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

Abstract

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 ϭ 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 ϭ Ϫ0.50, P Ͻ 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 ϭ Ϫ0.71, P Ͻ 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.

Helicobacter pylori Infection as a Risk Factor for Insulin Resistance

“…It has been recently mentioned that healthy men with exposure to common pathogens (herpes virus types I and II, enteroviruses, and Chlamydia pneumonia), all of which are characterized by high frequency of exposure in the general population and persistent and chronic infection, might show increased fat mass and insulin resistance. The greater the exposure to these pathogens (inferred from serum antibody response), the higher the serum levels of inflammatory markers and the lower the insulin sensitivity [22,23].…”

Circulating osteocalcin concentrations are associated with parameters of liver fat infiltration and increase in parallel to decreased liver enzymes after weight loss

“…Serum insulin levels were measured in duplicate by monoclonal immunoradiometric assay (IRMA or EASIA, Medgenix Diagnostics, Fleunes, Belgium). Intraassay and interassay coefficients of variation were similar to those previously reported [20,21]. Serum AST, ALT, and gammaglutamyltransferase were measured colorimetrically by automated tests (Roche Diagnostics GmbH).…”

“…Basal blood samples were drawn at −30, −10, and −5 min, after which glucose (300 mg/kg body weight) was injected over 1 min starting at time 0, and insulin (Actrapid, Novo, Denmark; 0.03 U/kg) was administered at time 20 min. Additional samples were obtained from a contralateral antecubital vein up to 180 min, as previously published [20,21].…”

Chlamydia antibodies and self-reported symptoms of oligo-amenorrhea and hirsutism: A new etiologic factor in polycystic ovary syndrome?

“…pneumoniae infections have been associated with cardiovascular diseases, such as coronary heart diseases and acute myocardial infarction (8), suggesting that C. pneumoniae infection is involved in the development of atherosclerosis and its complications. Exposure to various pathogens, such as herpes simplex viruses 1 and 2, enteroviruses, and C. pneumoniae, was associated with decreased insulin sensitivity, and this effect became more significant when the pathogen burden increased, suggesting a role of chronic lowgrade inflammation in the development of insulin resistance (17). In another report, C. pneumoniae seropositivity showed a significant association with metabolic syndrome in men and women (18).…”

“…C. pneumonia infection may play a role in inducing both systemic inflammation and insulin resistance, and a possible link between these events could be an elevation in markers/mediators of inflammation such as CRP. A recent study has demonstrated a correlation between the C. pneumonia seropositivity index and insulin resistance (17), and another report showed a significant association with metabolic syndrome (18).…”