title: Urine π-Glutathione S-transferase but not Tamm-Horsfall protein correlates with carotid artery intima media thickness in childhood type1 diabetes.
abstract: BACKGROUND
  Renal disease remains a serious threat in patients with insulin-dependent (type1) diabetes. Hence its detection early in the life of patients with type1 diabetes is crucial. Several lines of evidence suggest similar mechanisms for the development of both renal and arterial disease. We sought to investigate in young patients with type1 diabetes whether π-Glutathione S-transferase to creatinine (π-GST:crea) and Tamm-Horsfall protein to creatinine (THP:crea) ratios, markers of distal tubular renal function, relate to subclinical markers of arterial disease, which appear to onset early and develop rapidly in type1 diabetes.
  
  
  METHODS
  Seventy-one children and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type1 diabetes for at least 6 months were assessed for timed urine levels of π-GST, THP, HbA1c, albumin, and plasma C-reactive protein (CRP). Carotid artery intima-media thickness (IMT), brachial artery flow-mediated dilatation (FMD), and cutaneous microvascular function were assessed by high-resolution ultrasound and laser Doppler, respectively.
  
  
  RESULTS
  Two patients had microalbuminuria (> 20 μg/min), and were therefore removed from the study population. π-GST:crea ratio and THP:crea showed no relationship to the demographic, diabetes, or inflammatory indices. Lower π-GST:crea ratio was associated with greater IMT (p = 0.01, r = -0.29), particularly in female patients (p = 0.004, r = -0.49). The association of π-GST:crea ratio with IMT was stronger in patients with passive smoke exposure (p = 0.002, r = -0.43). Among post-pubertal patients, lower π-GST:crea ratio was also associated with lower microvascular response to Ach (acetylcholine; p = 0.03, r = 0.49).
  
  
  CONCLUSIONS
  In young patients with type1 diabetes, proximal tubular dysfunction as suggested by lower levels of π-GST:crea ratio seems to be paralleled by changes in arterial structure and microvascular function.
authors.affiliation: Division of Endocrinology, Department of Paediatrics, Lund University Hospita, S-22185 Lund, Sweden. Peter.Holmquist@med.lu.se.
authors.forename: Peter
authors.initials: P
authors.lastname: Holmquist
authors.forename: Petru
authors.initials: P
authors.lastname: Liuba
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D015415:Biomarkers / Q000652:urine; D001916:Brachial Artery / Q000503:physiopathology; D002340:Carotid Artery Diseases / Q000175:diagnosis / Q000209:etiology*; D059168:Carotid Intima-Media Thickness; D002648:Child; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000175:diagnosis / Q000652:urine; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology / Q000652:urine; D005260:Female; D051549:Glutathione S-Transferase pi / Q000652:urine*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000503:physiopathology; D008297:Male; D055806:Microvessels / Q000503:physiopathology; D011237:Predictive Value of Tests; D012307:Risk Factors; D058949:Uromodulin / Q000652:urine*; D014664:Vasodilation
chemical_list: D015415:Biomarkers; C548612:UMOD protein, human; D058949:Uromodulin; D003404:Creatinine; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi