Structural involvement in type 1 and type 2 diabetic nephropathy

Structural changes underlying diabetic nephropathy in Type 1 diabetes are p redominant in the glomerulus [thickening of glomerular basement membrane (G BM) and mesangial expansion], but also include arteriolar, tubular and inte rstitial lesions. The structural measure that correlates best with all rena l functional para meters in Type 1 diabetes is mesangial fractional volume [Vv(mes/glom)], an estimate of mesangial expansion. Structural-functional r elationships in Type 2 diabetes are much less known. These studies investig ated renal structure in the early stages of nephropathy [microalbuminuria ( MA)I in patients with Type 1 and Type 2 diabetes. Diabetic glomerulopathy w as quite advanced in Type I diabetic patients with MA, and both Vv (mes/glo m) and GEM width were increased as compared to normoalbuminuric (NA) patien ts when the albumin excretion rate (AER) was > 30 mu g/min Serial renal bio psies were performed 5 years apart in 11 Type 1 diabetic patients to evalua te whether glomerular and interstitial lesions progress jointly. AER increa sed significantly in 5 years, while the glomerular filtration rate remained unchanged. All structural parameters were initially abnormal. Vv(mes/glom) and mean glomerular volume increased significantly, whereas GEM width and the interstitial volume fraction were unchanged. Moreover, the change in Vv (mes/glom) was correlated with the change in AER(r = 0.64, p < 0.05). Thus , at the disease stage during which some patients progress to MA or protein uria, continuing mesangial expansion is the main variable, whereas further interstitial expansion does not occur A large number of Type 2 patients wer e also studied. Early diabetic glomerulopathy was detected by electron micr oscopy in NA patients and found to be more advanced in those with MA and pr oteinuria. However, lesions were milder than in Type 1 diabetic patients, a nd there was considerable overlap between groups. Morphometric results by e lectron microscopy were similar to those by light microscopy, demonstrating the heterogeneity of renal structure in Type 2 diabetic patients. In fact, only 30% of MA patients had typical diabetic glomerulopathy, while 40% had more advanced tubulo-interstitial and/or vascular lesions and 30% had norm al renal structure.