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Current Drug Safety

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ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Research Article

Increased Risk of Falls, Fall-related Injuries and Fractures in People with Type 1 and Type 2 Diabetes - A Nationwide Cohort Study

Author(s): Nicklas H. Rasmussen*, Jakob Dal, Joop Van den Bergh, Frank de Vries, Morten Hasselstrøm Jensen and Peter Vestergaard

Volume 16, Issue 1, 2021

Published on: 08 September, 2020

Page: [52 - 61] Pages: 10

DOI: 10.2174/1574886315666200908110058

Price: $65

Abstract

Introduction: People with diabetes could have an increased risk of falls as they show more complications, morbidity and use of medication compared to the general population. This study aimed to estimate the risk of falls and to identify risk factors associated with falls in people with diabetes. The second aim was to estimate fall-related injuries, such as lesions and fractures, including their anatomic localization in people with diabetes compared with the general population.

Methods: From the Danish National Patient Register, we identified people with Type 1 Diabetes (T1D) (n=12,975) Type 2 Diabetes (T2D) (n=407,009). The cohort was divided into two groups, with respective control groups matched on age and sex (1:1). All episodes of people hospitalized with a first fall from 1996 to 2017 were analyzed using a Cox proportional-hazards model. Risk factors such as age, sex, diabetic complications, a history of alcohol abuse and the use of medication were included in an adjusted analysis. The incidence rate, incidence rate difference and incidence rate ratio (IRR) of falls and the anatomic localization of fall-related injuries as lesions and fractures were identified.

Results and Discussion: The cumulative incidence, of falls requiring hospital treatment, was 13.3% in T1D, 11.9% in T2D. In the adjusted analysis, T1D and T2D were associated with a higher risk of falls [T1D, Hazard Ratio (HR): 1.33 (95% CI: 1.25 - 1.43), T2D, HR: 1.19 (95% CI:1.16 - 1.22), respectively]. Women [group 1, HR 1.21 (CI:95%:1.13 - 1.29), group 2, HR 1.61 (CI:95%:1.58-1.64)], aged >65 years [groups 1, HR 1.52 (CI:95%:1.39 - 1.61), group 2, HR 1.32 (CI:95%:1.58-1.64)], use of selective serotonin receptor inhibitors (SSRI) [group 1, HR 1.35 (CI:95%:1.1.30 - 1.40), group 2, HR 1.32 (CI:95%:1.27-1.38)], opioids [group 1, HR 1.15 (CI:95%:1.12 - 1.19), group 2, HR 1.09 (CI:95%:1.05-1.12)] and a history of alcohol abuse [group 1, HR 1.77 (CI:95%:1.17 - 2.15), group 2, HR 1.88 (CI:95%:1.65-2.15)] were significantly associated with an increased risk of falls in both groups. The IRR of fall-related injuries as hip, radius, humerus and skull/facial fractures were higher in people with T2D than controls [IRR 1.02 (CI:95%:1.01-1.04), IRR 1.39 (CI:95%: 1.18-1.61), IRR 1.24 (CI:95%: 1.12-1.37) and IRR 1.15 (CI:95%:1.07-1.24)]. People with T1D had a higher IRR of hip fractures than controls [IRR: 1.11 (CI:95%:1.02 – 1.23)].

Conclusion: People with diabetes have an increased risk of first fall and a higher incidence of fall- related injuries, including fractures. Advanced aging and sex are non-modifiable risk factors, whereas diabetes, the use of SSRIs and opioids and alcohol abuse could be potentially modifiable risk factors for falls. Gaining information on risk factors for falls could guide the management of diabetes treatment, i.e., choice of drugs, which enables us to improve treatment, particularly in people with a high risk of falls and fractures associated with high mortality.

Keywords: Type 1 diabetes, type 2 diabetes, falls, fall-related injuries, lesions, fractures.

Graphical Abstract
[1]
Vos T, Barber RM, Bell B, et al. Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015; 386(9995): 743-800.
[http://dx.doi.org/10.1016/S0140-6736(15)60692-4] [PMID: 26063472]
[3]
Thapa PB, Brockman KG, Gideon P, Fought RL, Ray WA. Injurious falls in nonambulatory nursing home residents: A comparative study of circumstances, incidence, and risk factors. J Am Geriatr Soc 1996; 44(3): 273-8.
[http://dx.doi.org/10.1111/j.1532-5415.1996.tb00913.x] [PMID: 8600195]
[4]
Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319(26): 1701-7.
[http://dx.doi.org/10.1056/NEJM198812293192604] [PMID: 3205267]
[5]
Toft AMH, Møller H, Laursen B. The years after an injury: long-term consequences of injury on self-rated health. J Trauma 2010; 69(1): 26-30.
[http://dx.doi.org/10.1097/TA.0b013e3181d3cbf2] [PMID: 20622575]
[6]
Laursen B, Møller H. Long-term health effects of unintentional injuries in Danish adults. Dan Med J 2012; 59(5): A4423.
[PMID: 22549487]
[7]
Cummings SR, Nevitt MC. Study of Osteoporotic Fractures Research Group. Non-skeletal determinants of fractures: The potential importance of the mechanics of falls. Osteoporos Int 1994; 4(Suppl. 1): 67-70.
[http://dx.doi.org/10.1007/BF01623439] [PMID: 8081063]
[8]
Sarodnik C, Bours SPG, Schaper NC, et al. Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Osteoporos Int 2018; 18: 427-44.
[9]
Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol 2007; 166(5): 495-505.
[http://dx.doi.org/10.1093/aje/kwm106] [PMID: 17575306]
[10]
Shah VN, Shah CS, Snell-Bergeon JK. Type 1 diabetes and risk of fracture: Meta-analysis and review of the literature. Diabet Med 2015; 32(9): 1134-42.
[http://dx.doi.org/10.1111/dme.12734] [PMID: 26096918]
[11]
Rasmussen NH, Dal J. Falls and Fractures in Diabetes-More than Bone Fragility. Curr Osteoporos Rep 2019; 17(3): 147-56.
[http://dx.doi.org/10.1007/s11914-019-00513-1] [PMID: 30915638]
[12]
Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes- a meta-analysis. Osteoporos Int 2007; 18(4): 427-44.
[http://dx.doi.org/10.1007/s00198-006-0253-4] [PMID: 17068657]
[13]
Starup-Linde J, Vestergaard P. Management of endocrine disease: Diabetes and osteoporosis: Cause for concern? Eur J Endocrinol 2015; 173(3): R93-9.
[http://dx.doi.org/10.1530/EJE-15-0155] [PMID: 26243638]
[14]
Starup-Linde J, Lykkeboe S, Gregersen S, et al. Bone structure and predictors of fracture in type 1 and type 2 diabetes. J Clin Endocrinol Metab 2016; 101(3): 928-36.
[http://dx.doi.org/10.1210/jc.2015-3882] [PMID: 26756117]
[15]
Starup-Linde J, Lykkeboe S, Gregersen S, et al. Differences in biochemical bone markers by diabetes type and the impact of glucose. Bone 2016; 83: 149-55.
[http://dx.doi.org/10.1016/j.bone.2015.11.004] [PMID: 26555635]
[16]
Roman de Mettelinge T, Cambier D, Calders P, Van Den Noortgate N, Delbaere K. Understanding the relationship between type 2 diabetes mellitus and falls in older adults: A prospective cohort study. PLoS One 2013; 8(6)e67055
[http://dx.doi.org/10.1371/journal.pone.0067055] [PMID: 23825617]
[17]
de Waard EAC, Koster A, Melai T, et al. The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older-the Maastricht Study. Osteoporos Int 2016; 27(11): 3207-16.
[http://dx.doi.org/10.1007/s00198-016-3645-0] [PMID: 27234668]
[18]
Yang Y, Hu X, Zhang Q, Zou R. Diabetes mellitus and risk of falls in older adults: A systematic review and meta-analysis. Age Ageing 2016; 45(6): 761-7.
[http://dx.doi.org/10.1093/ageing/afw140] [PMID: 27515679]
[19]
Frank L. Epidemiology. When an entire country is a cohort. Science 2000; 287(5462): 2398-9.
[http://dx.doi.org/10.1126/science.287.5462.2398] [PMID: 10766613]
[20]
Andersen TF, Madsen M, Jørgensen J, Mellemkjoer L, Olsen JH. The Danish National Hospital Register. A valuable source of data for modern health sciences. Dan Med Bull 1999; 46(3): 263-8.
[PMID: 10421985]
[21]
Kildemoes HW, Sørensen HT, Hallas J. The Danish National Prescription Registry. Scand J Public Health 2011; 39(7)(Suppl.): 38-41.
[http://dx.doi.org/10.1177/1403494810394717] [PMID: 21775349]
[22]
Dipietro L, Campbell WW, Buchner DM, et al. 2018 PHYSICAL ACTIVITY GUIDELINES ADVISORY COMMITTEE*. Physical Activity, Injurious Falls, and Physical Function in Aging: An Umbrella Review. Med Sci Sports Exerc 2019; 51(6): 1303-13.
[http://dx.doi.org/10.1249/MSS.0000000000001942] [PMID: 31095087]
[23]
Hopkins RB, Pullenayegum E, Goeree R, et al. Estimation of the lifetime risk of hip fracture for women and men in Canada. Osteoporos Int 2012; 23(3): 921-7.
[http://dx.doi.org/10.1007/s00198-011-1652-8] [PMID: 21557096]
[24]
Taylor CA, Bell JM, Breiding MJ, Xu L. Traumatic brain injury-related emergency department visits, hospitalizations, and deaths - United States, 2007 and 2013. MMWR Surveill Summ 2017; 66(9): 1-16.
[http://dx.doi.org/10.15585/mmwr.ss6609a1] [PMID: 28301451]
[25]
Breuil V, Roux CH, Carle GF. Pelvic fractures: Epidemiology, consequences, and medical management. Curr Opin Rheumatol 2016; 28(4): 442-7.
[http://dx.doi.org/10.1097/BOR.0000000000000293] [PMID: 27077891]
[26]
Stahel PF, Hammerberg EM. History of pelvic fracture management: A review. World J Emerg Surg 2016; 11: 18.
[http://dx.doi.org/10.1186/s13017-016-0075-4] [PMID: 27148396]
[27]
Seppala LJ, Wermelink AMAT, de Vries M, et al. EUGMS task and Finish group on fall-risk-increasing drugs. Fall-Risk-Increasing Drugs: A Systematic Review and Meta-Analysis: II. Psychotropics. J Am Med Dir Assoc 2018; 19(4): 371.e11-7.
[http://dx.doi.org/10.1016/j.jamda.2017.12.098] [PMID: 29402652]
[28]
Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med 2009; 169(21): 1952-60.
[http://dx.doi.org/10.1001/archinternmed.2009.357] [PMID: 19933955]
[29]
Antidepressant Prescriptions: An Acute Window for Falls in the Nursing Home https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3202899/
[30]
Vestergaard P. Drugs Causing Bone Loss. Handb Exp Pharmacol 2020; 262: 475-97
[http://dx.doi.org/10.1007/164_2019_340]
[31]
Javed S, Petropoulos IN, Alam U, Malik RA. Treatment of painful diabetic neuropathy. Ther Adv Chronic Dis 2015; 6(1): 15-28.
[http://dx.doi.org/10.1177/2040622314552071] [PMID: 25553239]
[32]
Kvelde T, McVeigh C, Toson B, et al. Depressive symptomatology as a risk factor for falls in older people: Systematic review and meta-analysis. J Am Geriatr Soc 2013; 61(5): 694-706.
[http://dx.doi.org/10.1111/jgs.12209] [PMID: 23617614]
[33]
Khaledi M, Haghighatdoost F, Feizi A, Aminorroaya A. The prevalence of comorbid depression in patients with type 2 diabetes: An updated systematic review and meta-analysis on huge number of observational studies. Acta Diabetol 2019; 56(6): 631-50.
[http://dx.doi.org/10.1007/s00592-019-01295-9] [PMID: 30903433]
[34]
Feldman EL, Callaghan BC, Pop-Busui R, et al. Diabetic neuropathy. Nat Rev Dis Prim 2019.
[35]
Machado-Duque ME, Castaño-Montoya JP, Medina-Morales DA, Castro-Rodríguez A, González-Montoya A, Machado-Alba JE. Association between the use of benzodiazepines and opioids with the risk of falls and hip fractures in older adults. Int Psychogeriatr 2018; 30(7): 941-6.
[http://dx.doi.org/10.1017/S1041610217002745] [PMID: 29223172]
[36]
S.P. Raul, L. Groeneveld, A.S. koopman, J.W.J. Beulens, A.P.D. Jansens, M.Brenners, A.A.W.A. van der Heijden, P.J. Elders J.M. Dekkar, G. Nijpels, J.G. Hugtenburg etal. The use of antidepressants, anxiolytics, and hypnotics in people with type 2 diabetes and patterns associated with use: the hoorn diabetes care sys https://www-ncbi-nlm-nih-gov.auh.aub.aau.dk/pubmed/28232942
[37]
Milos V, Bondesson Å, Magnusson M, Jakobsson U, Westerlund T, Midlöv P. Fall risk-increasing drugs and falls: A cross-sectional study among elderly patients in primary care. BMC Geriatr 2014; 14: 40.
[http://dx.doi.org/10.1186/1471-2318-14-40] [PMID: 24674152]
[38]
Huang ES, Karter AJ, Danielson KK, Warton EM, Ahmed AT. The association between the number of prescription medications and incident falls in a multi-ethnic population of adult type-2 diabetes patients: The diabetes and aging study. J Gen Intern Med 2010; 25(2): 141-6.
[http://dx.doi.org/10.1007/s11606-009-1179-2] [PMID: 19967465]
[39]
Paik JM, Deshpande R, Golabi P, Younossi I, Henry L, Younossi ZM. The impact of modifiable risk factors on the long-term outcomes of non-alcoholic fatty liver disease. Aliment Pharmacol Ther 2020; 51(2): 291-304.
[http://dx.doi.org/10.1111/apt.15580] [PMID: 31782543]
[40]
Starup-Linde J, Gregersen S, Vestergaard P. Associations with fracture in patients with diabetes: A nested case-control study. BMJ Open 2016; 6(2)e009686
[http://dx.doi.org/10.1136/bmjopen-2015-009686] [PMID: 26873048]
[41]
Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int 2005; 16(7): 737-42.
[http://dx.doi.org/10.1007/s00198-004-1734-y] [PMID: 15455194]
[42]
Rico: Alcohol and bone disease - Google Scholar https://scholar- google-com.auh.aub.aau.dk/scholar_lookup?author=1990.
[43]
Jensen MH, Hejlesen O, Vestergaard P. Risk of major cardiovascular events, severe hypoglycaemia, and all-cause mortality for users of insulin degludec versus insulin glargine U100-A Danish cohort study. Diabetes Metab Res Rev 2020; 36(1)e3225
[http://dx.doi.org/10.1002/dmrr.3225] [PMID: 31647163]
[44]
Høidrup S, Sørensen TIA, Grønbaek M, Schroll M. Incidence and characteristics of falls leading to hospital treatment: A one-year population surveillance study of the Danish population aged 45 years and over. Scand J Public Health 2003; 31(1): 24-30.
[http://dx.doi.org/10.1080/14034940210134185] [PMID: 12623521]
[45]
Gazibara T, Kurtagic I, Kisic-Tepavcevic D, et al. Falls, Risk Factors and Fear of Falling Among Persons Older than 65 years of Age. Psychogeriatrics 2017; 17(4): 215-23.
[http://dx.doi.org/10.1111/psyg.12217] [PMID: 28130862]
[46]
Ensrud KE. Epidemiology of fracture risk with advancing age. journals gerontol ser a biol sci. Med Sci 2013; 68: 1236-42.
[47]
Schilcher J, Koeppen V, Aspenberg P, Michaëlsson K. Risk of atypical femoral fracture during and after bisphosphonate use. Acta Orthop 2015; 86(1): 100-7.
[http://dx.doi.org/10.3109/17453674.2015.1004149] [PMID: 25582459]
[48]
Shafiee G, Keshtkar A, Soltani A, Ahadi Z, Larijani B, Heshmat R. Prevalence of sarcopenia in the world: A systematic review and meta- analysis of general population studies. J Diabetes Metab Disord 2017; 16: 21.
[http://dx.doi.org/10.1186/s40200-017-0302-x] [PMID: 28523252]
[49]
Kirchengast S, Huber J. Gender and age differences in lean soft tissue mass and sarcopenia among healthy elderly. Anthropol Anz 2009; 67(2): 139-51.
[http://dx.doi.org/10.1127/0003-5548/2009/0018] [PMID: 19739465]
[50]
Park SW, Goodpaster BH, Strotmeyer ES, et al. Health, Aging, and Body Composition Study. Accelerated loss of skeletal muscle strength in older adults with type 2 diabetes: The health, aging, and body composition study. Diabetes Care 2007; 30(6): 1507-12.
[http://dx.doi.org/10.2337/dc06-2537] [PMID: 17363749]
[51]
Guerrero N, Bunout D, Hirsch S, et al. Premature loss of muscle mass and function in type 2 diabetes. Diabetes Res Clin Pract 2016; 117: 32-8.
[http://dx.doi.org/10.1016/j.diabres.2016.04.011] [PMID: 27329020]
[52]
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.
[http://dx.doi.org/10.2147/CLEP.S91125] [PMID: 26604824]
[53]
Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing 2019; 48(1): 16-31.
[http://dx.doi.org/10.1093/ageing/afy169] [PMID: 30312372]
[54]
Nielson CM, Srikanth P, Orwoll ES. Obesity and fracture in men and women: An epidemiologic perspective. J Bone Miner Res 2012; 27(1): 1-10.
[http://dx.doi.org/10.1002/jbmr.1486] [PMID: 23348758]
[55]
Maffeis C, Birkebaek NH, Konstantinova M, et al. SWEET Study Group. Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry. Pediatr Diabetes 2018; 19(7): 1211-20.
[http://dx.doi.org/10.1111/pedi.12730] [PMID: 30033651]
[56]
NOMESKO. Nordisk, 8. No Title 1987.

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