Glomerular structure and function in proteinuric Type 2 (non-insulin-dependent) diabetic patients

Abstract

Glomerular ultrastructure was examined in a series of 20 Type 2 (non-insulin-dependent) diabetic patients with proteinuria. Reference was made to data previously obtained in non-diabetic kidney donors and in Type 1 (insulin-dependent) diabetic patients with similar degrees of proteinuria. The Type 2 diabetic patients demonstrated the changes which characterize the diabetic glomerulopathy seen in Type 1 diabetic patients: basement membrane thickening, and increase in the mesangium and mesangial matrix expressed as fraction of the glomerular volume. Among the Type 2 diabetic patients there was more variation than among the Type 1 diabetic patients, as this group included subjects with normal parameters. The group means and coefficients of variation (= SD/mean) of the glomerulopathy parameters combined in the glomerulopathy index = basement membrane thickness/10+ Vv(matrix/glom).100 were 81 (0.30) and 92 (0.15) in the two diabetic groups, clearly different from the non-diabetic index, 42 (0.16). All Type 2 diabetic patients who also had retinopathy had a glomerulopathy index above the normal range. Similar changes in glomerular composition were seen in the two diabetic groups: with increasing glomerulopathy the volume of matrix dominated over the peripheral basement membrane, and a shift in the ratio of interfaces was seen: mesangial surface towards capillary lumen increased relative to the urinary surface, and peripheral capillary surface comprised less of the total capillary surface. Data indicated marked glomerular hypertrophy, which correlated with the mesangial volume fraction, thus encompassing preserved filtration surface per glomerulus.(ABSTRACT TRUNCATED AT 250 WORDS)

Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

“…However, we have previously shown that type 1 diabetic patients with clinical proteinuria and long duration (24-26 years) had larger glomeruli than proteinuric patients of shorter diabetes duration (14-16 years) [27]. In type 2 diabetic patients the time of onset of diabetes is often unknown, but Østerby et al demonstrated large glomeruli in type 2 diabetic patients with known diabetes duration of only 7 years [4]. The type 2 diabetic patients in our study were re-biopsied after 2 years and there was no significant difference in glomerular volume from baseline to follow-up [34].…”

“…We and others have shown that structural-functional relationships are similar in type 1 and 2 diabetic patients with clinical proteinuria [4,11]. However, there is greater heterogeneity of structural lesions and GFR in both microalbuminuric and proteinuric type 2 diabetic patients [4,8,12,13].…”

“…The development of glomerular and interstitial lesions is also common to the two types of diabetes [3][4][5][6]. However, the reported rate of progress varies, particularly in type 2 diabetic patients, where the decline in GFR can range from +3.1 to −22.0 ml min −1 year −1 [2,[7][8][9].…”

“…However, there is greater heterogeneity of structural lesions and GFR in both microalbuminuric and proteinuric type 2 diabetic patients [4,8,12,13]. Some type 2 diabetic patients have a relatively well preserved GFR despite increased proteinuria and blood pressure; this may be related to the more pronounced glomerular enlargement that is seen in these patients [4]. Glomerular enlargement is a well recognised feature of diabetes and has been noted at both early (microalbuminuric) and late (proteinuric) stages of nephropathy [14].…”

End-stage renal disease in NIDDM: a consequence of microangiopathy alone?

“…Indeed, most of the early descriptions were in mixed populations of diabetic patients as insulin was the only available treatment [11][12][13]. More recently, studies at the light and electron microscope level in carefully defined IDDM and NIDDM patients with nephropathy have failed to show any consistent differences [14].…”