Risk Factors of Progression to Frailty: Findings from the Singapore Longitudinal Ageing Study.

OBJECTIVES: To investigate risk factors of incident physical frailty. DESIGN: A population-based observational longitudinal study. SETTING: Community-dwelling elderly with age 55 years and above recruited from 2009 through 2011 in the second wave Singapore Longitudinal Ageing Study-2 (SLAS-2) were followed up 3-5 years later. PARTICIPANTS: A total of 1297 participants, mean age of 65.6 ±0.19, who were free of physical frailty. MEASUREMENTS: Incident frailty defined by three or more criteria of the physical phenotype used in the Cardiovascular Health Study was determined at follow-up. Potential risk factors assessed at baseline included demographic, socioeconomic, medical, psychological factors, and biochemical markers. RESULTS: A total of 204 (15.7%) participants, including 81 (10.87%) of the robust and 123 (22.28%) of the prefrail transited to frailty at follow-up. Age, no education, MMSE score, diabetes, prediabetes and diabetes, arthritis, ≥5 medications, fair and poor self-rated health, moderate to high nutritional risk (NSI ≥3), Hb (g/dL), CRP (mg/L), low B12, low folate, albumin (g/L), low total cholesterol, adjusted for sex, age and education, were significantly associated (p<0.05) with incident frailty. In stepwise selection models, age (year) (OR=1.07, 95%CI=1.03-1.10, p<0.001), albumin (g/L) (OR=0.85, 95%CI=0.77-0.94, p=0.002), MMSE score (OR=0.88, 95%CI=0.78-0.98, p=0.02), low folate (OR=3.72, 95%CI=1.17-11.86, p=0.03, and previous hospitalization (OR=2.26, 95%CI=1.01-5.04,p=0.05) were significantly associated with incident frailty. CONCLUSIONS: The study revealed multiple modifiable risk factors, especially related to poor nutrition, for which preventive measures and early management could potentially halt or delay the development of frailty.

Sex modulates the association of fibroblast growth factor 21 with end-stage renal disease in Asian people with Type 2 diabetes: a 6.3-year prospective cohort study.

AIM: To study whether plasma fibroblast growth factor 21 independently predicts the risk of end-stage renal disease in Asian people with Type 2 diabetes. METHODS: In this prospective cohort study, 1700 Asian people with Type 2 diabetes were followed for a mean of 6.3 years in a regional hospital in Singapore. Incident end-stage renal disease was identified by linkage with a national renal registry. The association of baseline fibroblast growth factor 21 levels with risk of progression to end-stage renal disease was studied using survival analyses. RESULTS: Participants were aged 60 ± 10 years, with an average diabetes duration of 12 years. Their estimated GFR was 73 ± 28 ml/min/1.73 m2 and 62% had albuminuria at baseline. A total of 179 incident end-stage renal disease cases were identified. Plasma fibroblast growth factor 21 interacted with sex in its association with end-stage renal disease (Pinteraction = 0.003). A 1-sd increment in fibroblast growth factor 21 (natural log-transformed) was associated with a 1.32-fold (95% CI 1.05-1.66, P = 0.02) increased hazard for end-stage renal disease in women, after adjustment for traditional risk factors including estimated GFR and albuminuria. Taking death as a competing risk did not materially change the outcome [sub-distribution hazard ratio 1.35 (95% CI 1.11-1.66, P = 0.003)]. Fibroblast growth factor 21 did not predict end-stage renal disease risk in men after adjustment for baseline estimated GFR and albuminuria [hazard ratio 1.07 (95% CI 0.89-1.28, P = 0.49)]. CONCLUSIONS: Plasma fibroblast growth factor 21 level independently predicted risk of progression to end-stage renal disease in women with Type 2 diabetes. The pathophysiological relationships among FGF21, sex and renal progression warrant further study.