Abstract
Summary
Hypoglycemia is a major concern in glycemic control. Using the Taiwan National Health Insurance Research Database, we found that the risk of hip fracture was associated with emergency or hospitalization visits of severe hypoglycemia in patients with type 2 diabetes; greater visits were associated with higher incidence of hip fracture.
Introduction
The objective of the study was to assess the risk of hip fracture among patients with type 2 diabetes mellitus (T2DM) and severe hypoglycemia.
Methods
Using the National Health Insurance Research database in Taiwan, we identified 2588 patients with T2DM who had developed severe hypoglycemia from 2001 to 2009. A comparison cohort who had never developed severe hypoglycemia was frequency matched at a ratio of approximately 1:2. Multivariate Cox proportional hazard regression analysis was used to evaluate the risk of hip fracture.
Results
During a median follow-up period of 3.9 years, there were 219 hip fracture events in 5173 comparison cohorts and 148 hip fracture events in 2588 hypoglycemia cohorts. The incidence of hip fracture was higher in patients with severe hypoglycemia than without severe hypoglycemia (17.19 vs. 8.83 per 1000 person-years; adjusted HR 1.71, 95% CI = 1.35–2.16). Approximately half of the individuals developed hip fracture within 2 years from the first occurrence of severe hypoglycemia. There was a significant associated trend towards increased hip fracture risk with increasing average visit of severe hypoglycemia per year (p for trend <0.001). Medication analysis showed that patients taking sulfonylurea alone, insulin alone, and insulin secretagogues combined with insulin had a higher associated risk to develop hip fracture.
Conclusions
Severe hypoglycemia was associated with a higher risk to develop hip fracture. The more the visits of severe hypoglycemia per year indicated the higher associated risk in patients with T2DM. Fall is likely an important reason for severe hypoglycemia in relation to increased risk of hip fracture.
Similar content being viewed by others
Abbreviations
- T2DM:
-
Type 2 diabetes mellitus
- TZD:
-
Thiazolidinedione
- DPP4:
-
Dipeptidyl peptidase 4
References
UK Prospective Diabetes Study (UKPDS) Group (1998) Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 352:837–853
Zoungas S, Patel A, Chalmers J, ADVANCE Collaborative Group et al (2010) Severe hypoglycemia and risks of vascular events and death. N Engl J Med 363:1410–1418
Johnston SS, Conner C, Aagren M, Smith DM, Bouchard J, Brett J (2011) Evidence linking hypoglycemic events to an increased risk of acute cardiovascular events in patients with type 2 diabetes. Diabetes Care 34:1164–1170
Hsu PF, Sung SH, Cheng HM et al (2013) Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 36:894–900
Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767
Martinez-Laguna D, Tebe C, Javaid MK et al (2015) Incident type 2 diabetes and hip fracture risk: a population-based matched cohort study. Osteoporos Int 26:827–833
Koh WP, Wang R, Ang LW et al (2010) Diabetes and risk of hip fracture in the Singapore Chinese Health Study. Diabetes Care 33:1766–1770
Chen HF, Ho CA, Li CY (2008) Increased risks of hip fracture in diabetic patients of Taiwan: a population-based study. Diabetes Care 31:75–80
Lipscombe LL, Jamal SA, Booth GL, Hawker GA (2007) The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care 30:835–841
Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses’ Health Study. Diabetes Care 29:1573–1578
Forsen L, Meyer HE, Midthjell K, Edna TH (1999) Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 42:920–925
Nicodemus KK, Folsom AR (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192–1197
Hothersall EJ, Livingstone SJ, Looker HC et al (2014) Contemporary risk of hip fracture in type 1 and type 2 diabetes: a national registry study from Scotland. J Bone Miner Res 29:1054–1060
Lu CL, Hsu PC, Shen HN, Chang YH, Chen HF, Li CY (2015) Association between history of severe hypoglycemia and risk of falls in younger and older patients with diabetes. Medicine (Baltimore) 94:e1339
Cheng CL, Kao Yang YH, Lin SJ, Lee CH, Lai ML (2011) Validation of the National Health Insurance Research Database with ischemic stroke cases in Taiwan. Pharmacoepidemiol Drug Saf 20:236–242
Cheng CL, Lee CH, Chen PS, Li YH, Lin SJ, Kao Yang YH (2014) Validation of acute myocardial infarction cases in the National Health Insurance Research Database in Taiwan. J Epidemiol 24:500–507
Cheng CL, Chien HC, Lee CH, Lin SJ, Kao Yang YH (2015) Validity of in-hospital mortality data among patients with acute myocardial infarction or stroke in National Health Insurance Research Database in Taiwan. Int J Cardiol 201:96–101
Chen YJ, Yang CC, Huang LC, Chen L, Hwu CM (2015) Increasing trend in emergency department visits for hypoglycemia from patients with type 2 diabetes mellitus in Taiwan. Prim Care Diabetes 9:490–496
Pathak RD, Schroeder EB, Seaquist ER, SUPREME-DM Study Group et al (2016) Severe hypoglycemia requiring medical intervention in a large cohort of adults with diabetes receiving care in U.S. integrated health care delivery systems: 2005-2011. Diabetes Care 39:363–370
Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291:335–342
Johnston SS, Conner C, Aagren M, Ruiz K, Bouchard J (2012) Association between hypoglycaemic events and fall-related fractures in Medicare-covered patients with type 2 diabetes. Diabetes Obes Metab 14:634–643
Cummings SR, Black DM, Rubin SM (1989) Lifetime risks of hip, Colles’, or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 149:2445–2448
Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572
American Diabetes Association (2016) Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes 34:3–21
Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326
Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373:232–242
Schwartz AV, Chen H, Ambrosius WT et al (2015) Effects of TZD use and discontinuation on fracture rates in ACCORD Bone Study. J Clin Endocrinol Metab 100:4059–4066
Cheng BH, Chen PC, Yang YH, Lee CP, Huang KE, Chen VC (2016) Effects of depression and antidepressant medications on hip fracture: a population-based cohort study in Taiwan. Medicine (Baltimore) 95(36):e4655
Budnitz DS, Lovegrove MC, Shehab N, Richards CL (2011) Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 365:2002–2012
Geller AI, Shehab N, Lovegrove MC et al (2014) National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Intern Med 174:678–686
Rajpathak SN, Fu C, Brodovicz KG, Engel SS, Lapane K (2015) Sulfonylurea use and risk of hip fractures among elderly men and women with type 2 diabetes. Drugs Aging 32:321–327
Acknowledgments
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW105-TDU-B-212-133019) and a grant from the China Medical University Hospital (DMR-103-014); Academia Sinica Taiwan Biobank, Stroke Biosignature Project (BM10501010037); NRPB Stroke Clinical Trial Consortium (MOST105-2325-B-039-003); Tseng-Lien Lin Foundation, Taichung, Taiwan; Taiwan Brain Disease Foundation, Taipei, Taiwan; and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the Ethics Review Board at China Medical University (CMU-REC-101-012).
Conflicts of interest
None.
Electronic supplementary material
.
Table S
(DOCX 13 kb)
Rights and permissions
About this article
Cite this article
Hung, Y.C., Lin, C.C., Chen, H.J. et al. Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study. Osteoporos Int 28, 2053–2060 (2017). https://doi.org/10.1007/s00198-017-4021-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-017-4021-4