DIABETIC GLOMERULOPATHY IN THE SHR N-CORPULENT RAT - ROLE OF DIETARY CARBOHYDRATE IN A MODEL OF NIDDM/

We evaluated the course of diabetes and nephropathy in the SHR/N-cp (c orpulent) rat characterized by genetic obesity, non-insulin-dependent diabetes (NIDDM), and hypertension, and examined whether the nephropat hy in this model is influenced by the type of carbohydrate intake. Two groups of obese and lean SHR/N-cp rats were fed diets containing 54% carbohydrate, as either sucrose or starch for 3 months (group I) and 9 months (group II). After 3 months on either diet, group I obese rats had higher 2-h response serum glucose levels and urinary glucose excre tion than lean rats. Sucrose feeding was associated with greater prote inuria and a higher percentage of abnormal glomeruli in obese rats. Mo rphometric evaluation of glomeruli (by computerized image analysis) sh owed greater mean renal corpuscular Volume and mesangial fraction in o bese than in lean rats fed similar diets. Mean renal corpuscular volum e and mesangial fraction were also greater in sucrose-fed obese rats t han in starch-fed obese rats. After 9 months, group II obese rats had substantial reductions in serum and urine glucose levels but they were still hyperinsulinaemic and showed more proteinuria than lean rats an d a higher percentage of sclerotic glomeruli compared with group I obe se rats. At this time, mean mesangial fraction but not renal corpuscul ar volume was still higher in obese than in lean rats. In group I obes e rats, a significant correlation was found between mesangial fraction and urinary protein excretion (r = 0.67, p < 0.05). In group II obese rats, renal corpuscular volume was correlated with percentage of glom erular sclerosis (r = 0.60, p < 0.05). Thus, obese SHR/N-cp rats devel op persistent proteinuria and glomerulopathy marked by glomerular enla rgement, increased mesangial matrix, and progressive glomerular sclero sis. Sucrose feeding accentuates mesangial expansion and glomeruloscle rosis in obese rats.