title: Increased plasma concentrations of midregional proatrial natriuretic Peptide is associated with risk of cardiorenal dysfunction in type 1 diabetes.
abstract: BACKGROUND
  To examine possible associations between midregional proatrial natriuretic peptide (MR-proANP) and diabetic complications at baseline and risk of mortality and end-stage renal disease (ESRD) during follow-up in type 1 diabetes.
  
  
  METHODS
  Observational study including 667 patients, with plasma MR-proANP measured at baseline. Complications were defined as micro- (n = 168) or macroalbuminuria (n = 190) (urinary albumin excretion rate (UAER) 30-299 or ≥ 300 mg/24h), previous cardiovascular disease (CVD) (n = 143), cardiac autonomic dysfunction (heart rate variability < 11 beats/min) (n = 369), and retinopathy (n = 523). Adjustments included gender, age, systolic blood pressure, estimated glomerular filtration rate (eGFR), UAER, HbA1c, total cholesterol, 24-hour urinary sodium excretion (24h-U(Na)), body mass index, daily insulin dose, antihypertensive treatment, and smoking in linear regression analyses and analysis of covariance models. Development of ESRD (dialysis, renal transplantation, or GFR/eGFR < 15 ml/min/1.73 m(2)) and mortality was recorded through national registers.
  
  
  RESULTS
  The cohort included 293 (44%) females, aged 55 ± 13 years. Plasma MR-proANP (median (interquartile)) was 74.7 (49.2-116.8) pmol/L. Adjusted, MR-proANP correlated positively with age and UAER and negatively with eGFR, 24h-U(Na), total cholesterol, and HbA1c (P < 0.05). Moreover, MR-proANP levels increased with albuminuria degree and were higher in patients with previous CVD (P ≤ 0.001), but similar in patients with or without autonomic dysfunction or retinopathy (P ≥ 0.076). During follow-up (3.5 (3.1-4.0) years), higher MR-proANP concentrations predicted ESRD and mortality combined (n = 35) adjusted for gender, age, systolic blood pressure, eGFR, and previous CVD (hazard ratio per 1SD increase in logANP: 2.8 (1.6-4.7; P < 0.001)).
  
  
  CONCLUSIONS
  Increased plasma MR-proANP was associated with impaired renal function, increased albuminuria, and previous CVD. Moreover, MR-proANP concentrations were associated with increased risk of development of ESRD and mortality combined during follow-up.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; ktld@steno.dk.
authors.forename: Simone
authors.initials: S
authors.lastname: Theilade
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark;
authors.forename: Tine Willum
authors.initials: TW
authors.lastname: Hansen
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark;
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Goetze
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark; Faculty of Health Sciences, Aarhus University, Aarhus, Denmark; Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Rossing
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D048909:Diabetes Complications / Q000097:blood / Q000453:epidemiology / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006334:Heart Function Tests; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D065667:Renal Elimination; D012307:Risk Factors; D013223:Statistics as Topic
chemical_list: D015415:Biomarkers; C552580:midregional pro-atrial natriuretic peptide, human; D009320:Atrial Natriuretic Factor
keywords: atrial natriuretic peptide; blood pressure; diabetic complications; hypertension; natriuretic peptide; type 1 diabetes.