Obesity Is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes

The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (HbA1c [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed (3 years), drug-naive, type 2 diabetic subjects (fasting plasma glucose 10 mmol/l), we examined a representative subgroup (n =3D 921) of the U.S. cohort in ADOPT (A Diabetes Outcome Progression Trial). The relationship between levels of CRP, fibrinogen, PAI-1 antigen and PAI-1 activity, and baseline variables including National Cholesterol Education Program Adult Treatment Panel III metabolic syndrome phenotype were explored. All four factors increased significantly with increasing numbers of metabolic syndrome components (P =3D 0.0136 to P < 0.0001). BMI (P < 0.0001) and HOMA-IR (P < 0.0001) but not A1C (P =3D 0.65) increased with increasing numbers of metabolic syndrome components. Adjustment of CRP levels for BMI eliminated the association between CRP and the number of metabolic syndrome components, while adjusting for HOMA-IR did not (P =3D 0.0028). The relationships of PAI-1 antigen and PAI-1 activity with the number of metabolic syndrome components were maintained after adjusting for BMI (P =3D 0.0002 and P =3D <0.0001, respectively) or HOMA-IR (P =3D 0.0008 and P =3D