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).

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.

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.

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 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).

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.

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.

Distinct genetic subtypes of adiposity and glycemic changes in response to weight-loss diet intervention: the POUNDS Lost trial.

PURPOSE: Obesity is a heterogeneous condition and distinct adiposity subtypes may differentially affect type 2 diabetes risk. We assessed relations between genetically determined subtypes of adiposity and changes in glycemic traits in a dietary intervention trial. METHODS: The four genetic subtypes of adiposity including waist-hip ratio-increase only (WHRonly+), body mass index-increase only (BMIonly+), WHR-increase and BMI-increase (BMI+WHR+), and WHR-decrease and BMI-increase (BMI+WHR-) were assessed by polygenetic scores (PGSs), calculated based on 159 single nucleotide polymorphisms related to BMI and/or WHR. We examined the associations between the four PGSs and changes in fasting glucose, insulin, ß-cell function (HOMA-B) and insulin resistance (HOMA-IR) in 692 overweight participants (84% white Americans) who were randomly assigned to one of four weight-loss diets in a 2-year intervention trial. RESULTS: Higher BMI+WHR-PGS was associated with a greater decrease in 2-year changes in waist circumference in white participants (P = 0.002). We also found significant interactions between WHRonly+PGS and dietary protein in 2-year changes in fasting glucose and HOMA-B (P = 0.0007 and < 0.0001, respectively). When consuming an average-protein diet, participants with higher WHRonly+PGS showed less increased fasting glucose (ß = - 0.46, P = 0.006) and less reduction in HOMA-B (ß = 0.02, P = 0.005) compared with lower WHRonly+PGS. Conversely, eating high-protein diet was associated with less decreased HOMA-B among individuals with lower than higher WHRonly+PGS (ß = - 0.02, P = 0.006). CONCLUSIONS: Distinct genetically determined adiposity subtypes may differentially modify the effects of weight-loss diets on improving glucose metabolism in white Americans. This trial was registered at clinicaltrials.gov as NCT00072995.

Relationship of abnormal mid-term oral glucose tolerance test and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus.

To explore the correlation of mid-term oral glucose tolerance test (OGTT) and maternal weight gain with adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM). A total of 2611 pregnant women with GDM who were examined and delivered in Women's Hospital, Zhejiang University School of Medicine from July 1st 2017 to 30th June 2018 were enrolled in this study. According to the number of abnormal items of mid-term OGTT results or maternal gestational weight gain (GWG), patients were classified. The incidence of adverse perinatal outcomes in each group and its relation with OGTT results and GWG were analyzed. The incidence of gestational hypertension, premature delivery, macrosomia and large for gestational age infant (LGA) in three abnormal items GDM patients were significantly higher than those in one or two abnormal items GDM patients (all <0.017). The incidence of gestational hypertension and premature delivery in two abnormal items GDM patients were higher than those in one abnormal item GDM patients (all <0.017). The incidence of gestational hypertension and macrosomia in excessive GWG patients were significantly higher than those in inadequate and appropriate GWG patients (all <0.017), and the incidence of LGA were higher than that in inadequate GWG patients (all <0.017). The incidence of premature delivery and low birth weight infants in appropriate GWG patients were significantly lower than those in inadequate and excessive GWG patients, and the incidence of small for gestational age infant (SGA) were significantly lower than that in inadequate GWG patients (all <0.017). In one abnormal item GDM patients, inadequate GWG was a risk factor for premature delivery and SGA (=1.66, 95%: 1.10-2.52; =2.20, 95%: 1.07-4.53), and protective factor for LGA (=0.40, 95%: 0.27-0.59). And excessive GWG was a risk factor for gestational hypertension, premature delivery and low birth weight infants (=2.15, 95%: 1.35-3.41; =1.80, 95%: 1.20-2.72; =2.18, 95%: 1.10-4.30).In two abnormal items GDM patients, inadequate GWG was a protective factor for macrosomia and LGA (=0.24, 95%: 0.09-0.67; =0.54, 95%: 0.34-0.86), while excessive GWG was risk factor for premature delivery (=1.98, 95%: 1.23-3.18).In three abnormal items GDM patients, there was no significant relationship between GWG and adverse pregnancy outcomes. For GDM women with one or two items of elevated blood glucose in OGTT, reasonable weight management during pregnancy can reduce the occurrence of adverse pregnancy outcomes. For those with three items of elevated blood glucose in OGTT, more strict blood glucose monitoring and active intervention measures should be taken in addition to weight management during pregnancy.

Impact of pre-pregnancy body mass index, weight gain and blood lipid level during pregnancy on pregnancy outcome in patients with gestational diabetes mellitus.

To explore the effects of pre-pregnancy body mass index (BMI), weight gain and blood lipid level during pregnancy on pregnancy outcome in patients with and without gestational diabetes mellitus(GDM). A total of 12 650 singleton pregnant women without history of hypertension and diabetes who were admitted at Women's Hospital, Zhejiang University School of Medicine for delivery from January 2018 to April 2019 were enrolled in the study. There were 2381 cases complicated with gestational diabetes (GDM group) and 10 269 cases without GDM (non-GDM group). The pre-pregnancy BMI and weight gain during pregnancy were documented in two groups. The factors related to perinatal outcome were analyzed. In both GDM and non-GDM pregnant women, pre-pregnancy overweight and excessive weight gain during pregnancy were independent factors of large for gestational age infant (LGA), small for gestational age infant (SGA) and first cesarean section (<0.01 or <0.05). Excessive weight gain during pregnancy was also an independent risk factor of preeclampsia (<0.05). Triglyceride levels in the second trimester were independently associated with multiple adverse pregnancy outcomes, such as LGA, preeclampsia, initial cesarean delivery, premature delivery. Controlling excessive or insufficient weight gain during pregnancy can significantly reduce the incidence of LGA and SGA. And controlling BMI before pregnancy can effectively reduce the incidence of LGA, preeclampsia and the first cesarean section. For non-GDM pregnant women, abnormal blood lipid levels in the second trimester may be closely related to multiple adverse pregnancy outcomes, and active dietary guidance or treatment is also required.

Chemerin-induced macrophages pyroptosis in fetal brain tissue leads to cognitive disorder in offspring of diabetic dams.

BACKGROUND: Chemerin is highly expressed in the serum, placenta tissue, and umbilical cord blood of diabetic mother; however, the impact of chemerin on cognitive disorders of offspring from mothers with diabetes in pregnancy remains unclear. METHODS: A diabetic phenotype in pregnant mice dams was induced by streptozocin (STZ) injection or intraperitoneal injection of chemerin. Behavioral changes in offspring of diabetic dams and nondiabetic controls were assessed, and changes in chemerin, two receptors of chemerin [chemerin receptor 23 (ChemR23) and chemokine (C-C motif) receptor-like 2 (CCRL2)], macrophages, and neurons in the brain tissue were studied to reveal the underlying mechanism of the behavioral changes. RESULTS: Chemerin treatment mimicked the STZ-induced symptom of maternal diabetes in mice along with the altered behavior of offspring in the open field test (OFT) assay. In the exploring process for potential mechanism, the brain tissues of offspring from chemerin-treated dams were observed with an increase level of macrophage infiltration and a decrease number of neuron cells. Moreover, an increased level of NOD-like receptor family pyrin domain containing 3 (NLRP3) and apoptosis-associated speck-like (Asc) protein as well as pyroptosis [characterized by increased active caspase-1 content and secretion of cytokines such as interleukin (IL) 1 beta (IL-1ß) and IL-18] more activated in macrophages is also observed in the brain of these diabetic dam's offspring, in the presence of ChemR23. In vitro, it was found that pyroptosis activation was increased in macrophages separated from the abdominal cavity of normal mice, after chemerin treatment. However, depletion of CCRL2 decreased the level of chemerin in the brain tissues of diabetic dams' offspring; depletion of ChemR23 decreased macrophage pyroptosis, and depletion of either receptor reversed chemerin-mediated neurodevelopmental deficits and cognitive impairment of offspring of diabetic pregnant dams. CONCLUSIONS: Chemerin induced diabetic pregnant disease and CCRL2 were required to enrich chemerin in the brain of offspring. Aggregation of chemerin could lead to macrophage recruitment, activation of pyroptosis, the release of inflammatory cytokines, a decrease in the number of neurons, and cognitive impairment in offspring in a ChemR23-dependent manner. Targeting CCRL2 and/or ChemR23 could be useful for treating neuropsychological deficits in offspring of dams with diabetes in pregnancy.

Second-trimester maternal lipid profiles predict pregnancy complications in an age-dependent manner.

PURPOSE: Our objective was to investigate the combinatorial effect of maternal age and second-trimester maternal lipid profiles for pregnancy complications. METHODS: With 1:4 matching, this retrospective study selected 499 advanced maternal age women and 1996 younger controls. Logistic regression analysis was used to estimate the correlation between second-trimester lipid profiles [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] and pregnancy complications [gestational diabetes mellitus (GDM), pregnancy-induced hypertension syndrome (PIH), preterm labor (PTL), and macrosomia]. Optimal cutoff points were determined by ROC curve analysis. RESULTS: In women aged 20-34 years, TG are a risk factor for PIH (OR 1.54, 95% CI 1.16-2.04) and PTL (OR 1.34, 95% CI 1.04-1.72). LDL-C was positively associated with macrosomia (OR 1.25, 95% CI 1.04-1.50), while HDL-C was negatively associated with PIH (OR 0.45, 95% CI 0.21-0.93). The optimal cutoff points for TG predicting PIH and PTL were separately ≥ 2.135 and 2.305 mmol/L. The optimal cutoff point for HDL-C identifying PIH was ≤ 1.995 mmol/L and for LDL-C identifying macrosomia was ≥ 3.425 mmol/L. As for advanced maternal age, only TG was an independent risk factor for PIH (OR 1.60, 95% CI 1.01-2.54), and its optimal cutoff point was ≥ 2.375 mmol/L. CONCLUSIONS: Second-trimester lipid profiles might predict pregnancy complications varied by maternal age. This suggested that individualized prenatal care strategies should be established for women with advanced and normal maternal age to prevent pregnancy complications.

Is Chemerin associated with gestational diabetes mellitus? An evidence-based clinical research from Chinese women.

The present study aimed to explore the association between gestational diabetes mellitus (GDM) and Chemerin, by analysing Chemerin level, clinical data and biochemical parameters among 46 GDM patients and 43 controls. It was found that the Chemerin levels from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group than those in the control group (p < .05 for all). Maternal insulin resistance (IR) index and serum inflammation parameters, including C-reactive protein and white blood cells, were also higher in GDM group (p < .05 for all). Moreover, maternal IR index and circulating insulin level were both positively correlated with maternal circulating Chemerin level (p < .05 for both). Our findings suggest that Chemerin, associated with IR and more expressed in GDM women, might participate in the pathogenesis of GDM. Impact Statement What is already known on this subject: Chemerin, a recently-discovered adipocytokine, has been widely-considered to be involved in metabolic diseases, and several studies have investigated it in gestational diabetes mellitus (GDM), but with no consensus about the level comparison between GDM and controls. What the results of this study add: The present case-control study found that the levels of Chemerin from cord blood, peripheral blood, adipose tissue and placenta tissue were all significantly higher in the GDM group. What the implications are of these findings for clinical practice and/or further research: Also, the circulating Chemerin level was positively correlated with insulin index, which we thought would add to the evidence that Chemerin does be associated with GDM, contributing to elucidating the pathogenesis of GDM.

Increased retinol-free RBP4 contributes to insulin resistance in gestational diabetes mellitus.

PURPOSE: Retinol-binding protein 4 (RBP4) is a circulating retinol transporter that is strongly associated with insulin resistance. The aim of this study was to evaluate the RBP4 and retinol level in rat model of gestational diabetes mellitus and the relationship between retinol-free RBP4 (apo-RBP4), retinol-bound RBP4 (holo-RBP4) and insulin resistance. METHODS: Pregnant rats were administered streptozotocin to induce diabetes. The RBP4 and retinol levels were evaluated in GDM and normal pregnant rats. After then, normal pregnant rats were divided into two groups to receive either apo-RBP4 or vehicle injection. The metabolic parameters and insulin signaling in adipose tissue, skeletal muscle and liver were determined in apo-RBP4 and control groups. Primary human adipocytes were cultured in vitro with different proportions of apo-RBP4 and holo-RBP4 for 24 h. The interaction between RBP4 and STRA6 was assessed by co-immunoprecipitation, and the expression of JAK-STAT pathway and insulin signaling were detected by Western blotting and immunofluorescence. RESULTS: We found increases in serum RBP4 levels and the RBP4:retinol ratio but not in the retinol levels in GDM rats. Exogenous apo-RBP4 injection attenuated insulin sensitivity in pregnant rats. In vitro, a prolonged interaction between RBP4 and STRA6 was observed when apo-RBP4 was present. In response to increased apo-RBP4 levels, cells showed elevated activation of the JAK2/STAT5 cascade and SOCS3 expression, decreased phosphorylation of IR and IRS1, and attenuated GLUT4 translocation and glucose uptake upon insulin stimulation. CONCLUSION: Apo-RBP4 is a ligand that activates the STRA6 signaling cascade, inducing insulin resistance in GDM.

The Relationship between Retinol-Binding Protein 4 Concentrations and Gestational Diabetes Mellitus in Chinese Women.

BACKGROUND: This study aimed to investigate the relationship between retinol-binding protein 4 (RBP4) and gestational diabetes mellitus (GDM). METHODS: Seventy-six women with and without GDM were recruited. Their blood samples were collected to detect RBP4, fasting plasma glucose (FPG), fasting insulin (Fins), triglyceride (TG), total cholesterol (TC), low-density lipoprotein, high-density lipoprotein (HDL) and glycosylated hemoglobin (HbA1c) levels. RESULTS: RBP4 (21.42 ± 3.846 vs. 39.08 ± 8.293 µg/ml), FPG, Fins, homeostasis model assessment of insulin resistance (HOMA-IR), HbA1c, and TG levels were higher, while HDL levels were lower in women with GDM (p < 0.01). In healthy controls, RBP4 concentrations were positively correlated with HOMA-IR and TG and inversely correlated with FPG and HDL (p < 0.05). Serum concentrations of RBP4 in women with GDM were inversely correlated with TC and positively correlated with maternal weight gain during pregnancy (p < 0.05). The ROC curve was drawn with a correct rate of 93.4%. CONCLUSIONS: Concentrations of serum RBP4 were significantly higher in women with GDM, suggesting that elevated RPB4 level may play a role in the pathogenesis of GDM. Meanwhile, RBP4 might be a good predictor of GDM. RBP4 is correlated with TG and HDL, indicating that RBP4 plays a role in alterations of lipid metabolism in pregnant women. © 2015 S. Karger AG, Basel.

Beneficial effects of short-term breastfeeding versus non-breastfeeding in early life against childhood obesity: findings from the US-based population study NHANES.

BACKGROUND: Breastfeeding is widely recognized for its potential to reduce childhood obesity. However, research investigating these benefits in children breastfed for a short duration (up to 6 months) remains limited despite this being a common practice globally. METHODS: This study focused on a population breastfed for 6 months or less to determine the potential benefits of short-term breastfeeding for preventing childhood obesity. Data were collected from five survey cycles of an US-based population study (the National Health and Nutrition Examination Survey (NHANES)), spanning 2009-2020. A sample of 3,211 children aged 2-6 years was selected, including 1,373 never breastfed and 1,838 ever breastfed. Logistic regression analysis examined the direct association between short-term breastfeeding and childhood obesity. Subsequent subgroup analyses were conducted. Additionally, stratified logistic regression explored the relationship between childhood obesity and the introduction of other early nutrition in both ever-breastfed and never-breastfed children. RESULTS: Overall, breastfeeding for 6 months or less did not directly prevent childhood obesity. However, among participants with older mothers (aged 35 or above), short-term breastfeeding was associated with a lower risk of childhood obesity compared to never being breastfed (OR 0.31, 95% CI: 0.17, 0.59). Similarly, children aged 3-4 years who were breastfed for > 3 ~ 6 months exhibited a lower obesity risk (OR 0.56, 95% CI: 0.35, 0.89). In ever-breastfed children, delayed infant formula introduction was linked to a lower risk of obesity (P-trend < 0.05: introduction at age ≤ 1 vs. >1 ~ 3 vs. >3 months). Conversely, for non-breastfed children, introducing milk (other than breast milk or formula) later (≥ 12 versus < 12 months) and introducing alternatives to whole cow's milk were associated with lower obesity risks (OR 0.54, 95% CI: 0.37, 0.78; OR 0.21, 95% CI: 0.08, 0.60, respectively). Notably, these trends were not observed in ever-breastfed children. CONCLUSIONS: Short-term breastfeeding may offer some benefits in preventing childhood obesity for specific populations. Additionally, it could potentially mitigate risks associated with the introduction of formula and cow's milk at inappropriate times.

Gestational diabetes mellitus, body mass index, and cardiometabolic multimorbidity: a prospective cohort study.

PURPOSE: Gestational diabetes mellitus (GDM) could increase the risks of type 2 diabetes mellitus (T2DM) and cardiovascular disease. However, evidence on its association with cardiometabolic multimorbidity (CMM) was limited. This study aimed to evaluate the association between GDM and the prevalence, incidence, patterns, and progression of CMM; and the role of body mass index (BMI) in such association. METHODS: This study included 203,372 women who have given birth in UK Biobank. The diagnoses of GDM and cardiometabolic diseases (including stroke, coronary heart disease [CHD], and T2DM) were reported by participants or obtained through linkage to inpatient hospital data until 31st December 2020. BMI was assessed at the baseline assessment. CMM was defined as having two or more of included cardiometabolic diseases. Logistic regression models and Cox proportional hazard models were used to assess the association between GDM and CMM, and the modifications on both additive and multiplicative scales were assessed to evaluate the effect of BMI on such association. RESULTS: A total of 1,217 women had a history of GDM, 2,351 participants had CMM at the end of follow-up and 1,601 was newly diagnosed during follow-up. GDM was associated with higher prevalence (odds ratio [OR]=4.64, 95% confidence interval [95% CI]=3.54-6.08) and incidence (hazard ratio [HR]=3.62, 95% CI=2.62-5.00) of CMM. In particular, GDM was associated with higher odds of T2DM, coexisting T2DM and vascular disease, and T2DM followed by vascular disease. Formal testing for effect modification suggested multiplicative modification by BMI for the association between GDM and incident CMM. CONCLUSIONS: GDM was associated with CMM in women's late life, with multiplicative modification effects of BMI. Our results suggest that maternal and lifestyle interventions (e.g., weight management) are warranted for the primary and secondary prevention of CMM, particularly in women with a history of GDM.

Association between changes in glycosylated hemoglobin during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy.

OBJECTIVE: To explore the relationship between changes in glycated hemoglobin (HbA1c) during the second and third trimesters and adverse pregnancy outcomes among women without hyperglycemia in pregnancy (HIP). RESEARCH DESIGN AND METHODS: A total of 1,057 pregnant women who underwent serum HbA1c and delivered at Women's Hospital, Zhejiang University School of Medicine from May 2022 to March 2023, were included in this study. They were divided into four groups. Associations were evaluated using multivariate logistic regression analysis. RESULTS: In our study, an upward trend in HbA1c levels in the second trimester (HbA1c_S) and third trimester (HbA1c_T) among women without HIP was demonstrated. Multivariate logistics regression analysis showed significant associations: Pregnant women with HbA1c_S<5.5 %, HbA1c_T≥6.1 %, or with HbA1c_S≥5.5 %, HbA1c_T<6.1 % had a significant correlation with hypertensive disorders of pregnancy (HDP) (aOR:2.72, 95 %CI=1.24-5.97；aOR:2.59, 95 %CI=1.15-5.84). Furthermore, for each 1 % increase in the difference value of HbA1c between the second and third trimesters, the risk of HDP increased about 1.96 times, and the risk of delivering a large-for-gestational-age baby increased about 1.30 times. CONCLUSION: Among pregnant women without HIP, elevated HbA1c levels in the second or third trimester are associated with increased risks of adverse pregnancy outcomes.

A new classification method for gestational diabetes mellitus: a study on the relationship between abnormal blood glucose values at different time points in oral glucose tolerance test and adverse maternal and neonatal outcomes in pregnant women with gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM) can lead to various adverse pregnancy outcomes for both mothers and infants, including gestational hypertension, premature rupture of membranes, preterm birth, macrosomia, large for gestational age (LGA) infants, and neonatal hypoglycemia. Previous studies have mainly focused on the overall risk of GDM for adverse maternal and neonatal outcomes, but there has been limited research specifically investigating the relationship between different patterns of abnormal oral glucose tolerance test (OGTT) results and adverse maternal and neonatal outcomes. Objective: The study aimed to analyze the maternal and neonatal outcomes among GDM women with different OGTT patterns and to explore a new classification method capable of stratifying GDM into high-risk (GDM-HR) and low-risk subtypes based on OGTT results. Study Design: We conducted a retrospective cohort study at the Women's Hospital, School of Medicine, Zhejiang University, spanning from November 1, 2015, to April 30, 2018. During the study period, a total of 3268 cases of GDM were enrolled. Based on the results of the OGTT, these GDM cases were classified into 7 subtypes, and the composition ratio of each subtype and their maternal and neonatal outcomes were analyzed. Innovatively, we proposed to categorize GDM-HR (characterized by elevated fasting blood glucose [FBG] levels, including T0, T0+1, T0+2, and T0+1+2) and low-risk GDM (GDM-LR, without elevated FBG, including T1, T2, and T1+2) and compared the maternal and neonatal outcomes between the two subtypes. Results: (1) In this cohort of 3268 GDM cases, the composition ratios of the 7 GDM subtypes were as follows: T0 (7.9%, n=260), T1 (24.2%, n=791), T2 (27.4%, n=897), T0+1 (5.4%, n=175), T0+2 (1.7%, n=56), T1+2 (26.2%, n=855), and T0+1+2 (7.2%, n=234). (2) GDM subtypes with elevated FBG levels (GDM-HR) exhibit more severe adverse prognostic outcomes compared to those without elevated FBG levels (GDM-LR). (3) Multiple logistic regression analysis revealed that compared to the GDM-LR group, the GDM-HR group showed increased fetal birth weight (by approximately 150 grams), and had higher rates of cesarean section (adjusted odds ratio [aOR]: 1.45, 95% confidence interval [CI]: 1.19-1.76), hypertensive disorders of pregnancy (aOR: 1.78, 95% CI: 1.35-2.35), preterm birth (aOR: 1.59, 95% CI: 1.17-2.16), macrosomia (aOR: 2.66, 95% CI: 2.07-3.43), LGA infants (aOR: 2.46, 95% CI: 2.05-2.97), and neonatal hypoglycemia (aOR: 2.00, 95% CI: 1.37-2.91). Partial correlation analysis shows a positive correlation between fetal birth weight and FBG levels, with r=0.222, P<.001. Multiple linear regression indicates that for every 1 mmol/L increase in FBG, the fetal weight is estimated to increase by approximately 188 grams. Conclusion: The composition ratio of GDM subtypes with elevated FBG (GDM-HR) is relatively low within GDM cases, yet it presents with a higher risk of adverse outcomes compared to subtypes without elevated FBG (GDM-LR), warranting increased attention from obstetricians. Applying this new classification method in clinical practice enables better differentiation and individualized management of GDM.

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.