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.

DESIGN:

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).

CONCLUSION:

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: Peter Holmquist, Petru Liuba
• Journal: Journal of diabetes and its complications (J Diabetes Complications) 2012 May-Jun Vol. 26 Issue 3 Pg. 199-204 ISSN: 1873-460X [Electronic] United States
• PMID: 22534514 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Albumins
• Isoenzymes
• Glutathione Transferase
• glutathione S-transferase alpha

Topics

• Adolescent
• Albumins (metabolism)
• Albuminuria (diagnosis, urine)
• Arteries (physiopathology)
• Case-Control Studies
• Child
• Cohort Studies
• Diabetes Mellitus, Type 1 (complications, physiopathology, urine)
• Female
• Follow-Up Studies
• Glomerular Filtration Rate
• Glutathione Transferase (urine)
• Humans
• Inflammation (complications, physiopathology, urine)
• Isoenzymes (urine)
• Male
• Young Adult