Search

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 ( 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 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 p p 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.

Yu-Jie Wang,1,&ast; Chun-Hua Jin,2,&ast; Jiang-Feng Ke,1 Jun-Wei Wang,1 Yi-Lin Ma,1 Jun-Xi Lu,1 Mei-Fang Li,3 Lian-Xi Li1 1Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, People’s Republic of China; 2Department of Endocrinology and Metabolism, Shanghai Songjiang District Central Hospital, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (Preparatory Stage), Shanghai, People’s Republic of China; 3Department of Emergency, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei-Fang Li, Department of Emergency, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 18930170426, Email 15821955054@126.com Lian-Xi Li, Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86 21 64369181x58337, Email lilx@sjtu.edu.cnPurpose: 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.Keywords: diabetes mellitus, type 2, metabolic dysfunction-associated fatty liver disease, osteocalcin, insulin resistance, inflammation

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 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.

Fengjing Liu, Si Chen, Weijing Zhao, Mingyun Chen, Jiangfeng Ke, Zhihui Zhang, Junxi Lu, Lianxi Li Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, People’s Republic of ChinaCorrespondence: Lianxi LiDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, People’s Republic of ChinaTel +86 21 64369181x58337Email lilx@sjtu.edu.cnPurpose: 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.Keywords: urine uric acid excretion, type 2 diabetes, obesity, abdominal obesity, chronic kidney disease

Background: The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN) / carotid atherosclerotic lesions in type 2 diabetic patients with normal thyroid function is still unclear. The purpose of our study was to explore the relationships of FT3 with DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function.Methods: A total of 2477 type 2 diabetes inpatients with euthyroid function were recruited in this cross-sectional study, and they were stratified into quartiles by FT3 levels. 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: After adjusting for potential confounders, there was a significant decrease in the prevalence of DPN in the patients with type 2 diabetes across the FT3 quartiles (23.5%, 20.9%, 18.9%, and 11.2%, respectively, p < 0.001). Logistical regression analysis further 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 in 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 plaques (55.8%) and carotid stenosis (1.3%) than non-DPN patients (44.8%; 0.5%). However, no statistical association was observed between FT3 quartiles and carotid atherosclerotic lesions.Conclusions: Lower FT3 within the normal range was independently associated with DPN, but not with carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function.

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 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.

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 2), 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 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.

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.

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

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.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.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).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.

Background To investigate the prevalence and clinical characteristics of hypertension (HTN) and metabolic syndrome (MetS) in newly diagnosed diabetes with ketosis-onset. Methods A cross-sectional study was adopted in 734 newly diagnosed diabetics including 83 type 1 diabetics with positive islet-associated autoantibodies, 279 ketosis-onset diabetics without islet-associated autoantibodies and 372 non-ketotic type 2 diabetics. The clinical characteristics of HTN and MetS were compared across the three groups, and the risk factors of them were appraised in each group. Results The prevalence of HTN and MetS were substantially higher in the ketosis-onset diabetics (34.4% for HTN and 58.8% for MetS) than in the type 1 diabetics (15.7% for HTN, P = 0.004; 25.3% for MetS, P

Aims To compare the features of urine uric acid excretion (UUAE) between type 1 and type 2 diabetes mellitus (T1DM and T2DM). Methods This observational study was carried out in 234 T1DM and 2898 T2DM subjects. UUAE levels were determined enzymatically from a single 24-h urine collection. The clinical features of UUAE were compared between T1DM and T2DM. The factors influencing UUAE levels were also been analyzed in both T1DM and T2DM subjects, respectively. Results The levels of UUAE were significantly higher only in the T2DM subjects without chronic kidney disease (CKD) [2887 (2290–3656) μmol/24h] than in the T1DM subjects without CKD [2562 (2053–3253), p Conclusions Despite some similarities, the clinical characteristics of UUAE are significantly different between T1DM and T2DM.

To investigate whether hyper-uricaemia and decreased urinary uric acid excretion (UUAE) are associated with increased risk of chronic kidney disease (CKD), and whether the coexistence of hyper-uricaemia and low UUAE further increases CKD risk in type 2 diabetes mellitus (T2DM).In this cross-sectional study based on serum uric acid (SUA) and UUAE levels, 2846 T2DM inpatients were divided into those with normal SUA and UUAE (group 1), normal SUA and low UUAE (group 2), hyper-uricaemia and normal UUAE (group 3), and hyper-uricaemia and low UUAE (group 4). Hyper-uricaemia was defined as SUA levels ≥ 420 μmol/L in men and ≥ 360 μmol/L in women. Low UUAE was defined as levels below the first UUAE quintiles ( 2161 μmol/24 h in men, 1977 μmol/24 h in women).There were trends for significantly increased prevalences of CKD (4.3%, 12.6%, 18.3%, 47.8%; P 0.001), albuminuria (20.2%, 26.4%, 36.9%, 54.9%; P 0.001) and macroalbuminuria (3.3%, 10.1%, 10.7%, 31.9%; P 0.001) from groups 1 to 4, respectively. After controlling for multiple confounding factors, prevalences of CKD (P 0.001) and urinary albumin levels (P = 0.013) showed significantly increasing trends, whereas eGFR levels were markedly decreased from groups 1 to 4 (P 0.001).Hyper-uricaemia and low UUAE levels are closely associated with presence of CKD, and the concomitant presence of hyper-uricaemia and decreased UUAE levels further increased CKD risk in T2DM. Thus, the combined consideration of SUA and UUAE levels may help to identify those T2DM patients at higher CKD risk.

Aims: To investigate whether hyperuricemia and decreased urine uric acid excretion (UUAE) are associated with increased risk of chronic kidney disease (CKD), and whether the coexistence of hyperuricemia and low UUAE further increases the CKD risk in type 2 diabetes mellitus (T2DM). Methods: Based on serum uric acid (SUA) and UUAE levels, 2 846 T2DM inpatients were divided into patients with SUA and UUAE (group 1), normal SUA and low UUAE (group 2), hyperuricemia and normal UUAE (group 3), and hyperuricemia and low UUAE (group 4). Hyperuricemia was defined as SUA levels ≥ 420 μmol/L in men and ≥ 360 μmol/L in women. Low UUAE was defined as UUAE levels < the first UUAE quintiles (< 2161 μmol/24h in men and 1977 μmol/24h in women). Results: There was significantly increased trend of the prevalence of CKD (4.3%, 12.6%, 18.3% and 47.8%, p< 0.001), albuminuria (20.2%, 26.4%, 36.9% and 54.9%, p< 0.001), and macroalbuminuria (3.3%, 10.1%, 10.7% and 31.9%, p< 0.001) from group 1 to 4. After controlling for multiple confounding factors, the prevalence of CKD (p