Twenty-four type 1 and type 2 diabetic patients with obesity and overt nephropathy were studied for 12 months after hypocaloric diet change from 1870 to 1410 kcal/day (without changes of protein:carbohydrate ratio). Several parameters were evaluated: arterial blood pressure, blood glucose, fructosamine, HbA1c, proteinuria, albuminuria, glomerular filtration rate (GFR), creatinine clearance, triglycerides, HDL and total cholesterol. A significant reduction of body weight (body mass index from 33 +/- 1.6 to 26 +/- 1.8 kg/m2, P less than 0.001), concomitantly with a decrease of blood pressure levels (P less than 0.002) was demonstrated at the end of the study. Triglyceride (P less than 0.002), HDL (P less than 0.002), HDL (P less than 0.05) and total cholesterol (P less than 0.01) levels were reduced after diet-therapy, while a mild improvement of glycometabolic profile was observed in the same period. A marked decrease of proteinuria (from 1280 +/- 511 to 623 +/- 307 mg/24 h, P less than 0.01) and albuminuria (from 723 +/- 388 to 492 +/- 170 micrograms/min, P less than 0.01), and an improvement of GFR (from 66 +/- 13 to 81 +/- 11 ml/min/1.73 m2, P less than 0.01) and creatinine clearance (from 79 +/- 14 to 91 +/- 13 ml/min, P less than 0.01) was demonstrated after 12 months of diet-treatment. Our data suggest that body weight reduction by hypocaloric diet may delay the progression of clinical nephropathy in obese diabetic patients.