A 100-kDa urinary protein is associated with insulin resistance in offspring of type 2 diabetic patients.
OBJECTIVE
One-third of normoalbuminuric type 1 diabetic patients show immunoreactive nephrin in urine. Offspring of type 2 diabetic patients are insulin-resistant 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 insulin 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 whole-body glucose uptake divided by the steady-state insulin level x 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 micromol kg(-1)min(-1)pmol(-1)l(-1), p=0.008).


CONCLUSIONS
A 100-kDa urinary protein detectable with a nephrin antibody is associated with insulin resistance in offspring of type 2 diabetic patients.
Pätäri
A
A
Department of Bacteriology and Immunology, University of Helsinki and Research Program in Molecular Medicine, Biomedicum Helsinki, Helsinki, Finland.
Karhapää
P
P
Taipale
H
H
Salmenniemi
U
U
Ruotsalainen
E
E
Vanninen
P
P
Holthöfer
H
H
Laakso
M
M
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000503:physiopathology* / Q000652:urine; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000139:chemically induced; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology*; D008297:Male; D009679:Nuclear Family; D011507:Proteinuria; D012016:Reference Values
D001786:Blood Glucose; D007328:Insulin