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Published in: Osteoporosis International 7/2017

01-07-2017 | Original Article

Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study

Authors: Y. C. Hung, C. C. Lin, H. J. Chen, M. P. Chang, K. C. Huang, Y. H. Chen, C. C. Chen

Published in: Osteoporosis International | Issue 7/2017

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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.
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Literature
1.
go back to reference 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 352:837–853CrossRef 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 352:837–853CrossRef
2.
go back to reference 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 363:1410–1418CrossRefPubMed 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 363:1410–1418CrossRefPubMed
3.
go back to reference 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 34:1164–1170CrossRefPubMedPubMedCentral 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 34:1164–1170CrossRefPubMedPubMedCentral
4.
go back to reference 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 36:894–900CrossRefPubMedPubMedCentral 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 36:894–900CrossRefPubMedPubMedCentral
5.
go back to reference Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767CrossRefPubMed
6.
go back to reference 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 26:827–833CrossRefPubMed 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 26:827–833CrossRefPubMed
8.
go back to reference Chen HF, Ho CA, Li CY (2008) Increased risks of hip fracture in diabetic patients of Taiwan: a population-based study. Diabetes Care 31:75–80CrossRefPubMed Chen HF, Ho CA, Li CY (2008) Increased risks of hip fracture in diabetic patients of Taiwan: a population-based study. Diabetes Care 31:75–80CrossRefPubMed
9.
go back to reference 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 30:835–841CrossRefPubMed 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 30:835–841CrossRefPubMed
10.
go back to reference Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses’ Health Study. Diabetes Care 29:1573–1578CrossRefPubMed Janghorbani M, Feskanich D, Willett WC, Hu F (2006) Prospective study of diabetes and risk of hip fracture: the Nurses’ Health Study. Diabetes Care 29:1573–1578CrossRefPubMed
11.
go back to reference 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 42:920–925CrossRefPubMed 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 42:920–925CrossRefPubMed
12.
go back to reference Nicodemus KK, Folsom AR (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192–1197CrossRefPubMed Nicodemus KK, Folsom AR (2001) Type 1 and type 2 diabetes and incident hip fractures in postmenopausal women. Diabetes Care 24:1192–1197CrossRefPubMed
13.
go back to reference 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 29:1054–1060CrossRefPubMed 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 29:1054–1060CrossRefPubMed
14.
go back to reference 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:e1339CrossRef 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:e1339CrossRef
15.
go back to reference 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 20:236–242CrossRefPubMed 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 20:236–242CrossRefPubMed
16.
go back to reference 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 24:500–507CrossRefPubMedPubMedCentral 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 24:500–507CrossRefPubMedPubMedCentral
17.
go back to reference 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 201:96–101CrossRefPubMed 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 201:96–101CrossRefPubMed
18.
go back to reference 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 9:490–496CrossRefPubMed 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 9:490–496CrossRefPubMed
19.
go back to reference 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 39:363–370CrossRefPubMed 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 39:363–370CrossRefPubMed
20.
go back to reference Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291:335–342CrossRefPubMed Saydah SH, Fradkin J, Cowie CC (2004) Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. JAMA 291:335–342CrossRefPubMed
21.
go back to reference 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 14:634–643CrossRefPubMed 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 14:634–643CrossRefPubMed
22.
go back to reference 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 149:2445–2448CrossRefPubMed 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 149:2445–2448CrossRefPubMed
23.
go back to reference 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 301:1565–1572CrossRefPubMedPubMedCentral 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 301:1565–1572CrossRefPubMedPubMedCentral
24.
go back to reference American Diabetes Association (2016) Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes 34:3–21CrossRefPubMedCentral American Diabetes Association (2016) Standards of medical care in diabetes-2016 abridged for primary care providers. Clin Diabetes 34:3–21CrossRefPubMedCentral
25.
go back to reference Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326CrossRefPubMed Scirica BM, Bhatt DL, Braunwald E et al (2013) Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 369:1317–1326CrossRefPubMed
26.
go back to reference Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373:232–242CrossRefPubMed Green JB, Bethel MA, Armstrong PW et al (2015) Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med 373:232–242CrossRefPubMed
27.
go back to reference 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 100:4059–4066CrossRefPubMedPubMedCentral 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 100:4059–4066CrossRefPubMedPubMedCentral
28.
go back to reference 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):e4655CrossRef 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):e4655CrossRef
29.
go back to reference Budnitz DS, Lovegrove MC, Shehab N, Richards CL (2011) Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 365:2002–2012CrossRefPubMed Budnitz DS, Lovegrove MC, Shehab N, Richards CL (2011) Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med 365:2002–2012CrossRefPubMed
30.
go back to reference 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 174:678–686CrossRefPubMedPubMedCentral 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 174:678–686CrossRefPubMedPubMedCentral
31.
go back to reference 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 32:321–327CrossRefPubMed 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 32:321–327CrossRefPubMed
Metadata
Title
Severe hypoglycemia and hip fracture in patients with type 2 diabetes: a nationwide population-based cohort study
Authors
Y. C. Hung
C. C. Lin
H. J. Chen
M. P. Chang
K. C. Huang
Y. H. Chen
C. C. Chen
Publication date
01-07-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 7/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-017-4021-4

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