title: High urinary ACE2 concentrations are associated with severity of glucose intolerance and microalbuminuria.
abstract: OBJECTIVE
  Angiotensin-converting enzyme 2 (ACE2) plays an important role in glucose metabolism and renal function. However, the relationship between ACE2 and hyperglycemia or microalbuminuria has not been established in humans. We investigated whether urinary ACE2 levels are associated with abnormal glucose homeostasis and urinary albumin excretion.
  
  
  METHODS
  We developed an ELISA for quantifying ACE2 in urine. The ELISA was used to measure urinary ACE2 levels in 621 subjects with: normal glucose tolerance (NGT; n=77); impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) (n=132); and type 2 diabetes mellitus (T2DM, n=412). Insulin resistance was assessed by homeostasis model assessment for insulin resistance (HOMA-IR) index and urinary albumin excretion by urine albumin-to-creatinine ratio (ACR). Other biochemical and anthropometric parameters were measured.
  
  
  RESULTS
  Urinary ACE2 levels were significantly higher in insulin-resistant subjects with IFG, IGT, and T2DM than in the NGT group (P<0.001). Urinary ACE2 concentrations appeared to correlate with HOMA-IR, fasting blood glucose, triglyceride, high-sensitivity C-reactive protein, serum creatinine, urinary ACR, and systolic blood pressure (all P<0.05). After adjustment for impaired renal function and other metabolic parameters, urinary ACE2 concentration was still associated with a higher risk for T2DM (OR 1.80, 95% CI 1.05-3.08, P=0.02). In addition, urinary ACE2 levels were highly predictive of microalbuminuria after adjusting for clinical risk factors (OR 2.68, 95% CI 1.55-4.64, P<0.001).
  
  
  CONCLUSIONS
  Our data suggest that the urinary ACE2 level is closely associated with T2DM and is an independent risk factor for microalbuminuria.
authors.affiliation: Department of Endocrinology and Metabolism, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Park
authors.forename: Won Jun
authors.initials: WJ
authors.lastname: Kim
authors.forename: Sung Woo
authors.initials: SW
authors.lastname: Park
authors.forename: Ji Woo
authors.initials: JW
authors.lastname: Park
authors.forename: Namseok
authors.initials: N
authors.lastname: Lee
authors.forename: Cheol-Young
authors.initials: CY
authors.lastname: Park
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Youn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000503:physiopathology / Q000652:urine*; D001786:Blood Glucose; D002097:C-Reactive Protein; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology / Q000652:urine*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018149:Glucose Intolerance / Q000503:physiopathology / Q000652:urine*; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000652:urine*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose; D002097:C-Reactive Protein; D003404:Creatinine; D007703:Peptidyl-Dipeptidase A