Skip to main content

Type 2 Diabetes Mellitus and Alzheimer’s Disease: Overlapping Biologic Mechanisms and Environmental Risk Factors

Abstract

Purpose of Review

A number of studies over the past two decades have suggested that type 2 diabetes mellitus (T2DM) patients are at an increased risk of Alzheimer’s disease (AD). Several common molecular pathways to cellular and metabolic dysfunction have been implicated in the etiology of both diseases. Here, we review the emerging evidence from observational studies that investigate the relationship between T2DM and AD, and of shared environmental risk factors, specifically air pollution and pesticides, associated with both chronic disorders.

Recent Findings

Particulate matter and traffic-related air pollution have been widely associated with T2DM, and multiple studies have associated exposures with AD or cognitive function. Organochlorine (OC) and organophosphate (OP) pesticides have been associated with T2DM in multiple independent populations. Two populations have observed increased risks for OC and OP exposures and AD. Other studies, limited in exposure assessment, have reported increased risk of AD with any pesticide exposure assessments.

Summary

This may suggest shared pathogenic pathways between environmental risk factors, T2DM, and AD. Research focusing on exposures related to both T2DM and AD could provide new disease insights on shared mechanisms and help shape innovative preventative measures and policy decisions.

This is a preview of subscription content, access via your institution.

Fig. 1

Abbreviations

DDT:

Dichlorodiphenyltrichloroethane

DDE:

Dichlorodiphenyldichloroethylene

HCB:

Hexachlorobenzene

ppb:

Parts per billion

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. United Nations. Report of the Second World Assembly on Ageing: Madrid, 8-12 April 2002. United Nations Publications; 2002. http://www.un.org/en/ga/search/view_doc.asp?symbol=A/CONF.197/9.

  2. Prince M, Bryce R, Albanese E, Wimo A, Ribeiro W, Ferri CP. The global prevalence of dementia: a systematic review and metaanalysis. Alzheimers Dement. 2013;9(1):63–75. https://doi.org/10.1016/j.jalz.2012.11.007.

    Article  PubMed  Google Scholar 

  3. Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94(3):311–21. https://doi.org/10.1016/j.diabres.2011.10.029.

    Article  PubMed  Google Scholar 

  4. Han W, Li C. Linking type 2 diabetes and Alzheimer’s disease. Proc Natl Acad Sci. 2010;107(15):6557–8. https://doi.org/10.1073/pnas.1002555107.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  5. Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM. Synaptic impairment in Alzheimer’s disease: a dysregulated symphony. Trends Neurosci. 2017;40(6):347–57. https://doi.org/10.1016/j.tins.2017.04.002.

    CAS  Article  PubMed  Google Scholar 

  6. Morrison CD. Leptin signaling in brain: a link between nutrition and cognition? Biochim Biophys Acta Mol Basis Dis. 2009;1792(5):401–8. https://doi.org/10.1016/j.bbadis.2008.12.004.

    CAS  Article  Google Scholar 

  7. Zhao WQ, Alkon DL. Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol. 2001;177(1–2):125–34. https://doi.org/10.1016/S0303-7207(01)00455-5.

    CAS  Article  PubMed  Google Scholar 

  8. Chiu SL, Chen CM, Cline HT. Insulin receptor signaling regulates synapse number, dendritic plasticity, and circuit function in vivo. Neuron. 2008;58(5):708–19. https://doi.org/10.1016/j.neuron.2008.04.014.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  9. Harvey J. Leptin regulation of neuronal excitability and cognitive function. Curr Opin Pharmacol. 2007;7(6):643–7. https://doi.org/10.1016/j.coph.2007.10.006.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  10. Eckman EA, Eckman CB. Abeta-degrading enzymes: modulators of Alzheimer’s disease pathogenesis and targets for therapeutic intervention. Biochem Soc Trans. 2005;33(Pt 5):1101–5. https://doi.org/10.1042/BST20051101.

    CAS  PubMed  Google Scholar 

  11. Farris W, Mansourian S, Chang Y, et al. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A. 2003;100(7):4162–7. https://doi.org/10.1073/pnas.0230450100.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  12. FEWLASS DC. Obesity-related leptin regulates Alzheimer’s Aβ. FASEB J. 2004;18(15):1870–8. https://doi.org/10.1096/fj.04-2572com.

    Article  PubMed  Google Scholar 

  13. Phiel CJ, Wilson CA, Lee VM-Y, Klein PS. GSK-3alpha regulates production of Alzheimer’s disease amyloid-beta peptides. Nature. 2003;423(lane 2):435–9. https://doi.org/10.1038/nature01640.

    CAS  Article  PubMed  Google Scholar 

  14. Takeda S, Sato N, Uchio-Yamada K, et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and a deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci. 2010;107(15):7036–41. https://doi.org/10.1073/pnas.1000645107.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  15. • de la Monte SM, Wands JR. Alzheimer’s disease is type 3 diabetes—evidence reviewed. J Diabetes Sci Technol. 2008;2(6):1101–13. https://doi.org/10.1177/193229680800200619. This article reviews the literature pointing toward insulin deficiency and insulin resistance as mediators of AD-type neurodegeneration.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Vella RE, Pillon NJ, Zarrouki B, Croze ML, Koppe L, Guichardant M, et al. Ozone exposure triggers insulin resistance through muscle c-Jun N-terminal kinase activation. Diabetes. 2015;64(3):1011–24. https://doi.org/10.2337/db13-1181.

    CAS  Article  PubMed  Google Scholar 

  17. Bass V, Gordon CJ, Jarema KA, MacPhail RC, Cascio WE, Phillips PM, et al. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats. Toxicol Appl Pharmacol. 2013;273(3):551–60. https://doi.org/10.1016/j.taap.2013.09.029.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  18. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999;53(9):1937–42. https://doi.org/10.1212/WNL.53.9.1937.

    CAS  Article  PubMed  Google Scholar 

  19. MacKnight C, Rockwood K, Awalt E, McDowell I. Diabetes mellitus and the risk of dementia, Alzheimer’s disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord. 2002;14(2):77–83. https://doi.org/10.1159/000064928.

    Article  PubMed  Google Scholar 

  20. Hassing LB, Johansson B, Nilsson SE, et al. Diabetes mellitus is a risk factor for vascular dementia, but not for Alzheimer’s disease: a population-based study of the oldest old. Int Psychogeriatrics. 2002;14(3):239–48. https://doi.org/10.1017/S104161020200844X.

    Article  Google Scholar 

  21. Peila R, Rodriguez BL, Launer LJ. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies. Diabetes. 2002;51(April):1256–62. https://doi.org/10.2337/diabetes.51.4.1256.

    CAS  Article  PubMed  Google Scholar 

  22. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61(5):661–6. https://doi.org/10.1001/archneur.61.5.661.

    Article  PubMed  Google Scholar 

  23. Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology. 2004;63(7):1181–6. https://doi.org/10.1212/01.WNL.0000140291.86406.D1.

    CAS  Article  PubMed  Google Scholar 

  24. Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R. Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005;65(4):545–51. https://doi.org/10.1212/01.wnl.0000172914.08967.dc.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  25. Akomolafe A, Beiser A, Meigs JB, et al. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch Neurol. 2006;63(11):1551–5. https://doi.org/10.1001/archneur.63.11.1551.

    Article  PubMed  Google Scholar 

  26. Raffaitin C, Gin H, Empana J-P, et al. Metabolic syndrome and risk for incident Alzheimer’s disease or vascular dementia: the Three-City study. Diabetes Care. 2009;32(1):169–74. https://doi.org/10.2337/dc08-0272.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Al-Emam A, Elhaddad AA, Ramadan E. The risk of clinically diagnosed alzheimer disease in patients with non insulin dependent diabetes mellitus. Egypt J Neurol Psychiatry Neurosurg. 2010;47(3):419–24.

    Google Scholar 

  28. Ahtiluoto S, Polvikoski T, Peltonen M, et al. Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology. 2010;75(13):1195–202. https://doi.org/10.1212/WNL.0b013e3181f4d7f8.

    CAS  Article  PubMed  Google Scholar 

  29. Kimm H, Lee PH, Shin YJ, et al. Mid-life and late-life vascular risk factors and dementia in Korean men and women. Arch Gerontol Geriatr 2011;52(3). https://doi.org/10.1016/j.archger.2010.09.004.

  30. Ohara T, Doi Y, Ninomiya T, Hirakawa Y, Hata J, Iwaki T, et al. Glucose tolerance status and risk of dementia in the community: the Hisayama Study. Neurology. 2011;77(12):1126–34. https://doi.org/10.1212/WNL.0b013e31822f0435.

    CAS  Article  PubMed  Google Scholar 

  31. Wang K-C, Woung L-C, Tsai M-T, Liu C-C, Su Y-H, Li C-Y. Risk of Alzheimer’s disease in relation to diabetes: a population-based cohort study. Neuroepidemiology. 2012;38(4):237–44. https://doi.org/10.1159/000337428.

    Article  PubMed  Google Scholar 

  32. Huang C-C, Chung C-M, Leu H-B, Lin LY, Chiu CC, Hsu CY, et al. Diabetes mellitus and the risk of Alzheimer’s disease: a Nationwide population-based study. PLoS One. 2014;9(1):e87095. https://doi.org/10.1371/journal.pone.0087095.

    Article  PubMed Central  PubMed  Google Scholar 

  33. Katon W, Pedersen HS, Ribe AR, Fenger-Grøn M, Davydow D, Waldorff FB, et al. Effect of depression and diabetes mellitus on the risk for dementia: a National Population-Based Cohort Study. JAMA Psychiatry. 2015;98195(6):1–8. https://doi.org/10.1001/jamapsychiatry.2015.0082.

    Google Scholar 

  34. Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National patient registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449–90. https://doi.org/10.2147/CLEP.S91125.

    Article  PubMed Central  PubMed  Google Scholar 

  35. Vagelatos NT, Eslick GD. Type 2 diabetes as a risk factor for Alzheimer’s disease: the confounders, interactions, and neuropathology associated with this relationship. Epidemiol Rev. 2013;35(1):152–60. https://doi.org/10.1093/epirev/mxs012.

    Article  PubMed  Google Scholar 

  36. Brook RD, Rajagopalan S, Pope CA, et al. Particulate matter air pollution and cardiovascular disease. Circulation. 2010;121(21):2331–78. https://doi.org/10.1161/CIR.0b013e3181dbece1.

    CAS  Article  PubMed  Google Scholar 

  37. Wang B, Xu D, Jing Z, Liu D, Yan S, Wang Y. Effect of long-term exposure to air pollution on type 2 diabetes mellitus risk: a systemic review and meta-analysis of cohort studies. Eur J Endocrinol. 2014;171(5):R173–82. https://doi.org/10.1530/EJE-14-0365.

    CAS  Article  PubMed  Google Scholar 

  38. Raaschou-Nielsen O, Andersen ZJ, Beelen R, Samoli E, Stafoggia M, Weinmayr G, et al. Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE). Lancet Oncol. 2013;14(9):813–22. https://doi.org/10.1016/S1470-2045(13)70279-1.

    Article  PubMed  Google Scholar 

  39. Block ML, Elder A, Auten RL, et al. The outdoor air pollution and brain health workshop. Neurotoxicology. 2012;33(5):972–84. https://doi.org/10.1016/j.neuro.2012.08.014.

    Article  PubMed Central  PubMed  Google Scholar 

  40. Evangelou E, Ntritsos G, Chondrogiorgi M, et al. Exposure to pesticides and diabetes: a systematic review and meta-analysis. Environ Int. 2016;91:60–8. https://doi.org/10.1016/j.envint.2016.02.013.

    CAS  Article  PubMed  Google Scholar 

  41. • Zaganas I, Kapetanaki S, Mastorodemos V, et al. Linking pesticide exposure and dementia: what is the evidence? Toxicology. 2013;307:3–11. https://doi.org/10.1016/j.tox.2013.02.002. This article reviews the epidemiological links between dementia and pesticide exposure and discusses the possible pathophysiological mechanisms and clinical implications of this association.

    CAS  Article  PubMed  Google Scholar 

  42. Brook RD, Jerrett M, Brook JR, Bard RL, Finkelstein MM. The relationship between diabetes mellitus and traffic-related air pollution. J Occup Environ Med. 2008;50(1):32–8. https://doi.org/10.1097/JOM.0b013e31815dba70.

    CAS  Article  PubMed  Google Scholar 

  43. Coogan PF, White LF, Jerrett M, et al. Air pollution and incidence of hypertension and diabetes in African American women living in Los Angeles. Circulation. 2012. https://doi.org/10.1161/CIRCULATIONAHA.111.052753.

  44. Andersen ZJ, Raaschou-Nielsen O, Ketzel M, et al. Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes Care. 2012;35(1):92–8. https://doi.org/10.2337/dc11-1155.

    CAS  Article  PubMed  Google Scholar 

  45. Krämer U, Herder C, Sugiri D, et al. Traffic-related air pollution and incident type 2 diabetes: results from the SALIA cohort study. Environ Health Perspect. 2010;118(9):1273–9. https://doi.org/10.1289/ehp.0901689.

    Article  PubMed Central  PubMed  Google Scholar 

  46. G W, K F, F H, et al. Industry and traffic related air pollution and diabetes type two incidence: results from a German cohort study. Eur J Epidemiol. 2012;27(1 SUPPL. 1):S12. http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed14&NEWS=N&AN=71302821

    Google Scholar 

  47. Eze IC, Schaffner E, Fischer E, et al. Long-term air pollution exposure and diabetes in a population-based Swiss cohort. Environ Int. 2014;70:95–105. https://doi.org/10.1016/j.envint.2014.05.014.

    CAS  Article  PubMed  Google Scholar 

  48. Park SK, Adar SD, O’Neill MS, et al. Long-term exposure to air pollution and type 2 diabetes mellitus in a multiethnic cohort. Am J Epidemiol. 2015;181(5):327–36. https://doi.org/10.1093/aje/kwu280.

    Article  PubMed Central  PubMed  Google Scholar 

  49. Brook RD, Cakmak S, Turner MC, et al. Long-term fine particulate matter exposure and mortality from diabetes in Canada. Diabetes Care. 2013;36(10):3313–20. https://doi.org/10.2337/dc12-2189.

    Article  PubMed Central  PubMed  Google Scholar 

  50. Chen H, Burnett RT, Kwong JC, Villeneuve PJ, Goldberg MS, Brook RD, et al. Risk of incident diabetes in relation to long-term exposure to fine particulate matter in Ontario, Canada. Environ Health Perspect. 2013;121(7):804–10. https://doi.org/10.1289/ehp.1205958.

    Article  PubMed Central  PubMed  Google Scholar 

  51. Puett RC, Hart JE, Schwartz J, Hu FB, Liese AD, Laden F. Are particulate matter exposures associated with risk of type 2 diabetes? Environ Health Perspect. 2011;119(3):384–9. https://doi.org/10.1289/ehp.1002344.

    Article  PubMed  Google Scholar 

  52. Weinmayr G, Hennig F, Fuks K, et al. Long-term exposure to fine particulate matter and incidence of type 2 diabetes mellitus in a cohort study: effects of total and traffic-specific air pollution. Environ Health. 2015;14(1):53. https://doi.org/10.1186/s12940-015-0031-x.

    Article  PubMed Central  PubMed  Google Scholar 

  53. Jung C-R, Lin Y-T, Hwang B-F. Ozone, particulate matter, and newly diagnosed Alzheimer’s disease: a population-based cohort study in Taiwan. J Alzheimers Dis. 2015;44(2):573–84. https://doi.org/10.3233/JAD-140855.

    CAS  PubMed  Google Scholar 

  54. Kioumourtzoglou MA, Schwartz JD, Weisskopf MG, et al. Long-term PM exposure and neurological hospital admissions in the northeastern United States. Environ Health Perspect. 2015;124(1):23–9. https://doi.org/10.1289/ehp.1408973.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Weuve J, Puett RC, Schwartz J, Yanosky JD, Laden F, Grodstein F. Exposure to particulate air pollution and cognitive decline in older women. Arch Intern Med. 2012;172(3):219–27. https://doi.org/10.1001/archinternmed.2011.683.

    Article  PubMed Central  PubMed  Google Scholar 

  56. Loop MS, Kent ST, Al-Hamdan MZ, Crosson WL, Estes SM, Estes MG, et al. Fine particulate matter and incident cognitive impairment in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. PLoS One. 2013;8(9):e75001. https://doi.org/10.1371/journal.pone.0075001.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  57. Tonne C, Elbaz A, Beevers S, Singh-Manoux A. Traffic-related air pollution in relation to cognitive function in older adults. Epidemiology. 2014;25(5):674–81. https://doi.org/10.1097/EDE.0000000000000144.

    Article  PubMed Central  PubMed  Google Scholar 

  58. Schikowski T, Vossoughi M, Vierkötter A, et al. Association of air pollution with cognitive functions and its modification by APOE gene variants in elderly women. Environ Res. 2015;142:10–6. https://doi.org/10.1016/j.envres.2015.06.009.

    CAS  Article  PubMed  Google Scholar 

  59. Wu Y-C, Lin Y-C, Yu H-L, Chen JH, Chen TF, Sun Y, et al. Association between air pollutants and dementia risk in the elderly. Alzheimer’s Dement Diagnosis Assess Dis Monit. 2015;1(2):220–8. https://doi.org/10.1016/j.dadm.2014.11.015.

    Google Scholar 

  60. Oudin A, Forsberg B, Adolfsson AN, et al. Traffic-related air pollution and dementia incidence in Northern Sweden: a longitudinal study. Environ Health Perspect. 2016;124(3):306–12. https://doi.org/10.1289/ehp.1408322.

    PubMed  Google Scholar 

  61. Chang K-H, Chang M-Y, Muo C-H, Wu T-N, Chen C-Y, Kao C-H. Increased risk of dementia in patients exposed to nitrogen dioxide and carbon monoxide: a population-based retrospective cohort study. PLoS One. 2014;9(8):e103078. https://doi.org/10.1371/journal.pone.0103078.

    Article  PubMed Central  PubMed  Google Scholar 

  62. Eze IC, Hemkens LG, Bucher HC, Hoffmann B, Schindler C, Künzli N, et al. Association between ambient air pollution and diabetes mellitus in Europe and North America: systematic review and meta-analysis. Envi Health Perspect. 2015;123(5):381–9. https://doi.org/10.1289/ehp.1307823.

    CAS  Google Scholar 

  63. Mazure CM, Swendsen J. Sex differences in Alzheimer’s disease and other dementias. Lancet Neurol. 2016;15(5):451–2. https://doi.org/10.1016/S1474-4422(16)00067-3.

    Article  PubMed Central  PubMed  Google Scholar 

  64. Power MC, Weisskopf MG, Alexeeff SE, Coull BA, Avron S, Schwartz J. Traffic-related air pollution and cognitive function in a cohort of older men. Environ Health Perspect. 2011;119(5):682–7. https://doi.org/10.1289/ehp.1002767.

    CAS  Article  PubMed  Google Scholar 

  65. Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, et al. Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med. 2007;356(5):447–58. https://doi.org/10.1056/NEJMoa054409.

    CAS  Article  PubMed  Google Scholar 

  66. Bro-Rasmussen F. Contamination by persistent chemicals in food chain and human health. Sci Total Environ. 1996;188 https://doi.org/10.1016/0048-9697(96)05276-X.

  67. Committee to review the health effects in Vietnam Veterans of exposure to herbicides (Tenth Biennial Update) C, on the Health of select populations B, of Medicine I, of Sciences Engineering, Medicine. Veterans and Agent Orange: Update 2014.; 2016. https://doi.org/10.17226/21845.

  68. Taylor KW, Novak RF, Anderson HA, Birnbaum LS, Blystone C, DeVito M, et al. Evaluation of the association between persistent organic pollutants (POPs) and diabetes in epidemiological studies: a national toxicology program workshop review. Environ Health Perspect. 2013;121(7):774–83. https://doi.org/10.1289/ehp.1205502.

    Article  PubMed Central  PubMed  Google Scholar 

  69. Morgan DP, Lin LI, Saikaly HH. Morbidity and mortality in workers occupationally exposed to pesticides. Arch Environ Contam Toxicol. 1980;9(3):349–82. http://www.ncbi.nlm.nih.gov/pubmed/7396557. https://doi.org/10.1007/BF01057414.

    CAS  Article  PubMed  Google Scholar 

  70. Lee D-H, Lee I-K, Song K, Steffes M, Toscano W, Baker BA, et al. A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002. Diabetes Care. 2006;29(7):1638–44. https://doi.org/10.2337/dc06-0543.

    CAS  Article  PubMed  Google Scholar 

  71. Montgomery MP, Kamel F, Saldana TM, Alavanja MCR, Sandler DP. Incident diabetes and pesticide exposure among licensed pesticide applicators: Agricultural Health Study, 1993-2003. Am J Epidemiol. 2008;167(10):1235–46. https://doi.org/10.1093/aje/kwn028.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  72. Turyk M, Anderson H, Knobeloch L, Imm P, Persky V. Organochlorine exposure and incidence of diabetes in a cohort of great lakes sport fish consumers. Environ Health Perspect. 2009;117(7):1076–82. https://doi.org/10.1289/ehp.0800281.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  73. Lee D-H, Steffes MW, Sjödin A, Jones RS, Needham LL, Jacobs DR. Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case–control study. Environ Health Perspect. 2010;118(9):1235–42. https://doi.org/10.1289/ehp.0901480.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  74. Lee DH, Lind PM, Jacobs DR, Salihovic S, Van Bavel B, Lind L. Polychlorinated biphenyls and organochlorine pesticides in plasma predict development of type 2 diabetes in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Diabetes Care. 2011;34(8):1778–84. https://doi.org/10.2337/dc10-2116.

    Article  PubMed Central  PubMed  Google Scholar 

  75. Wu H, Bertrand KA, Choi AL, Hu FB, Laden F, Grandjean P, et al. Persistent organic pollutants and type 2 diabetes: a prospective analysis in the nurses’ health study and meta-analysis. Environ Health Perspect. 2013;121(2):153–61. https://doi.org/10.1289/ehp.1205248.

    PubMed  Google Scholar 

  76. Starling AP, Umbach DM, Kamel F, Long S, Sandler DP, Hoppin JA. Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study. Occup Environ Med. 2014;71(9):629–35. https://doi.org/10.1136/oemed-2013-101659.

    Article  PubMed Central  PubMed  Google Scholar 

  77. McDowell I, Hill G, Lindsay J, et al. The Canadian study of health and aging: risk-factors for Alzheimer’s disease in Canada. Neurology. 1994;44(11):2073–80.

    Article  Google Scholar 

  78. Tyas SL, Manfreda J, Strain A, Montgomery PR. Risk factors for Alzheimer’s disease: a population-based, longitudinal study in Manitoba, Canada. Int J Epidemiol. 2001;30(3):590–7. https://doi.org/10.1093/ije/30.3.590.

    CAS  Article  PubMed  Google Scholar 

  79. Baldi I, Lebailly P, Mohammed-Brahim B, Letenneur L, Dartigues JF, Brochard P. Neurodegenerative diseases and exposure to pesticides in the elderly. Am J Epidemiol. 2003;157(5):409–14. https://doi.org/10.1093/aje/kwf216.

    Article  PubMed  Google Scholar 

  80. Hayden KM, Norton MC, Darcey D, Ostbye T, Zandi PP, Breitner JCS, et al. Occupational exposure to pesticides increases the risk of incident AD: the Cache County study. Neurology. 2010;74(19):1524–30. https://doi.org/10.1212/WNL.0b013e3181dd4423.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  81. Parrón T, Requena M, Hernández AF, Alarcón R. Association between environmental exposure to pesticides and neurodegenerative diseases. Toxicol Appl Pharmacol. 2011;256(3):379–85. https://doi.org/10.1016/j.taap.2011.05.006.

    Article  PubMed  Google Scholar 

  82. Richardson JR, Roy A, Shalat SL, et al. Elevated serum pesticide levels and risk for Alzheimer disease. JAMA Neurol. 2014;71(3):284. https://doi.org/10.1001/jamaneurol.2013.6030.

    Article  PubMed Central  PubMed  Google Scholar 

  83. Koeman T, Schouten LJ, van den Brandt PA, Slottje P, Huss A, Peters S, et al. Occupational exposures and risk of dementia-related mortality in the prospective Netherlands Cohort study. Am J Ind Med. 2015;58(6):625–35. https://doi.org/10.1002/ajim.22462.

    CAS  Article  PubMed  Google Scholar 

  84. Lin J-N, Lin C-L, Lin M-C, Lai CH, Lin HH, Yang CH, et al. Increased risk of dementia in patients with acute organophosphate and carbamate poisoning: a Nationwide population-based cohort study. Medicine (Baltimore). 2015;94(29):e1187. https://doi.org/10.1097/MD.0000000000001187.

    Article  Google Scholar 

  85. Gauthier E, Fortier I, Courchesne F, Pepin P, Mortimer J, Gauvreau D. Environmental pesticide exposure as a risk factor for Alzheimer’s disease: a case-control study. Environ Res. 2001;86(1):37–45. https://doi.org/10.1006/enrs.2001.4254.

    CAS  Article  PubMed  Google Scholar 

  86. Jerrett M, Arain A, Kanaroglou P, et al. A review and evaluation of intraurban air pollution exposure models. J Expo Anal Environ Epidemiol. 2005;15(2):185–204. https://doi.org/10.1038/sj.jea.7500388.

    CAS  Article  PubMed  Google Scholar 

  87. de Hoogh K, Korek M, Vienneau D, et al. Comparing land use regression and dispersion modelling to assess residential exposure to ambient air pollution for epidemiological studies. Environ Int. 2014;73:382–92. https://doi.org/10.1016/j.envint.2014.08.011.

    Article  PubMed  Google Scholar 

  88. Teschke K, Olshan AF, Daniels JL, et al. Occupational exposure assessment in case-control studies: opportunities for improvement. Occup Environ Med. 2002;59(9):575–93; discussion 594. https://doi.org/10.1136/oem.59.9.575.

    CAS  Article  PubMed Central  PubMed  Google Scholar 

  89. McGuire V, Nelson LM, Koepsell TD, Checkoway H, Longstreth WT. Assessment of occupational exposures in community-based case-control studies. Annu Rev Public Health. 1998;19(19):35–53. https://doi.org/10.1146/annurev.publhealth.19.1.35.

    CAS  Article  PubMed  Google Scholar 

  90. • Brouwer M, Kromhout H, Vermeulen R, et al. Assessment of residential environmental exposure to pesticides from agricultural fields in the Netherlands. J Expo Sci Environ Epidemiol. 2017. This article describes a spatio-temporal model to estimate lifetime exposure to pesticides in the Netherlands based on residential histories.

  91. Milner AM, Boyd IL. Toward pesticidovigilance. Science (80-). 2017;357(6357):1232–4. https://doi.org/10.1126/science.aan2683.

    CAS  Article  Google Scholar 

Download references

Funding

This work was supported by the National Institute of Environmental Health Sciences (F32-ES028087 (KP), 2R01-ES010544 (BR), R01-ES023451 (BR, MJ).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Beate Ritz.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Susceptibility Factors in Environmental Health

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Paul, K.C., Jerrett, M. & Ritz, B. Type 2 Diabetes Mellitus and Alzheimer’s Disease: Overlapping Biologic Mechanisms and Environmental Risk Factors. Curr Envir Health Rpt 5, 44–58 (2018). https://doi.org/10.1007/s40572-018-0176-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40572-018-0176-1

Keywords

  • Type 2 diabetes mellitus
  • Alzheimer’s disease
  • Environment
  • Air pollution
  • Pesticides