The Journal of International Medical Research 2010; 38:

Transcription

1 The Journal of International Medical Research 2010; 38: The New Unified International Diabetes Federation/American Heart Association/ National Heart, Lung, and Blood Institute Metabolic Syndrome Definition: Does It Correlate Better with C-reactive Protein in Chinese Patients Diagnosed with Type 2 Diabetes? B LU 1,2,3 *, S ZHANG 1,2,3 *, J WEN 1,2,3, Y YANG 1,2,3, Z YANG 1,2,3, Z ZHANG 1,2,3, X WANG 1,2,3 AND R HU 1,2,3 1 Department of Endocrinology and Metabolism, HuaShan Hospital, Shanghai, China; 2 Department of Endocrinology and Metabolism, Shanghai Medical College, Fudan University, Shanghai, China; 3 Institute of Endocrinology and Diabetology at Fudan University, Shanghai, China This study evaluated the association between high-sensitivity C-reactive protein (hscrp) and metabolic syndrome, defined by the definition proposed by the International Diabetes Federation (IDF), American Heart Association (AHA) and National Heart, Lung, and Blood Institute (NHLBI) versus the older IDF definition, in 506 Chinese patients with type 2 diabetes. Anthropometric and biochemical parameters were compared and analysed using multivariate linear regression models. Serum hscrp was higher in patients with metabolic syndrome compared with those without metabolic syndrome for both definitions and increased as the number of components of metabolic syndrome increased (after adjusting for age, gender and smoking). Patients with metabolic syndrome according to the IDF/AHA/NHLBI but not the IDF definition had significantly higher hscrp levels than those not meeting either definition and similar hscrp levels to those meeting both definitions. Serum hscrp levels were significantly associated with metabolic syndrome according to the IDF definition after adjusting for age, gender and smoking. Adding metabolic syndrome status according to the IDF/AHA/NHLBI definition significantly increased the fit of the multivariate linear regression model. The new IDF/AHA/NHLBI definition of metabolic syndrome may have a stronger relationship with serum hscrp than the IDF definition. KEY WORDS: METABOLIC SYNDROME; TYPE 2 DIABETES; C-REACTIVE PROTEIN; IDF/AHA/NHLBI DEFINITION *B Lu and S Zhang contributed equally to this work. 1923

2 Introduction Metabolic syndrome is a cluster of dangerous risk factors including diabetes and impaired glucose regulation, central obesity, hyper - tension and dyslipidaemia. People with metabolic syndrome are at increased risk of cardiovascular disease and have high mortality rates. 1 4 Chronic inflammation may be a trigger factor in the origin of metabolic syndrome and the development of type 2 diabetes. 5 A stimulus such as over-nutrition could result in cytokine hypersecretion, eventually leading to insulin resistance and diabetes in genetically and metabolically predisposed individuals. C-reactive protein, which is an important predictor of type 2 diabetes and cardiovascular disease, 6 8 has been reported to be associated with metabolic syndrome, as set out in the World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP- ATP III) and International Diabetes Federation (IDF) definitions. 9,10 The IDF, American Heart Association (AHA) and National Heart, Lung, and Blood Institute (NHLBI) has proposed a new unified definition for the clinical diagnosis of metabolic syndrome. 10 Although there are numerous studies comparing the NCEP-ATP III and IDF definitions with health outcomes, 11,12 there are no studies comparing the new IDF/AHA/NHLBI definition with the older IDF definition. The present study of Chinese patients with type 2 diabetes had two goals: first, to examine whether high-sensitivity C-reactive protein (hscrp) levels correlated with metabolic syndrome, as set out by the new unified IDF/AHA/NHLBI definition; secondly, to compare the new IDF/AHA/ NHLBI and the older IDF metabolic syndrome definitions using multivariate linear regression models, with logarithmic transformed hscrp as the dependent variable. Patients and methods PATIENTS Data were obtained from a cross-sectional study undertaken to evaluate the prevalence of diabetic complications in Chinese patients with type 2 diabetes, aged over 30 years and living in downtown Shanghai Twenty residential areas administered by 20 residents committees were cluster sampled in the central area of Shanghai between 1 February and 31 July Questionnaires to identify a history of diabetes were sent to every household in these residential areas and were collected by primary care clinicians and endocrinologists. Chinese patients diagnosed with type 2 diabetes were identified by the questionnaire using the diagnostic criteria recommended by the American Diabetic Association in Enrolled patients were recruited to the present study and included in the final analysis if their hscrp levels had been measured and were 10 mg/l: hscrp levels > 10 mg/l reflect acute inflammation, and the present study focused only on patients with low-grade systemic inflammation. The study protocol was approved by the Ethics Committee of HuaShan Hospital, Shanghai, and written informed consent was obtained from all participants. ASSESSMENT OF PHYSICAL PARAMETERS Body height and weight were measured using a health scale (Horse Head TZ-120, Shanghai Guangzheng Medical Equipment, Shanghai, China), with patients wearing light clothing without shoes. The body mass index (BMI) was calculated as the patient s weight (in kg) divided by their height (in m 2 ). Waist circumference was measured to the 1924

3 nearest 0.1 cm, using a calibrated plastic tape measure at the umbilical level in the late exhalation phase while standing. Mean systolic and diastolic blood pressure measurements were calculated from the last two measurements in the patient s records. ASSESSMENT OF LABORATORY PARAMETERS Using the Hitachi clinical analyser (Hitachi High-Technologies Corporation, Tokyo, Japan), serum cholesterol was determined by the cholesterol oxidase paraaminophenazone method (Shanghai Jingyuan Medical Appliances, Shanghai, China), serum triglycerides by the glycerol phosphate oxidase para-aminophenazone method (Shanghai Jingyuan Medical Appliances), high-density lipoproteincholesterol (HDL-C) by the International Reagents Corporation method (Daiichi Pure Chemicals, Tokyo, Japan), low-density lipoprotein-cholesterol (LDL-C) by the catalase method (Daiichi Pure Chemicals), and serum creatinine by the sarcosine oxidase para-aminophenazone method (Shanghai Kehua Dongling Diagnostic Products, Shanghai, China). Blood urea nitrogen levels were measured using the UVglutamate dehydrogenase (GLDH) method (Cat. No. S507; Shanghai Kehua Dongling Diagnostic Products, Shanghai, China) and uric acid was measured using the uricase peroxidase coupling method (Cat. No. S710; Shanghai Kehua Dongling Diagnostic Products), according to the manufacturer s instructions. Glycosylated haemoglobin (HbA 1c ) was determined by high-pressure liquid chromatography using an automated HLC- 723G7 analyser (Tosoh Corporation, Tokyo, Japan). Serum insulin was evaluated by radioimmunoassay, after fasting and then following a 2-h oral glucose tolerance test (Beijing Atom HighTech, Beijing, China). Plasma glucose levels were measured by the glucose oxidase method (Shanghai Jingyuan Medical Appliances) using a Hitachi clinical analyser. Insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) as follows: fasting serum insulin (miu/ml) fasting plasma glucose (mmol/l)/22.5. Serum hscrp levels were measured by a chemiluminescence assay using an automatic analyser (Dade Behring, Marburg, Germany). This assay has a sensitivity of mg/l. Inter- and intraassay coefficients of variation were < 5% for the measurements. DEFINITIONS OF METABOLIC SYNDROME IDF definition The IDF definition 9 states that patients with metabolic syndrome should have central obesity (defined as a waist circumference 90 cm for Chinese men and 80 cm for Chinese women) plus any two of the following four components: (i) triglycerides 150 mg/dl (1.7 mmol/l) or specific treatment for this lipid abnormality; (ii) HDL-C < 40 mg/dl (1.0 mmol/l) in males and < 50 mg/dl (1.3 mmol/l) in females, or specific treatment for this lipid abnormality; (iii) systolic blood pressure 130 mmhg or diastolic blood pressure 85 mmhg, or treatment of previously diagnosed hypertension; (iv) fasting plasma glucose 100 mg/dl (5.6 mmol/l), or previously diagnosed type 2 diabetes. IDF/AHA/NHLBI definition The IDF/AHA/NHLBI definition 10 states that Asian patients have metabolic syndrome if they have three or more of the following: (i) abdominal obesity, defined as a waist circumference 90 cm in men or 80 cm in 1925

4 women; (ii) triglycerides 150 mg/dl (1.7 mmol/l) or current use of medication for dyslipidaemia; (iii) HDL-C < 40 mg/dl (1.0 mmol/l) in men or < 50 mg/dl (1.3 mmol/l) in women, or current use of medication for dyslipidaemia; (iv) blood pressure 130/85 mmhg or current use of medication for hypertension; (v) fasting plasma glucose 100 mg/dl (5.6 mmol/l) or current use of medication for diabetes mellitus. STATISTICAL ANALYSES Data are presented as the mean ± SD for continuous variables and as percentages for categorical variables. One-way analysis of variance (ANOVA) and Pearson s χ 2 -test were used to identify differences between those with and without metabolic syndrome. Linear regression was used to test the trend of hscrp compared with the number of components of metabolic syndrome after adjusting for age, gender and smoking. Serum hscrp levels were logarithmically transformed to give a normal distribution and were then compared by post hoc tests in three groups: those with metabolic syndrome as defined by both IDF/AHA/NHLBI and IDF criteria, 9,10 those with metabolic syndrome as defined by IDF/AHA/NHLBI but not by IDF criteria, and those without metabolic syndrome (i.e. those who did not meet either definition). Multivariate linear regression models were performed using logarithmic - ally transformed hscrp as the dependent variable. Statistical analyses were carried out using the SPSS statistical package, version 16.0 (SPSS Inc., Chicago, IL, USA) for Windows. A P-value < 0.05 was considered to be statistically significant. Results PATIENTS A total of 1120 Chinese patients diagnosed with type 2 diabetes were identified by the questionnaire; hscrp was measured in the last 574 of the enrolled participants and these patients were recruited for the study. Of the 574 patients, 54 had hscrp levels > 10 mg/l and were excluded from the analysis. Full data were available for 506 of the remaining patients, of whom 189 were male and 317 were female. The mean age was ± 12.1 years and the mean duration of diabetes was 7.14 ± 6.77 years. In total, 276 patients (67 men and 200 women) met both definitions, 178 (94 men and 84 women) did not meet either definition, and 61 (28 men and 33 women) met the IDF/AHA/NHLBI but not the IDF definition. PHYSICAL AND CLINICAL PARAMETERS The physical and clinical characteristics of patients with and without metabolic syndrome, as defined by both definitions, 9,10 are shown in Table 1. Compared with nonmetabolic syndrome patients, age, waist circumference, BMI, systolic blood pressure, diastolic blood pressure, triglycerides and serum uric acid levels were significantly higher in metabolic syndrome patients according to either definition (P 0.03 for all comparisons). The prevalence of metabolic syndrome in females was much higher than in males, for both definitions. The median HOMA-IR was significantly higher in metabolic syndrome patients than in nonmetabolic syndrome patients for both definitions (P < 0.001). HDL-C values were significantly lower in metabolic syndrome patients compared with non-metabolic syndrome patients when defined by the IDF/AHA/NHLBI definition (P < 0.001), but not in those with metabolic syndrome classified using the IDF definition. Serum LDL- C and HbA 1c levels were significantly higher in those with metabolic syndrome than in non-metabolic syndrome patients classified 1926

5 TABLE 1: Demographic, anthropometric and metabolic characteristics in Chinese patients diagnosed with type 2 diabetes classified according to the IDF/AHA/NHLBI 10 and IDF 9 definitions of metabolic syndrome IDF/AHA/NHLBI definition IDF definition Metabolic Non-metabolic Metabolic Non-metabolic syndrome syndrome Statistical syndrome syndrome Statistical Characteristic (n = 328) (n = 178) significance a (n = 267) (n = 239) significance a Age (years) ± ± P < ± ± P < Gender, n P < P < Female Male Duration of diabetes (years) 7.33 ± ± 6.99 NS 7.30 ± ± 6.97 NS Body mass index (kg/m 2 ) ± ± 2.82 P < ± ± 2.74 P < Waist circumference (cm) ± ± 8.11 P < ± ± 7.54 P < Systolic blood pressure (mmhg) ± ± P < ± ± P < Diastolic blood pressure (mmhg) ± ± P < ± ± P < Serum cholesterol (mmol/l) 5.42 ± ± 1.04 P = ± ± 1.08 P < LDL-C (mmol/l) 3.17 ± ± 0.73 NS 3.24 ± ± 0.77 P = HDL-C (mmol/l) 1.17 ± ± 0.37 P < ± ± 0.37 NS Triglycerides (mmol/l) 2.36 ± ± 0.65 P < ± ± 1.22 P < HbA 1c (%) 7.29 ± ± 1.84 NS 7.38 ± ± 1.73 P = HOMA-IR, median P < P < Blood urea nitrogen (mmol/l) 6.04 ± ± 1.69 NS 6.02 ± ± 1.73 NS Creatinine (µmol/l) ± ± NS ± ± NS Uric acid (µmol/l) ± ± P = ± ± P = 0.03 hscrp, median (mg/l) P < P < a One-way analysis of variance or Pearson s χ 2 -test. Data presented as mean ± SD unless stated otherwise. IDF, International Diabetes Federation; AHA, American Heart Association; NHLBI, National Heart, Lung, and Blood Institute; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; HbA 1c, glycosylated haemoglobin; HOMA-IR, homeostasis model assessment of insulin resistance; hscrp, high-sensitivity C-reactive protein; NS, not statistically significant (P > 0.05). 1927

6 using the IDF definition (P < 0.001), but not in those with metabolic syndrome classified using the IDF/AHA/NHLBI definition. SERUM HSCRP One-way ANOVA after logarithmic transformation of serum hscrp levels showed that hscrp was higher in metabolic syndrome patients compared with nonmetabolic syndrome patients when classified using either definition. There was no significant difference between serum hscrp levels in patients with metabolic syndrome according to the IDF definition versus patients with metabolic syndrome according to the IDF/AHA/NHLBI definition. Serum hscrp levels were significantly correlated with the following metabolic syndrome components: waist circumference (correlation coefficient 0.212, P < 0.001); systolic blood pressure (correlation coefficient 0.219, P < 0.001); diastolic blood pressure (correlation coefficient 0.266, P < 0.001); triglycerides (correlation coefficient 0.200, P < 0.001); and HbA 1c (correlation coefficient 0.124, P = 0.006). Serum hscrp levels increased as the number of metabolic syndrome components increased when using either the IDF or IDF/AHA/NHLBI definitions (P < after adjusting for age, sex and smoking). For those who met the criteria for one through five components of metabolic syndrome, the median serum hscrp levels were 0.64, 1.53, 1.70, 2.56 and 2.32 mg/l, respectively, using either the IDF or the IDF/AHA/NHLBI definitions. There was a significant difference in serum hscrp levels between patients grouped according to whether they met both definitions, only the IDF/AHA/NHLBI definition, or neither definition: median serum hscrp was 2.37 mg/l in the 267 patients who met both definitions, 1.63 mg/l in the 61 patients (28 men and 33 women) who met the IDF/AHA/NHLBI definition but not the IDF definition, and 1.08 mg/l in the 178 patients who did not meet either definition (P < 0.001). After serum hscrp levels were logarithmically transformed, post hoc comparison showed that those with metabolic syndrome by the IDF/AHA/NHLBI definition, but not the IDF definition, had significantly higher hscrp levels than those who did not meet either definition (P = 0.004) and similar hscrp levels to metabolic syndrome patients who met both definitions. The results of multivariate linear regression using logarithmically transformed hscrp as the dependent variable are given in Table 2. The presence of metabolic syndrome was correlated with higher serum hscrp levels after adjusting for age, gender and smoking for both definitions (models 1 and 2; P < 0.001). The status of metabolic syndrome according to the IDF/AHA/NHLBI definition was significantly correlated (P = 0.006) with serum hscrp levels after adjusting for age, gender, smoking and the status of metabolic syndrome according to the IDF definition (model 3). The partial correlation coefficient of metabolic syndrome according to the IDF/AHA/NHLBI definition was significant, suggesting that adding the status of metabolic syndrome according to the IDF/AHA/NHLBI definition increased the fit of the model. In contrast, the status of metabolic syndrome according to the IDF definition was no longer correlated with serum hscrp levels after adjusting for age, gender, smoking and the status of metabolic syndrome according to the IDF/AHA/NHLBI definition (model 3). Adding the status of metabolic syndrome according to the IDF definition to model 1 did not increase the fit of the model, since its partial correlation coefficient was not significant (model 3). 1928

7 TABLE 2: Multivariate linear regression models using logarithmic-transformed high-sensitivity C-reactive protein as the dependent variable in Chinese patients diagnosed with type 2 diabetes classified according to the IDF/AHA/NHLBI 10 and IDF 9 definitions of metabolic syndrome Model 1 a Model 2 b Model 3 c Statistical Statistical Statistical b r significance b r significance b r significance Age P = P = P = Gender NS NS NS Smoking habit P = P = P = Metabolic syndrome P < NS IDF definition Metabolic syndrome P < P = IDF/AHA/NHLBI definition a Model 1, after adjusting for age, gender and smoking for the IDF definition. b Model 2, adjusted for age, gender and smoking for the IDF/AHA/NHLBI definition. c Model 3, after adjusting for age, gender, smoking and the status of metabolic syndrome according to the IDF definition. IDF, International Diabetes Federation; AHA, American Heart Association; NHLBI, National Heart, Lung, and Blood Institute; β, regression coefficient; r, partial correlation coefficient; NS, not statistically significant (P > 0.05). 1929

8 Discussion Several studies conducted in Chinese populations have demonstrated that hscrp levels are closely related to individual metabolic syndrome components and the metabolic syndrome itself. Ye et al. 18 found that the hscrp level was highly associated with metabolic syndrome, as defined by NCEP-ATP III, among people years old after adjusting for gender. Lao et al. 19 revealed a strong relationship between hscrp and the constellation of the metabolic syndrome components defined by the IDF, but did not find any gender-specific associations between hscrp and metabolic syndrome. Wen et al. 20 reported that the hscrp concentration was lower in a rural Chinese population than in Caucasians and was strongly related to the metabolic syndrome, especially in women. In the present study, serum hscrp levels were higher in metabolic syndrome patients than in non-metabolic syndrome patients when classified by either definition. In addition, hscrp levels increased as the number of metabolic syndrome components increased. This association between low-grade inflammation and metabolic syndrome is in agreement with the findings of Esposito and Giugliano 21 who suggested that heightened inflammatory responses could lead to insulin resistance and compensatory hyper - insulinaemia, largely attributable to the action of inflammatory cytokines released from adipocytes. The pro-inflammatory state that accompanies metabolic syndrome is associated with both insulin resistance and endothelial dysfunction, providing a connection between inflammation and metabolic processes that is highly deleterious for vascular function. 22 The presence of metabolic syndrome is used to identify individuals at high risk of type 2 diabetes and cardiovascular disease. Serum hscrp levels have been shown to correlate with, and predict, future cardiovascular events. 23,24 Moreover, hscrp may have direct harmful effects on vessel walls, 25 leading to altered endothelial permeability and diminished peripheral blood flow which, in turn, results in limited insulin delivery and insulin resistance, both of which are important characteristics of type 2 diabetes. In light of this, a good definition of metabolic syndrome should distinguish between patients who have high or low serum hscrp levels. The present study suggests that the IDF/AHA/NHLBI definition of metabolic syndrome 10 may be better than the IDF definition, 9 since it has a stronger relationship with hscrp. The major difference between the two classification systems is that central obesity is essential for the IDF definition, but not for the IDF/AHA/NHLBI definition. This may lead to the different relationships with hscrp that were observed in the present study. In the present study, 61 patients were classified as having metabolic syndrome using the IDF/AHA/NHLBI definition but not the IDF definition, as their waist circumference did not meet the criteria for central obesity. Post hoc comparison of these patients showed that they had similar hscrp levels to metabolic syndrome patients who met both definitions and higher hscrp levels than those who did not meet either definition. Adipose tissue in centrally obese subjects produces pro-inflammatory cytokines, such as tumour necrosis factor-α and interleukin-6 which, in turn, increase hepatic hscrp production. 26 Other components of metabolic syndrome such as hypertension and dyslipidaemia could, however, also directly cause endothelial dysfunction and subclinical atherosclerosis, leading to inflammation and a raised hscrp level. 24 The fact that components of metabolic syndrome other than central 1930

9 obesity can lead to raised hscrp levels may explain why, in the present study, the IDF/AHA/NHLBI definition (in which central obesity is not an essential criteria) showed a better correlation with hscrp levels than the IDF definition. In conclusion, the present study in Chinese patients with type 2 diabetes showed that those with metabolic syndrome, as classified by the new IDF/AHA/NHLBI and previous IDF definitions 9,10 have higher serum hscrp levels than those who do not have metabolic syndrome. The new IDF/AHA/NHLBI definition of metabolic syndrome may have a stronger relationship with serum hscrp levels than the older IDF definition. This suggests that central obesity might not be an essential component of metabolic syndrome and that the new unified IDF/AHA/NHLBI definition of metabolic syndrome should be adopted in Chinese patients with type 2 diabetes. Acknowledgements This study was funded by a grant from the Shanghai Science and Technology Commission (04dz19504) to Professor Renming Hu, a grant from Fudan University (08FQ37) to Dr Bin Lu, a grant from the National Nature Science Foundation of China (No ) to Dr Shuo Zhang, and a grant from the Youth Science Foundation of Shanghai Health Bureau (2008Y040) to Yehong Yang. We thank Drs Jingchong Fang, Min He, Wei Li, Ji Hu, Xiajuan Wang, Xiufang Yang, Kuixiang Huang, Jingjun Jin and Kejun Yang for their help in visiting patients. Conflicts of interest The authors had no conflicts of interest to declare in relation to this article. Received for publication 8 June 2010 Accepted subject to revision 21 June 2010 Revised accepted 9 October 2010 Copyright 2010 Field House Publishing LLP References 1 Hu G, Qiao Q, Tuomilehto J, et al: Prevalence of the metabolic syndrome and its relation to allcause and cardiovascular mortality in nondiabetic European men and women. Arch Intern Med 2004; 164: Girman CJ, Rhodes T, Mercuri M, et al: The metabolic syndrome and risk of major coronary events in the Scandinavian Simvastatin Survival Study (4S) and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Am J Cardiol 2004; 93: Lakka HM, Laaksonen DE, Lakka TA, et al: The metabolic syndrome and total and cardiovascular disease mortality in middleaged men. JAMA 2002; 288: Malik S, Wong ND, Franklin SS, et al: Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults. Circulation 2004; 110: Pickup JC, Mattock MB, Chusney GD, et al: NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997; 40: Pradhan AD, Manson JE, Rifai N, et al: C- reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 2001; 286: Tracy RP, Kuller LH: C-reactive protein, heart disease risk, and the popular media. Arch Intern Med 2005; 165: Onat A, Can G, Hergenç G: Serum C-reactive protein is an independent risk factor predicting cardiometabolic risk. Metabolism 2008; 57: Alberti KG, Zimmet P, Shaw J for the IDF Epidemiology Task Force Consensus Group: The metabolic syndrome a new worldwide definition. Lancet 2005; 366: Alberti KG, Eckel RH, Grundy SM, et al: Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009; 120:

10 11 de Simone G, Devereux RB, Chinali M, et al on behalf of the Strong Heart Study Investigators: Prognostic impact of metabolic syndrome by different definitions in a population with high prevalence of obesity and diabetes: the Strong Heart Study. Diabetes Care 2007; 30: Luk AO, Ma RC, So WY, et al: The NCEP-ATPIII but not the IDF criteria for the metabolic syndrome identify type 2 diabetic patients at increased risk of chronic kidney disease. Diabet Med 2008; 25: Lu B, Yang Y, Song X, et al: An evaluation of the International Diabetes Federation definition of metabolic syndrome in Chinese patients older than 30 years and diagnosed with type 2 diabetes mellitus. Metabolism 2006; 55: Lu B, Wen J, Song XY, et al: High prevalence of albuminuria in population-based patients diagnosed with type 2 diabetes in the Shanghai downtown. Diabetes Res Clin Pract 2007; 75: Lu B, Song X, Dong X, et al: High prevalence of chronic kidney disease in population-based patients diagnosed with type 2 diabetes in downtown Shanghai. J Diabetes Complications 2008; 22: Dong X, He M, Song X, et al: Performance and comparison of the Cockcroft Gault and simplified Modification of Diet in Renal Disease formulae in estimating glomerular filtration rate in a Chinese type 2 diabetic population. Diabet Med 2007; 24: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: Ye X, Yu Z, Li H, et al: Distributions of C-reactive protein and its association with metabolic syndrome in middle-aged and older Chinese people. J Am Coll Cardiol 2007; 49: Lao XQ, Thomas GN, Jiang CQ, et al: C-reactive protein and the metabolic syndrome in older Chinese: Guangzhou Biobank Cohort Study. Atherosclerosis 2007; 194: Wen J, Liang Y, Wang F, et al: Association of C- reactive protein and metabolic syndrome in a rural Chinese population. Clin Biochem 2009; 42: Esposito K, Giugliano D: The metabolic syndrome and inflammation: association or causation? Nutr Metab Cardiovasc Dis 2004; 14: Ritchie SA, Connell JM: The link between abdominal obesity, metabolic syndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis 2007;17: Hoekstra T, Geleijnse JM, Schouten EG, et al: Relationship of C-reactive protein with components of the metabolic syndrome in normal-weight and overweight elderly. Nutr Metab Cardiovasc Dis 2005; 15: Rutter MK, Meigs JB, Sullivan LM, et al: C- reactive protein, the metabolic syndrome, and prediction of cardiovascular events in the Framingham Offspring Study. Circulation 2004; 110: Pasceri V, Willerson JT, Yeh ET: Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: Park HS, Park JY, Yu R: Relationship of obesity and visceral adiposity with serum concentrations of CRP, TNF-α and IL-6. Diabetes Res Clin Pract 2005; 69: Author s address for correspondence Professor Renming Hu Department of Endocrinology and Metabolism, HuaShan Hospital, 12 Wulumuqi Road, Shanghai , China. renminghu@fudan.edu.cn 1932