Marianthi-Anna Kioumourtzoglou1, Ran S Rotem1, Ryan M Seals2, Ole Gredal3, Johnni Hansen4, Marc G Weisskopf2. 1. Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts. 2. 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. 3. National Rehabilitation Center for Neuromuscular Disorders, Copenhagen, Denmark. 4. Danish Cancer Society Research Center, Copenhagen, Denmark.
Abstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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: Anne-Marie Wills; Jane Hubbard; Eric A Macklin; Jonathan Glass; Rup Tandan; Ericka P Simpson; Benjamin Brooks; Deborah Gelinas; Hiroshi Mitsumoto; Tahseen Mozaffar; Gregory P Hanes; Shafeeq S Ladha; Terry Heiman-Patterson; Jonathan Katz; Jau-Shin Lou; Katy Mahoney; Daniela Grasso; Robert Lawson; Hong Yu; Merit Cudkowicz Journal: Lancet Date: 2014-02-28 Impact factor: 79.321
Authors: L Dupuis; P Corcia; A Fergani; J-L Gonzalez De Aguilar; D Bonnefont-Rousselot; R Bittar; D Seilhean; J-J Hauw; L Lacomblez; J-P Loeffler; V Meininger Journal: Neurology Date: 2008-01-16 Impact factor: 9.910
Authors: Michaela Scheuermann-Freestone; Per L Madsen; David Manners; Andrew M Blamire; Robin E Buckingham; Peter Styles; George K Radda; Stefan Neubauer; Kieran Clarke Journal: Circulation Date: 2003-06-16 Impact factor: 29.690
Authors: Marianthi-Anna Kioumourtzoglou; Ryan M Seals; Ole Gredal; Murray A Mittleman; Johnni Hansen; Marc G Weisskopf Journal: Amyotroph Lateral Scler Frontotemporal Degener Date: 2016-07-20 Impact factor: 4.092
Authors: Britney E Graham; Christian Darabos; Minjun Huang; Louis J Muglia; Jason H Moore; Scott M Williams Journal: Genet Epidemiol Date: 2017-09-25 Impact factor: 2.135
Authors: Hari Krishna Raju Sagiraju; Sasa Živković; Anne C VanCott; Huned Patwa; David Gimeno Ruiz de Porras; Megan E Amuan; Mary Jo V Pugh Journal: Mil Med Date: 2020-03-02 Impact factor: 1.437