title: Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control.
abstract: OBJECTIVE
  Elevated plasma asymmetric dimethylarginine (ADMA) levels have been observed in patients with insulin resistance and diabetes, and have been reported to predict adverse cardiovascular events in type 2 diabetic patients. However, the relationship between ADMA and glycemic control in patients with type 2 diabetes remained controversial.
  
  
  RESULTS
  We evaluated 270 patients with type 2 diabetes and measured their plasma ADMA and hemoglobin A1c (HbA1c) levels by high performance liquid chromatography. The mean age was 67 ± 12 years. The mean plasma ADMA and HbA1c level were 0.46 ± 0.09 μmol/l and 7.8 ± 1.6%, respectively. There was no significant correlation between plasma ADMA level and HbA1c level (r = -0.09, p = 0.13). During the median follow-up period of 5.7 years (inter-quartile range: 5.0 - 7.3 years), major adverse cardiovascular event (MACE, including cardiovascular death, myocardial infarction and stroke) was observed in 55 patients (20.4%). Multivariate Cox regression analysis revealed that the ADMA tertile was an independent risk factor for MACE (ADMA tertile III versus ADMA tertile I: p = 0.026, HR: 2.31, 95% CI: 1.10 - 4.81). The prognosis predictive power of ADMA disappeared in patients with well glycemic control (HbA1c ≤6.5%), and the ADMA-HbA1c interaction p value was 0.01.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes, ADMA might be an independent risk factor for long-term adverse cardiovascular events. However, ADMA was not correlated with serum HbA1c level, and in diabetic patients with HbA1c ≤6.5%, elevated ADMA level was no longer associated with increased risk of long-term prognosis. Our findings suggested that the prognosis predictive value of ADMA in type 2 diabetes might be modified by the glycemic control.
authors.affiliation: Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. hsucp@vghtpe.gov.tw.|School of Medicine, National Yang-Ming University, Taipei, Taiwan. hsucp@vghtpe.gov.tw.
authors.forename: Chiao-Po
authors.initials: CP
authors.lastname: Hsu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan. pfhsu57@gmail.com.|Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. pfhsu57@gmail.com.
authors.forename: Pai-Feng
authors.initials: PF
authors.lastname: Hsu
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan. mychung@vghtpe.gov.tw.|Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan. mychung@vghtpe.gov.tw.
authors.forename: Ming-Yi
authors.initials: MY
authors.lastname: Chung
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan. sjlin@vghtpe.gov.tw.|Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. sjlin@vghtpe.gov.tw.|Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan. sjlin@vghtpe.gov.tw.
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan. tmlu@vghtpe.gov.tw.|Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. tmlu@vghtpe.gov.tw.
authors.forename: Tse-Min
authors.initials: TM
authors.lastname: Lu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis*; D002318:Cardiovascular Diseases / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D001120:Arginine; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C487735:dimethylarginine