anxi Li

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

BackgroundThe 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.MethodsIn 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.ResultsThe 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.ConclusionsThe 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.

The combination of carotid and lower extremity ultrasonography increases the detection of atherosclerosis in type 2 diabetes patients.

OBJECTIVE To evaluate the prevalence of atherosclerosis detected by both carotid and lower extremity ultrasonography in hospitalized Chinese type 2 diabetic patients and to examine whether plaque formation in the carotid arteries could be an indicator of generalized atherosclerosis in type 2 diabetes mellitus. METHODS Totally, 709 hospitalized Chinese type 2 diabetic patients (men 357, women 352) aged from 18 to 88 years were included. Both carotid and lower extremity atherosclerosis were assessed by Doppler ultrasound. Atherosclerosis was defined as the presence of either the carotid or lower extremity plaque in any of the above-mentioned arteries segments. The prevalence of atherosclerosis was calculated, and the risk factors associated with atherosclerosis were evaluated using binary logistic regression. RESULTS The prevalence of atherosclerosis was 81.23% in male and 77.56% in female type 2 diabetic patients, respectively. There was no significant difference in the prevalence of atherosclerosis in patients between the sexes. The prevalence of atherosclerosis was significantly higher in the lower extremity arteries than in the carotid arteries (73.91% and 44.43%, respectively, P<.001). Atherosclerosis was significantly associated with smoking, age, duration of diabetes, systolic blood pressure, total number of white blood cells, and mean carotid and femoral intima-media thickness (IMT). CONCLUSIONS The prevalence of atherosclerosis was very high in Chinese inpatients with type 2 diabetes. Carotid atherosclerosis could not be an indicator of generalized atherosclerosis in type 2 diabetes. The combination of carotid and lower extremity ultrasound examination can significantly improve the detection of atherosclerosis in type 2 diabetes.

Serum fibroblast growth factor 21 levels is associated with lower extremity atherosclerotic disease in Chinese female diabetic patients

BackgroundFibroblast growth factor 21 (FGF21) is an emerging metabolic regulator associated with glucose and lipid metabolism, and it is still unclear whether FGF21 is related to atherosclerosis. Here, we explored the potential link between FGF21 and lower extremity atherosclerotic disease (LEAD) in type 2 diabetic patients.MethodsA cross-sectional study was conducted on 504 type 2 diabetic patients (283 men, 221 women). LEAD was defined by Ankle-brachial index (ABI) <0.9 and lower extremity arterial plaque evaluated by color Doppler ultrasound. Serum FGF21 concentrations were quantified by a sandwich enzyme-linked immunosorbent assay.ResultsThe total FGF21 levels of male and female patients had no significant differenence ((299.14(177.31-534.49) vs 362.50(214.01-578.73), P=0.516). Serum FGF21 levels in LEAD group were significantly higher than non-LEAD group in females (385.34(243.89-661.54) vs 313.13(156.38-485.79), P=0.006), while not in male patients (295.52(177.09-549.64) vs 342.09 (198.70-549.87), P=0.613). In diabetic women, subjects with LEAD had significantly higher serum FGF21 regardless of non-alcoholic fatty liver disease (NAFLD) (P < 0.05). And serum FGF21 levels were positively correlated with waist circumference and systolic blood pressure after adjusted for age and BMI (r=0.198, P=0.004; r=0.152, P=0.027; respectively). Moreover, FGF21 was independently tied to femoral intima-media thickness (FIMT) (β=0.208, P=0.031). After adjusted for other LEAD risk factors, FGF21 was demonstrated to be an independent risk factor for LEAD in type 2 diabetic women (OR, 1.106; 95%CI 1.008-1.223; P=0.028). In addition, FGF21 was negatively correlated with estradiol in premenopausal diabetic women (r=−0.368, P=0.009). After adjusted for estradiol, serum FGF21 levels were still positively associated with FIMT in premenopausal diabetic women (r=0.381, P=0.007). In diabetic men, serum FGF21 levels were correlated with triglyceride and C-reactive protein even after adjusted for age and BMI (r=0.204, P=0.001; r=0.312, P < 0.001; respectively). However, serum FGF21 was not an independent impact factor for LEAD in men (P > 0.05).ConclusionsSerum FGF21 level independently and positively links LEAD in Chinese women with type 2 diabetes. The gender difference may be due to different estrogen levels.

Serum uric acid levels are associated with hypertension and metabolic syndrome but not atherosclerosis in Chinese inpatients with type 2 diabetes

Objective: Serum uric acid (SUA) is associated with many cardiovascular risk factors such as hypertension (HTN) and metabolic syndrome (MetS). However, the association of SUA with atherosclerosis remains controversial. Our aim was to investigate the relationships of SUA with HTN, MetS and atherosclerosis in Chinese inpatients with type 2 diabetes. Methods: This cross-sectional study was performed with a sample of 2388 hospitalized Chinese patients with type 2 diabetes. Both carotid and lower limb atherosclerotic lesions were assessed for intima–media thickness, plaque and stenosis by Doppler ultrasound. Atherosclerotic plaque and stenosis were defined as the presence of either carotid or lower limb plaques and stenoses, respectively. Results: There were significant increases in the prevalence of both HTN and MetS across the SUA quartiles (HTN: 43.4, 49.6, 56.1 and 66.3% for the first, second, third and fourth quartiles, respectively, P < 0.001; MetS: 59.9, 68.8, 74.7 and 84.9% for the first, second, third and fourth quartiles, respectively, P < 0.001). A fully adjusted multiple logistic regression analysis revealed that SUA quartile was independently associated with the presence of HTN (P = 0.001) and MetS (P = 0.006). The prevalence of atherosclerotic plaque and stenosis was obviously higher in the patients with either HTN or MetS than in those without HTN or MetS. However, there was no significant association of SUA quartile with the presence of atherosclerotic lesions. Conclusions: SUA levels were closely associated with HTN and MetS, but not with atherosclerosis in type 2 diabetes. Our findings strongly suggest that, in select populations such as those with type 2 diabetes, the role of uric acid in atherosclerosis might be attributable to other cardiovascular risk factors, such as HTN and MetS.

Cystatin C: a strong marker for lower limb ischemia in Chinese type 2 diabetic patients?

Objective Cystatin C is growing to be an ideal indicator for renal function and cardiovascular events. The aim of this study was to investigate the relationship between serum cystatin C levels and peripheral arterial disease and to explore its diagnostic value for lower limb ischemia (LLI) in type 2 diabetic population. Methods A total of 1609 T2DM patients were included in this cross-sectional study. Their clinical and biochemical characteristics, ankle-brachial index (ABI), carotid and lower extremity arterial ultrasound were detected. LLI was defined by ABI <0.9 and lower extremity arterial stenosis >50% by ultrasound examination. Patients were divided to two groups: with LLI and without. The risk factors of LLI were explored by binary logistic regression analysis. Results The serum concentrations of cystatin C were 1.53±0.60 and 1.08±0.30 mg/L in patients with and without LLI, respectively. Binary logistic regression analysis showed that the significant risk factors were cystatin C (P = 0.007, OR = 5.081), the presence of hypertension (P = 0.011, OR = 3.527), age (P<0.001, OR = 1.181), GA (P = 0.002, OR = 1.089) and diabetes duration (P = 0.008, OR = 1.074). The prevalence of coronary artery disease, cerebral infarction and LLI increased with cystatin C (P<0.01), and the prevalence of LLI in patients with cystatin C >1.2 mg/L was much higher than other three quartile groups. Receiver operating characteristic curve analysis revealed the cut point of cystatin C for LLI was 1.2 mg/L. The risk of LLI dramatically increased in patients with cystatin C >1.2 mg/L (OR = 21.793, 95% confidence interval 10.046−47.280, P<0.001). After adjusting for sex, age, duration, HbA1c, GA and hypertension, its OR still remained 3.395 (95% confidence interval 1.335–8.634). Conclusions There was a strong and independent association between cystatin C and limb arterial disease in diabetic population, and cystatin C >1.2 mg/L indicated a great increased risk of LLI.

Association between serum cystatin C and diabetic peripheral neuropathy: a cross-sectional study of a Chinese type 2 diabetic population.

OBJECTIVE Serum cystatin C (CysC) is a sensitive marker of kidney function and recent studies have shown that CysC plays a critical role in degenerative diseases in both the central and the peripheral nervous systems. The aim of this study was to explore the relationship between serum CysC and diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes. METHODS In total, 937 type 2 diabetic patients were enrolled in this cross-sectional study. Serum CysC concentration was measured by immunoturbidimetry. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer, and electromyogram. RESULTS Serum CysC levels were significantly higher in DPN patients (1.3 (1.1-1.5) mg/l) compared with patients with signs of DPN (1.1 (0.9-1.3) mg/l, P<0.001) and non-DPN patients (1.0 (0.9-1.3) mg/l, P<0.001). Multiple regression analysis revealed that DPN was associated with age, diabetes duration, HbA1c, and serum CysC. Spearmans correlation analysis showed that serum CysC was closely related with age, sex, diabetes duration, hypertension, glomerular infiltration rate, and serum creatinine (Cr) level. The patients were divided into quartiles according to the serum CysC levels. Compared with quartile 1 (referent), the risk of DPN was significantly higher in quartile 2 (odds ratio (OR), 1.753; 95% CI, 1.055-2.912; P<0.05), quartile 3 (OR, 2.463; 95% CI, 1.445-4.917; P<0.01), and quartile 4 (OR, 5.867; 95% CI, 2.075-16.589; P<0.01). Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum CysC to indicate DPN was 1.25 mg/l in male patients and 1.05 mg/l in female patients. High serum CysC level indicated a onefold higher risk of DPN. CONCLUSIONS High serum CysC level is closely associated with DPN and may be a potential biomarker for DPN in type 2 diabetic patients.

Comparison of carotid and lower limb atherosclerotic lesions in both previously known and newly diagnosed type 2 diabetes mellitus.

To compare carotid and lower limb atherosclerotic lesions, and examine if carotid atherosclerotic lesions are in line with lower limb atherosclerotic lesions, and can reflect generalized atherosclerosis in inpatients with type 2 diabetes.

High Glucose Increases the Expression of Inflammatory Cytokine Genes in Macrophages Through H3K9 Methyltransferase Mechanism.

Recent studies suggest that histone modification is one of the mechanisms regulating inflammatory cytokine gene expression in hyperglycemic conditions. However, it remains unknown how histone methylation is initiated and involved in changes of inflammatory cytokine gene expression under high glucose (HG) conditions. Our aim was to investigate whether H3K9 methylation was involved in HG-induced expression of inflammatory cytokines in macrophages. Expression profile of cytokine genes under hyperglycemia in THP-1-derived macrophages was determined by human cytokine antibody array. Based on the results from the human cytokine antibody array analyses, the H3K9me3 levels of 4 inflammatory cytokine genes, including interleukin-6 (IL-6), IL-12p40, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β under HG were determined by ChIP assays. Furthermore, the expression of these 4 inflammatory cytokine genes under either HG or chaetocin (an inhibitor of SUV39H1 methyltransferase) exposure or overexpression of SUV39H1 (a H3K9me3-specific methyltransferase) was analyzed by quantitative polymerase chain reaction. Macrophages cultured in HG conditions showed increased gene expression and decreased H3K9me3 levels of inflammatory cytokine genes compared with macrophages incubated in normal glucose (NG) culture. Inhibition of SUV39H1 with chaetocin in NG-treated macrophages also increased the expression of IL-6, IL-12p40, MIP-1α, and MIP-1β. Furthermore, inhibition of SUV39H1 with chaetocin in HG-treated macrophages further increased the expression of these inflammatory cytokines. Contrarily, NG-treated macrophages transfected with SUV39H1 plasmids show decreased expression of inflammatory cytokines. Furthermore, overexpression of SUV39H1 in HG-treated macrophages alleviated the expression of inflammatory cytokines under HG conditions. Finally, HG also increases the expression of inflammation cytokines in mouse bone marrow-derived macrophages. Our data demonstrated that HG increases the expression of inflammatory cytokines in macrophages through decreased H3K9me3 levels, which was partly mediated by SUV39H1. Dysregulation of epigenetic histone modification may be one of the underlying mechanisms for HG-induced inflammatory cytokine expression in macrophages.

High Ankle–Brachial Index Indicates Cardiovascular and Peripheral Arterial Disease in Patients With Type 2 Diabetes:

We assessed the association between high ankle–brachial index (ABI) and cardiovascular disease (CVD) and peripheral arterial disease (PAD) in Chinese patients with type 2 diabetes mellitus (T2DM). The ABI was measured, and foot inspection was performed in 2080 outpatients with T2DM. The clinical characters in different ABI levels were analyzed, and the diagnostic value of high ABI to CVD and PAD was determined. Compared with the normal ABI group, the high ABI (>1.3) group had a higher prevalence of CVD and PAD but less than the low ABI (≤0.9) group. High ABI was an independent risk factor for the development of CVD and PAD. Receiver–operating characteristic curve analysis showed that the optimal cutoff of high ABI to predict CVD and PAD was 1.43 and 1.45, respectively. The odds ratio of high ABI for CVD and PAD was 2.25 and 6.97, respectively, after adjusting for other confounding risk factors. In conclusion, high ABI indicated the risk of CVD and PAD in Chinese populations with T2DM.

High cystatin C levels predict severe retinopathy in type 2 diabetes patients.

Diabetes mellitus affects over 18.2 million people (or 6.3 % of the total population) in the US and over 800,000 new cases of type 2 diabetes are diagnosed every year [1]. Meanwhile, diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, resulting in blindness for over 10,000 people with diabetes per year [1]. Cystatin C is a member of the cystatin superfamily of cystine protease inhibitors, which are produced by nucleated cells at a constant rate [2]. Evidences have shown that serum cystatin C could predict early prognostic stages of diabetic nephropathy (DN) [3] and was implicated in the mechanism of age-related macular degeneration (AMD) [4]. Charumathi et al. recently reported that elevated levels of serum cystatin C were associated with prediabetes in a nationally representative sample of nonobese US adults [5]. In order to investigate the relationship between cystatin C and diabetic retinopathy (DR) to clarify the predictive value of cystatin C for DR, we recruited a total of 954 type 2 diabetes mellitus patients from Shanghai Clinical Medical Center of Diabetes from January 2012 to November 2012. Type 2 diabetes mellitus was diagnosed according to the 1999 World Health Organization criteria and 2012 American Diabetes Association standards [6]. Patients of type 1 diabetes mellitus or specific types of diabetes mellitus, acute complications of diabetes, fundus lesions owing to orbital tumor, trauma or other definite causes and secondary nephropathy caused by acute glomerulonephritis, pyelonephritis and nephrolithiasis were excluded. Written informed consents were obtained from all participants. The study was approved by the Human Research and Ethics Committee of Shanghai Sixth People’s Hospital and adhered to the tenets of the Declaration of Helsinki. Totally, 544 males (57.02 %) and 410 females (42.98 %) were enrolled at an average age of 57.44 ± 11.24 years and the mean diabetes duration of 8.75 ± 6.43 years. Information on sex, age, duration of diabetes, and the history of smoking, coronary artery disease, hypertension and cerebral apoplexy were obtained using a questionnaire. Anthropometric measurement included weight, height and body mass index (BMI). Venous blood was drawn from all patients after an overnight fast. The levels of serum cystatin C were measured using high sensitive latex-enhanced immunoturbidimetric method and patients were categorized in quartiles based on the serum cystatin C (mg/L) as: Q1 (Quartiles 1, cystatin C B 0.8) (n = 175), Q2 (Quartiles 2, 0.9 B cystatin C B 1.0) (n = 329), Q3 (Quartiles 3, 1.1 B cystatin C B 1.2) (n = 227) and Q4 (Quartiles 4, cystatin C C 1.3) (n = 223). Other laboratory parameters included total cholesterol Rui He and Jing Shen have contributed equally to this work.