title: The Haptoglobin genotype predicts cardio-renal mortality in type 1 diabetes.
abstract: OBJECTIVE
  The Haptoglobin (HP) 2-2 genotype increases cardiovascular diabetes complication incidence. In type 1 diabetes, HP 2-2 also predicts declining kidney function and end-stage renal disease. We investigated whether HP 2-2 predisposes to cardio-renal mortality, while considering other causes of death as competing risks.
  
  
  METHODS
  Individuals with type 1 diabetes and HP data available (n=486; mean baseline age, 27 and duration, 19 years) were selected for study. Vital status was assessed as of 8/31/2014. The underlying cause of death was determined and classified based on standardized procedures.
  
  
  RESULTS
  During 25 years of follow-up, 79 (16.3%) cardio-renal deaths and 43 (8.8%) deaths related to other causes occurred. Although total mortality did not differ by HP (25.4% with HP 1 versus 24.6% with HP 2-2, p=0.84), a greater proportion of HP 2-2 carriers exhibited a cardio-renal death (19.0 versus 14.2, p=0.05). In time-to-event analyses, HP 2-2 was associated with a statistically significant increase of the sub-distribution hazard ratio for cardio-renal mortality (HR=1.64, p=0.03), although this effect was somewhat attenuated after multivariable adjustment (HR=1.58, p=0.05).
  
  
  CONCLUSIONS
  Our results suggest that in addition to predicting the incidence of cardio-renal complications, HP 2-2 also increases susceptibility for cardio-renal mortality in type 1 diabetes. These findings require validation in other cohorts.
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA. Electronic address: CostacouT@edc.pitt.edu.
authors.forename: Tina
authors.initials: T
authors.lastname: Costacou
authors.affiliation: Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
mesh_terms: D000293:Adolescent; D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000235:genetics / Q000401:mortality*; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics / Q000401:mortality; D008297:Male; D011379:Prognosis; D055815:Young Adult
chemical_list: D006242:Haptoglobins
keywords: Cardiovascular mortality; Competing risk; Haptoglobin genotype; Kidney disease mortality; Mortality; Type 1 diabetes