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Type 2 Diabetic Patients with Nephropathy Show Structural—Functional Relationships that Are Similar to Type 1 Disease

KATHRYN ELIZABETH WHITE^*, RUDOLF WILLIAM BILOUS and THE COLLABORATIVE STUDY GROUP^,a

^* Department of Medicine, The Medical School, University of Newcastle upon Tyne, United Kingdom.
South Cleveland Hospital, Middlesbrough, United Kingdom.

Correspondence to Kathryn Elizabeth White, Department of Medicine, The Medical School, University of Newcastle upon Tyne, Framlington Place, Newcastle upon Tyne, NE2 4HH United Kingdom. Phone: +44 191 222 7020; +44 191 222 0723; K.E.White{at}ncl.ac.uk

Abstract. Glomerular structural—functional relationships were investigated in 21 type 2 diabetic patients with proteinuria. Structural parameters were quantified using both light and electron microscopy and standard stereologic techniques. Data were also available on 14 nondiabetic subjects. Mesangial and matrix volume fractions and glomerular basement membrane (GBM) width were increased in type 2 patients when compared with nondiabetic subjects (mean ± SD: 0.45 ± 0.13 versus 0.18 ± 0.03, P < 0.001; 0.28 ± 0.09 versus 0.10 ± 0.02, P < 0.001; and 665 ± 138 versus 361 ± 51 nm, P < 0.001, respectively). An increase in mesangial volume fraction was associated with high levels of proteinuria and low creatinine clearance (r = 0.64, P = 0.002; r = -0.58, P = 0.006, respectively). GBM width and mesangial foot process width (FPW_mes) also correlated with proteinuria (r = 0.58, P = 0.006; r = 0.60, P = 0.004, respectively). Volume fraction of interstitium correlated with creatinine clearance (r = -0.58, P = 0.006). Patients had previously been defined by light microscopy as having either diffuse or nodular glomerulosclerosis; those with nodules had larger mesangial and matrix volume fractions and more proteinuria than those classified as diffuse (mean ± SD: 0.51 ± 0.12 versus 0.36 ± 0.08, P = 0.007; 0.32 ± 0.08 versus 0.21 ± 0.05, P = 0.003; median, range: 4.3, 1.1 to 9.6 versus 1.1, 0.9 to 12.7 g/24 h, P = 0.027). Creatinine clearance did not differ significantly between the groups. Type 2 diabetic patients with proteinuria have established glomerulopathy, which is more advanced in those with nodular glomerulosclerosis. Creatinine clearance correlated with both mesangial and interstitial expansion, whereas proteinuria correlated only with glomerular pathology. These results suggest that type 2 patients with advanced nephropathy have structural—functional relationships similar to type 1, consistent with a common pathogenesis, and strongly support an important role of the tubulointerstitium in the role of renal impairment.

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