In Reply: I agree with Dr Stefan and colleagues that the study in the EPIC-Potsdam cohort provides additional evidence supporting an association of higher serum fetuin-A level and diabetes risk and extends the observation over a broader age range.1
Emerging evidence suggests that fetuin-A might also regulate adipogenesis,2 and in our study in the Health ABC cohort, higher fetuin-A levels were associated with increased visceral adiposity. Visceral adiposity is increased in older individuals3 and is strongly associated with diabetes risk.4 However, in the EPIC-Potsdam study and other studies, older age was associated with lower fetuin-A levels.1,5 These observations lead to several important questions regarding aging and changes in body composition and glucose metabolism and how fetuin-A may be involved in these processes. For example, what promotes hepatic fetuin-A production and secretion into serum, and what factors lead to maintenance of higher fetuin-A levels throughout an individual's life? Do individuals with these factors develop more visceral adiposity or have increased risk for diabetes? If so, to what degree does fetuin-A explain these associations? Currently, little is known about the metabolism of fetuin-A. Future studies that determine the metabolism of fetuin-A may provide new insights into mechanisms of obesity and diabetes risk and may unravel how this risk changes over time.
Ix JH. Association of Fetuin-A Level and Diabetes Risk—Reply. JAMA. 2008;300(19):2247-2248. doi:10.1001/jama.2008.615