Combined Use of Serum Adiponectin and Tumor Necrosis Factor-Alpha Receptor 2 Levels Was Comparable to 2-Hour Post-Load Glucose in Diabetes Prediction

Background: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. Methods: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-α R2), interleukin-6 (IL-6), adipocyte-fatty acid binding protein (A-FABP) and high-sensitivity C-reactive protein (hsCRP) were measured in baseline samples. Results: Seventy-six participants developed diabetes over 5.3 years (median). All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP) model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, "adiponectin + TNF-α R2" improved the area under ROC curve (AUC) of the CDP model from 0.802 to 0.830 (P = 0.03), rendering its performance comparable to the "CDP + 2-hour post-OGTT glucose" model (AUC = 0.852, P = 0.30). A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-α R2), had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]). Conclusions: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT. © 2012 Woo et al.published_or_final_versio

The KCNJ11 E23K Polymorphism and Progression of Glycaemia in Southern Chinese: A Long-Term Prospective Study

Context: The KCNJ11 E23K variant is associated with type 2 diabetes mellitus (T2DM) in cross-sectional studies, but conflicting findings have been reported from prospective studies. Objective: This study aimed to evaluate whether the E23K variant could predict glycaemic progression in a Southern Chinese population. Methods/Principal Findings: We performed a long-term prospective study on 1912 subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS). The KCNJ11 E23K variant was associated with the progression to prediabetes after a median interval of 12 years on multinomial logistic regression analysis, even after adjustment for traditional risk factors (OR 1.29, P age, sex, BMI and fasting plasma glucose [FPG] adjusted = 0.02). Based on Cox proportional hazard regression analysis, the E23K variant also predicted incident prediabetes (HR 1.18, P age, sex, BMI and FPG adjusted = 0.021). However, E23K was not associated with the progression to T2DM in either multinomial or Cox regression analysis, and the association of E23K with glycaemic progression to either prediabetes or T2DM was significant only in unadjusted Cox regression analysis (P = 0.039). In a meta-analysis of eight prospective studies including our own, involving 15680 subjects, the E23K variant was associated with incident T2DM (fixed effect: OR 1.10, P = 4×10 -3; random effect: OR 1.11, P = 0.035). Conclusions: Our study has provided supporting evidence for the role of the E23K variant in glycaemic progression in Chinese, with its effect being more evident in the early stage of T2DM, as the subjects progressed from normal glucose tolerance to prediabetes. © 2011 Cheung et al.published_or_final_versio

Protein Markers Adipocyte Fatty Acid–Binding Protein Is a Plasma Biomarker Closely Associated with Obesity and Metabolic Syndrome

FABP) is traditionally thought to be a cytosolic fatty acid chaperone expressed in adipocytes. Mice with targeted disruption of the A-FABP gene exhibit a striking phenotype with strong protection from insulin resistance, hyperglycemia, and atherosclerosis. The clinical relevance of these findings remains to be confirmed. Methods: We used tandem mass spectrometry–based proteomic analysis to identify proteins secreted from adipocytes and present in human serum. We measured serum A-FABP concentrations in 229 persons (121 men and 108 women; age range, 33–72 years), including 100 lean [body mass index (BMI) <25 kg/m 2] and 129 overweight/obese individuals (BMI>25 kg/m 2) selected from a previous cross-sectional study. Results: A-FABP was released from adipocytes and was abundantly present in human serum. Mean (SD) circulating concentrations of A-FABP were significantly higher in overweight/obese than in lean persons [32.3 (14.8) vs 20.0 (9.8) �g/L; P <0.001]. Age- and sex-adjusted serum A-FABP concentrations correlated positively (P <0.005) with waist circumference, blood pressure, dyslipidemia, fasting insulin, and the homeostasis model assessment insulin resistance index. Moreover, we observed a significant increase in A-FABP concentrations corresponding with increases in the number of components of the metabolic syndrome (P <0.05)

Comparisons of AUCs of different diabetes prediction models.

<p>AUC, Area under the curve; All biomarker levels were sex-specific except for hsCRP;</p><p>CDP: Sex, Age, Waist circumference, fasting glucose, hypertension, dyslipidaemia, family history of diabetes, physical activity and smoking status.</p><p>TNF-α R2: tumor neurosis factor-alpha receptor 2; hsCRP, high sensitivity C-reactive protein; IL-6, Interleukin-6; A-FABP, adipocyte-fatty acid-binding protein.</p

Multivariate prediction of diabetes according to CDP and biomarker risk score.

<p>WC, waist circumference; FG, fasting glucose; HT, hypertension; TNF-α R2: tumor neurosis factor-alpha receptor 2.</p

Log-likelihood ratio tests comparing the change before and after addition of biomarkers.

<p>-2LL, -2log-likelihood; p-value (χ², df = 1);</p><p>All biomarker levels were sex specific (except for hsCRP).</p><p>CDP: Sex, Age, Waist circumference, fasting glucose, hypertension, dyslipidaemia, family history of diabetes, physical activity and smoking status.</p><p>TNF-α R2: tumor neurosis factor-alpha receptor 2; hsCRP, high sensitivity C-reactive protein; IL-6, Interleukin-6; A-FABP, adipocyte-fatty acid-binding protein.</p

Baseline clinical and biochemical characteristics of subjects with and without incident type 2 DM in 5.3 years.

<p>Mean ± SD, median (interquartile-range), or percentage as appropriate.</p>a<p>Physical activity: active if having moderate intensity exercise for at least 30 minutes in one month. ^bSex-adjusted; ^cAdjusted for hypertensive treatment; ^dLog transformed before analysis. ^eExcluded subjects on lipid treatment;</p><p>Central obesity: waist circumference ≥90 cm (M)/80 cm (F).</p><p>Hypertension: systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg, or on hypertensive treatment.</p><p>Dyslipidaemia: triglycerides ≥1.7 mmol/L, HDL cholesterol <1.0 mmol/L (M)/1.3 mmol/L (F), LDL cholesterol ≥3.4 mmol/L, or on lipid treatment.</p