title: N-terminal fragment of probrain natriuretic peptide is associated with diabetes microvascular complications in type 2 diabetes.
abstract: OBJECTIVE
  Circulating levels of N-terminal fragment of probrain natriuretic peptide (NT-proBNP) are established as a risk factor for cardiovascular disease and mortality in patients with diabetes, as well as in the general population. We sought to examine the possibility of NT-proBNP as a biomarker of microvascular complications in patients with type 2 diabetes.
  
  
  METHODS
  In total, 277 outpatients with type 2 diabetes were consecutively enrolled as a hospital cohort. Two hundred and seventeen of these patients (132 males; mean age, 63.4 years) were designated as cases with any of the diabetic complications (retinopathy, neuropathy, nephropathy, ischemic heart disease, strokes, peripheral artery disease), and 60 (42 males; mean age, 54.1 years) were set as controls without clinical evidence of diabetic complications. Diabetic complications were evaluated by medical record and routine laboratory examinations. NT-proBNP was measured and investigated with regard to the associations with diabetic complications.
  
  
  RESULTS
  Mean NT-proBNP levels were significantly higher in patients with any of the diabetic complications (59 versus 33 pg/mL; P<0.0001). In logistic regression analysis, NT-proBNP levels >79 pg/mL, which was the highest tertile, were independently associated with a 5.04 fold increased risk of all complications (P<0.0051) compared to the lowest tertile (NT-proBNP levels <31 pg/mL). Odd ratios of cardiovascular disease and nephropathy, neuropathy, and retinopathy were 9.33, 6.23, 6.6 and 13.78 respectively, in patients with NT-proBNP values in the highest tertile (>79 pg/mL), independently of age, sex, duration of diabetes or other risk factors, such as body mass index or hemoglobin A1c. In addition, NT-proBNP levels were associated with surrogate markers of atherosclerosis, such as brachial-ankle pulse wave velocity (r=0.449, P<0.0001) and left ventricular hypertrophy (r=0.212, P<0.001).
  
  
  CONCLUSIONS
  In this hospital-based cohort of type 2 diabetes, the NT-proBNP levels were associated with systemic atherosclerosis and comorbid diabetic microvascular as well as macrovascular complications. It is useful to stratify high-risk diabetic patients by measuring NT-proBNP and to start comprehensive care for preventing the progression of diabetic complications. It is necessary to elucidate the underlying mechanism for the progression of diabetic complications represented by an elevation of NT-proBNP and to demonstrate the ability of NT-proBNP as a predictive global biomarker for diabetic complications in Japanese type 2 diabetic patients.
authors.affiliation: Department of Diabetes and Endocrinology, Kanto Rosai Hospital, Kawasaki, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Hamano
authors.affiliation: Department of Diabetes and Endocrinology, Kanto Rosai Hospital, Kawasaki, Japan.
authors.forename: Ikue
authors.initials: I
authors.lastname: Nakadaira
authors.affiliation: Department of Diabetes and Endocrinology, Kanto Rosai Hospital, Kawasaki, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Suzuki
authors.affiliation: Department of Diabetes and Endocrinology, Kanto Rosai Hospital, Kawasaki, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Gonai
mesh_terms: D000368:Aged; D044466:Asian People; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000208:ethnology / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000209:etiology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007564:Japan; D016015:Logistic Models; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D016017:Odds Ratio; D010446:Peptide Fragments / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: NT-proBNP; biomarker; diabetic complication