title: Lower-extremity amputation as a marker for renal and cardiovascular events and mortality in patients with long standing type 1 diabetes.
abstract: BACKGROUND
  We evaluated the risks of renal and cardiovascular complications, and mortality associated with lower extremity amputation (LEA) in patients with type 1 diabetes.
  
  
  METHODS
  We studied two cohorts of people with long standing type 1 diabetes: GENEDIAB (n = 456) and GENESIS (n = 611). Subsets of the cohorts (n = 260, n = 544) were followed for 9 and 5 years, respectively. Outcomes were the incidence of end stage renal disease (ESRD), myocardial infarction, stroke and mortality during follow-up. Analyses were performed in pooled cohorts.
  
  
  RESULTS
  The prevalence of LEA at baseline was 9.3 % (n = 99). A positive history of LEA was associated with the baseline prevalence of established (OR 4.50, 95 % CI 2.33-8.91, p < 0.0001) and advanced diabetic nephropathy (OR 5.50, 95 % CI 2.89-10.78, p < 0.0001), ESRD (OR 2.86, 95 % CI 1.43-5.50, p = 0.004), myocardial infarction (OR 3.25, 95 % CI 1.68-6.15, p = 0.0006) and stroke (OR 3.88, 95 % CI 1.67-8.72, p = 0.002, adjusted for sex, age, and cohort membership). A positive history of LEA at baseline was associated with the incidence during follow-up of ESRD (HR 2.69, 95 % CI 1.17-6.20, p = 0.02), and myocardial infarction (HR 3.53, 95 % CI 1.79-6.97, p = 0.0001). History of LEA was also associated with increased risk for all-cause (HR 3.55, 95 % CI 2.05-6.16, p < 0.0001), cardiovascular (HR 3.30, 95 % CI 1.36-8.02, p = 0.008), infectious disease (HR 5.18, 95 % CI 1.13-23.84, p = 0.03) and other-cause mortality (HR 2.81, 95 % CI 1.09-7.26, p = 0.03). History of LEA at baseline was associated with a 40 % reduction in the duration of survival in the subset of patients who died during follow-up. Population attributable risk of the history of LEA at baseline for total mortality during follow-up was 0.31.
  
  
  CONCLUSIONS
  Patients with LEA have a higher risk of ESRD, myocardial infarction and cardiovascular and non-cardiovascular mortality. Our results highlight the importance of LEA as a key-predictor for major vascular events and premature death in type 1 diabetic patients.
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. kamel.mohammedi@bch.aphp.fr.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. kamel.mohammedi@bch.aphp.fr.
authors.forename: Kamel
authors.initials: K
authors.lastname: Mohammedi
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. louis.potier@aphp.fr.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. louis.potier@aphp.fr.|Univ Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. louis.potier@aphp.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Potier
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. b.narimene@gmail.com.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. b.narimene@gmail.com.
authors.forename: Narimène
authors.initials: N
authors.lastname: Belhatem
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. lynda-matallah@hotmail.fr.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. lynda-matallah@hotmail.fr.
authors.forename: Nadia
authors.initials: N
authors.lastname: Matallah
authors.affiliation: Department of Endocrinology and Diabetology, Centre Hospitalier Universitaire de Poitiers, Poitiers, France. samy.hadjadj@gmail.com.|INSERM, Research Unit 1082, Poitiers, France. samy.hadjadj@gmail.com.|INSERM, CIC 1402, Poitiers, France. samy.hadjadj@gmail.com.|UFR de Médecine et Pharmacie, Université de Poitiers, Poitiers, France. samy.hadjadj@gmail.com.
authors.forename: Samy
authors.initials: S
authors.lastname: Hadjadj
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. ronan.roussel@gmail.com.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. ronan.roussel@gmail.com.|Univ Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. ronan.roussel@gmail.com.
authors.forename: Ronan
authors.initials: R
authors.lastname: Roussel
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. marre.michel@gmail.com.|Department of Diabetology, Endocrinology and Nutrition, Assistance Publique Hôpitaux de Paris, Bichat Hospital, DHU FIRE, Paris, France. marre.michel@gmail.com.|Univ Paris Diderot, Sorbonne Paris Cité, UFR de Médecine, Paris, France. marre.michel@gmail.com.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: INSERM, UMRS 1138, Centre de Recherche des Cordeliers, Paris, France. gilberto.velho@inserm.fr.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Velho
mesh_terms: D000328:Adult; D000671:Amputation, Surgical / Q000009:adverse effects* / Q000379:methods; D001530:Belgium; D016009:Chi-Square Distribution; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D003928:Diabetic Nephropathies / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005602:France; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D016015:Logistic Models; D035002:Lower Extremity / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D016017:Odds Ratio; D015995:Prevalence; D016016:Proportional Hazards Models; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D013997:Time Factors