Circulating Adipocyte Fatty Acid-binding Protein Levels Research Articles

Development of a therapeutic monoclonal antibody against circulating adipocyte fatty acid binding protein to treat ischaemic stroke.

Adipocyte fatty acid-binding protein (A-FABP) exacerbates cerebral ischaemia injury by disrupting the blood-brain barrier (BBB) through inducing expression of MMP-9. Circulating A-FABP levels positively correlate with infarct size in stroke patients. We hypothesized that targeting circulating A-FABP by a neutralizing antibody would alleviate ischaemic stroke outcome. Monoclonal antibodies (mAbs) against A-FABP were generated using mouse hybridoma techniques. Binding affinities of a generated mAb named 6H2 towards various FABPs were determined using Biacore. Molecular docking studies were performed to characterize the 6H2-A-FABP complex structure and epitope. The therapeutic potential and safety of 6H2 were evaluated in mice with transient middle cerebral artery occlusion (MCAO) and healthy mice, respectively. Replenishment of recombinant A-FABP exaggerated the stroke outcome in A-FABP-deficient mice. 6H2 exhibited nanomolar to picomolar affinities to human and mouse A-FABP, respectively, with minimal cross-reactivities with heart and epidermal FABPs. 6H2 effectively neutralized JNK/c-Jun activation elicited by A-FABP and reduced MMP-9 production in macrophages. Molecular docking suggested that 6H2 interacts with the "lid" of the fatty acid binding pocket of A-FABP, thus likely hindering the binding of its substrates. In mice with transient MCAO, 6H2 significantly attenuated BBB disruption, cerebral oedema, infarction, neurological deficits, and decreased mortality associated with reduced cytokine and MMP-9 production. Chronic 6H2 treatment showed no obvious adverse effects in healthy mice. These results establish circulating A-FABP as a viable therapeutic target for ischaemic stroke, and provide a highly promising antibody drug candidate with high affinity and specificity.

Serum Adipocyte Fatty-Acid Binding Protein as an Independent Marker of Peripheral Artery Disease in Patients with Type-2 Diabetes Mellitus.

The adipocyte fatty-acid binding protein (A-FABP) is predominantly expressed in macrophages and adipocytes and is an essential mediator of inflammation and atherosclerosis pathogenesis. Atherosclerosis is an aggravating factor for peripheral arterial disease (PAD). Our study intended to study the association between PAD and serum A-FABP levels in type-2 diabetes mellitus (T2DM) patients. One hundred and twenty T2DM subjects were enrolled in the study. Fasting blood samples were collected to determine biochemical data and A-FABP levels. By the automatic oscillometric method, the ankle–brachial index (ABI) was measured. Low ABI was defined as any value < 0.9. Twenty participants with T2DM (16.7%) were included in the low ABI group. Low ABI T2DM participants had an increased mean body mass index, body fat mass, systolic blood pressure, C-reactive protein, urine albumin–creatinine ratio, and A-FABP levels compared to those in the normal ABI group. After variables significantly associated with PAD were adjusted by multivariate logistic regression analyses, circulating A-FABP levels (odds ratio [OR]: 1.138; 95 percent confidence interval [CI]: 1.023–1.266; p = 0.017) were identified as the independent marker of PAD. In conclusion, fasting serum A-FABP value has positive association with PAD in T2DM patients.

Prospective association of serum adipocyte fatty acid-binding protein with heart failure hospitalization in diabetes.

AimsAdipocyte fatty acid‐binding protein (AFABP) is associated with cardiovascular diseases in type 2 diabetes. Whether circulating AFABP levels are associated with the risk of heart failure (HF) in type 2 diabetes remains undefined. We investigated the prospective association of circulating AFABP levels with incident HF hospitalization in type 2 diabetes, and its relationship to the use of sodium glucose co‐transporter 2 inhibitors (SGLT2i) which reduce HF risk.Methods and resultsBaseline serum AFABP level was measured in 3322 Chinese participants without known history of cardiovascular diseases or hospitalization for HF, recruited from the Hong Kong West Diabetes Registry. Its association with incident HF hospitalization was evaluated using multivariable Cox regression analysis. Use of SGLT2i was included as a time‐dependent covariate. Among these 3322 participants (52.9% men; mean age 60.0 ± 12.6), 176 (5.3%) developed HF hospitalization over a median follow‐up of 8 years. Seven hundred and thirty‐one (22%) were started on SGLT2i during the study period (empagliflozin 55.1%, dapagliflozin 44.2%, canagliflozin 0.4%, and ertugliflozin 0.3%). Serum AFABP levels were significantly higher in participants who developed HF hospitalization than those who did not (men: 14.8 vs. 8.3 ng/mL; women: 21.5 vs. 14.6 ng/mL; all: 18.6 vs. 10.9 ng/mL, P < 0.001). In multivariable Cox regression analysis, baseline serum AFABP level was significantly associated with incident HF hospitalization [hazard ratio (HR) 1.38, 95% confidence interval (CI) 1.06–1.80, P = 0.019] independent of the use of SGLT2i, in a model also consisting of age; sex; body mass index; smoking status; duration of diabetes; hypertension, dyslipidaemia; atrial fibrillation; presence of chronic kidney disease and albuminuria; glycated haemoglobin and high‐sensitivity C‐reactive protein levels; and use of metformin, insulin, aspirin, furosemide, and beta‐blockers at baseline. High cumulative defined daily dose (cDDD) of SGLT2i was protective of incident HF hospitalization (HR 0.10, 95% CI 0.01–0.68, P = 0.019). The addition of circulating AFABP level to a clinical model of conventional HF risk factors provided significant improvement in the category‐free net reclassification index (11.5%, 95% CI 1.6–22.1, P = 0.02) and integrated discrimination improvement (0.3%, 95% CI 0.1–1.7, P = 0.04). A dose‐dependent reduction in cumulative incidence of HF hospitalization in response to SGLT2i, based on cDDD, was more clearly observed in participants with a higher baseline AFABP level above the sex‐specific median (P for trend <0.01).ConclusionsCirculating AFABP level is independently associated with incident HF hospitalization in type 2 diabetes and is potentially helpful in risk stratification for the prevention of HF hospitalization.

Adipocyte Fatty Acid-Binding Protein, Cardiovascular Diseases and Mortality.

It has been increasingly recognized that inflammation plays an important role in the pathogenesis of cardiovascular disease (CVD). In obesity, adipose tissue inflammation, especially in the visceral fat depots, contributes to systemic inflammation and promotes the development of atherosclerosis. Adipocyte fatty acid-binding protein (AFABP), a lipid chaperone abundantly secreted from the adipocytes and macrophages, is one of the key players mediating this adipose-vascular cross-talk, in part via its interaction with c-Jun NH2-terminal kinase (JNK) and activator protein-1 (AP-1) to form a positive feedback loop, and perpetuate inflammatory responses. In mice, selective JNK inactivation in the adipose tissue significantly reduced the expression of AFABP in their adipose tissue, as well as circulating AFABP levels. Importantly, fat transplant experiments showed that adipose-specific JNK inactivation in the visceral fat was sufficient to protect mice with apoE deficiency from atherosclerosis, with the beneficial effects attenuated by the continuous infusion of recombinant AFABP, supporting the role of AFABP as the link between visceral fat inflammation and atherosclerosis. In humans, raised circulating AFABP levels are associated with incident metabolic syndrome, type 2 diabetes and CVD, as well as non-alcoholic steatohepatitis, diabetic nephropathy and adverse renal outcomes, all being conditions closely related to inflammation and enhanced CV mortality. Collectively, these clinical data have provided support to AFABP as an important adipokine linking obesity, inflammation and CVD. This review will discuss recent findings on the role of AFABP in CVD and mortality, the possible underlying mechanisms, and pharmacological inhibition of AFABP as a potential strategy to combat CVD.

Association between adipocyte fatty acid-binding protein with left ventricular remodelling and diastolic function in type 2 diabetes: a prospective echocardiography study

BackgroundThe relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM.MethodsCirculating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively.ResultsThe median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e′ (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16–6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease.ConclusionCirculating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.

Circulating adipocyte fatty acid-binding protein is reduced by continuous positive airway pressure treatment for obstructive sleep apnea-a randomized controlled study.

The circulating level of adipocyte fatty acid-binding protein (AFABP), a biomarker with prognostic and therapeutic importance in metabolic disorders, has been shown to be elevated in obstructive sleep apnea (OSA). This randomized controlled study aimed to investigate the effect of continuous positive airway pressure (CPAP) treatment for OSA on AFABP levels. Consecutive subjects attending sleep study were invited if they were confirmed to have severe OSA and were free of metabolic diseases. Participants were randomized (1:1) into CPAP or observation group for 4weeks. Demographics, anthropometric data, and circulating biomarkers were checked at baseline and after the 4-week study period. Ninety subjects were randomized. The mean age was 46 ± 9years old; 82% were male. Their mean body mass index (BMI) was 29 ± 5kg/m2. By intention-to-treat approach, the CPAP group showed significant reductions in Epworth sleepiness scale and morning systolic blood pressure (- 7.2mmHg, - 12.7 to - 1.7mmHg, p = 0.011), but no significant difference in AFABP, adiponectin, C-reactive protein (CRP), and 8-isoprostane levels. In the per-protocol analysis, when only those who were compliant to CPAP were included, a significant reduction in AFABP (- 7.32ng/ml, - 13.58, - 1.06, p = 0.023) were found in the CPAP-treated group compared with the control group, along with improvements in clinical parameters. Changes in AFABP were independently associated with both systolic blood pressure (β = 0.289, p = 0.028) and diastolic blood pressure (β = 0.217, p = 0.030). CPAP therapy used regularly over 4weeks for severe OSA lowered circulating AFABP level, suggesting a potential beneficial effect of OSA treatment on alleviating metabolic risks. The research protocol was registered at the National Institutes of Health clinical trials registry (NCT01173432).

Prospective associations of circulating adipocyte fatty acid-binding protein levels with risks of renal outcomes and mortality in type 2 diabetes.

Elevated circulating adipocyte fatty acid-binding protein (AFABP) levels have been found to correlate with diabetic nephropathy staging in cross-sectional studies. However, it remains unclear whether these higher serum levels reflect a role of AFABP in the development of diabetic kidney disease (DKD), or simply result from its impaired renal clearance in DKD. Here we investigated prospectively the prognostic importance of serum AFABP level in the development of adverse renal outcomes in a large clinic-based cohort of participants with type 2 diabetes. Baseline serum AFABP levels were measured in 5454 Chinese participants from the Hong Kong West Diabetes Registry. The association between circulating AFABP levels and incident adverse renal outcomes-defined as a composite endpoint of a sustained 40% decline in eGFR, end-stage renal disease requiring renal replacement therapy or kidney transplantation, or renal deaths-was evaluated using multivariable Cox regression analysis. Over a median follow-up of 5years, 754 of the 5454 participants developed incident adverse renal outcomes. Elevated circulating AFABP levels were independently associated with incident adverse renal outcomes (HR 1.43, 95% CI 1.31, 1.57, p < 0.001) after adjustments for conventional risk factors for DKD progression. Importantly, the prognostic role of serum AFABP was independent of the baseline albuminuria status or eGFR levels of the study participants. Circulating AFABP levels were predictive of incident adverse renal outcomes, even in participants with relatively well-preserved kidney function at baseline, suggesting its potential to be a useful marker for early risk stratification in DKD.

Deficiency of adipocyte fatty-acid-binding protein alleviates myocardial ischaemia/reperfusion injury and diabetes-induced cardiac dysfunction.

Clinical evidence shows that circulating levels of adipocyte fatty-acid-binding protein (A-FABP) are elevated in patients with diabetes and closely associated with ischaemic heart disease. Patients with diabetes are more susceptible to myocardial ischaemia/reperfusion (MI/R) injury. The experiments in the present study investigated the role of A-FABP in MI/R injury with or without diabetes. Non-diabetic and diabetic (streptozotocin-induced) A-FABP knockout and wild-type mice were subjected to MI/R or sham intervention. After MI/R, A-FABP knockout mice exhibited reductions in myocardial infarct size, apoptotic index, oxidative and nitrative stress, and inflammation. These reductions were accompanied by an improved left ventricular function compared with the relative controls under non-diabetic or diabetic conditions. After diabetes induction, A-FABP knockout mice exhibited a preserved cardiac function compared with that in wild-type mice. Endothelial cells, but not cardiomyocytes, were identified as the most likely source of cardiac A-FABP. Cardiac and circulating A-FABP levels were significantly increased in mice with diabetes or MI/R. Diabetes-induced superoxide anion production was significantly elevated in wild-type mice, but diminished in A-FABP knockout mice, and this elevation contributed to the exaggeration of MI/R-induced cardiac injury. Phosphorylation of endothelial nitric oxide synthase (eNOS) and production of nitric oxide (NO) were enhanced in both diabetic and non-diabetic A-FABP knockout mice after MI/R injury, but diminished in wild-type mice. The beneficial effects of A-FABP deficiency on MI/R injury were abolished by the NOS inhibitor N(G)-nitro-L-arginine methyl ester. Thus, A-FABP deficiency protects mice against MI/R-induced and/or diabetes-induced cardiac injury at least partially through activation of the eNOS/NO pathway and reduction in superoxide anion production.

Lipocalin-2, A-FABP and inflammatory markers in relation to flow-mediated vasodilatation in patients with essential hypertension

Lipocalin families including lipocalin-2 and adipocyte fatty acid binding protein (A-FABP) were recently identified as novel adipokines to be associated with the cardiovascular risk variables of the metabolic syndrome. We evaluated the lipocalin-2 and A-FABP levels in 62 patients with essential hypertension (EHT) and 16 age-, gender- and body mass index-matched normotensive healthy subjects (NT). Furthermore, we evaluated the correlation between lipocalin-2, A-FABP levels, inflammatory markers including hsCRP and IL-10, and flow-mediated vasodilatation (FMD). In EHT, circulating lipocalin-2 levels were significantly higher than in NT (85.0 ± 37.6 ng/ml versus 43.8 ± 13.1 ng/ml, p < 0.001). However, A-FABP levels were not different between patients with EHT and NT. Serum lipocalin-2 levels were positively associated with SBP (r = 0.54, p < 0.001), DBP (r = 0.34, p = 0.003) and fasting glucose levels (r = 0.25, p = 0.032), On the other hand, circulating A-FABP levels were significantly associated with variables such as BMI, fasting insulin, insulin resistance index and hsCRP. Multiple linear regression analysis showed that mean arterial pressure was associated with fasting glucose, lipocalin-2 levels, age, BMI and hsCRP levels (R2 = 0.456). However, circulating lipocalin-2 levels were not associated with FMD. In conclusion, lipocalin-2 levels were significantly higher in patients with EHT, and were independently associated with mean arterial pressure.

Association between serum adipocyte fatty-acid binding protein concentrations, left ventricular function and myocardial perfusion abnormalities in patients with coronary artery disease

BackgroundAdipokines, including adipocyte fatty acid-binding protein (A-FABP), have been demonstrated to be involved in the pathogenesis of atherosclerosis. In the present study, we investigated the association of circulating A-FABP level with severity of myocardial perfusion abnormalities analyzed by Tl-201 dipyridamole single-photon emission computed tomography.MethodsA total of 170 patients with coronary artery disease (CAD) from cardiovascular clinics were enrolled in the study. Serum A-FABP levels, echocardiography, and stress myocardial perfusion imaging results were analyzed.ResultsCompared with the patients with mild CAD (summed stress score [SSS] ≤ 8), those with moderate to severe CAD (SSS > 8) had significantly higher A-FABP concentrations. However, the difference was attenuated in the subgroup of patients with heart failure. In the correlation analyses, A-FABP level was correlated with age, body mass index, waist circumference, levels of creatinine, fasting glucose, high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, adiponectin, and several echocardiographic parameters, including left ventricular ejection fraction. Multivariate logistic regression analysis demonstrated that the A-FABP level was not only associated with higher SSS (odds ratio, 1.30; 95% confidence interval [CI], 1.01–1.69; P = 0.048), but also an independent risk factor for heart failure (odds ratio 2.71, 95% CI, 1.23–5.94; P = 0.013).ConclusionsSerum A-FABP levels not only were associated with myocardial perfusion abnormalities and left ventricular function, but also predicted the presence of heart failure in our patients with CAD.

Circulating Adipocyte Fatty Acid-Binding Protein Levels and Cardiovascular Morbidity and Mortality in Patients With Coronary Heart Disease

Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1-120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22-3.92, P<0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18-1.95; P=0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98-1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17-2.62, P=0.007). Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.

Serum Adipocyte Fatty Acid-Binding Protein Is Associated Independently with Vascular Inflammation: Analysis with18F-Fluorodeoxyglucose Positron Emission Tomography

The inflammatory status of atherosclerotic lesions is a major factor triggering acute cardiovascular events. Growing evidence has shown that adipocyte fatty acid-binding protein (A-FABP) has an important role in the development of atherosclerosis. The objective of the study was to determine the association between circulating A-FABP levels with vascular inflammation as measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a novel imaging technique for noninvasive measurement of atherosclerotic inflammation. This was a cross-sectional study. Eighty-seven men without previously diagnosed cardiovascular disease or diabetes participated in the study. We measured the serum A-FABP, adiponectin, and leptin levels as well as other cardiovascular risk factors. Vascular inflammation in the carotid arterial wall, as indicated by the target to background ratio (TBR), was analyzed using FDG-PET. The circulating A-FABP and leptin levels had positive correlations with maximum TBR values (r = 0.38, P < 0.001; and r = 0.28, P = 0.010, respectively), whereas the adiponectin levels had a negative correlation (r = -0.31, P = 0.004). The maximum TBR levels exhibited an additive linear increment according to the rise in tertiles of the A-FABP levels in subjects with and without metabolic syndrome. Multiple regression analysis showed that serum A-FABP levels were independently associated with maximum TBR after adjustment for other cardiovascular risk factors (P = 0.006). Circulating A-FABP, adiponectin, and leptin levels were shown to be associated with vascular inflammation, as measured using FDG-PET. Specifically, the A-FABP level was an independent risk factor for vascular inflammation in Korean men without cardiovascular disease or diabetes.

Effect of exercise training on A‐FABP, lipocalin‐2 and RBP4 levels in obese women

Lipocalin family proteins, including adipocyte fatty acid-binding protein (A-FABP), lipocalin-2 and retinol-binding protein 4 (RBP4), have recently been identified as novel adipokines associated with obesity, type 2 diabetes and the metabolic syndrome. We have evaluated the effect of exercise training on lipocalin family proteins and inflammatory markers. Thirty obese Korean women and 15 age-matched nonobese control subjects were studied. Concentrations of the lipocalin family proteins were compared between obese and nonobese women and were evaluated before and 3 months after an exercise programme consisting of aerobic exercise (45 min/session, 300 kcal/day) and muscle strength training (20 min/session, 100 kcal/day) five times a week. Obese women exhibited higher A-FABP levels compared to nonobese women (21.4 +/- 6.4 microg/l vs. 13.6 +/- 4.4 microg/l, P < 0.001). However, neither lipocalin-2 nor RBP4 levels were significantly different between the two groups, although the difference in lipocalin-2 was marginally significant (P = 0.054). Circulating A-FABP levels were significantly associated with body mass index (BMI), waist circumference, triglyceride, alanine aminotransferase (ALT), lipocalin-2 and high-sensitivity C-reactive protein (hsCRP) levels. After 3 months of the exercise training programme, serum A-FABP levels decreased significantly from 21.4 +/- 6.4 microg/l to 19.3 +/- 6.8 microg/l (P = 0.038), along with a reduction in weight, BMI, waist circumference, fasting glucose and total cholesterol levels. There was no significant change in the lipocalin-2 and RBP4 levels, although IL-6 levels increased after the exercise programme. Exercise training with weight loss induced a significant reduction in circulating A-FABP levels in obese Korean women.

Serum levels of adipocyte fatty acid‐binding protein (AFABP) are increased in chronic haemodialysis (CD)

Adipocyte fatty acid-binding protein (AFABP) was recently introduced as an adipocyte-expressed factor, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In the current study, we investigated renal elimination of this protein by comparing circulating AFABP levels in patients on chronic haemodialysis (CD) with controls. We hypothesized that if renal filtration is a significant route of elimination of AFABP, it would accumulate in CD patients. AFABP was determined by ELISA in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation, in both groups. Median serum AFABP levels were more than 10-fold higher in CD patients (510.9 +/- 294.7 microg/l) as compared to controls (44.3 +/- 35.2 microg/l). Furthermore, CD independently predicted AFABP concentrations in multiple regression analysis. In addition, body mass index and free fatty acids were independently associated with circulating AFABP. Renal filtration appears as an important route of elimination of AFABP. Future studies should elucidate whether this adipocyte-expressed factor contributes to the increased risk of cardiovascular disease found in end-stage renal disease.

Serum Adipocyte Fatty Acid–Binding Protein as a New Biomarker Predicting the Development of Type 2 Diabetes

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. 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. At baseline, serum sex-adjusted A-FABP levels were higher in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) (P < 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 = 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 = 0.018). Serum A-FABP was associated with glucose dysregulation and predicted the development of type 2 diabetes in a Chinese cohort.