Fetuin-A and incident diabetes mellitus in older persons.
BACKGROUND
Fetuin-A is a hepatic secretory protein that binds the insulin receptor and inhibits insulin action in vitro. In prior cross-sectional studies in humans, higher fetuin-A levels were associated with insulin resistance. However, the longitudinal association of fetuin-A with incident type 2 diabetes mellitus is unknown.


OBJECTIVE
To determine whether fetuin-A levels are associated with incident diabetes in older persons.


METHODS
Observational study among 3075 well-functioning persons aged 70 to 79 years. In this case-cohort study, we retrospectively measured fetuin-A levels in baseline serum among 406 randomly selected participants without prevalent diabetes, and all participants who developed incident diabetes mellitus during a 6-year follow-up (to August 31, 2005).


METHODS
Incident diabetes mellitus.


RESULTS
Incident diabetes developed in 135 participants (10.1 cases/1000 person-years). Participants with fetuin-A levels within the highest tertile (> 0.97 g/L) had an increased risk of incident diabetes (13.3 cases/1000 person-years) compared with participants in the lowest tertile (< or = 0.76 g/L) (6.5 cases/1000 person-years) in models adjusted for age, sex, race, waist circumference, body weight, physical activity, blood pressure level, fasting glucose level, high-density lipoprotein cholesterol concentration, triglyceride concentration, and C-reactive protein level (adjusted hazard ratio, 2.41; 95% confidence interval, 1.28-4.53; P = .007). The association was not affected by adipocytokine levels but was moderately attenuated by adjustment for visceral adiposity (adjusted hazard ratio of highest vs lowest tertile 1.72; 95% confidence interval, 0.98-3.05; P = .06).


CONCLUSIONS
Among well-functioning older persons, serum fetuin-A is associated with incident diabetes, independent of other markers of insulin resistance.
Ix
Joachim H
JH
Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, and San Diego Veterans Affairs Healthcare System, 3350 La Jolla Village Dr, Mail Code 111-H, San Diego, CA 92161, USA. joeix@ucsd.edu
Wassel
Christina L
CL
Kanaya
Alka M
AM
Vittinghoff
Eric
E
Johnson
Karen C
KC
Koster
Annemarie
A
Cauley
Jane A
JA
Harris
Tamara B
TB
Cummings
Steven R
SR
Shlipak
Michael G
MG
D050153:Abdominal Fat; D050154:Adiposity; D000367:Age Factors; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D001823:Body Composition; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006304:Health Status; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D012189:Retrospective Studies; D012307:Risk Factors; D060749:alpha-2-HS-Glycoprotein
C556354:AHSG protein, human; D015415:Biomarkers; D001798:Blood Proteins; D060749:alpha-2-HS-Glycoprotein