Na/Li countertransport abnormalities in type 1 diabetes with and without nephropathy are familial.
OBJECTIVE
To determine whether there is a familial abnormality in erythrocyte Na/Li countertransport (CT) kinetics in the approximate one-third of type 1 diabetic patients that succumb to a familial predisposition to nephropathy.


METHODS
Erythrocyte Na/Li CT kinetics were measured in nondiabetic first-degree relatives of type 1 diabetic patients with nephropathy (DNrel) (n = 32) or without nephropathy (DCrel) (n = 22) and normal control subjects ( n = 25).


RESULTS
Increases in outside-site Na ion association rate constant and turnover rate of Na/Li countertransport (CT) in DNrels caused increases in Vmax/Km and Vmax, respectively. Thiol alkylation with N-ethy]maleimide (NEM) modifies these kinetic parameters abnormally in nephropathy. With Na ions at the outside site of the transporter, thiol alkylation causes a large decrease in Vmax; but in their absence, Vmax is decreased in normal control subjects, unchanged in DCrels, or increased in DNrels. The relationship between Vmax values after thiol alkylation with or without Na ions was different in DNrels (P < 0.001). Kinetic parameters with and without thiol alkylation identified 60% of DNrels and 20% of DCrels as abnormal. The single-flux rate assay of Na/Li CT did not give this discrimination, and its use may cause discrepancy between studies.


CONCLUSIONS
Clinically normal untreated DNrels have the same abnormality in Na/Li CT as the affected patients. DNrels had a metabolic syndrome with increased BMI and plasma triglycerides, but no elevation in blood pressure. Na/Li CT can detect those type 1 diabetic patients at risk of nephropathy who have a familial abnormality in a membrane thiol protein.
Mead
P A
PA
Department of Medicine, School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, UK.
Wilkinson
R
R
Thomas
T H
TH
D000328:Adult; D017920:Antiporters / Q000097:blood*; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D002794:Choline / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000235:genetics*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000097:blood; D008297:Male; D009679:Nuclear Family; D012016:Reference Values; D012964:Sodium / Q000097:blood; D014280:Triglycerides / Q000097:blood
D017920:Antiporters; D014280:Triglycerides; C045885:sodium-lithium countertransporter; D002784:Cholesterol; D008094:Lithium; D012964:Sodium; D002794:Choline; D005033:Ethylmaleimide