A study published in the July 9 issue of JAMA finds an association between higher than normal levels of the protein fetuin-A and an increased risk of developing diabetes. Fetuin-A is one of several blood proteins that is produced in the liver and secreted into the blood stream, and it is involved with the transport of various substances in the blood stream.

Joachim H. Ix, M.D., M.A.S. (University of California, San Diego, and San Diego Veterans Affairs Healthcare System) and colleagues, authors of the JAMA study, write that, “Type 2 diabetes mellitus has become a global epidemic and the increased prevalence of obesity is a major contributing factor. However, diabetes does not develop in all obese individuals and there is a strong genetic contribution to risk. Despite significant recent advances, mechanisms responsible for individual differences in clinical phenotype remain largely unknown.” Though there has been no evidence to link the protein to type 2 diabetes, other studies have demonstrated an association between higher fetuin-A levels and resistance to insulin.

To examine the potential relationship between higher fetuin-A levels and the occurrence of diabetes in older persons, Ix and colleagues studied 406 people, age 70 to 79 years, who did not have diabetes. Their fetuin-A levels were measured at the beginning of the study and again after six years of follow-up. The rate of diabetes occurrence was 10.1 cases/1,000 person-years, as 135 participants developed the disease.

The researchers found that as fetuin-A levels increased, the incidence of diabetes also increased. The incidence rate for the third of the sample with the highest fetuin-A levels was 13.3 cases/1,000 person-years, while the rate for the third with the lowest levels of the protein was 6.5 cases/1,000 person-years – the former more than two times the latter. The association held after the researchers statistically controlled for sex, race, obesity status, physical activity, inflammatory biomarkers, and other known measures of insulin resistance. However, there was a slight weakening in the association when controlling for fat accumulation around the abdomen (visceral adiposity).

“Future studies should evaluate whether the results may generalize to middle-aged individuals in whom the [diabetes] incidence rate is highest. If confirmed in future studies, fetuin-A may ultimately prove useful as a target for therapeutics, and its study may provide novel insights to glucose metabolism in humans,” conclude the authors.

Fetuin-A and Incident Diabetes Mellitus in Older Persons
Joachim H. Ix; Christina L. Wassel; Alka M. Kanaya; Eric Vittinghoff; Karen C. Johnson; Annemarie Koster; Jane A. Cauley; Tamara B. Harris; Steven R. Cummings; Michael G. Shlipak; for the Health ABC Study
JAMA (2008). 300[2]: pp. 182 – 188.
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Written by: Peter M Crosta