Urine pi-Glutathion S-transferase but not Tamm-Horsfall protein correlates with Carotid artery intima media thickness in childhood type 1 diabetes

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 pi-Glutathione S-transferase to creatinine (pi-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 pi-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 mu g/min), and were therefore removed from the study population. p-GST: crea ratio and THP: crea showed no relationship to the demographic, diabetes, or inflammatory indices. Lower p-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 p-GST: crea ratio with IMT was stronger in patients with passive smoke exposure (p = 0.002, r = -0.43). Among post-pubertal patients, lower pi-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 p-GST: crea ratio seems to be paralleled by changes in arterial structure and microvascular function