title: Sodium-lithium countertransport is increased in normoalbuminuric type 1 diabetes but is not related to other risk factors for microangiopathy.
abstract: BACKGROUND
  It has been reported that sodium-lithium countertransport (Na/Li CT) activity is increased in patients with diabetes mellitus and that this increased Na/Li CT activity is associated with the development of diabetic nephropathy. It is unclear however, whether Na/Li CT is related to other pathophysiological factors in diabetic patients. We studied kinetic parameters of Na/Li CT activity together with other putative risk factors for microangiopathy in normoalbuminuric type 1 diabetic patients and matched control subjects.
  
  
  METHODS
  We measured maximum velocity (Vmax) and sodium affinity (Km) of Na/Li CT in 53 diabetic patients and 45 healthy controls. Endothelial function was assessed by monitoring forearm vascular response to intrabrachial infusion of acetylcholine. Blood samples were collected for measurement of HbA1c, glucose, insulin and lipids. Blood pressure was measured intra-arterially. Renal haemodynamics were measured by inulin/p-aminohippurate clearance. Urinary albumin was measured by enzyme-linked immunosorbent assay. Transcapillary escape of albumin (TERalb) was calculated by the disappearance curve of 125I-labelled albumin.
  
  
  RESULTS
  Vmax was increased in diabetic patients (779 +/- 36 micromol Li+ h-1 L-1 erythrocytes vs. 623 +/- 35 in controls, P < 0.01), whereas Km was decreased (64 +/- 16 mmol L-1 vs. 76 +/- 27 in controls, P = 0.03). The ratio of Vmax : Km was 12.4 +/- 0.6 in diabetic patients and 8.9 +/- 0.9 in controls (P < 0.001). When comparing diabetic patients in the lowest and highest quartile of Vmax or Km there were no differences in blood pressure, renal haemodynamics, urinary albumin excretion, TERalb, endothelial function, HbA1c, glucose, insulin, or lipid profile.
  
  
  CONCLUSIONS
  Na/Li CT is increased in uncomplicated type 1 diabetes and characterized by an increase in Vmax and a decrease in Km. The increase in Na/Li CT is not associated with changes in endothelial function, degree of metabolic control, blood pressure or renal haemodynamics.
authors.affiliation: University Medical Center Nijmegen, Nijmegen, the Netherlands. G.Vervoort@aig.azn.nL
authors.forename: G
authors.initials: G
authors.lastname: Vervoort
authors.forename: L D
authors.initials: LD
authors.lastname: Elving
authors.forename: J F M
authors.initials: JF
authors.lastname: Wetzels
authors.forename: J A
authors.initials: JA
authors.lastname: Lutterman
authors.forename: P
authors.initials: P
authors.lastname: Smits
authors.forename: J J H H M
authors.initials: JJ
authors.lastname: de Pont
authors.forename: J H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000419:Albuminuria / Q000097:blood / Q000503:physiopathology; D017920:Antiporters / Q000097:blood*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D004912:Erythrocytes / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D017136:Ion Transport; D007700:Kinetics; D012079:Renal Circulation; D012307:Risk Factors
chemical_list: D017920:Antiporters; C045885:sodium-lithium countertransporter