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.

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.

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.

Serum uric acid levels are associated with obesity but not cardio-cerebrovascular events in Chinese inpatients with type 2 diabetes.

We aim to explore the associations between serum uric acid (SUA) and obesity and cardio-cerebrovascular events (CCEs) in Chinese inpatients with type 2 diabetes mellitus (T2DM). 2 962 inpatients with T2DM were stratified into quartile based on SUA concentrations. There were significant increases in the prevalence of both obesity (32.6%, 41.9%, 50.1%, and 62.8%, respectively, p < 0.001 for trend) and severe obesity (0.4%, 0.6%, 0.8%, and 1.3%, respectively, p < 0.001 for trend) across the SUA quartiles. A fully adjusted multiple logistic regression analysis revealed that SUA quartiles were independently associated with the presence of obesity (p < 0.001). The prevalence of CCEs was significantly higher in the obese diabetics than in the nonobese diabetics (16.8% vs. 13.2%, p = 0.027). After controlling for multiple confounding factors, BMI levels were also significantly correlated with the presence of CCEs (p = 0.020). However, there was no significant association of SUA quartiles/SUA levels with the presence of CCEs in T2DM. This study suggested that SUA levels were independently associated with obesity but not with CCEs in patients with T2DM. In selected populations such as subjects with T2DM, the role of uric acid in cardiovascular complications might be attributable to other cardiovascular risk factors, such as obesity.

Urine uric acid excretion is associated with nonalcoholic fatty liver disease in patients with type 2 diabetes.

AIMS: Elevated serum uric acid is closely associated with nonalcoholic fatty liver disease (NAFLD). However, the association of urine uric acid excretion (UUAE) with NAFLD has not been investigated. Our aims were to explore the associations between UUAE and NAFLD and serum alanine aminotransferase (ALT) in type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study included 2042 Chinese inpatients with T2DM. UUAE was determined enzymatically using a single 24-h urine collection. The subjects were stratified into quartile based on UUAE levels. NAFLD was determined by ultrasonography. Elevated ALT level was defined with an ALT value >65U/L. RESULTS: There was an obvious increase in both NAFLD prevalence (26.3%, 34.6%, 43.8%, and 56.2%, respectively, p<0.001 for trend) and ALT value [16 (12-24), 17 (13-27), 20 (14-30), and 24 (15-38) U/L, respectively, p<0.001 for trend] across the UUAE quartiles after controlling for confounders. Multiple logistic regression analyses revealed independent associations between UUAE and NAFLD (p=0.002) and elevated ALT level (p<0.001). Compared with the patients in the first quartile of UUAE, those in the second, third and fourth quartiles had 1.528-, 1.869-, and 1.906-fold risk of NAFLD, and 3.620-, 6.223-, and 10.506-fold risk of elevated ALT level in T2DM, respectively. CONCLUSIONS: Increased UUAE levels were significantly associated with the presence of NAFLD and increase of ALT in T2DM. UUAE may be a clinically significant measure in assessing the risk of NAFLD in T2DM.

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.

Prevalence and clinical characteristics of lower limb atherosclerotic lesions in newly diagnosed patients with ketosis-onset diabetes: a cross-sectional study.

BACKGROUND: The clinical features of atherosclerotic lesions in ketosis-onset diabetes are largely absent. We aimed to compare the characteristics of lower limb atherosclerotic lesions among type 1, ketosis-onset and non-ketotic type 2 diabetes. METHODS: A cross-sectional study was performed in newly diagnosed Chinese patients with diabetes, including 53 type 1 diabetics with positive islet-associated autoantibodies, 208 ketosis-onset diabetics without islet-associated autoantibodies, and 215 non-ketotic type 2 diabetics. Sixty-two subjects without diabetes were used as control. Femoral intima-media thickness (FIMT), lower limb atherosclerotic plaque and stenosis were evaluated and compared among the four groups based on ultrasonography. The risk factors associated with lower limb atherosclerotic plaque were evaluated via binary logistic regression in patients with diabetes. RESULTS: After adjusting for age and sex, the prevalence of lower limb plaque in the patients with ketosis-onset diabetes (47.6%) was significantly higher than in the control subjects (25.8%, p = 0.013), and showed a higher trend compared with the patients with type 1 diabetes (39.6%, p = 0.072), but no difference was observed in comparison to the patients with non-ketotic type 2 diabetes (62.3%, p = 0.859). The mean FIMT in the ketosis-onset diabetics (0.73 ± 0.17 mm) was markedly greater than that in the control subjects (0.69 ± 0.13 mm, p = 0.045) after controlling for age and sex, but no significant differences were found between the ketosis-onset diabetics and the type 1 diabetics (0.71 ± 0.16 mm, p = 0.373), and the non-ketotic type 2 diabetics (0.80 ± 0.22 mm, p = 0.280), respectively. Age and FIMT were independent risk factors for the presence of lower limb plaque in both the ketosis-onset and non-ketotic type 2 diabetic patients, while sex and age in the type 1 diabetic patients. CONCLUSIONS: The prevalence and risk of lower limb atherosclerotic plaque in the ketosis-onset diabetes were remarkably higher than in the control subjects without diabetes. The features and risk factors of lower limb atherosclerotic lesions in the ketosis-onset diabetes resembled those in the non-ketotic type 2 diabetes, but different from those in the type 1 diabetes. Our findings provide further evidences to support the classification of ketosis-onset diabetes as a subtype of type 2 diabetes rather than idiopathic type 1 diabetes.

Retinal microvascular abnormalities are associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes mellitus.

OBJECTIVE: Controversies concerning the association of retinal microvascular abnormalities (RMAs) with atherosclerosis in patients with diabetes exist. The objective of this study was to investigate the association between RMAs and carotid atherosclerotic lesions in Chinese inpatients with type 2 diabetes. METHODS: This cross-sectional study involved 2870 type 2 diabetic patients including 1602 men aged 15-90 years and 1268 women aged 17-88 years. Both retinal arteriosclerosis (RA) and diabetic retinopathy (DR) were determined by digital fundus photography using a standardized protocol. RMAs are defined as the presence of either RA or DR. Carotid atherosclerotic lesions including carotid intima-media thickness (CIMT), carotid atherosclerotic plaque and stenosis were assessed and compared between patients with and without RMAs based on Doppler ultrasound. The association of RMAs with carotid atherosclerotic lesions was analyzed by linear and binary logistic regression analyses. RESULTS: The CIMT values in both male and female diabetics with RMAs were significantly greater than in those without RMAs after controlling for age (0.88±0.21 vs. 0.77±0.20 mm for men, p=0.002; and 0.84±0.19 vs. 0.76±0.21 mm for women, p=0.002). The prevalence of carotid plaque was also markedly higher in patients with RMAs than in those without RMAs after adjusting for age (54.3% vs. 23.9% for men, p<0.001; 48.4% vs. 32.0% for women, p=0.046). However, no significant difference was observed in the prevalence of carotid stenosis in either men or women with or without RMAs. After controlling for multiple confounding factors, RMAs were independently associated with increased CIMT in both men (ß: 0.067, 95% CI: 0.026-0.269, p=0.018) and women (ß: 0.087, 95% CI: 0.058-0.334, p=0.005) with type 2 diabetes, and they were also closely associated with the presence of carotid plaque (OR: 2.17, 95% CI: 1.54-3.05, p<0.001 for men; OR: 1.38, 95% CI: 0.91-2.08, p=0.129 for women) in men with type 2 diabetes. CONCLUSIONS: RMAs were closely associated with early carotid atherosclerotic lesions in hospitalized Chinese patients with type 2 diabetes. Our results suggested that changes in retinal microvasculature may play a role in the pathogenesis of atherosclerosis and may be used as an indicator of early atherosclerosis in patients with type 2 diabetes.

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.