate and appropriate GWG (P < 0.05). When GWG was appropriate, the risk of hypertensive disorders during pregnancy in the elevated HbA1c group was higher than that in the normal HbA1c group. When GWG was excessive, the risks of postpartum hemorrhage, macrosomia, and neonatal asphyxia in the elevated HbA1c group were significantly higher than in the normal HbA1c group (P < 0.05). Conclusion: Monitoring and controlling blood glucose levels have shown effectiveness in reducing the adverse pregnancy outcomes in women with GDM, particularly for those who had excessive GWG.

An early prediction model for gestational diabetes mellitus based on genetic variants and clinical characteristics in China.

OBJECTIVES: To evaluate the influence of genetic variants and clinical characteristics on the risk of gestational diabetes mellitus (GDM) and to construct and verify a prediction model of GDM in early pregnancy. METHODS: Four hundred seventy five women with GDM and 487 women without, as a control, were included to construct the prediction model of GDM in early pregnancy. Both groups had complete genotyping results and clinical data. They were randomly divided into a trial cohort (70%) and a test cohort (30%). Then, the model validation cohort, including 985 pregnant women, was used for the external validation of the GDM early pregnancy prediction model. RESULTS: We found maternal age, gravidity, parity, BMI and family history of diabetes were significantly associated with GDM (OR > 1; P < 0.001), and assisted reproduction was a critical risk factor for GDM (OR = 1.553, P = 0.055). MTNR1B rs10830963, C2CD4A/B rs1436953 and rs7172432, CMIP rs16955379 were significantly correlated with the incidence of GDM (AOR > 1, P < 0.05). Therefore, these four genetic susceptible single nucleotide polymorphisms (SNPs) and six clinical characteristics were included in the construction of the GDM early pregnancy prediction model. In the trial cohort, a predictive model of GDM in early pregnancy was constructed, in which genetic risk score was independently associated with GDM (AOR = 2.061, P < 0.001) and was the most effective predictor with the exception of family history of diabetes. The ROC-AUC of the prediction model was 0.727 (95% CI 0.690-0.765), and the sensitivity and specificity were 69.9% and 64.0%, respectively. The predictive power was also verified in the test cohort and the validation cohort. CONCLUSIONS: Based on the genetic variants and clinical characteristics, this study developed and verified the early pregnancy prediction model of GDM. This model can help screen out the population at high-risk for GDM in early pregnancy, and lifestyle interventions can be performed for them in a timely manner in early pregnancy.

Comparison of the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter in term nulliparous women with borderline oligohydramnios.

BACKGROUNDS: At present, there is no consensus on the induction methods in term pregnancy with borderline oligohydramnios. This study aimed to compare the effectiveness and pregnancy outcomes of labor induction with dinoprostone or single-balloon catheter (SBC) in term nulliparous women with borderline oligohydramnios. METHODS: We conducted a retrospective cohort study from January 2016 to November 2018. During the study period, a total of 244 cases were enrolled. Of these, 103 cases were selected for induction using dinoprostone and 141 cases were selected for induction with SBC. The pregnancy outcomes between the two groups were compared. Primary outcomes were successful vaginal delivery rates. Secondary outcomes were maternal and neonatal adverse events. Multivariate logistic regression was used to assess the risk factors for vaginal delivery failure in the two groups. RESULTS: The successful vaginal delivery rates were similar between the dinoprostone group and the SBC group (64.1% [66/103] vs. 59.6%, [84/141] P = 0.475), even after adjustment for potential confounding factors (adjusted odds ratio [aOR]: 1.07, 95% confidence interval [CI]: 0.57-2.00, P = 0.835). The incidence of intra-amniotic infection was lower in the dinoprostone group than in the SBC group (1.9% [2/103] vs. 7.8%, [11/141] P < 0.001), but the presence of non-reassuring fetal heart rate was higher in the dinoprostone group than in the SBC group (12.6% [13/103] vs. 0.7%, [1/141] P < 0.001). Multivariate logistic regression showed that nuchal cord was a risk factor for vaginal delivery failure after induction with dinoprostone (aOR: 6.71, 95% CI: 1.96-22.95). There were three factors related to vaginal delivery failure after induction with SBC, namely gestational age (aOR: 1.51, 95% CI: 1.07-2.14), body mass index (BMI) >30 kg/m2 (aOR: 2.98, 95% CI: 1.10-8.02), and fetal weight >3500 g (aOR: 2.49, 95% CI: 1.12-5.50). CONCLUSIONS: Term nulliparous women with borderline oligohydramnios have similar successful vaginal delivery rates after induction with dinoprostone or SBC, with their advantages and disadvantages. In women with nuchal cord, the risk of vaginal delivery failure is increased if dinoprostone is used in the induction of labor. BMI >30 kg/m2, large gestational age, and estimated fetal weight >3500 g are risk factors for vaginal delivery failure after induction with SBC.

Obesity and the relation between joint exposure to ambient air pollutants and incident type 2 diabetes: A cohort study in UK Biobank.

BACKGROUND: Air pollution has been related to incidence of type 2 diabetes (T2D). We assessed the joint association of various air pollutants with the risk of T2D and examined potential modification by obesity status and genetic susceptibility on the relationship. METHODS AND FINDINGS: A total of 449,006 participants from UK Biobank free of T2D at baseline were included. Of all the study population, 90.9% were white and 45.7% were male. The participants had a mean age of 56.6 (SD 8.1) years old and a mean body mass index (BMI) of 27.4 (SD 4.8) kg/m2. Ambient air pollutants, including particulate matter (PM) with diameters ≤2.5 µm (PM2.5), between 2.5 µm and 10 µm (PM2.5-10), nitrogen dioxide (NO2), and nitric oxide (NO) were measured. An air pollution score was created to assess the joint exposure to the 4 air pollutants. During a median of 11 years follow-up, we documented 18,239 incident T2D cases. The air pollution score was significantly associated with a higher risk of T2D. Compared to the lowest quintile of air pollution score, the hazard ratio (HR) (95% confidence interval [CI]) for T2D was 1.05 (0.99 to 1.10, p = 0.11), 1.06 (1.00 to 1.11, p = 0.051), 1.09 (1.03 to 1.15, p = 0.002), and 1.12 (1.06 to 1.19, p < 0.001) for the second to fifth quintile, respectively, after adjustment for sociodemographic characteristics, lifestyle factors, genetic factors, and other covariates. In addition, we found a significant interaction between the air pollution score and obesity status on the risk of T2D (p-interaction < 0.001). The observed association was more pronounced among overweight and obese participants than in the normal-weight people. Genetic risk score (GRS) for T2D or obesity did not modify the relationship between air pollution and risk of T2D. Key study limitations include unavailable data on other potential T2D-related air pollutants and single-time measurement on air pollutants. CONCLUSIONS: We found that various air pollutants PM2.5, PM2.5-10, NO2, and NO, individually or jointly, were associated with an increased risk of T2D in the population. The stratified analyses indicate that such associations were more strongly associated with T2D risk among those with higher adiposity.