Abstract MP036: The Sex-Specific Association of Fetuin-A with Diabetes in Older Adults: The Rancho Bernardo Study
Authors: Laughlin Gail A , Cummins Kevin M , Wassel Christina L , Barrett-Connor Elizabeth , Ix Joachim H 
Published: July 2021

Fetuin-A is a hepatic-secretory protein that induces insulin resistance in animals and is elevated in humans with insulin resistance and fatty liver disease. In population-based studies, higher fetuin-A has been shown to predict the development of type 2 diabetes; however, the sex-specific nature of the fetuin-A-diabetes link is unclear. This study tested the hypothesis of a sex-specific association of fetuin-A with prevalent and incident diabetes in a population of 1742 older community-dwelling adults (mean age 71.4 years). Fetuin-A levels (mean, SD in ng/ml) were highest in women using oral estrogen therapy (ET) (55.5, 11.6), intermediate in women not using ET (51.4, 10.2), and lowest in men (50.2, 9.6) (P<.001 for all). At baseline, 14% (n=129) of women and 19% (n=113) of men had prevalent diabetes; during the median 9.1 year follow-up, 32 women and 53 men developed incident diabetes. In combined analyses, there was a significant interaction by sex for the fetuin-A association with both prevalent (P=.007) and incident (P=.020) diabetes.
Table 1
presents odds ratios for prevalent diabetes and hazards ratios for incident diabetes per sex-specific SD increase in fetuin-A. Among women, a 1 SD increase in fetuin-A was associated with 79% increased odds of prevalent diabetes and 66% increased risk of incident diabetes adjusting for age and oral ET. Risk estimates for women were only modestly attenuated by additional adjustment for lifestyle, body size, lipids, blood pressure, fasting plasma glucose and insulin resistance. In contrast, among men, although a minor association was suggested in age-adjusted models, risk estimates were attenuated to one in multivariate models. In conclusion, higher fetuin-A levels predict type 2 diabetes in older women independent of established risk factors, but are not related to diabetes risk in older men. Whether these sex-specific associations are relevant to the observation that diabetes is a stronger risk factor for cardiovascular mortality in women than men merits further investigation.

Table 1.

Odds of Prevalent Diabetes and Risk of Incident Diabetes per SD increase in Fetuin-A

Prevalent Diabetes, OR (95% CI)

Women (n=1043)

Men (n=672)

Model 1

1.79 (1.47, 2.17)

1.15 (0.94, 1.41)

Model 2

1.69 (1.38, 2.07)

1.14 (0.92, 1.41)

Model 3

1.54 (1.25, 1.90)

1.05 (0.83, 1.31)

Model 4

1.60 (1.26, 2.03)

1.14 (0.83, 1.56)

Model 5

1.54 (1.24, 1.91)

1.02 (0.80, 1.32)

Incident Diabetes, HR (95% CI)

Women (n=782)

Men (n=477)

Model 1

1.66 (1.18, 2.34)

1.24 (0.93, 1.65)

Model 2

1.64 (1.16, 2.32)

1.12 (0.81, 1.53)

Model 3

1.53 (1.04, 2.25)

0.96 (0.69, 1.33)

Model 4

1.51 (1.02, 2.23)

0.94 (0.66, 1.34)

Model 5

1.51 (1.03, 2.22)

0.91 (0.65, 1.27)

Funding(This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont)