Serum fibroblast growth factor 21 is a superior biomarker to other adipokines in predicting incident diabetes

OBJECTIVE: Fibroblast growth factor 21 (FGF21) improves glucose and lipid metabolism, but high circulating levels are found in type 2 diabetes, suggesting FGF21 resistance. Serum FGF21 predicts incident diabetes, but its performance compared to established and emerging predictors is not known. We aimed to study the performance of FGF21 in diabetes prediction, relative to other adipokines and established risk factors including 2-h plasma glucose (2hG) during the oral glucose tolerance test (OGTT). DESIGN/PARTICIPANTS/MEASUREMENTS: We studied 1380 nondiabetic subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study using the second visit (2000-2004) as baseline when serum levels of FGF21 and other adipokines were measured. Glycaemic status was assessed by OGTT. Incident diabetes was defined as fasting glucose level (FG) ≥ 7 mmol/l or 2hG ≥ 11·1 mmol/l or use of antidiabetic agents, at subsequent visits. RESULTS: A total of 123 participants developed diabetes over 9·0 years (median). On multivariable logistic regression analysis, FGF21 (P = 0·003), adipocyte fatty acid-binding protein (P = 0·003) and adiponectin (P = 0·035) were independent predictors of incident diabetes. FGF21 had the best change in log likelihood when added to a diabetes prediction model (DP) based on age, family history, smoking, hypertension, BMI, dyslipidaemia and FG. It also improved the area under ROC curve (AUROC) of diabetes prediction (DP) from 0·797 to 0·819 (P = 0·0072), rendering its performance comparable to the 'DP + 2hG' model (AUROC=0·838, P = 0·19). CONCLUSIONS: As a biomarker for diabetes prediction, serum FGF21 appeared to be superior to other adipokines and, on its own, could be considered as an alternative to the OGTT. © 2016 John Wiley & Sons Ltd.postprin

Plasma lipocalin-2 concentration is related to blood pressure and is increased in hypertension

Poster Sessions: no. P085INTRODUCTION: Lipocalin-2 is secreted by adipocytes and is upregulated in obesity. As obesity is known to be a cause of hypertension, we investigated whether the plasma level of lipocalin-2 is related to blood pressure and hypertension …postprin

Plasma lipocalin-2 concentration is related to blood pressure and is increased in hypertension

Oral PresentationINTRODUCTION: Lipocalin-2 is secreted by adipocytes and is upregulated in obesity. As obesity is known to be a cause of hypertension, we investigated whether the plasma level of lipocalin-2 is related to blood pressure and hypertension. METHODS: The plasma concentration of lipocalin-2 was measured by immunoassay in 1925 subjects of …published_or_final_versionThe 17th Medical Research Conference, The University of Hong Kong, Hong Kong, 14 January 2012. In Hong Kong Medical Journal, 2012, v. 18 suppl. 1, p. 18, abstract no. 1

Optimal Cut-Offs of Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) to Identify Dysglycemia and Type 2 Diabetes Mellitus: A 15-Year Prospective Study in Chinese

BACKGROUND: The optimal reference range of homeostasis model assessment of insulin resistance (HOMA-IR) in normal Chinese population has not been clearly defined. Here we address this issue using the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS), a prospective population-based cohort study with long-term follow-up. MATERIAL & METHODS: In this study, normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) were defined according to the 1998 World Health Organization criteria. Dysglycemia referred to IFG, IGT or T2DM. This study comprised two parts. Part one was a cross-sectional study involving 2,649 Hong Kong Chinese subjects, aged 25-74 years, at baseline CRISPS-1 (1995-1996). The optimal HOMA-IR cut-offs for dysglycemia and T2DM were determined by the receiver-operating characteristic (ROC) curve. Part two was a prospective study involving 872 subjects who had persistent NGT at CRISPS-4 (2010-2012) after 15 years of follow-up. RESULTS: At baseline, the optimal HOMA-IR cut-offs to identify dysglyceia and T2DM were 1.37 (AUC = 0.735; 95% confidence interval [CI] = 0.713-0.758; Sensitivity [Se] = 65.6%, Specificity [Sp] = 71.3%] and 1.97 (AUC = 0.807; 95% CI = 0.777-0.886; Se = 65.5%, Sp = 82.9%) respectively. These cut-offs, derived from the cross-sectional study at baseline, corresponded closely to the 75th (1.44) and 90th (2.03) percentiles, respectively, of the HOMA-IR reference range derived from the prospective study of subjects with persistent NGT. CONCLUSIONS: HOMA-IR cut-offs, of 1.4 and 2.0, which discriminated dysglycemia and T2DM respectively from NGT in Southern Chinese, can be usefully employed as references in clinical research involving the assessment of insulin resistance.published_or_final_versio

Role of Circulating Fibroblast Growth Factor 21 Measurement in Primary Prevention of Coronary Heart Disease Among Chinese Patients With Type 2 Diabetes Mellitus

BACKGROUND: Fibroblast growth factor 21 (FGF21) has demonstrated beneficial effects on lipid and carbohydrate metabolism. In cross-sectional studies, an association of raised circulating FGF21 levels with coronary heart disease (CHD) was found in some but not all studies. Here we investigated prospectively whether baseline serum FGF21 levels could predict incident CHD in subjects with type 2 diabetes mellitus and no known cardiovascular diseases. METHODS AND RESULTS: Baseline serum FGF21 levels were measured in 3528 Chinese subjects with type 2 diabetes mellitus recruited from the Hong Kong West Diabetes Registry. The role of baseline serum FGF21 levels in predicting incident CHD over a median follow-up of 3.8 years was analyzed using Cox regression analysis. Among 3528 recruited subjects without known cardiovascular diseases, 147 (4.2%) developed CHD over a mean follow-up of 4 years. Baseline serum log-transformed FGF21 levels were significantly higher in those who had incident CHD than those who did not (222.7 pg/mL [92.8-438.4] versus 151.1 pg/mL [75.6-274.6]; P<0.001). On multivariable Cox regression analysis, baseline serum FGF21 levels, using an optimal cutoff of 206.22 pg/mL derived from our study, independently predicted incident CHD (hazard ratio, 1.55; 95% CI, 1.10-2.19; P=0.013) and significantly improved net reclassification index and integrated discrimination improvement after adjustment for conventional cardiovascular risk factors. CONCLUSIONS: We have demonstrated, for the first time, that serum FGF21 level is an independent predictor of incident CHD and might be usefully utilized as a biomarker for identifying type 2 diabetes mellitus subjects with raised CHD risk, for primary prevention.published_or_final_versio

Plasma fibrinogen level as a predictor of incident metabolic syndrome in a community-based prospective study in Hong Kong Chinese

BACKGROUND AND AIMS: Metabolic syndrome (MS) comprises a constellation of metabolic abnormalities associated with a high risk of developing diabetes and cardiovascular diseases. Central obesity, with related insulin resistance and inflammation are considered the core of the underlying pathogenesis of MS. Fibrinogen, an acute-phase reactant in the coagulation cascade, has been shown to play pivotal role in determining the extent of local or systemic inflammation. In this study, we examined whether plasma fibrinogen was predictive of incident MS in a community-based Chinese cohort. MATERIALS AND METHODS: Subjects were recruited from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) cohort. 2780 subjects were recruited in 1995-6 with baseline assessment performed. 1416 subjects without MS at …postprin

Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population

© Georg Thieme Verlag KG Stuttgart New York.Identification of germline mutation in patients with apparently sporadic pheochromocytomas and paragangliomas is crucial. Clinical indicators, which include young age, bilateral or multifocal, extra-adrenal, malignant, or recurrent tumors, predict the likelihood of harboring germline mutation in Caucasian subjects. However, data on the prevalence of germline mutation, as well as the applicability of these clinical indicators in Chinese, are lacking. We conducted a cross-sectional study at a single endocrine tertiary referral center in Hong Kong. Subjects with pheochromocytomas and paragangliomas were evaluated for the presence of germline mutations involving 10 susceptibility genes, which included NF1, RET, VHL, SDHA, SDHB, SDHC, SDHD, TMEM 127, MAX, and FH genes. Clinical indicators were assessed for their association with the presence of germline mutations. Germline mutations, 2 being novel, were found in 24.4% of the 41 Chinese subjects recruited and 11.4% among those with apparently sporadic presentation. The increasing number of the afore-mentioned clinical indicators significantly correlated with the likelihood of harboring germline mutation in one of the 10 susceptibility genes. (r=0.757, p=0.026). The presence of 2 or more clinical indicators should prompt genetic testing for germline mutations in Chinese subjects. In conclusion, our study confirmed that a significant proportion of Chinese subjects with apparently sporadic pheochromocytoma and paraganglioma harbored germline mutations and these clinical indicators identified from Caucasians series were also applicable in Chinese subjects. This information will be of clinical relevance in the design of appropriate genetic screening strategies in Chinese populations.postprin

Pro-inflammatory adipokines as predictors of incident cancers in a chinese cohort of low obesity prevalence in Hong Kong

published_or_final_versio

Validation of the diabetes screening tools proposed by the American Diabetes Association in an aging Chinese population

published_or_final_versio

Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma

OBJECTIVE: Androgen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens. SUBJECTS AND METHODS: This was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011. RESULTS: After a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41-9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47-13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46-11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18-8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT. CONCLUSIONS: Fracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes.published_or_final_versio