A man with a blistering eruption and tuberculosis.

published_or_final_versio

Skin autofluorescence is associated with microvascular complications in type 2 diabetes

Poster session: PS 086 Pumps and new devicesBackground and aims: Skin autofluorescence (AF) is a marker of advanced glycation endproduct (AGE) accumulation in the body. AGEs are molecules formed through the non-enzymatic reactions of reducing sugars with proteins, lipids and nucleic acids. They accumulate at a constant but slow rate in the normal body. With increased glucose availability in diabetes, their formation is accelerated, and their deleterious effects on proteins have been implicated in diabetic complications. Upon excitation at 370 nm, AGEs have an emission spectrum at 440 nm, which is quantifiable as skin AF. This cross-sectional study investigated the relationship between skin AF and microvascular complications in Chinese type 2 diabetic subjects. Material and methods: Subjects were recruited from the diabetic complication assessment program of our hospital. Skin AF was measured over the volar surface of the forearms using the AGE Reader. Three measurements were taken over each forearm according to the manufacturer's instructions, and the skin AF, in arbitrary units (AU), was recorded as the average of the three measurements on each side. To adjust for the effect of skin pigmentation, which absorbs light and thus influences skin AF, the AGE Reader automatically compared skin reflectance measurements across the 300 to 420 nm range with those of a white Teflon block, which was assumed to have 100% reflectance. Anthropometric and biochemical data includingbody height and weight, blood pressure, fasting glucose and lipids and HbA1c were collected. Statistical analysis was performed with SPSS 19.0. Results: Skin AF was measured in 322 Chinese type 2 diabetic subjects (192 male, 130 female, 63.9+/-11.0 years), of which 229 had one or more microvascular complication(s). The median DM duration was 10 years (interquartile range 6-15 years) and the mean HbA1c was 7.84+/-1.35%. Skin AF correlated positively with age (r=0.350, p<0.001), DM duration (r=0.256, p<0.001), serum creatinine (r=0.280, p<0.001) and smoking pack-years (r=0.287, p=0.006), but not HbA1c (p=0.306). There was no gender difference in skin AF (p=0.73). Subjects with any microvascular complication had higher skin AF than those without (2.41+/-0.48 AU vs. 2.17 +/- 0.37 AU, p<0.001). Skin AF was higher in subjects with retinopathy (2.41+/-0.46 AU vs. 2.26 +/-0.45 AU, p=0.006), nephropathy (2.49+/-0.49 AU vs. 2.20+/-3.98 AU, p<0.001) and neuropathy (2.56+/-0.51 AU vs. 2.27+/-0.42 AU, p<0.001) compared to those without the respective complication. Skin AF was independently associated with nephropathy (OR for one AU increase in AF 2.65 [1.42-4.95]; p=0.002) and neuropathy (OR for one AU increase in AF 2.28 [1.15-4.54]; p=0.019) after adjusting for gender, age, smoking status and DM duration. The optimal skin AF cut-off value for having any microvascular complication, nephropathy and neuropathy were 2.263 AU (sensitivity 59.8%, specificity 63.6%), 2.263 AU (sensitivity 68.8%, specificity 62.0%) and 2.307 (sensitivity 70.1%, specificity 57.6%) respectively on ROC analysis. Conclusion: Skin AF was associated with diabetic complications, in particular nephropathy and neuropathy, in Chinese type 2 diabetic subjects. The AGE Reader might serve as a simple and non-invasive method to evaluate the risk of diabetic microvascular complication.link_to_OA_fulltex

Obesity indices in the prediction of incident type 2 diabetes mellitus in a long- term cohort study of Hong Kong Chinese

Aim: Obesity is closely related to the development of type 2 diabetes mellitus (T2DM). We investigated the usefulness of various obesity indices in the prediction of incident T2DM in Chinese, based on the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) cohort with up to 17 years of follow-up. Methods: The Hong Kong CRISPS is a population-based prospective cohort study of Chinese men and women, aged 25-74 years, initiated in 1995. Subjects were contacted for regular reassessment visits from 1995 to 2012 (CRISPS 1-4). A total of 1512 subjects with no diabetes at CRISPS1, who returned for follow-up at CRISPS4, were included for analysis. Cumulative incidence of T2DM, based on oral glucose tolerance test or taking anti-diabetic drugs, was ascertained until December 2012. The associations of baseline obesity indices at CRISPS1, including body mass index (BMI), waist circumference (WC) and waist-hip ratio (WHR), with the development of T2DM were evaluated by logistic regression. The optimal cut-offs of these indices in the prediction of incident T2DM were evaluated by receiver operating characteristics curve. Results: A total of 286 subjects (18.9%), aged 43.2 ± 10.9 years at CRISPS1, developed T2DM over 17 years of follow-up. Their baseline BMI, WC and WHR were 24.1±3.53kg/m2, 78.6±9.85cm and 0.83±0.08 respectively. All three indices independently predicted the development of T2DM after 17 years (BMI sex-adjusted odds ratio [OR] 1.25, 95% confidence interval [CI] 1.20-1.30, p <0.001; WC sex-adjusted OR 1.10, 95% CI 1.08-1.11, p <0.001; WHR sex-adjusted OR 1.09, 95% CI 1.07-1.12, p <0.001). The area under the curve (AUC) for BMI, WC and WHR were 73.0 (95% CI 69.7-76.3), 72.8 (95% CI 69.6-76.0) and 71.5 (95% CI 68.4-74.7) respectively, although Delong test did not suggest superiority of any obesity index over the others. The optimal cut-off of BMI was 24.5kg/m2, which yielded a sensitivity of 70.3% and a specificity of 66.5%. Using a BMI cut-off of 23kg/m2, the sensitivity increased to 83.2% with a specificity of 45.5%. Conclusion: Simple obesity indices are useful tools in the prediction of incident T2DM in Chinese. A BMI cut-off of 23kg/m2 provides good sensitivity with reasonable specificity in our population. Our findings are in keeping with the latest recommendations from the American Diabetes Association, not only in using BMI as a prerequisite for screening, but also the BMI cut-off used when testing asymptomatic Asian adults for diabetes

Which creatinine-based estimated glomerular filtration rate equation best predicts all-cause mortality in Chinese subjects with type 2 diabetes?

AIM: In Chinese, ethnicity-based and/or diabetes specific modifications of the Modification of Diet in Renal Disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations have been developed for determining estimated glomerular filtrate rate (eGFR). This study aimed to compare the performance of five different creatinine-based eGFR equations in predicting all-cause mortality among Chinese subjects with type 2 diabetes (T2DM). METHODS: A total of 6739 Chinese subjects with T2DM were included. Their eGFR was calculated using the MDRD, CKD-EPI, their respective modified equations for Chinese, and the diabetes specific CKD-EPI Chinese T2DM equations. Multiple Cox regression analysis was used to evaluate the associations of eGFR with all-cause mortality. C-statistics, net reclassification index (NRI) and integrated discrimination index (IDI) were applied to assess the discrimination and reclassification of each eGFR equation in predicting mortality outcome. RESULTS: Over a follow-up of 5.7years, the incidence of all-cause mortality was 12.9% (N=867). The CKD-EPI equation discriminated all-cause mortality better than the MDRD equation (C-statistics: 0.714 vs. 0.689, p<0.0001), and Chinese modification of their respective equations did not improve discrimination. Among the five eGFR equations evaluated, the CKD-EPI Chinese T2DM equation provided the best discrimination in predicting all-cause mortality among Chinese subjects with T2DM, and was the only equation providing a significantly positive NRI and IDI relative to the CKD-EPI equation. CONCLUSIONS: Among Chinese subjects with T2DM, our findings suggested that the CKD-EPI Chinese T2DM equation best predicted all-cause mortality, and relative to the CKD-EPI equation, conferred improved discrimination and reclassification.postprin

Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

BACKGROUND: Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. METHOD: Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. RESULTS: At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m(2), serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01-1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06-1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1-3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. CONCLUSIONS: Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy

Elevated fibroblast growth factor-21 is associated with increased carotid intima media thickness

Presentation no. MON-165OBJECTIVE: Elevated circulating concentrations of fibroblast growth factor-21 (FGF21), a recently recognised regulator of glucose and lipid metabolism, have been reported in type 2 diabetes, coronary artery disease, and in dialysis-dependent patients with end-stage renal failure. In this study, we investigated the relationship of serum FGF21 levels with carotid atherosclerosis in subjects with normal serum creatinine level. Design and METHODS: In 670 Chinese subjects, anthropometric and biochemical parameters, serum FGF21 concentrations and carotid intima media thickness (IMT) were measured. The relationships between serum FGF21 concentrations, various cardiometabolic risk factors, and IMT were analysed. RESULTS: Carotid IMT was measured in 285 men and 385 women mean age 58.2±12.9 years). Men had higher IMT (0.73±0.17 mm vs. 0.68±0.14 mm, p<0.001). Serum FGF21 was similar between men and women, being 248[159.6-368.2] ng/l and 251 [136.8-415.2] ng/l, median [Inter-quartile range] respectively, and correlated positively with age (p<0.001), anthropometric parameters (p<0.05), blood pressure, LDL, triglycerides, serum creatinine level, and negatively with HDL and estimated glomerular filtration rate (eGFR) (all p<0.001). A significant positive correlation was found between serum FGF21 concentration and carotid IMT (r=0.32; p<0.001) in women but not in men. This relationship remained significant even after adjusting for age, waist circumference, hypertension, fasting glucose, serum creatinine level, dyslipidaemia and smoking status (standardized beta=0.103; p=0.021). Using eGFR instead of serum creatinine level in the regression model did not alter the finding. CONCLUSIONS: Our results suggested a positive correlation between circulating levels of FGF21 and carotid IMT, a marker of carotid atherosclerosis, being demonstrable in women. This relationship was independent of various cardiometabolic risk factors. These observations would support a role for FGF21 or FGF21 resistance in the pathogenesis of atherosclerosis

Additional file 1 of Prospective associations of circulating thrombospondin-2 level with heart failure hospitalization, left ventricular remodeling and diastolic function in type 2 diabetes

Supplementary Material 1. Supplemental Table S1 Pearson correlation analysis of serum TSP2 level with clinical variables at baseline. Supplemental Table S2 Serum TSP2 level and baseline clinical characteristics at baseline. Supplementary Table S3 Sensitivity analysis showing the association between baseline circulating TSP2 levels and incident HF hospitalization in participants who survived and remained free of outcome events in 2015 (N = 4812). Supplementary Table S4 Baseline characteristics of the participants by serum TSP2 levels in Part 2 of the study (N = 146)