title: ADMA is a correlate of insulin resistance in early-stage diabetes independent of hs-CRP and body adiposity.
abstract: OBJECTIVE
  It has been shown that insulin resistance is associated with a state of chronic low-grade inflammation. Furthermore, depletion of nitric oxide (NO) or ineffectiveness of NO-mediated vasodilator mechanisms are associated with arterial stiffness and progression of insulin resistance to type-2 diabetes. In this study, we decided to evaluate the association between asymmetric dimethylarginine ([ADMA], an endogenous NO synthase inhibitor), high-sensitivity C-reactive protein ([hs-CRP]; a marker of chronic inflammation) and insulin resistance in early-stage type-2 diabetes.
  
  
  METHODS
  A total of 40 diabetic patients and 40 age-, sex- and body mass index (BMI)-matched healthy adult volunteers were recruited in this case-control study. Diabetic patients were recently diagnosed and did not have a history of any diabetes-related complications. Fasting blood samples were obtained and fasting plasma glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, creatinine, insulin, ADMA and hs-CRP were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) was also calculated.
  
  
  RESULTS
  ADMA (0.9+/-0.2 vs 0.7+/-0.2 micromol/L; p<0.001) and hs-CRP (3.0+/-2.1 vs 1.3+/-1.0mg/L; p<0.001) were significantly higher in diabetic participants vs healthy controls. Age- and sex-adjusted ADMA values were significantly (p<0.05) correlated with hs-CRP (r=0.279) and HOMA-IR (r=0.288) in diabetic patients. These associations were not significant in healthy controls. The association between ADMA and HOMA-IR in diabetic patients remained significant (r=0.255; p<0.05), after adjustment for BMI, waist circumference, serum lipids, and hs-CRP. In multivariate regression analysis, ADMA and hs-CRP were independently correlated with diabetes.
  
  
  CONCLUSIONS
  In early-stage type-2 diabetic patients, ADMA is an independent predictor of insulin resistance. Our results could possibly point to an independent mechanism for contribution of ADMA in development of insulin resistance.
authors.affiliation: Endocrinology and Metabolism Research Center, Vali-Asr Hospital, Tehran University of Medical Sciences, P.O Box 13145-784, Tehran, Iran. nakhjavanim@tums.ac.ir
authors.forename: M
authors.initials: M
authors.lastname: Nakhjavani
authors.forename: H
authors.initials: H
authors.lastname: Karimi-Jafari
authors.forename: A
authors.initials: A
authors.lastname: Esteghamati
authors.forename: O
authors.initials: O
authors.lastname: Khalilzadeh
authors.forename: F
authors.initials: F
authors.lastname: Asgarani
authors.forename: A
authors.initials: A
authors.lastname: Ghadiri-Anari
mesh_terms: D050154:Adiposity; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005215:Fasting / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007249:Inflammation / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine; D003404:Creatinine