Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c

et al. (2013) Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c. PLoS ONE 8(7): e67759. doi:10.1371/journal.pone.0067759 Association of Serum Uric Acid with 2-Hour Postload Glucose in Chinese with Impaired Fasting Plasma Glucose and/or HbA1c Hong-Qi Fan 0 Wei Tang 0 Zhi-Xiao Wang 0 Su-Juan Wang 0 Yue-Hua Qin 0 Qi Fu 0 Yuan Gao 0 Min Sun 0 Mei Zhang 0 Hong-Wen Zhou 0 Tao Yang 0 Yiqing Song, Brigham & Women's Hospital, and Harvard Medical School, United States of America 0 1 Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, Jiangsu , China , 2 Department of Endocrinology, The Affiliated Jiangyin Hospital of Southeast University Medical College , Jiangyin, Jiangsu , China Objective: To examine whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in Chinese with impaired fasting plasma glucose (IFG) and/or HbA1c (IA1C). Research Design and Methods: Anthropometric and biochemical examinations, such as SUA concentration, were performed in 3763 individuals from all the villages in Baqiao County, China. A 75-g oral glucose tolerance test (OGTT) was conducted in 1197 Chinese with prediabetes as having IFG (110# fasting plasma glucose [FPG] ,126 mg/dl and HbA1c ,6.5%), IA1C (5.7% # HbA1c ,6.5% and FPG ,126 mg/dl), or both. Results: The present study included 1197 participants with IFG and/or IA1C (mean age 56.5610.3 years; 50.6% men). In multivariate linear regression, after adjustment for gender, age, smoking and drinking, body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), lipid profiles, logarithmic transformed C-reactive protein (log-CRP), estimated glomerular filtration rate (e-GFR), FPG and HbA1c, with a 1-mg/dl increment of SUA, 2-h PG increased by 5.0460.72 (P,0.001), 3.0661.08 (P = 0.001), 5.4061.26 (P,0.001), and 2.3462.16 mg/dl (P = 0.056) in all participants, in participants with normal glucose tolerance (NGT), with impaired glucose tolerance (IGT), and with 2-h newly diagnosed diabetes (2-h NDM, with 2-h PG $200 mg/dl), respectively. In both men and women, 2-h PG increased progressively and significantly from the lower to the upper SUA tertiles (P,0.001). Moreover, in multivariate logistic regression, 1-standard deviation (SD; 1.53 mg/dl) increment of SUA was significantly associated with a 36% higher risk for 2-h NDM (Odds ratio [CI 95%]: 1.36 [1.09-1.99]; P = 0.03). Conclusions: SUA is significantly associated with 2-h PG in Chinese with IFG and/or IA1C. - Funding: This study was supported by grants from the National Natural Science Foundation of China (81100578), the National Key Technologies R&D Program of China, during the 11th Five-Year Plan Period (2007BAI07A10) and the Jiangsu Province Science and Technology Support Program (BE2009613). Competing Interests: The authors have declared that no competing interests exist. . These authors contributed equally to this work. Serum uric acid (SUA), the end product of purine metabolism, possesses both antioxidant and pro-oxidant properties, which depend on its chemical microenvironment. In clinical investigations, SUA was reported to be associated with gout, hypertension, atherosclerosis, metabolic syndrome, diabetes and prediabetes [1 3]. More recently, hyperuricemia was documented in subjects with cardiovascular diseases [4] and recognized as an independent predictor of myocardial infarction and stroke [5]. On the other hand, type 2 diabetes is a recognized and independent risk factor for cardiovascular disease [68], even in the absence of coronary artery disease or hypertension [9]. Patients with prediabetes (based on impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired HbA1c [IA1C] of 5.76.4%) are at high risk of future type 2 diabetes, with 70% of them developing type 2 diabetes within 10 years [10]. More importantly, patients with prediabetes seem to share the similar concomitant damage to end target organs, as patients with diabetes [11]. High blood glucose concentration or elevated HbA1c was shown to be a risk factor for cardiovascular complications, even in nondiabetic individuals [12]. Although the underlying mechanism is still controversial, fasting plasma glucose (FPG) and HbA1c, the most common glycemic indexes, could not completely explain the observed risk. Recently, in the Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in Europe (DECODE) study, it was demonstrated that FPG concentrations alone could not identify individuals at increased risk of cardiovascular complications associated with hyperglycemia, and the oral glucose tolerance test (OGTT) could provide additional prognostic information [13]. In addition, in the Diabetes Control and Complications Trial, it was reported that the degree of glucose load, which was not completely reflected by mean HbA1c, was more strongly associated with the observed risk of cardiovascular diseases [14]. Although many studies have indicated a critical role of postload glucose in the development of complications, the postchallenge values are still frequently being neglected [15]. This is probably due to the inconvenience and costs of an OGTT measurement. Considering the importance of postload hyperglycemia in the DECODE study [13] and others [14,16,17], and the crucial role of SUA in the development of cardiovascular diseases [25], we therefore aimed to investigate the association of SUA and 2-h PG in patients with IFG and/or IA1C. Study Population The present study was conducted from January to May in 2010 in the framework of routine health examinations in all the villages in Baqiao County in Gaoyou, a newly established rural residential area about 299 kilometers northwest to Shanghai, China. Study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Nanjing Medical University. From the local authorities, we obtained the population data of 10008 inhabitants aged from 18 to 74 years. Proportionately stratified random sampling was used to select a representative sample from the total population, and the population size was set at 5000 participants. 3918 individuals, out of the 5000 (78.4%), participated after having given informed written consent. 155 individuals were excluded from the present study, because they had established diabetes (n = 82; defined as the use of glucose-lowering agents, or diagnosed diabetes, or both), missing information on history of diabetes (n = 17), FPG (n = 18) or HbA1c (n = 8), selfreported gout or using of allopurinol or uricosuric agents (n = 30). After further exclusion of individuals with normal FPG (,110 mg/dl) and HbA1c (,5.7%) (n = 1831) and newly diabetes (FPG$126 mg/dl, or HbA1c$6.5% or both [n = 272]), 1660 individuals, out of the 3763, with IFG (110#FPG,126 mg/dl and HbA1c,6.5%), or IA1C (HbA1c: 5.7% # HbA1c,6.5% and FPG,126 mg/dl), or both, were selected and invited for (...truncated)