Thyroid V40 is a good predictor for subclinical hypothyroidism in patients with nasopharyngeal carcinoma after intensity modulated radiation therapy: a randomized clinical trial.

BACKGROUND: Hypothyroidism (HT) and subclinical HT after radiotherapy is frequent in nasopharyngeal carcinoma (NPC) patients, results in negative impact on patients' quality of life. The percentage of thyroid volume receiving more than 40 Gy (V40) ≤ 85% was reported to be a useful dose constraint to adopt during intensity-modulated radiation therapy (IMRT) planning. This study aims to verify whether V40 ≤ 85% can be used as an effective dose constraint in IMRT planning in a randomized clinical trial. METHODS: This single-center 1:1 randomized clinical trial was conducted in Fujian province hospital between March 2018 and September 2022. All patients were treated with IMRT and randomized to induction chemo followed by concurrent chemo-IMRT or concurrent chemo-IMRT alone. Ninety-two clinically NPC patients were included in this study. The thyroid function tests were performed for all patients before and after radiation at regular intervals. Thyroid dose-constraint was defined as V40 ≤ 85%. The primary outcome in this study was subclinical HT. RESULTS: Median follow up was 34 months. Significant difference in the incidence of subclinical HT between the thyroid dose-constraint group and unrestricted group was observed (P = 0.023). The risk of subclinical HT in the thyroid dose-constraint group was lower than that in the unrestricted group (P = 0.022). Univariate and multivariate cox regression analysis indicated that thyroid dose-constraint was a protective effect of subclinical HT (HR = 0.408, 95% CI 0.184-0.904; HRadjusted = 0.361, 95% CI 0.155-0.841). CONCLUSION: V40 ≤ 85% can be used as an effective dose constraint in IMRT planning to prevent radiation-induced subclinical HT.

Associations of maternal pre-pregnancy BMI and gestational weight gain with the risks of adverse pregnancy outcomes in Chinese women with gestational diabetes mellitus.

BACKGROUND: Give the high background risk of adverse pregnancy outcomes (APOs), it is important to understand the associations of maternal pre-pregnancy body mass index (ppBMI), gestational weight gain (GWG) with APOs in women with gestational diabetes mellitus (GDM). We addressed the independent and joint associations of maternal ppBMI and GWG with APOs in Chinese women with GDM. METHODS: 764 GDM women with singleton delivery were studied and they were stratified into three weight groups by ppBMI (underweight, normal weight and overweight/obesity) following classification standards for Chinese adults and three GWG groups (inadequate, adequate, excessive GWG) by the 2009 Institute of Medicine guidelines, respectively. Univariate and multivariate logistic regression analyses were performed to estimate the odds ratios of APOs. RESULTS: Maternal overweight/obesity was associated with increased odds of pregnancy-induced hypertension [PIH, adjusted odds ratio (aOR): 2.828, 95% confidence interval (CI) 1.382-5.787], cesarean delivery (CS) (aOR 2.466, 95%CI 1.694-3.590), preterm delivery (aOR 2.466, 95%CI 1.233-4.854), LGA (aOR 1.664, 95%CI 1.120-2.472), macrosomia (aOR 2.682, 95%CI 1.511-4.760) and any pregnancy complication (aOR 2.766, 95%CI 1.840-4.158) compared with healthy weight. Inadequate GWG was less likely to develop PIH (aOR 0.215, 95%CI 0.055-0.835), CS (aOR 0.612, 95%CI 0.421-0.889) and any pregnancy complication (aOR 0.628, 95%CI 0.435-0.907), but had higher risk of preterm birth (aOR 2.261, 95%CI 1.089-4.692), while excessive GWG was more vulnerable to LGA (aOR 1.929, 95%CI 1.272-2.923), macrosomia (aOR 2.753, 95%CI 1.519-4.989) and any pregnancy complication (aOR 1.548, 95%CI 1.006-2.382) as compared to adequate GWG. Furthermore, compared to normal weight mothers with adequate GWG, obese mothers with excessive GWG had the highest risk of any pregnancy complication (aOR 3.064, 95%CI 1.636-5.739). CONCLUSIONS: Maternal overweight/obesity and GWG were associated with APOs in the already high-risk settings of GDM. Obese mothers with excessive GWG may confer the greatest risk of adverse outcomes. It was very helpful to reduce the burden of APOs and benefit GDM women by promoting a healthy pre-pregnancy BMI and GWG.

Blood lactate levels are associated with an increased risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: a real-world study.

Aim: To investigate the association between blood lactate levels and metabolic dysfunction-associated fatty liver disease (MAFLD) in type 2 diabetes mellitus (T2DM). Methods: 4628 Chinese T2DM patients were divided into quartiles according to blood lactate levels in this real-world study. Abdominal ultrasonography was used to diagnosis MAFLD. The associations of blood lactate levels and quartiles with MAFLD were analyzed by logistic regression. Results: There were a significantly increased trend in both MAFLD prevalence (28.9%, 36.5%, 43.5%, and 54.7%) and HOMA2-IR value (1.31(0.80-2.03), 1.44(0.87-2.20), 1.59(0.99-2.36), 1.82(1.15-2.59)) across the blood lactate quartiles in T2DM patients after adjustment for age, sex, diabetic duration, and metformin use (all p<0.001 for trend). After correcting for other confounding factors, not only increased blood lactate levels were obviously associated with MAFLD presence in the patients with (OR=1.378, 95%CI: 1.210-1.569, p<0.001) and without taking metformin (OR=1.181, 95%CI: 1.010-1.381, p=0.037), but also blood lactate quartiles were independently correlated to the increased risk of MAFLD in T2DM patients (p<0.001 for trend). Compared with the subjects in the lowest blood lactate quartiles, the risk of MAFLD increased to 1.436-, 1.473-, and 2.055-fold, respectively, in those from the second to the highest lactate quartiles. Conclusions: The blood lactate levels in T2DM subjects were independently associated with an increased risk of MAFLD, which was not affected by metformin-taking and might closely related to insulin resistance. Blood lactate levels might be used as a practical indicator for assessing the risk of MAFLD in T2DM patients.

High-normal serum bilirubin decreased the risk of lower limb atherosclerosis in type 2 diabetes: a real-world study.

BACKGROUND: Bilirubin has been found to protect against overt atherosclerotic diseases, but to date, few studies have investigated the effects of bilirubin especially within the normal range on lower limb atherosclerosis. Therefore, we aimed to assess the associations of bilirubin within normal limits including total bilirubin (TB), conjugated bilirubin (CB) and unconjugated bilirubin (UCB) with lower limb atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: 7284 T2DM patients with normal levels of serum bilirubin were included in this cross-sectional, real-world study. Patients were divided into quintiles by TB levels (< 8.7, 8.7-10.19, 10.20-11.99, 12-13.99, > 13.99 µmol/L). Lower limb ultrasonography was conducted to detect lower limb plaque and stenosis. The association between serum bilirubin and lower limb atherosclerosis was explored by multiple logistic regression. RESULTS: A remarkable decrease in the prevalence of lower limb plaque (77.5, 75.3, 70.7, 71.7 and 67.9%) and stenosis (21.1, 17.2, 13.3, 13.0 and 12.0%) was observed across the TB quintiles. Multivariable regression analysis showed that serum TB levels were negatively correlated with higher risks of lower limb plaque and stenosis, both as a continuous variable [OR (95%CI): 0.870 (0.784-0.964), p = 0.008 for plaque; and 0.835 (0.737-0.946), p = 0.005 for stenosis] and as categorized in quintiles (p = 0.015 and 0.016 for plaque and stenosis). Interestingly, serum CB levels were only negatively correlated with lower limb stenosis [OR (95%CI): 0.767 (0.685-0.858), p < 0.001], whereas serum UCB levels were only negatively associated with lower limb plaque [ OR (95%CI): 0.864 (0.784-0.952), p = 0.003] after a fully-adjusted analysis. Furthermore, serum CRP was significantly decreased across the TB quintiles and negatively associated with serum TB (r = -0.107, p < 0.001), CB (r = -0.054, p < 0.001), and UCB (r = -0.103, p < 0.001). CONCLUSIONS: High-normal serum bilirubin levels were independently and significantly related to reduced risks of lower limb atherosclerosis in T2DM patients. Furthermore, serum bilirubin levels including TB, CB and UCB were inversely correlated with CRP. These results suggested that higher-normal serum bilirubin may exhibit an anti-inflammatory and protective effect against lower limb atherosclerotic progression in T2DM subjects.

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes.

Purpose: The association between serum osteocalcin (OCN) levels and metabolic dysfunction-associated fatty liver disease (MAFLD) is still controversial. Moreover, few studies have explored their relationship in type 2 diabetes mellitus (T2DM) patients so far. The present study aimed to investigate the association of serum OCN levels with MAFLD in Chinese T2DM patients. Methods: This cross-sectional, real-world study included 1889 Chinese T2DM inpatients. MAFLD was diagnosed by abdominal ultrasonography. Participants were divided into four groups according to serum OCN quartiles, among which the clinical characteristics were compared. The association of serum OCN levels with the presence of MAFLD was also analyzed in subjects. Results: After controlling for sex, age, and diabetes duration, the prevalence of MAFLD significantly decreased across the serum OCN quartiles (55.3%, 52.0%, 48.6%, and 42.1% for the first, second, third, and fourth quartiles, respectively, P < 0.001 for trend). A fully adjusted multiple logistic regression analysis showed that serum OCN levels were independently and negatively associated with the presence of MAFLD in T2DM patients (odds ratio, 0.832; 95% confidence interval, 0.719-0.962; P = 0.013). Furthermore, there were significant decreases in HOMA-IR (P = 0.001 for trend) and C-reactive protein (P < 0.001 for trend) levels across the serum OCN quartiles after controlling for sex, age, and diabetes duration. Conclusion: Serum OCN levels were independently and negatively associated with the presence of MAFLD in Chinese T2DM patients, partially due to the improvement of insulin resistance and inflammation mediated by OCN. Serum OCN may be used as a biomarker to assess the risk of MAFLD in T2DM patients.

GA/HbA1c ratio is a simple and practical indicator to evaluate the risk of metabolic dysfunction-associated fatty liver disease in type 2 diabetes: an observational study.

BACKGROUND: It is still debatable whether glycated albumin/glycated hemoglobin A1C (GA/HbA1C) ratio is associated with metabolic dysfunction-associated fatty liver disease (MAFLD), and few studies have been conducted in type 2 diabetes mellitus (T2DM). Therefore, we aimed to investigate the association between GA/HbA1C ratio and MAFLD and to evaluate whether GA/HbA1C ratio can be used an indicator of MAFLD in Chinese patients with T2DM. METHODS: This cross-sectional study consisted of 7117 T2DM patients including 3296 men and 3821 women from real-world settings. Abdominal ultrasonography was performed to diagnose MAFLD. In addition to comparing the clinical characteristics among the GA/HbA1C ratio quartile groups, we also investigated the associations of GA/HbA1C ratio and quartiles with MAFLD in T2DM subjects. RESULTS: There was a significantly decreased trend in the MAFLD prevalence across the GA/HbA1C ratio quartiles (56.3%, 47.4%, 37.8%, and 35.6% for the first, second, third, and fourth quartile, respectively, P < 0.001 for trend) after adjusting for gender, age, and diabetes duration. Fully adjusted Binary logistic regression indicated that both GA/HbA1C ratio (OR: 0.575, 95% CI: 0.471 to 0.702, P < 0.001) and quartiles (P < 0.001 for trend) were inversely associated with the presence of MAFLD among T2DM patients. Additionally, HOMA2-IR values were clearly increased in the T2DM subjects with MAFLD compared with those without MAFLD (P < 0.001), and markedly increased from the highest to the lowest GA/HbA1C ratio quartile (P < 0.001 for trend). CONCLUSIONS: GA/HbA1C ratio is closely and negatively associated with MAFLD in T2DM subjects, which may attribute to that GA/HbA1C ratio reflects the degree of insulin resistance. GA/HbA1C ratio may act as a simple and practical indicator to evaluate the risk of MAFLD in T2DM.

Low-normal serum unconjugated bilirubin levels are associated with late but not early carotid atherosclerotic lesions in T2DM subjects.

Aims: We aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (<6.2, 6.2-7.9, 8.0-8.9, 9.0-10.9, and >10.9 µmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression. Results: The prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747-0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647-0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles. Conclusions: Serum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes.

Background: As an indicator of abdominal obesity, waist circumference (WC) varied with race and gender in diagnosing metabolic syndrome (MetS). Therefore, it is clinically important to find an alternative indicator of abdominal obesity independent of these factors to diagnose MetS. Our aims were to evaluate the association between waist-to-height ratio (WHtR) and MetS and further determine whether WHtR could be used as a simple and practical alternative to WC to diagnose MetS in patients with type 2 diabetes mellitus (T2DM). Methods: This cross-sectional, real-world study recruited 8488 hospitalized T2DM patients including 3719 women (43.8%) aged from 18 to 94 years and 4769 men (56.2%) aged from 18 to 91 years. A WHtR cut-off of 0.52 was used to diagnose MetS in both men and women T2DM patients based on our previous study. The association of WHtR with MetS in T2DM patients was analyzed by binary logistic regression. The consistency of two diagnostic criteria for MetS according to WC and WHtR was determined by Kappa test. Results: The prevalence of MetS according to WHtR was 79.4% in women and 68.6% in men T2DM patients, which was very close to the prevalence of MetS according to WC in both women (82.6%) and men (68.3%). The prevalence of MetS diagnosed by WC in both men and women with WHtR ≥ 0.52 was significantly higher than in those with WHtR < 0.52 after adjustment for age and duration of diabetes (89.2 vs. 38.7% for men; 92.8 vs. 57.4% for women; respectively, all p < 0.001). Binary logistic regression analysis displayed that after adjusting for confounding factors, WHtR was significantly associated with the presence of MetS in both men and women (men: OR = 4.821, 95% CI: 3.949-5.885; women: OR = 3.096, 95% CI: 2.484-3.860; respectively, all p < 0.001). Kappa test revealed that there was an excellent consistency between the diagnosis of MetS based on WC and on WHtR in T2DM patients (men: kappa value = 0.929, 95% CI: 0.918-0.940; women: kappa value = 0.874, 95% CI: 0.854-0.894; total: kappa value = 0.911, 95% CI: 0.901-0.921; respectively, all p < 0.001). Conclusion: WHtR is independently associated with the presence of MetS and can be used as a simple and practical alternative to WC to diagnose MetS regardless of gender in T2DM patients.

Serum iron is closely associated with metabolic dysfunction-associated fatty liver disease in type 2 diabetes: A real-world study.

Aims: There is still a debate about the relationship between serum iron and metabolic dysfunction-associated fatty liver disease (MAFLD). Furthermore, few relevant studies were conducted in type 2 diabetes mellitus (T2DM). Therefore, this study aimed to explore the association of serum iron levels with MAFLD in Chinese patients with T2DM. Methods: This cross-sectional, real-world study consisted of 1,467 Chinese T2DM patients. MAFLD was diagnosed by abdominal ultrasonography. Based on serum iron quartiles, the patients were classified into four groups. Clinical characteristics were compared among the four groups, and binary logistic analyses were used to assess the associations of serum iron levels and quartiles with the presence of MAFLD in T2DM. Results: After adjusting for gender, age, and diabetes duration, significantly higher prevalence of MAFLD was found in the second (45.7%), third (45.2%), and fourth (47.0%) serum iron quartiles than in the first quartiles (26.8%), with the highest MAFLD prevalence in the fourth quartile (p < 0.001 for trend). Moreover, increased HOMA2-IR (p = 0.003 for trend) and decreased HOMA2-S (p = 0.003 for trend) were observed across the serum iron quartiles. Fully adjusted binary logistic regression analyses indicated that both increased serum iron levels (OR: 1.725, 95% CI: 1.427 to 2.085, p < 0.001) and quartiles (p < 0.001 for trend) were still closely associated with the presence of MAFLD in T2DM patients even after controlling for multiple confounding factors. Conclusions: There is a positive correlation between the presence of MAFLD and serum iron levels in T2DM patients, which may be attributed to the close association between serum iron and insulin resistance. Serum iron levels may act as one of the indicators for evaluating the risk of MAFLD in T2DM individuals.

Albuminuria but not low eGFR is closely associated with atherosclerosis in patients with type 2 diabetes: an observational study.

BACKGROUND: There is still controversy regarding the associations of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Therefore, it is necessary to explore the correlation between them in T2DM patients. METHODS: We conducted a survey involving 2565 T2DM patients from a single center. The study cohort was classified into three groups based on the levels of albuminuria: normal UAE (UAE < 30 mg/24 h), moderate UAE (UAE between 30 and 299 mg/24 h) and high UAE (UAE ≥ 300 mg/24 h). Additionally, the patients were divided into three separate groups according to eGFR levels, including low eGFR (eGFR < 60 ml/min/1.73 m2), intermediate eGFR (eGFR 60-89 ml/min/1.73 m2) and normal eGFR (eGFR ≥ 90 ml/min/1.73 m2) groups. Atherosclerotic lesions were compared among the three UAE and eGFR groups. Regression analyses were used to assess the associations of atherosclerotic lesions with UAE and eGFR in T2DM. RESULTS: After controlling for age, sex and diabetes duration, the prevalence of atherosclerotic plaque and stenosis were significantly increased from the normal to high UAE groups (plaque: 72.2%, 78.6% and 87.3%, respectively, p = 0.016 for trend; stenosis: 14.0%, 25.5% and 37.3%, respectively, p < 0.001 for trend). Likewise, the values of carotid intima-media thickness (CIMT) and femoral intima-media thickness (FIMT) were also obviously increased from the normal to high UAE groups (CIMT: p < 0.001 for trend; FIMT: p = 0.001 for trend). Conversely, only the FIMT value was clearly increased from the low to normal eGFR groups (p = 0.001 for trend). Fully adjusted regression analyses revealed that UAE was closely associated with the presence of atherosclerotic plaque (OR 1.20, 95% CI 1.03-1.40, p = 0.020) and stenosis (OR 1.17, 95% CI 1.01-1.35, p = 0.036), and with the values of CIMT (ß 0.05, 95% CI 0.01-0.10, p = 0.029) and FIMT (ß 0.07, 95% CI 0.03-0.11, p = 0.001) in T2DM patients. However, there was no significant association between eGFR levels and atherosclerotic lesions in T2DM after adjustment for multiple confounding factors. CONCLUSIONS: Overall, albuminuria rather than low eGFR is closely associated with atherosclerotic lesions in T2DM patients. Albuminuria is an independent risk factor for carotid and femoral atherosclerotic lesions in T2DM. Therefore, albuminuria may be a potential early marker to predict the development of atherosclerosis in patients with T2DM.

Chaetocin attenuates atherosclerosis progression and inhibits vascular smooth muscle cell phenotype switching.

We aimed to explore the effect of chaetocin on atherosclerosis and its possible mechanism. In vitro, we observed that chaetocin treatment significantly inhibited the proliferation of VSMCs in concentration- and time-dependent manner. We also found that chaetocin suppressed the migration of VSMCs. Moreover, chaetocin treatment induced a contractile phenotype in VSMCs by increasing α-SMA and SM22α expression. In addition, chaetocin treatment attenuated the accumulation of H3K9me3 on VSMCs contractile gene promoters, which promoted the expression of α-SMA and SM22α. In vivo, chaetocin treatment decreased the H3K9me3 expression, diminished atherosclerotic plaque formation, and increased plaque stability by decreasing necrotic core area and lipid accumulation and increasing collagen content and contractile VSMC phenotype. We demonstrated a new function of chaetocin in inhibiting atherosclerosis progression and increasing plaque stability partly by inhibiting pathological phenotypic switching of VSMCs. These newly identified roles of chaetocin might provide a novel therapeutic target in atherosclerosis.

Serum Retinol-Binding Protein Levels Are Associated with Nonalcoholic Fatty Liver Disease in Chinese Patients with Type 2 Diabetes Mellitus: A Real-World Study.

BACKGROUND: The association of serum retinol-binding protein (RBP) levels with nonalcoholic fatty liver disease (NAFLD) remains controversial. Furthermore, few studies have investigated their relationship in type 2 diabetes mellitus (T2DM) patients. Therefore, the aim of the present study was to explore the association between serum RBP levels and NAFLD in Chinese inpatients with T2DM. METHODS: This cross-sectional, real-world study included 2,263 Chinese T2DM inpatients. NAFLD was diagnosed by abdominal ultrasonography. The subjects were divided into four groups based on RBP quartiles, and clinical characteristics were compared among the four groups. The associations of both RBP levels and quartiles with the presence of NAFLD were also analyzed. RESULTS: After adjustment for sex, age, and diabetes duration, there was a significant increase in the prevalence of NAFLD from the lowest to the highest RBP quartiles (30.4%, 40.0%, 42.4%, and 44.7% for the first, second, third, and fourth quartiles, respectively, P<0.001 for trend). Fully adjusted multiple logistic regression analysis revealed that both increased RBP levels (odds ratio, 1.155; 95% confidence interval, 1.012 to 1.318; P=0.033) and quartiles (P=0.014 for trend) were independently associated with the presence of NAFLD in T2DM patients. CONCLUSION: Increased serum RBP levels were independently associated with the presence of NAFLD in Chinese T2DM inpatients. Serum RBP levels may be used as one of the indicators to assess the risk of NAFLD in T2DM patients.

Waist-to-height ratio has a stronger association with cardiovascular risks than waist circumference, waist-hip ratio and body mass index in type 2 diabetes.

AIMS: To compare the associations between four anthropometric indices including waist-to-height ratio (WHtR), waist circumference (WC), waist-hip-ratio (WHR) and body mass index (BMI) and cardio-cerebrovascular events (CCBVEs) in Chinese T2DM patients. METHODS: The associations of four anthropometric measures with CCBVEs and metabolic syndrome (MetS) were compared by multiple regression model in 3108 T2DM patients. CCBVEs was defined as a history of myocardial infarction, angina, angioplasty, coronary artery bypass surgery, transient ischemic attack, ischemic or hemorrhagic stroke. RESULTS: After controlling for age, sex and diabetes duration, the prevalence of CCBVEs and MetS significantly increased across the WHtR, WC, WHR and BMI quartiles in T2DM patients, respectively. However, when controlling for these four anthropometric measurements together, although four anthropometric measures were closely associated with MetS prevalence, only WHtR quartile was significantly associated with CCBVEs prevalence (6.5%, 13.8%, 16.9% and 21.3%, p < 0.001 for trend). After adjusting for multiple confounders including four anthropometric parameters, a regression analysis revealed that only WHtR was independently and positively associated with the presence of CCBVEs (p = 0.029). CONCLUSIONS: Compared with WC, WHR and BMI, WHtR have a stronger association with CCBVEs in T2DM subjects. WHtR maybe a better indicator than other anthropometric measurements for evaluating cardiovascular risks in T2DM.

Urine Uric Acid Excretion Levels are Positively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Patients without Chronic Kidney Disease.

PURPOSE: We aimed to investigate whether urine uric acid excretion (UUAE) levels are associated with obesity and abdominal obesity in patients with type 2 diabetes (T2D). METHODS: There were 2785 type 2 diabetic patients in this cross-sectional study. Obesity was defined as BMI ≥ 25 kg/m2, and abdominal obesity was defined as waist circumference (WC) ≥90 cm for men and WC ≥ 80 cm for women based on World Health Organization (WHO) recommendations for Asians. Chronic kidney disease (CKD) was defined as the estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and/or urinary albumin excretion (UAE) ≥300 mg/24h. 24-h UUAE was determined enzymatically using a single 24-hour urine collection. All the subjects were stratified into quartiles based on UUAE levels. Both obesity and abdominal obesity were compared among the UUAE quartile groups, respectively. Furthermore, the associations of UUAE with obesity and abdominal obesity were analyzed in both CKD and non-CKD patients, respectively. RESULTS: There was an obvious increased trend in both obesity prevalence (36.2%, 41.5%, 46.3%, and 63.4%, respectively, p < 0.001 for trend) and abdominal obesity prevalence (58.1%, 61.2%, 64.7%, and 75.8%, respectively, p < 0.001 for trend) in patients with T2D across the UUAE quartiles after controlling for age, sex and diabetes duration. Multiple logistic regression analyses revealed independent associations between UUAE quartiles and obesity (p < 0.001) and abdominal obesity (p < 0.001) in all patients. However, UUAE was significantly associated with obesity and abdominal obesity only in the T2D patients without CKD (p < 0.001 in model 1, model 2, model 3 and model 4, respectively). CONCLUSION: Increased UUAE levels were significantly associated with the presence of obesity, especially abdominal obesity in T2D patients without CKD.

Serum free triiodothyronine is inversely associated with diabetic peripheral neuropathy but not with carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes.

BACKGROUND: The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN)/carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes are still unclear. The purpose of our study was to explore the relations of FT3 to DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function. METHODS: 2477 euthyroid inpatients with type 2 diabetes were recruited and they were stratified into quartiles by FT3 levels in this cross-sectional study. Peripheral neuropathy was assessed by neurological symptoms and signs as well as nerve conduction velocity tests. Carotid atherosclerotic lesions, including carotid intima-media thickness, plaque and stenosis, were evaluated by Doppler ultrasound. RESULTS: The prevalence of DPN in type 2 diabetic patients exhibited the significant decrease across the FT3 quartiles (23.5%, 20.9%, 18.8%, and 11.2%, respectively, p < 0.001). Multiple logistical regression analysis also revealed that FT3 quartiles were significantly and inversely associated with DPN. Compared with the subjects in the highest FT3 quartile, the adjusted odds ratios (95% confidence interval) of DPN from the first to third FT3 quartile were successively 2.338 (1.407-3.884), 1.903 (1.134-3.194) and 1.598 (0.960-1.125). The patients with DPN had significantly higher prevalence of carotid atherosclerotic lesions compared with non-DPN patients. However, no statistical association was observed between FT3 quartiles and carotid atherosclerotic lesions after adjusting for confounder factors. CONCLUSIONS: Lower FT3 within the normal range was independently associated with DPN, but not with carotid atherosclerotic lesions in Chinese euthyroid inpatients with type 2 diabetes.

Deletion of Fam172a accelerates advanced atherosclerosis and induces plaque instability.

BACKGROUND AND AIMS: Vascular smooth muscle cells (VSMCs) play a critical role in atherosclerosis. The family with sequence similarity 172, member A (FAM172A) is a novel protein and its role in atherosclerosis has not been explored so far. Therefore, our aim is to investigate whether FAM172A affects atheroprogression through VSMCs and its possible mechanism. METHODS: Fam172a-/- mice were generated using CRISPR/Cas9 technology. Fam172a-/- and Apoe-/- double knockout (Fam172a-/-/Apoe-/-) mice and their littermates (Fam172a+/+/Apoe-/-) were fed with a Western diet for 18 weeks to induce advanced atherosclerotic lesions. The role and mechanism of Fam172a in phenotypic switching, proliferation and migration of VSMCs were investigated through in vivo and in vitro experiments. RESULTS: Compared with Fam172a+/+/Apoe-/- mice, Fam172a-/-/Apoe-/- mice showed increased atherosclerotic lesion size and plaque instability such as increased necrotic core area and decreased fiber deposition. Additionally, knockout of Fam172a promoted expression of CD68 and KLF4 and decreased expression of α-SMA and SM22α in atherosclerotic lesions. Furthermore, overexpression of Fam172a promoted Movas cells proliferation and migration, increased expression of α-SMA and SM22α and decreased expression of KLF4. Meanwhile, knockdown of Fam172a in Movas cells and deletion of Fam172a in VSMCs from Fam172a-/-/Apoe-/- mice showed opposite phenotypes. Similar phenotypes were also observed in human aortic smooth muscle cells. CONCLUSIONS: Our results provide the first direct evidence that Fam172a has a protective role in advanced atherosclerosis by increasing atherosclerotic plaque stability and inhibiting transition of VSMCs from contractile to synthetic phenotype, which may be through KLF4-dependent pathway.

Lutein attenuates angiotensin II- induced cardiac remodeling by inhibiting AP-1/IL-11 signaling.

RATIONALE: Oxidative stress plays a critical role in the development of cardiac remodeling and heart failure. Lutein, the predominant nonvitamin A carotenoid, has been shown to have profound effects on oxidative stress. However, the effect of lutein on angiotensin II (Ang II)-induced cardiac remodeling and heart failure remains unknown. OBJECTIVE: The aim of this study was to determine whether lutein is involved in cardiac remodeling and to elucidate the underlying molecular mechanisms. METHODS AND RESULTS: In vitro experiments with isolated neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) revealed that lutein significantly attenuated Ang II-induced collagen expression in CFs, and cardiomyocyte hypertrophy. The Ang II-induced increases in superoxide generation, inflammation and apoptosis in cultured CFs were strikingly prevented by lutein. In vivo, fibrosis, hypertrophic cardiomyocyte and superoxide generation were analyzed, and lutein was demonstrated to confer resistance to Ang II-induced cardiac remodeling in mice. Mechanistically, RNA sequencing revealed that interleukin-11 (IL-11) expression was significantly upregulated in mouse hearts in response to Ang II infusion and was significantly suppressed in the hearts of lutein-treated mice. Furthermore, IL-11 overexpression blocked the effects of lutein on fibrosis and oxidative stress in CFs and impaired the protective effect of lutein on cardiac remodeling. Notably, we discovered that lutein could reduce Ang II-induced IL-11 expression, at least partly through the regulation of activator protein (AP)-1 expression and activity. CONCLUSIONS: Lutein has potential as a treatment for cardiac remodeling and heart failure via the suppression of IL-11 expression.

Insulin Therapy Is Associated With an Increased Risk of Carotid Plaque in Type 2 Diabetes: A Real-World Study.

Background: Controversies concerning the association between insulin therapy and atherosclerotic lesions in type 2 diabetes mellitus (T2DM) remain to exist. The purpose of this study was to investigate whether insulin therapy in T2DM patients is linked with the increased risk of carotid atherosclerosis in real-world settings. Methods: We retrospectively enrolled 2,356 hospitalized patients with T2DM, including 1,716 subjects receiving insulin therapy and 640 subjects without receiving insulin therapy. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid plaque and carotid stenosis were assessed by Doppler ultrasonography and were compared between T2DM patients treated with and without insulin. Results: After adjusting for age and duration of diabetes, there was a significant increase in the prevalence of carotid plaque in both men (52.0 vs. 41.7%, p = 0.007) and women (49.6 vs. 39.7%, p = 0.003) receiving insulin therapy than in those without receiving insulin therapy. After further controlling for other confounding factors, compared with the patients without receiving insulin therapy, the risk of carotid plaque was still significantly increased not only in women treated with insulin (OR: 1.810; 95% CI: 1.155-2.837, p = 0.010), but also in men treated with insulin (OR: 1.867; 95% CI: 1.307-2.666; p = 0.001). Additionally, HOMA2-B% was higher in both women and men without receiving insulin therapy compared with those receiving insulin therapy (p < 0.001 in both men and women), but HOMA-IR was significantly higher in patients treated with insulin than in those without receiving insulin therapy (p < 0.001 in both men and women). Conclusions: Insulin therapy is associated with markedly increased risk of carotid atherosclerotic lesions in type 2 diabetes, which partly attribute to the more serious insulin resistance in T2DM patients receiving insulin therapy.

Maternal Pre-Pregnancy Obesity Combined With Abnormal Glucose Metabolism Further Increases Adverse Pregnancy Outcomes in Chinese Pregnant Women.

Aims: Our aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes. Methods: A total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups. Results: Compared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286-7.156]; 1.993 [1.171-3.393]; 8.495 [4.982-14.485]), preeclampsia (2.649 [1.224-5.735]; 2.129 [1.128-4.017]; 4.643 [2.217-9.727]), cesarean delivery (1.589 [1.212-2.083]; 1.328 [1.095-1.611]; 2.627 [1.908-3.617]), preterm delivery (1.899 [1.205-2.993]; 1.358 [0.937-1.968]; 2.301 [1.423-3.720]), macrosomia (2.449 [1.517-3.954]; 1.966 [1.356-2.851]; 4.576 [2.895-7.233]), and total adverse maternal outcomes (1.762 [1.331-2.332]; 1.365 [1.122-1.659]; 3.228 [2.272-4.587]) and neonatal outcomes (1.951 [1.361-2.798]; 1.547 [1.170-2.046]; 3.557 [2.471-5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone. Conclusions: Maternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

Effects of Maternal Subclinical Hypothyroidism in Early Pregnancy Diagnosed by Different Criteria on Adverse Perinatal Outcomes in Chinese Women With Negative TPOAb.

Aims: To compare the effects of maternal subclinical hypothyroidism (SCH) diagnosed by the 2011 or 2017 "Guidelines of the American Thyroid Association (ATA) for the diagnosis and management of thyroid disease during pregnancy and the postpartum" during the first trimester on adverse pregnancy outcomes in thyroid peroxidase antibody (TPOAb)-negative pregnant women. Methods: There were 1,556 Chinese singleton pregnant women with negative TPOAb diagnosed with either SCH or euthyroidism who were investigated, and the prevalence and risk of obstetric outcomes were compared between the two groups using 2011 and 2017 ATA standards, respectively. The effects of a mildly elevated thyroid-stimulating hormone (TSH) concentration on adverse pregnancy outcomes were evaluated by binary logistic regression. Results: Maternal SCH identified by the 2011 ATA guidelines correlated with higher rates and risks of pregnancy-induced hypertension (PIH), preeclampsia, and low-birth-weight infants, while maternal SCH diagnosed by the 2017 ATA guidelines was more likely to develop PIH, preeclampsia, cesarean delivery, preterm delivery, placenta previa, and total adverse maternal and neonatal outcomes. Moreover, a mildly elevated TSH level was significantly associated with PIH after adjustment for confounding factors. Conclusions: Compared with the 2011 ATA guidelines, the 2017 ATA guidelines could be more applicable to Chinese pregnant women to screen the effects of SCH on the majority of adverse pregnancy outcomes.