Abstract
Preclinical studies suggested that IgG2c isotype may specifically impair skeletal muscle insulin sensitivity in mice. In this study we investigated the association between serum levels of the four IgG subclasses and insulin sensitivity in non-diabetic individuals. Total IgG, IgG1, IgG2, IgG3 and IgG4 levels were measured in 262 subjects. Whole-body insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp. IgG2 levels were positively correlated with BMI, waist circumference, 2-h post-load glucose levels and complement C3. Serum IgG2, but not IgG1, IgG3 and IgG4 levels were negatively correlated with whole-body insulin sensitivity (r = -0.17; P = 0.003) and muscle insulin sensitivity index (r = -0.16; P = 0.03) after adjustment for age and gender. No significant correlation was found between IgG2 levels and hepatic insulin resistance assessed by HOMA-IR and liver IR index. In a multivariable regression analysis including variables known to affect insulin sensitivity such as age, gender, BMI, smoking, lipids, inflammatory markers, fasting and 2-h post-load glucose levels, IgG2 levels were independently associated with insulin-stimulated glucose disposal (β = -0.115, 95% CI: -0.541 to -0.024; P = 0.03). These data demonstrate the independent association between higher levels of IgG2 and decreased whole-body insulin sensitivity, thus confirming in humans the animal-based evidence indicating the pathogenic role of IgG2 in insulin resistance.