title: Urine α-Glutathione S-transferase, systemic inflammation and arterial function in juvenile type 1 diabetes.
abstract: BACKGROUND
  Despite marked improvement in therapy and monitoring of patients with insulin-dependent (type 1) diabetes, diabetic nephropathy remains a serious complication, with subsequent end-stage renal disease in about 20% of cases.
  
  
  OBJECTIVE
  To investigate in young patients with type 1 diabetes whether urine α-Glutathione S-transferase to creatinine ratio (α-GST:crea) relates to markers of systemic inflammation and subclinical vasculopathy.
  
  
  METHODS
  Children and adolescents (median age and diabetes duration 14 and 6 years, respectively) with type 1 diabetes screened in a previous study for proximal tubular (urine α-GST:crea ratio) and renal (plasma creatinine, cystatin C glomerular filtration rate (GFR), and timed urine albumin excretion rate (AER)) function were, within the same timeframe, also investigated for vascular (blood pressure, carotid artery intima-media thickness (IMT) and compliance (CAC), brachial artery flow-mediated dilatation (FMD) and plasma cyclic guanosine monophosphate (cGMP) and inflammatory (C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α)) profiles. Exposure to environmental tobacco smoke (ETS) was assessed through questionnaire (n=67 respondents).
  
  
  RESULTS
  None of the patients (n=69) had overt renal insufficiency. AER correlated with age (p=0.01, r=0.3), diabetes duration (p=0.02, r=0.3), FMD (p=0.04, r=-0.3, n=52), CAC (p=0.03, r=-0.3, n=62) and cGMP (p=0.01, r=-0.3, n=59). α-GST:crea was lower (p=0.03) in patients than in controls. α-GST:crea appeared to be particularly lower in older patients (p=0.004, r=-0.34 vs age), in those with worse diabetic control (p=0.03, r=-0.26 vs HbA1c), and in those with lower carotid artery elasticity (p=0.017, r=0.3 vs CAC). Although ETS had no direct significant impact on α-GST:crea, α-GST:crea correlated with FMD only in patients with ETS (r=0.5, p=0.009, n=13). α-GST:crea showed positive association with TNF-α (p=0.01, r=0.3).
  
  
  CONCLUSIONS
  In children and adolescents with type 1 diabetes, lower levels of urine excretion of α-GST:crea appear to be associated with decreasing elasticity and endothelial vasomotor function of peripheral arteries, especially in patients with ETS. In contrast, higher levels of α-GST:crea are more common in patients with elevated markers of systemic inflammation. Large scale prospective studies are needed to clarify the meaning and mechanisms of this association.
authors.affiliation: Department of Paediatrics, Division of Endocrinology, University Hospital Lund, S-221 85 Lund, Sweden. Peter.Holmquist@skane.se
authors.forename: Peter
authors.initials: P
authors.lastname: Holmquist
authors.forename: Petru
authors.initials: P
authors.lastname: Liuba
mesh_terms: D000293:Adolescent; D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000175:diagnosis / Q000652:urine; D001158:Arteries / Q000503:physiopathology*; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000503:physiopathology / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D005982:Glutathione Transferase / Q000652:urine*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000503:physiopathology / Q000652:urine; D007527:Isoenzymes / Q000652:urine*; D008297:Male; D055815:Young Adult
chemical_list: D000418:Albumins; D007527:Isoenzymes; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha