1. A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria
- Author
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De Cosmo, S, Argiolas, A, Miscio, G, Thomas, S, Piras, G, Trevisan, R, Perin, P, Bacci, S, Zucaro, L, Margaglione, M, Frittitta, L, Pizzuti, A, Tassi, V, Viberti, G, Trischitta, V, De Cosmo S, Argiolas A, Miscio G, Thomas S, Piras GP, Trevisan R, Perin PC, Bacci S, Zucaro L, Margaglione M, Frittitta L, Pizzuti A, Tassi V, Viberti GC, Trischitta V, De Cosmo, S, Argiolas, A, Miscio, G, Thomas, S, Piras, G, Trevisan, R, Perin, P, Bacci, S, Zucaro, L, Margaglione, M, Frittitta, L, Pizzuti, A, Tassi, V, Viberti, G, Trischitta, V, De Cosmo S, Argiolas A, Miscio G, Thomas S, Piras GP, Trevisan R, Perin PC, Bacci S, Zucaro L, Margaglione M, Frittitta L, Pizzuti A, Tassi V, Viberti GC, and Trischitta V
- Abstract
Insulin resistance characterizes type I diabetes in patients with albuminuria. A PC-1 glycoprotein amino acid variant, K121Q, is associated with insulin resistance. We examined the impact of the PC-1 K121Q variant on the rate of decline of the glomerular filtration rate (GFR) by creatinine clearance derived from the Cockroft-Gault formula in 77 type I diabetic patients with albuminuria who were followed for an average of 6.5 years (range 2.5-15). Patients carrying the Q allele (n = 22; 20 with KQ and 2 with QQ genotypes) had a faster GFR decline than those patients with the KK genotype (n = 55) (median 7.2 vs. 3.7 ml · min-1 · year-1; range 0.16 to 16.6 vs. -3.8 to 16.0 ml · min-1 · year-1; P< 0.001). Significantly more patients carrying the Q allele belonged to the highest tertile of GFR decline (odds ratio = 5.7, 95% CI 4.1-7.2, P = 0.02). Levels of blood pressure, HbA(1c), and albuminuria were comparable in the two genotype groups. Albuminuria (P = 0.001), mean blood pressure (P = 0.046), and PC-1 genotype (P = 0.036) independently correlated with GFR decline. Because all patients were receiving antihypertensive treatment, the faster GFR decline in the patients carrying the Q allele could be the result of reduced sensitivity to the renoprotective effect of antihypertensive therapy. PC-1 genotyping identifies type I diabetic patients with a faster progression of diabetic nephropathy.
- Published
- 2000