A 100-kDa urinary protein is associated with insulin resistance in offspring of type 2 diabetic patients

Abstract

Aims/hypothesis: One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulinresistant and susceptible to the development of diabetes. We investigated whether the offspring of type 2 diabetic patients show nephrin in urine and whether possible nephrinuria is associated with insulin resistance. Methods: : Urinary proteins from timed overnight urine collections from 128 offspring of type 2 diabetic patients and 9 control subjects were analysed by western blotting using an antibody against nephrin. Glucose metabolism was assessed by OGTT and IVGTT and the euglycaemic-hyperinsulinaemic clamp technique. Results: Of the offspring, 12.5% were strongly and 14.1% weakly positive for a 100-kDa urinary protein. All controls were negative. During the first 10 min of an IVGTT, the offspring strongly positive for the urinary protein had a higher inysulin response than the offspring without the protein (3,700 vs 2,306 pmol l −1 min −1 , p=0.007). Insulin sensitivity (the rate of wholebody glucose uptake divided by the steady-state insulin level×100) was lower among the offspring strongly positive for the urinary protein than among the offspring negative for the protein (11.3 vs 15.8 μmol kg −1 min −1 pmol −1 l −1 , p=0.008). Conclusions/interpretation: A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabetic patients.