High-normal unconjugated bilirubin is associated with decreased risk of chronic kidney disease in type 2 diabetes: A real-world study.

OBJECTIVE: To investigate the association between serum unconjugated bilirubin (UCB) within normal limits and chronic kidney disease (CKD) in T2DM patients. METHOD: This cross-sectional, real-world study was performed in 8661 hospitalised T2DM patients. The subjects were stratified into quintiles based on serum UCB levels. The clinical characteristics and CKD prevalence were compared among the UCB quantile groups. The associations of serum UCB levels and quintiles with CKD were also analysed by binary logistic regression. RESULTS: After controlling for age, sex, and diabetes duration (DD), the CKD prevalence (20.4%, 12.2%, 10.6%, 8.3%, and 6.4% for the first, second, third, fourth, and fifth quintiles, respectively, p < 0.001 for trend) was significantly decreased across the serum UCB quintiles. The fully adjusted regression model showed negative associations of serum UCB levels (OR: 0.660, 95% CI: 0.585-0.744; p < 0.001 for trend) and quintiles (p < 0.001) with the presence of CKD. Compared with the subjects in the lowest UCB quintile, the risk of CKD decreased by 36.2%, 54.3%, 53.8%, and 62.1%, respectively, in those from the second to the highest UCB quintile. Additionally, C-reactive protein (CRP) levels were significantly higher in the subjects with CKD than in those without CKD (p < 0.001), and significantly decreased across the UCB quintiles (p < 0.001 for trend). CONCLUSIONS: Serum UCB levels within the normal range were significantly and negatively linked to CKD in T2DM patients. High-normal UCB may be an independent protective factor for CKD by its antioxidant and the following anti-inflammatory activities through its signalling activity, which was indicated by clearly decreased CRP levels across the UCB quintiles.

The coexistence of hypercalcemia, osteoporosis and thymic enlargement in graves' disease: a case report.

BACKGROUND: Hyperthyroidism-induced hypercalcemia has been reported previously, but hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement in patients with hyperthyroidism is quite rare. We report the coexistence of hypercalcemia, osteoporosis and thymic enlargement in a patient with Graves' disease. CASE PRESENTATION: A 22-year-old female was diagnosed as Graves' disease with obviously elevated serum calcium and reduced parathyroid hormone levels. Dual-energy x-ray absorptiometry and chest enhanced computer tomography (CT) revealed severe osteoporosis and a significant enlargement of thymus. After the successful control of hyperthyroidism with methimazole, hypercalcemia was corrected, bone mineral density was improved and thymus also shrank obviously. CONCLUSION: This is a very rare case of hypercalcemia accompanied by severe osteoporosis and significant thymic enlargement induced by Graves' disease. In clinical practice, examination of thymus and bone density should be considered when a patient with Graves' disease was present with hypercalcemia.

The combination of nonthyroidal illness syndrome and renal dysfunction further increases mortality risk in patients with acute myocardial infarction: a prospective cohort study.

BACKGROUND: Both nonthyroidal illness syndrome and renal dysfunction are associated with increased mortality risk in acute myocardial infarction (AMI). However, it is unclear whether combined NTIS and renal dysfunction further increase mortality risk. Therefore, our aim is to investigate whether combined NTIS and renal dysfunction further increases mortality risk in patients with acute myocardial infarction (AMI). METHODS: A total of 1295 inpatients with AMI were divided into normal group (n = 692), NTIS group (n = 139), renal dysfunction group (n = 304), and combined NTIS and renal dysfunction group (n = 160). Heart function, in-hospital, all-cause and cardiovascular mortality were compared among the four groups. RESULTS: After adjustment for age and sex, left ventricular ejection fraction was significantly lower in the combined group (48 ± 11%) than in the NTIS group (52 ± 10%, P = 0.017), the renal dysfunction group (52 ± 10%, P = 0.001) and the normal group (56 ± 8%, P < 0.001). After controlling for confounding factors, compared with the normal group, the NTIS and the renal dysfunction group represented higher risks of in-hospital mortality (OR: 3.643, P = 0.028; OR:3.135, P = 0.042, respectively), all-cause mortality (HR: 2.138, P = 0.007; HR: 2.050, P = 0.003, respectively), and cardiovascular mortality (HR:2.134, P = 0.042; HR:2.237, P = 0.010, respectively). Compared to those in the NTIS and the renal dysfunction group, the patients in the combined group showed a further increased risk for in-hospital mortality (OR:2.916, P = 0.039; OR:2.487, P = 0.036, respectively), all-cause mortality (HR: 1.939, P = 0.015; HR: 2.020, P = 0.002, respectively) and cardiovascular mortality (HR:2.420, P = 0.010; HR:2.303, P = 0.002, respectively). CONCLUSIONS: Both NTIS and renal dysfunction increase short-term in-hospital mortality, and long-term all-cause and cardiovascular mortality risk in patients with AMI. Furthermore, the coexistence of NTIS and renal dysfunction presents further increased mortality risk in AMI patients.

The coexistence of carotid and lower extremity atherosclerosis further increases cardio-cerebrovascular risk in type 2 diabetes.

BACKGROUND: Both carotid and lower limb atherosclerosis are associated with increased cardiovascular and cerebrovascular risks. However, it is still unclear whether the concomitant presence of carotid and lower extremity atherosclerosis further increases the cardiovascular and cerebrovascular risks. Therefore, our aim is to investigate whether the coexistence of carotid and lower extremity atherosclerosis was associated with higher cardiovascular and cerebrovascular risks in patients with type 2 diabetes. METHODS: This cross-sectional study was performed in 2830 hospitalized patients with type 2 diabetes. Based on carotid and lower limb Doppler ultrasound results, the patients were divided into three groups including 711 subjects without atherosclerosis, 999 subjects with either carotid or lower limb atherosclerosis, and 1120 subjects with both carotid and lower limb atherosclerosis. And we compared the clinical characteristics and prevalence of both cardio-cerebrovascular events (CCBVEs) and self-reported cardio- cerebrovascular diseases (CCBVDs) among the three groups. RESULTS: After adjusting for age, sex, and duration of diabetes, there were significant increases in the prevalence of both CCBVEs (3.8 vs. 11.8 vs. 26.4 %, p < 0.001 for trend) and self-reported CCBVDs (6.9 vs. 19.9 vs. 36.5 %, p < 0.001 for trend) across the three groups (diabetics without atherosclerosis, diabetics with either carotid or lower limb atherosclerosis, and diabetics with both carotid and lower extremity atherosclerosis). A fully adjusted logistic regression analysis also revealed that compared with those without atherosclerosis, those with either carotid or lower limb atherosclerosis had higher risk of CCBVEs (OR 1.724, 95 % CI 1.001-2.966) and self-reported CCBVDs (OR 1.705, 95 % CI 1.115-2.605), and those with concomitant presence of carotid and lower extremity atherosclerosis had the highest risk of CCBVEs (OR 2.869, 95 % CI 1.660-4.960) and self-reported CCBVDs (2.147, 95 % CI 1.388-3.320)(p < 0.001 for trend in CCBVEs and p = 0.002 for trend in CCBVDs, respectively). CONCLUSIONS: Either carotid or lower limb atherosclerosis was obviously related to increased cardio-cerebrovascular risk in type 2 diabetes. The concomitant presence of carotid and lower extremity atherosclerosis further increased cardio-cerebrovascular risk in patients with type 2 diabetes. The combined application of carotid and lower extremity ultrasonography may help identify type 2 diabetics with higher cardio-cerebrovascular risk.

Decreased urine uric acid excretion is an independent risk factor for chronic kidney disease but not for carotid atherosclerosis in hospital-based patients with type 2 diabetes: a cross-sectional study.

BACKGROUND: The associations between urine uric acid excretion (UUAE) and chronic kidney disease (CKD)/atherosclerosis have not been investigated. Our aims were to investigate the relationships between UUAE and CKD and carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. METHODS: This was a cross-sectional study that was conducted with 2627 Chinese inpatients with type 2 diabetes. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartiles according to their UUAE levels. Carotid atherosclerotic lesions, including carotid intima-media thickness (CIMT), plaque and stenosis, were assessed by Doppler ultrasound. Both CKD and carotid atherosclerotic lesions were compared between the UUAE quartile groups. RESULTS: After adjustment for confounding factors, there was a significant decrease in the prevalence of CKD in the patients with type 2 diabetes across the UUAE quartiles (16.9%, 8.5%, 5.9%, and 4.9%; p < 0.001). Multiple logistic regression analyses revealed that the UUAE quartiles were significantly and inversely associated with the presence of CKD (p < 0.001). Compared with the diabetics in the highest UUAE quartile, those in the lowest quartile exhibited a nearly 4.2-fold increase in the risk of CKD (95% CI: 2.272-7.568; p < 0.001). The CIMT value (0.91 ± 0.22 mm for the diabetics with CKD and 0.82 ± 0.20 mm for the diabetics without CKD, p = 0.001) and the prevalence of carotid plaques (62.1% for the diabetics with CKD and 41.8% for the diabetics without CKD, p = 0.025) were significantly higher in the diabetics with CKD than in those without CKD. However, there was no obvious difference in carotid atherosclerotic lesions across the UUAE quartiles after controlling for the confounding factors. CONCLUSIONS: Decreased UUAE was closely associated with the presence of CKD but not with carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggest that UUAE is an independent risk factor for CKD in type 2 diabetes. In selected populations, such as patient with type 2 diabetes, the role of uric acid in atherosclerosis might be the result of other concomitant atherosclerotic risk factors, such as CKD.

Localized subacute thyroiditis presenting as a painful hot nodule.

BACKGROUND: A diagnosis of subacute thyroiditis is readily considered when patients present with a particular set of typical clinical characteristics. Subacute thyroiditis sometimes presents as a solitary cold nodule; however, the presence of a hot nodule in patients with subacute thyroiditis is exceedingly rare. CASE PRESENTATION: Here, the case of a 57-year-old woman complaining of pain in the left neck and fatigue for two weeks is presented. Physical examination revealed a painful and tender nodule with a diameter of approximately 1.5 cm in the left neck, although all laboratory tests, including white blood cell count, neutrophil percentage, erythrocyte sedimentation rate (ESR), thyroid function, and thyroglobin levels, were normal. A neck ultrasound revealed a hypoechoic mass (1.5 × 0.8 cm) in the left thyroid, and thyroid scintigraphy of the left thyroid with Technetium-99 m (99 m-Tc) demonstrated a focal accumulation of radiotracer. Furthermore, fine-needle aspiration biopsy from the nodule revealed the presence of multinuclear giant cells. The patient was well; there was no cervical mass detected upon palpation following two months of prednisone treatment, and follow-up ultrasound screening and scintigraphy demonstrated the disappearance of the nodule. CONCLUSION: This case, presenting with a localized painful hot nodule, normal thyroid function, normal ESR, and normal serum thyroglobulin levels, is a rare case of subacute thyroiditis, which should be considered during differential diagnosis.

Serum Magnesium Levels Are Negatively Associated with Obesity and Abdominal Obesity in Type 2 Diabetes Mellitus: A Real-World Study.

Background: There remains controversy over the relationship between serum magnesium levels and obesity in type 2 diabetes mellitus (T2DM). Therefore, the aim of this study was to assess whether there is any association of serum magnesium levels with obesity and abdominal obesity in T2DM. Methods: This cross-sectional, real-world study was conducted in 8,010 patients with T2DM, which were stratified into quintiles according to serum magnesium levels. The clinical characteristics and the prevalence of obesity and abdominal obesity were compared across serum magnesium quintiles in T2DM. Regression analyses were used to evaluate the relationship of serum magnesium with obesity and abdominal obesity in T2DM (clinical trial registration number: ChiCTR1800015893). Results: After adjustment for age, sex, and duration of diabetes, the prevalence of obesity and abdominal obesity was significantly declined across magnesium quintiles (obesity: 51.3%, 50.8%, 48.9%, 45.3%, and 43.8%, respectively, P<0.001 for trend; abdominal obesity: 71.5%, 70.5%, 68.2%, 66.4%, and 64.5%, respectively, P=0.001 for trend). After controlling for confounders, there were clearly negative associations of serum magnesium levels and quintiles with obesity and abdominal obesity in T2DM. Moreover, C-reactive protein partly mediates the effect of serum magnesium on obesity and abdominal obesity (P=0.016 and P=0.004, respectively). Conclusion: The significantly negative relationship between serum magnesium and the risk of obesity and abdominal obesity was observed in T2DM. Furthermore, the independently negative association of serum magnesium with obesity may be explained by its anti-inflammatory functions. Serum magnesium levels may be applied to assess the risk of obesity and abdominal obesity in T2DM.

Prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The features of carotid atherosclerosis in ketosis-onset diabetes have not been investigated. Our aim was to evaluate the prevalence and clinical characteristics of carotid atherosclerosis in newly diagnosed Chinese diabetic patients with ketosis but without islet-associated autoantibodies. METHODS: In total, 423 newly diagnosed Chinese patients with diabetes including 208 ketosis-onset diabetics without islet-associated autoantibodies, 215 non-ketotic type 2 diabetics and 79 control subjects without diabetes were studied. Carotid atherosclerosis was defined as the presence of atherosclerotic plaques in any of the carotid vessel segments. Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on Doppler ultrasound examination. The clinical features of carotid atherosclerotic lesions were analysed, and the risk factors associated with carotid atherosclerosis were evaluated using binary logistic regression in patients with diabetes. RESULTS: The prevalence of carotid atherosclerosis was significantly higher in the ketosis-onset diabetic group (30.80%) than in the control group (15.2%, p=0.020) after adjusting for age- and sex-related differences, but no significant difference was observed in comparison to the non-ketotic diabetic group (35.8%, p=0.487). The mean CIMT of the ketosis-onset diabetics (0.70±0.20 mm) was markedly higher than that of the control subjects (0.57±0.08 mm, p<0.001), but no significant difference was found compared with the non-ketotic type 2 diabetics (0.73±0.19 mm, p=0.582) after controlling for differences in age and sex. In both the ketosis-onset and the non-ketotic diabetes, the prevalence of carotid atherosclerosis was markedly increased with age (both p<0.001) after controlling for sex, but no sex difference was observed (p=0.479 and p=0.707, respectively) after controlling for age. In the ketosis-onset diabetics, the presence of carotid atherosclerosis was significantly associated with age, hypertension, low-density lipoprotein cholesterol and mean CIMT. CONCLUSIONS: The prevalence and risk of carotid atherosclerosis were significantly higher in the ketosis-onset diabetics than in the control subjects but similar to that in the non-ketotic type 2 diabetics. The characteristics of carotid atherosclerotic lesions in the ketosis-onset diabetics resembled those in the non-ketotic type 2 diabetics. Our findings support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes.

Low-grade albuminuria is associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes.

BACKGROUND: Low-grade albuminuria is associated with cardiovascular risk factors and mortality. Our aim was to investigate the association between low-grade albuminuria and carotid atherosclerotic lesions in community-based patients with type 2 diabetes. METHODS: A cross-sectional study was performed in 475 community-based patients with type 2 diabetes (190 males and 285 females) with normal urinary albumin-to-creatinine ratios (UACR) (< 3.5 mg/mmol) from Shanghai, China. The subjects were stratified into tertiles based on UACR levels (the lowest tertile was UACR ≤ 1.19 mg/mmol, and the highest tertile was UACR ≥ 2 mg/mmol). Carotid intima-media thickness (CIMT), carotid atherosclerotic plaque formation and stenosis were assessed and compared among the three groups based on ultrasonography. The urinary albumin excretion rate was determined as the mean of the values obtained from three separate early morning urine samples. RESULTS: Compared with the subjects with UACR in the lowest tertile, the subjects with UACR in the middle and highest tertiles had greater CIMT values (0.88 ± 0.35 mm, 0.99 ± 0.43 mm and 1.04 ± 0.35 mm, respectively; all p < 0.05) and a higher prevalence of carotid atherosclerotic plaques (25.3%, 39.0% and 46.2%, respectively; all p < 0.05) after adjusting for sex and age. Fully adjusted multiple linear regression and logistic regression analyses revealed that UACR tertiles were significantly associated with elevated CIMT (p = 0.007) and that, compared with the subjects in the first tertile of UACR, those in the second and third tertiles had 1.878- and 2.028-fold risk of carotid plaques, respectively. However, there was no statistical association between UACR tertile and the prevalence of carotid stenosis. CONCLUSIONS: Higher UACR within the normal range was independently associated with early but not late carotid atherosclerotic lesions in community-based patients with type 2 diabetes. Low-grade albuminuria contributes to the risk of carotid atherosclerosis and may be used as an early marker for the detection of atherosclerosis in patients with type 2 diabetes.

[Detection rates of atherosclerosis by carotid versus lower limb ultrasonography in newly diagnosed type 2 diabetics].

OBJECTIVE: To compare the detection rates of atherosclerosis by carotid versus lower limb ultrasound in newly diagnosed type 2 diabetics and analyze the relationship between atherosclerosis and cardio-cerebrovascular events. METHODS: A total of 148 newly diagnosed type 2 diabetics were recruited. Both carotid and lower extremity atherosclerosis were assessed by Doppler ultrasound. Diabetic atherosclerosis was defined as the presence of either carotid or lower extremity plaques in any of the above-mentioned arterial segments. A kappa value was computed to document the agreement between isolated carotid (or lower limb) atherosclerosis and diabetic atherosclerosis. The prevalence of cardio-cerebrovascular events was compared among different distribution types of atherosclerosis. RESULTS: According to the diagnostic criteria, the prevalence of diabetic atherosclerosis was 66.2% in the newly diagnosed type 2 diabetes. Based on carotid or lower extremity ultrasound, the prevalence of diabetic atherosclerosis was 27.0% and 62.2% respectively in newly diagnosed type 2 diabetes. The kappa values for the agreement between carotid/lower limb atherosclerosis and diabetic atherosclerosis were 0.32/0.91 (95% confidence interval 0.22-0.42 for carotid vs 0.84-0.98 for lower extremity). The combination of carotid and lower extremity arterial atherosclerosis was associated with a significantly increased detection rate of cardio-cerebrovascular events (26.5%) versus those with either carotid or lower extremity arterial atherosclerosis (0% and 10.3% respectively). CONCLUSION: The combination of carotid and lower extremity ultrasonography can more accurately reflect the atherosclerotic lesions in type 2 diabetes. Due to a higher prevalence of cardio-cerebrovascular events, type 2 diabetics with both carotid and lower extremity atherosclerosis should be managed more aggressively to reduce the risk of cardio-cerebrovascular events.

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.

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.

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.

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.

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.

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.

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.

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.

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.