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Diabetes Metab J. 2019 Mar 20. doi: 10.4093/dmj.2018.0171. [Epub ahead of print]

Plasma Fetuin-A Levels and Risk of Type 2 Diabetes Mellitus in A Chinese Population: A Nested Case-Control Study.

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Health Services and Systems Research, Duke-NUS Medical School, Singapore.
Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Division of Cancer Control and Population Sciences, UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.



Fetuin-A is a hepatokine that involved in the pathogenesis of insulin resistance. Previous epidemiological studies have found a positive association between blood fetuin-A and type 2 diabetes mellitus (T2DM) risk among Caucasians and African Americans. We aimed to investigate the prospective relationship between fetuin-A and T2DM in an Asian population for the first time.


A nested case-control study was established within a prospective cohort of Chinese living in Singapore. At blood collection (1999 to 2004), all participants were free of diagnosed T2DM and aged 50 to 79 years. At subsequent follow-up (2006 to 2010), 558 people reported to have T2DM and were classified as incident cases, and 558 controls were randomly chosen from the participants who did not develop T2DM to match with cases on age, sex, dialect group, and date of blood collection. Plasma fetuin-A levels were measured retrospectively in cases and controls using samples collected at baseline. Conditional logistic regression models were used to compute the odds ratio (OR) and 95% confidence interval (CI). Restricted cubic spline analysis was used to examine a potential non-linear association between fetuin-A levels and T2DM risk.


Compared with those in the lowest fetuin-A quintile, participants in the highest quintile had a two-fold increased risk of developing T2DM (OR, 2.06; 95% CI, 1.21 to 3.51). A non-linear association was observed (P nonlinearity=0.005), where the association between fetuin-A levels and T2DM risk plateaued at plasma concentrations around 830 μg/mL.


There is a positive association between plasma fetuin-A levels and risk of developing T2DM in this Chinese population.


Alpha-2-HS-glycoprotein; Association; Case-control studies; Diabetes mellitus, type 2; Epidemiology

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