Background-Adipocyte-fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria. Methods and Results-In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, Pϭ0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (Pϭ0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile, Pϭ0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components. Conclusions-Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.

OBJECTIVE -Adipocyte fatty acid-binding protein (A-FABP) is abundantly expressed in adipocytes and plays a role in glucose homeostasis in experimental animals. We have previously shown that circulating A-FABP levels are associated with the metabolic syndrome, which confers an increased risk of type 2 diabetes. Here we investigated whether serum A-FABP levels could predict the development of diabetes in a 10-year prospective study. RESEARCH DESIGN AND METHODS-Baseline serum A-FABP levels were measured with an enzyme-linked immunosorbent assay in 544 nondiabetic subjects, recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort, who were followed prospectively to assess the development of type 2 diabetes. The role of A-FABP in predicting the development of type 2 diabetes over 10 years was investigated using Cox regression analysis.RESULTS -At baseline, serum sex-adjusted A-FABP levels were higher in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) (P Ͻ 0.00001 versus normal glucose tolerance) and correlated positively with adverse cardiometabolic risk factors. Over 10 years, 96 subjects had developed type 2 diabetes. High baseline A-FABP was predictive of type 2 diabetes, independent of obesity, insulin resistance, or glycemic indexes (relative risk [RR] 2.25 [95% CI 1.40 -3.65]; P ϭ 0.001; above versus below sex-specific median). High A-FABP levels remained an independent predictor of type 2 diabetes in the high-risk IGT/IFG subgroup (adjusted RR 1.87 [1.12-3.15]; P ϭ 0.018).CONCLUSIONS -Serum A-FABP was associated with glucose dysregulation and predicted the development of type 2 diabetes in a Chinese cohort. Diabetes Care 30:2667-2672, 2007A dipocyte fatty acid-binding protein (A-FABP), also known as aP2 or FABP4, is one of the most abundant proteins in mature adipocytes (1). It belongs to a family of fatty acid-binding proteins, which are small cytoplasmic proteins expressed in a highly tissuespecific manner, thought to be important in mediating intracellular fatty acid trafficking and energy metabolism (2,3). Recent studies in animal models suggested that A-FABP may be important in glucose homeostasis. Deletion of the A-FABP gene protected mice from insulin resistance and hyperinsulinemia associated with both diet-induced obesity (4) and genetic obesity (5). In humans, a promoter polymorphism, T-87C, of the A-FABP gene that resulted in reduced adipose tissue A-FAPB mRNA expression was found to be associated with reduced risk for type 2 diabetes and cardiovascular disease (6).We have previously demonstrated that A-FABP, although traditionally considered to be an intracellular cytosolic protein, is present in the circulation (7). We have also reported the positive association between serum A-FABP levels and parameters of adiposity, hyperglycemia, insulin resistance, and the metabolic syndrome in cross-sectional (7,8) and longitudinal studies (9). As the metabolic syndrome is known to confer a more than threefold risk of development of type 2 diabetes (10),...

Abstract-Low circulating levels of adiponectin, an adipokine with insulin-sensitizing, antiatherogenic, and antiinflammatory properties, are found in hypertensive patients. Adiponectin replenishment ameliorated hypertension in adiponectin-deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting an etiologic role of adiponectin in hypertension. We aimed to determine, in this 5-year prospective study, whether hypoadiponectinemia could predict the development of hypertension in a nondiabetic Chinese cohort. A total of 577 subjects (249 men and 328 women) were recruited from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up for 5 years. The relationship of serum adiponectin with the development of hypertension (sitting blood pressure Ն140/90 mm Hg) was investigated in a nested case-control study consisting of 70 subjects who had developed hypertension on follow-up and 140 age-and sex-matched control subjects who were normotensive both at baseline and at year 5. At baseline, serum adiponectin level in the lowest sex-specific tertile was more likely to be associated with hypertension (Pϭ0.003 versus the highest tertile, after adjusting for age, body mass index, fasting insulin, and high-sensitivity C-reactive protein). At year 5, baseline serum adiponectin was a significant independent predictor of incident hypertension in the nested case-control study (Pϭ0.015; age adjusted), together with mean arterial pressure (PϽ0.001), high-sensitivity C-reactive protein (Pϭ0.018), and body mass index (Pϭ0.004). Normotensive subjects with baseline serum adiponectin levels in the lowest sex-specific tertile had an increased risk of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16; Pϭ0.037 versus highest tertile). Our data suggest that hypoadiponectinaemia may be involved in the pathogenesis of hypertension in humans.

Chinese patients in Hong Kong with the nondeletional type of hemoglobin H disease have more severe disease than those with the deletional type of the disease. Iron overload is a major cause of disability in both forms of the disease.

OBJECTIVETo investigate whether circulating levels of fibroblast growth factor 21 (FGF21), which previously has been shown to be elevated in obesity, could predict the development of type 2 diabetes in a 5.4-year, population-based, prospective study.RESEARCH DESIGN AND METHODSBaseline plasma FGF21 levels were measured using an enzyme-linked immunosorbent assay in 1,900 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). The prospective association of FGF21 with diabetes development over 5.4 years was analyzed using multiple logistic regression.RESULTSAt baseline, plasma levels of FGF21 increased progressively with worsening dysglycemia from normal glucose tolerance, through prediabetes, to diabetes (global trend, P < 0.001). Of 1,292 subjects without diabetes at baseline, a high baseline FGF21 level was a strong independent predictor for diabetes development (odds ratio 1.792; P < 0.01), together with waist circumference and fasting plasma glucose levels.CONCLUSIONSPlasma FGF21 levels were significantly increased in subjects with prediabetes and diabetes and predicted the development of diabetes in humans.

Objective-Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects. Approach and Results-The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (r=0.32; P<0.001), but not in men (r=0.06; P=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (P=0.039), together with age (P<0.001) and hypertension (P=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted R 2 =35.8%; P<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (P=0.01). with type 2 DM. 12,13 However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. To evaluate the relationship between serum FGF21 levels and atherosclerosis, we examined in 670 Southern Chinese subjects with no overt macrovascular disease the association between serum FGF21 levels and carotid intima-media thickness (IMT), a well-established marker of atherosclerosis. Conclusions-The14 Established cardiovascular risk factors and high sensitive C-reactive protein (CRP) were also measured to determine whether FGF21 is an independent risk factor for increased carotid IMT. Materials and MethodsMaterials and Methods are available in the online-only Supplement. ResultsThe demographic and biochemical characteristics of the subjects are summarized in Table 1. Of the 502 subjects recruited from the third assessment of the Hong Kong Cardiovascular Risk Factor Prevalence Study, 262, 128, and 112 had normal glucose tolerance, impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) and DM, respectively. In all, 176 (26.3%) and 76 (11.3%) of the 670 subjects were on antidiabetic and lipid-lowering medications, respectively. The former group comprised 109 metformin-treated subjects. For the use of peroxisome proliferator-activated receptors agonists, 20 subjects of the entire cohort were treated with fibrates and none of them was on thiazolidinediones. For these treatment modalities, there were no between-group differences in serum FGF21 levels based on analysis in which subjects were stratified according to the use of medication.Among subjects with different gl...

OBJECTIVE -We investigated the association of the metabolic syndrome with new-onset diabetes in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort.RESEARCH DESIGN AND METHODS -We followed up on 1,679 subjects without diabetes at baseline. Those with a previous diagnosis of diabetes or those who were receiving drug treatment were considered to be diabetic. The remaining subjects underwent a 75-g oral glucose tolerance test (OGTT). Diabetes was defined by plasma glucose Ն7.0 mmol/l with fasting and/or Ն11.1 mmol/l at 2 h.RESULTS -The prevalences of the metabolic syndrome at baseline were 14.5 and 11.4%, respectively, according to U.S. National Cholesterol Education Program (NCEP) and International Diabetes Federation (IDF) criteria. After a median of 6.4 years, there were 66 and 54 new cases of diabetes in men and women, respectively. The metabolic syndrome at baseline predicted incident diabetes. Hazard ratios (HRs) for the NCEP and IDF definitions of the syndrome were 4.1 [95% CI 2.8 -6.0] and 3.5 [2.3-5.2], respectively. HRs for fasting plasma glucose (FPG) Ն6.1 or 5.6 mmol/l were 6.9 [4.1-11.5] and 4.1 [2.8 -6.0], respectively. The NCEP and IDF criteria had 41.9 and 31.7% sensitivity and 87.5 and 90.2% specificity, respectively. Their positive predictive values were low, ϳ20%, but their negative predictive values were ϳ95%.CONCLUSIONS -The metabolic syndrome, particularly its component, elevated FPG, predicts diabetes in Chinese. An individual without the metabolic syndrome is unlikely to develop diabetes, but one who has it should practice therapeutic lifestyle changes and have periodic FPG measurements to detect new-onset diabetes. Diabetes Care 30:1430-1436, 2007T he metabolic syndrome has been promoted as a clinical tool for identifying individuals predisposed to diabetes and/or adverse cardiovascular outcomes (1-7). Attempts have been made by different consensus groups to produce diagnostic criteria for the syndrome, but there is still some controversy. The pathogenetic mechanism underlying the metabolic syndrome remains uncertain, although central obesity and insulin resistance have been proposed to play a causative role. Because insulin resistance, together with hyperinsulinemia, is a fundamental metabolic abnormality in type 2 diabetes, the metabolic syndrome may be expected to be a good predictor of the development of the latter. Asians are thought to have a higher body fat percentage and cardiovascular risks than Caucasians at a given BMI (8). These factors raise concerns that definitions of the metabolic syndrome for Caucasians, when applied to Asian populations, would underestimate the population at risk of developing adverse outcomes such as type 2 diabetes, cardiovascular disease, and mortality. Therefore, validation of the predictive value of the metabolic syndrome needs to be established in population-based cohorts of different ethnicities. The International Diabetes Federation (IDF) proposed a new definition of the metabolic syndrome, which uses ethnicspecific central obesity cri...

ALP is a marker of cardiometabolic risk, but it needs to be tested as part of a multivariate model in prospective studies.