Acute-Phase Serum Amyloid A Protein and Its Implication in the Development of Type 2 Diabetes in the KORA S4/F4 Study

Carola Marzi, MPH, Cornelia Huth, PHD, Christian Herder, PHD, Jens Baumert, PHD, Barbara Thorand, PHD, Wolfgang Rathmann, MD,
Christa Meisinger, MD, H.-Erich Wichmann, MD, PHD, Michael Roden, MD, Annette Peters, PHD, Harald Grallert, PHD, Wolfgang Koenig, MD and Thomas Illig, PHD

Diabetes Care December 13, 2012

Abstract

OBJECTIVE We sought to investigate whether elevated levels of acute-phase serum amyloid A (A-SAA) protein precede the onset of type 2 diabetes independently of other risk factors, including parameters of glucose metabolism.

RESEARCH DESIGN AND METHODS Within the population-based Cooperative Health Research in the Region of Augsburg (KORA) S4 study, we measured A-SAA concentrations in 836 initially nondiabetic subjects (55–74 years of age) without clinically overt inflammation who participated in a 7-year follow-up examination including an oral glucose tolerance test.

RESULTS A-SAA concentrations were significantly associated with incident type 2 diabetes (odds ratio [OR] for a one-SD increase of A-SAA adjusted for age and sex = 1.28 [95% CI 1.08–1.53], P = 0.005), particularly in younger subjects (P value for interaction = 0.047). The association attenuated when adjusting for parameters of glucose metabolism (fasting glucose, fasting insulin, HbA1c, and 2-h glucose; OR 1.16 [0.95–1.42], P = 0.15). Similar analyses for high-sensitive C-reactive protein (hs-CRP) yielded the following ORs: 1.39 (1.10–1.68, P = 0.0006) and 1.13 (0.88–1.45, P = 0.34), respectively. In contrast, A-SAA concentrations were significantly associated with 2-h glucose levels at follow-up even after adjustment for parameters of glucose metabolism (P = 0.008, n = 803).

CONCLUSIONS Our findings indicate similarly strong prospective associations with type 2 diabetes for A-SAA and hs-CRP and suggest a potential causal link via postchallenge hyperglycemia.