title: Diabetes Mellitus, Obesity, and Diagnosis of Amyotrophic Lateral Sclerosis: A Population-Based Study.
abstract: OBJECTIVE
  Although prior studies have suggested a role of cardiometabolic health on pathogenesis of amyotrophic lateral sclerosis (ALS), the association with diabetes mellitus has not been widely examined. Amyotrophic lateral sclerosis is the most common motor neuron disorder. Several vascular risk factors have been associated with decreased risk for ALS. Although diabetes is also a risk factor for vascular disease, the few studies of diabetes and ALS have been inconsistent.
  
  
  OBJECTIVE
  To examine the association between diabetes and obesity, each identified through International Statistical Classification of Diseases, Eighth or Tenth Revision codes in a hospital registry, and ALS using data from the Danish National Registers.
  
  
  METHODS
  Population-based nested case-control study of 3650 Danish residents diagnosed as having ALS between January 1, 1982, and December 31, 2009, and 365,000 controls (100 for each ALS case) matched on age and sex. The analysis was conducted in September and October 2014.
  
  
  METHODS
  Adjusted odds ratio for ALS associated with diabetes or obesity diagnoses at least 3 years prior to the ALS diagnosis date.
  
  
  RESULTS
  When considering diabetes and our obesity indicator together, the estimated odds ratio for ALS was 0.61 (95% CI, 0.46-0.80) for diabetes and 0.81 (95% CI, 0.57-1.16) for obesity. We observed no effect modification on the association with diabetes by sex. We did find a significant modification by age at ALS diagnosis and age at first mention of diabetes in the hospital registers. The protective association was stronger with increasing age at ALS diagnosis (P = .01), and the odds ratio for first mention of diabetes was 1.66 (95% CI, 0.85-3.21) before age 40 years but 0.52 (95% CI, 0.39-0.70) for older ages. These results are consistent with different associations for type 1 vs type 2 diabetes.
  
  
  CONCLUSIONS
  In this Danish nationwide study to investigate the association between diabetes and ALS diagnosis, our findings are in agreement with previous reports of a protective association between vascular risk factors and ALS and suggest that type 2 diabetes, but not type 1, is protective for ALS.
authors.affiliation: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Marianthi-Anna
authors.initials: MA
authors.lastname: Kioumourtzoglou
authors.affiliation: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Ran S
authors.initials: RS
authors.lastname: Rotem
authors.affiliation: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Seals
authors.affiliation: National Rehabilitation Center for Neuromuscular Disorders, Copenhagen, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Gredal
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Johnni
authors.initials: J
authors.lastname: Hansen
authors.affiliation: Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts2Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, Massachusetts.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Weisskopf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000175:diagnosis / Q000453:epidemiology*; D016022:Case-Control Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology*; D065840:Protective Factors; D012042:Registries; D012307:Risk Factors