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 SARS-CoV-2-related thyroiditis is increasingly recognized. The role of thyroid autoimmunity and SARS-CoV-2 viral load in SARS-CoV-2-related thyroid dysfunction is unclear. We evaluated the thyroid function of a cohort of COVID-19 patients, in relation to their clinical features, biochemical, immunological and inflammatory markers. Methods Consecutive adult patients, without known thyroid disorders, admitted to Queen Mary Hospital for COVID-19 from 21 July to 21 August, 2020 were included. Serum levels of thyroid-stimulating hormone (TSH), free thyroxine, free triiodothyronine (fT3) and anti-thyroid antibodies were measured on admission. Results Among 191 patients with COVID-19 (mean age 53.5 ± 17.2 years; 51.8% male), 84.3% were mild, 12.6% were moderate, and 3.1% were severe. 13.1% had abnormal thyroid function. Ten patients had isolated low TSH, suggestive of subclinical thyrotoxicosis due to thyroiditis, although the contribution of autoimmunity was likely in two of them. Autoimmune thyroiditis probably also contributed to subclinical hypothyroidism in another patient. Ten patients had isolated low fT3, likely representing non-thyroidal illness syndrome. Lower SARS-Cov-2 PCR cycle threshold values and elevated C-reactive protein were independently associated with occurrence of low TSH (p=0.030) and low fT3 (p=0.007) respectively. A decreasing trend of fT3 with increasing COVID-19 severity (p=0.032) was found. Patients with low fT3 had more adverse COVID-19-related outcomes. Conclusion Around 15% of patients with mild to moderate COVID-19 had thyroid dysfunction. There may be a direct effect of SARS-CoV-2 on thyroid function, potentially leading to exacerbation of pre-existing autoimmune thyroid disease. Low fT3, associated with systemic inflammation, may have a prognostic significance.

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.

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Coronavirus disease 2019 (COVID-19) has a wide spectrum of disease severity from mild upper respiratory symptoms to respiratory failure. The role of neutralizing antibody (NAb) response in disease progression remains elusive. This study determined the seroprevalence of 733 non-COVID-19 individuals from April 2018 to February 2020 in the Hong Kong Special Administrative Region and compared the neutralizing antibody (NAb) responses of eight COVID-19 patients admitted to the intensive care unit (ICU) with those of 42 patients not admitted to the ICU. We found that NAb against SARS-CoV-2 was not detectable in any of the anonymous serum specimens from the 733 non-COVID-19 individuals. The peak serum geometric mean NAb titer was significantly higher among the eight ICU patients than the 42 non-ICU patients (7280 [95% confidence interval (CI) 1468-36099]) vs (671 [95% CI, 368-1223]). Furthermore, NAb titer increased significantly at earlier infection stages among ICU patients than among non-ICU patients. The median number of days to reach the peak Nab titers after symptoms onset was shorter among the ICU patients (17.6) than that of the non-ICU patients (20.1). Multivariate analysis showed that oxygen requirement and fever during admission were the only clinical factors independently associated with higher NAb titers. Our data suggested that SARS-CoV-2 was unlikely to have silently spread before the COVID-19 emergence in Hong Kong. ICU patients had an accelerated and augmented NAb response compared to non-ICU patients, which was associated with disease severity. Further studies are required to understand the relationship between high NAb response and disease severity.

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Objective-Adipocyte fatty acid-binding protein (A-FABP) has been shown to be an important player in atherosclerosis in animal models. However, the clinical relevance of these findings is still unknown. This study aims to examine the relationship between serum A-FABP level and carotid intima-media thickness (IMT), an indicator of atherosclerosis in humans. Methods and Results-The study cohort included 479 Chinese subjects who underwent carotid IMT measurement.Serum A-FABP levels were determined by enzyme-linked immunosorbent assays. Serum A-FABP levels positively correlated with carotid IMT in both men (rϭ0.211, Pϭ0.001) and women (rϭ0.435, PϽ0.001). In women, but not in men, the presence of plaques was associated with significantly higher serum A-FABP levels (PϽ0.001 versus women without plaques). Stepwise multiple regression analysis showed that serum A-FABP level was independently associated with carotid IMT in women (Pϭ0.034), together with age and hypertension (both PϽ0.001). Conclusions-A-FABP is an independent determinant of carotid atherosclerosis in Chinese women, but not in men.This gender difference may be attributed to the lower serum A-FABP levels in men, and the effect of other risk factors, such as smoking, among our male participants. 2 Earlier animal studies showed that A-FABPnull mice were partially protected from developing hyperinsulinemia, hyperglycemia, and insulin resistance when challenged with dietary and genetic obesity. 3,4 In apolipoprotein E (apoE)-deficient mice, whether on a low-fat or high-fat diet, ablation of the A-FABP gene provided almost complete protection against atherosclerosis, independent of its effects on glucose and lipid metabolism. 5,6 Remarkably, after a high-fat atherogenic Western diet for 1 year, the survival rates of apoE Ϫ/Ϫ mice null for both A-FABP and mal1 were 67% higher than those of apoE Ϫ/Ϫ control mice, primarily because of the increased stability of atherosclerotic plaques. 7 These results suggest that A-FABP is a major mediator of atherosclerotic lesion formation in mice. In humans, A-FABP is expressed in monocytes on PPAR␥ activation, 8 and oxidized LDL has been shown to induce A-FABP expression in human THP-1 macrophage cell lines. 9 Furthermore, a genetic variant associated with increased A-FABP mRNA expression in adipose tissues predicted coronary artery disease in homozygous subjects. 10 These findings suggest that A-FABP may also play a role in the development of atherosclerotic diseases in humans.Although A-FABP was traditionally thought to be an intracellular protein, we have demonstrated that a small portion of A-FABP is released from mature adipocytes into the human blood stream, 11 with the serum concentrations being Ϸ8 to 60 ng/mL. In a cross-sectional study we observed a strong positive association between serum A-FABP levels and parameters of adiposity. In addition, serum A-FABP levels correlated closely with several key features of the metabolic syndrome, an aggregate of cardiometabolic risk factors associated with accelerated atheroscl...