ORCID Profile
0000-0002-0668-033X
Current Organisations
University of Hong Kong
,
The University of Hong Kong
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Publisher: Wiley
Date: 06-08-2021
DOI: 10.1002/EHF2.13472
Abstract: Adipocyte 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. Baseline 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 .01). Circulating 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.
Publisher: Springer Science and Business Media LLC
Date: 20-12-2022
DOI: 10.1038/S41467-022-35470-4
Abstract: Thyroid hormone (TH) is a thermogenic activator with anti-obesity potential. However, systemic TH administration has no obvious clinical benefits on weight reduction. Herein we selectively delivered triiodothyronine (T3) to adipose tissues by encapsulating T3 in liposomes modified with an adipose homing peptide (PLT3). Systemic T3 administration failed to promote thermogenesis in brown and white adipose tissues (WAT) due to a feedback suppression of sympathetic innervation. PLT3 therapy effectively obviated this feedback suppression on adrenergic inputs, and potently induced browning and thermogenesis of WAT, leading to alleviation of obesity, glucose intolerance, insulin resistance, and fatty liver in obese mice. Furthermore, PLT3 was much more effective than systemic T3 therapy in reducing hypercholesterolemia and atherosclerosis in apoE-deficient mice. These findings uncover WAT as a viable target mediating the therapeutic benefits of TH and provide a safe and efficient therapeutic strategy for obesity and its complications by delivering TH to adipose tissue.
Publisher: The Endocrine Society
Date: 28-02-2023
Abstract: Adipocyte fatty acid-binding protein (AFABP), fibroblast growth factor 21 (FGF21), and pigment epithelium–derived factor (PEDF) are 3 diabetes-related biomarkers whose circulating levels had been shown to associate with nephropathy progression in Chinese patients with type 2 diabetes. Here, we evaluated and compared their prospective associations with the development of sight-threatening DR (STDR), another important diabetic microvascular complication. Baseline serum AFABP, PEDF, and FGF21 levels were measured in 4760 Chinese in iduals with type 2 diabetes and without STDR at baseline. The associations of these biomarkers with incident STDR were analyzed using Cox regression analysis. Among these 4760 participants (mean diabetes duration of 11 years and ≥ 50% with nonproliferative DR at baseline), 172 participants developed STDR over a median follow-up of 8.8 years. Participants with incident STDR had comparable baseline serum FGF21 levels but significantly higher baseline serum AFABP and PEDF levels (both P & .001) than those without. However, in multivariable Cox regression analysis, only serum AFABP remained independently associated with incident STDR (hazard ratio 1.28 95% CI, 1.05-1.55 P = .013). The addition of serum AFABP to a clinical model of conventional STDR risk factors including diabetes duration, glycemic control, albuminuria, and baseline DR status significantly improved the c statistics (P & .001), net reclassification index (P = .0027), and integrated discrimination index (P = .033) in predicting incident STDR among participants without DR or with mild DR at baseline. Among the 3 diabetes-related biomarkers, serum AFABP level appeared to be a more clinically useful biomarker for predicting incident STDR in type 2 diabetes.
Start Date: 2003
End Date: 2006
Funder: Innovation and Technology Commission
View Funded ActivityStart Date: 2010
End Date: 2012
Funder: University Grants Committee
View Funded ActivityStart Date: 2011
End Date: 2012
Funder: University Grants Committee
View Funded ActivityStart Date: 2007
End Date: 2009
Funder: University Grants Committee
View Funded ActivityStart Date: 2011
End Date: 2014
Funder: University Grants Committee
View Funded ActivityStart Date: 2007
End Date: 2009
Funder: University Grants Committee
View Funded ActivityStart Date: 2009
End Date: 2011
Funder: University Grants Committee
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