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.

Cardiometabolic risk profile of participants with prediabetes diagnosed by HbA1c criteria in an urban Hong Kong Chinese population over 40 years of age.

AIMS: To investigate the usefulness of the additional measurement of HbA1c , compared with performing only the oral glucose tolerance test (OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. METHODS: All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c , according to American Diabetic Association 2010 criteria. RESULTS: Based on OGTT criteria alone, 3.5% of the study cohort (N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c , in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia (N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index (HOMA-IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia (N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance (N = 249; all P < 0.01). CONCLUSION: The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention.