Chy Fong

Circulating Fibroblast Growth Factor 21 Levels Predict Progressive Kidney Disease in Subjects With Type 2 Diabetes and Normoalbuminuria

BACKGROUND Elevated fibroblast growth factor 21 (FGF21) levels have been suggested, from cross-sectional studies, as an indicator of subclinical diabetic nephropathy. We investigated whether serum FGF21 was predictive of the development of diabetic nephropathy. METHOD Baseline serum FGF21 levels were measured in 1136 Chinese type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of serum FGF21 in predicting decline in estimated glomerular filtration rate (eGFR) over a median follow-up of 4 years was analyzed using Cox regression analysis. RESULTS At baseline, serum FGF21 levels increased progressively with eGFR category (P for trend <.001). Among 1071 subjects with baseline eGFR ≥ 30 mL/min/1.73 m(2), serum FGF21 levels were significantly higher in those with eGFR decline during follow-up (n = 171) than those without decline (n = 900) (P < .001). In multivariable Cox regression analysis, baseline serum FGF21 was independently associated with eGFR decline (hazard ratio, 1.21; 95% confidence interval [CI], 1.01-1.43; P = .036), even after adjustment for baseline eGFR. In a subgroup of 559 subjects with baseline eGFR ≥ 60 mL/min/1.73 m(2) and normoalbuminuria, serum FGF21 level remained an independent predictor of eGFR decline (hazard ratio, 1.36; 95% CI, 1.06-1.76; P = .016). Integrated discrimination improvement (IDI) suggested that the inclusion of baseline serum FGF21 significantly improved the prediction of eGFR decline (IDI, 1%; 95% CI, 0.1-3.0; P = .013) in this subgroup, but not in the initial cohort involving all subjects. CONCLUSIONS Elevated serum FGF21 levels may be a useful biomarker for predicting kidney disease progression, especially in the early stages of diabetic nephropathy.

Genetics of Apparently Sporadic Pheochromocytoma and Paraganglioma in a Chinese Population

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.

Lbps 02-06 Plasma Level of Fibroblast Growth Factor 21 Is Independently Related to Blood Pressure:

Objective: Fibroblast growth factor 21 (FGF21) plays an important role in glucose and lipid metabolism. Elevated blood FGF21 level is associated with obesity, diabetes and atherosclerosis. We therefore investigated its relationship with blood pressure. Design and Method: We measured FGF21 in the plasma of 1921 participants (891 men, 1030 women; 52 ± 12 years) taken at the start of the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS) using an enzyme-linked immunosorbent assay (Antibody & Immunoassay Services, University of Hong Kong). The log of FGF21 level was analysed for relationship with systolic and diastolic blood pressure (BP) at baseline and at the 5-year follow-up. Results: Plasma FGF21 level was 224.3 ± 7.4 in men and 214.1 ± 7.1 pg/ml in women. It correlated significantly (p < 0.001) with age (r = 0.30), waist circumference (r = 0.31), systolic BP (r = 0.32), diastolic BP (r = 0.22), triglyceride (r = 0.41), HDL-C (r = -0.27), fasting blood glucose (r = 0.27) and hsCRP (r = 0.27). In multivariate analysis, FGF21 was related to systolic and diastolic blood pressure at baseline (&bgr; = 0.076, p < 0.001 and &bgr; = 0.074, p = 0.001 respectively) and to diastolic blood pressure at follow-up (&bgr; = 0.06, p = 0.025). Conclusions: FGF21 level in blood is related to systolic and diastolic blood pressure, independent of age, obesity, lipids and blood glucose. FGF21 is related to the components of the metabolic syndrome and may have a pathophysiological role in hypertension. Support from the Hong Kong Research Grant Council (HKU2/CRF/12R) is gratefully acknowledged.