Insulin resistance contributes to obesity-related proteinuria

Proteinuria is a recognized complication of obesity, but the pathogenesis remains unclear. We undertook the present study to clarify the factors contributing to proteinuria associated with obesity.

We studied 12 obese patients with proteinuria. Twenty-seven age-matched obese subjects without proteinuria served as controls. A glucose tolerance test and renal biopsy were performed in all patients. Fasting serum insulin and homeostasis model assessment-insulin resistance (HOMA-IR) were regarded as reflecting insulin resistance. To delineate the relation between insulin resistance and proteinuria, troglitazone, which acts an insulin sensitizer was given to 6 of 12 patients with a regular diet for 8 weeks. The 6 others were observed without receiving troglitazone.

The 12 patients showed the presence of a cluster of insulin resistance factors: higher blood pressure, higher body mass index, higher fasting plasma glucose, higher fasting serum insulin, and higher HOMA-IR than controls. The renal biopsy specimens exhibited no histological abnormalities in 7, focal segmental glomerulosclerosis in 3 and benign nephrosclerosis in 2. Troglitazone attenuated HOMA-IR and ameliorated proteinuria, but did not affect body weight, creatinine clearance, or blood pressure. In contrast, the parameters in the patients not given troglitazone did not change.

Insulin resistance is a factor contributing to obesity-related proteinuria. The role of insulin resistance as a factor reducing proteinuria remains to be clarified.