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Burden of Infection and Insulin Resistance in Healthy Middle-Aged Men

¹ Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Girona, Spain
² Research Unit, University Hospital of Tarragona "Joan XXIII," Institut Pere Virgili, Tarragona, Spain

Address correspondence and reprint requests to J.M. Fernández-Real, MD, PhD, Section of Diabetes, Endocrinology and Nutrition, Institut d’Investigació Biomédica de Girona, Avinguda de França s/n, 17007 Girona, Spain. E-mail: uden.jmfernandezreal{at}htrueta.scs.es

OBJECTIVE—We hypothesized that burden of infection could be associated with chronic low-grade inflammation, resulting in insulin resistance. We aimed to study the effect of exposure to four infections on insulin sensitivity in apparently healthy middle-aged men (n = 124).

RESEARCH DESIGN AND METHODS—By inclusion criteria, all subjects were hepatitis C virus antibody seronegative. Each study subject’s serum was tested for specific IgG class antibodies against herpes simplex virus (HSV)-1, HSV-2, enteroviruses, and Chlamydia pneumoniae through the use of quantitative in vitro enzyme-linked immunosorbent assays. Insulin sensitivity was evaluated using minimal model analysis.

RESULTS—The HSV-2 titer was negatively associated with insulin sensitivity even after controlling for BMI, age, and C-reactive protein (CRP). The associations were stronger when considering the infection burden. In particular, in those subjects who were seropositive for C. pneumoniae, the relationship between the quantitative seropositivity index (a measure of the exposure to various pathogens) and insulin sensitivity was strengthened (r = –0.50, P < 0.0001). We also observed decreasing mean insulin sensitivity index with increasing seropositivity score in subjects positive for enteroviruses. In the latter, the relationship between insulin sensitivity and seropositivity was especially significant (r = –0.71, P < 0.0001). In a multivariate regression analysis, both BMI and quantitative seropositivity index (7%) independently predicted insulin sensitivity variance in subjects with C. pneumoniae seropositivity. When controlling for CRP, this association was no longer significant.

CONCLUSIONS—Pathogen burden showed the strongest association with insulin resistance, especially with enteroviruses and C. pneumoniae seropositivity. We hypothesize that exposure to multiple pathogens could cause a chronic low-grade inflammation, resulting in insulin resistance.

Abbreviations: CAD, coronary artery disease • CRP, C-reactive protein • ELISA, enzyme-linked immunosorbent assay • HSV, herpes simplex virus • TNFR, tumor necrosis factor receptor • WHR, waist-to-hip ratio

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