Advertisement

The Association Between Insulin Initiation and Adverse Outcomes After Hospital Discharge in Older Adults: a Population-Based Cohort Study

  • Zoe Lysy
  • Kinwah Fung
  • Vasily Giannakeas
  • Hadas D. Fischer
  • Chaim M. Bell
  • Lorraine L. LipscombeEmail author
Original Research

Abstract

Background

Starting insulin therapy in hospitalized patients may be associated with an increase in serious adverse events after discharge.

Objective

Determine whether post-discharge risks of death and rehospitalization are higher for older hospitalized patients prescribed new insulin therapy compared with oral hypoglycemic agents (OHAs).

Design

Retrospective population-based cohort study including hospital admissions in Ontario, Canada, between April 1, 2004, and Nov 30, 2013.

Patients

Persons aged 66 and over discharged after a hospitalization and dispensed a prescription for insulin and/or an OHA within 7 days of discharge. We included 104,525 individuals, subcategorized into four mutually exclusive exposure groups based on anti-hyperglycemic drug use in the 7 days post-discharge and the 365 days prior to the index admission.

Main Measures

Prescriptions at discharge were categorized as new insulin (no insulin before admission), prevalent insulin (prescribed insulin before admission), new OHA(s) (no OHA or insulin before admission), and prevalent OHA (prescribed OHA only before admission) as the referent category. The primary and secondary outcomes were 30-day deaths and emergency department (ED) visits or readmissions respectively.

Key Results

Of 104,525 patients, 9.2% were initiated on insulin, 4.1% died, and 26.2% had an ED visit or readmission within 30 days of discharge. Deaths occurred in 7.14% of new insulin users, 4.86% of prevalent insulin users, 3.25% of new OHA users, and 3.45% of prevalent OHA users. After adjustment for covariates, new insulin users had a significantly higher risk of death (adjusted hazard ratio (aHR) 1.59, 95% confidence interval (CI) 1.46 to 1.74) and ED visit/readmissions (aHR 1.17, 95% CI 1.12 to 1.22) than prevalent OHA users.

Conclusions

Initiation of insulin therapy in older hospitalized patients is associated with a higher risk of death and ED visits/readmissions after discharge, highlighting a need for better transitional care of insulin-treated patients.

KEY WORDS

diabetes care transitions health services research 

Notes

Acknowledgements

We thank IMS Brogan Inc. for the use of their drug information database.

Contributors

LL and ZL had the original idea for the study and contributed to the development of the data. HF, LL, ZL, and CB designed the study. KF and VG extracted data from the source database and validated the diagnostic codes from the database. ZL, KF, and VG undertook the statistical analysis. ZL reviewed the literature and wrote the first draft of the manuscript. LL co-drafted the manuscript and provided oversight for the project. CB, HF, and LL provided critical input to the analysis and design. All authors contributed to the critical review of the manuscript and approved its final submission. ZL and LL act as guarantors for the study.

Funding

Dr. Lipscombe is supported by a Diabetes Canada Investigator Award. This study was conducted with the support from a CIHR operating grant (MOP No. 123263). This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they do not have a conflict of interest.

Ethics Approval

This project was approved by the Institutional Review Board at Sunnybrook Hospital.

Disclaimer

Parts of this material are based on data and/or information compiled and provided by the Canadian Institute for Health Information (CIHI); however, the analyses, conclusions, opinions, and statements expressed in the material are those of the authors, and not necessarily those of CIHI.

References

  1. 1.
    Practices IfSM. ISMP List of High-Alert Medications in Acute Care Settings; https://www.ismp.org/sites/default/files/attachments/2018-10/highAlert2018new-Oct2018-v1.pdf Accessed Nov 24, 2018
  2. 2.
    Inzucchi SE. Clinical practice. Management of hyperglycemia in the hospital setting. N Engl J Med 2006;355(18):1903–1911.CrossRefGoogle Scholar
  3. 3.
    Gerstein HC, Pogue J, Mann JF, et al. The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis. Diabetologia 2005;48(9):1749–1755.CrossRefGoogle Scholar
  4. 4.
    UK Prospective Diabetes Study (UKPDS) Group. 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. 1998;352(9131):837–853.CrossRefGoogle Scholar
  5. 5.
    Ritsinger V, Malmberg K, Martensson A, Ryden L, Wedel H, Norhammar A. Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial. Lancet Diabetes Endocrinol 2014;2(8):627–633.CrossRefGoogle Scholar
  6. 6.
    Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ 1997;314(7093):1512–1515.CrossRefGoogle Scholar
  7. 7.
    Malmberg K, Ryden L, Wedel H, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005;26(7):650–661.CrossRefGoogle Scholar
  8. 8.
    Action to Control Cardiovascular Risk in Diabetes Study G, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358(24):2545–2559.CrossRefGoogle Scholar
  9. 9.
    McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care 2012;35(9):1897–1901.CrossRefGoogle Scholar
  10. 10.
    Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascular events and death. N Engl J Med 2010;363(15):1410–1418.CrossRefGoogle Scholar
  11. 11.
    Gamble JM, Simpson SH, Eurich DT, Majumdar SR, Johnson JA. Insulin use and increased risk of mortality in type 2 diabetes: a cohort study. Diabetes Obes Metab 2010;12(1):47–53.CrossRefGoogle Scholar
  12. 12.
    Currie CJ, Poole CD, Evans M, Peters JR, Morgan CL. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. J Clin Endocrinol Metab 2013;98(2):668–677.CrossRefGoogle Scholar
  13. 13.
    Roumie CL, Greevy RA, Grijalva CG, et al. Association between intensification of metformin treatment with insulin vs sulfonylureas and cardiovascular events and all-cause mortality among patients with diabetes. JAMA 2014;311(22):2288–2296.CrossRefGoogle Scholar
  14. 14.
    Shorr RI, Ray WA, Daugherty JR, Griffin MR. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med 1997;157(15):1681–1686.CrossRefGoogle Scholar
  15. 15.
    Garg R, Hurwitz S, Turchin A, Trivedi A. Hypoglycemia, with or without insulin therapy, is associated with increased mortality among hospitalized patients. Diabetes Care 2013;36(5):1107–1110.CrossRefGoogle Scholar
  16. 16.
    Claesen M, Gillard P, De Smet F, Callens M, De Moor B, Mathieu C. Mortality in Individuals Treated With Glucose-Lowering Agents: A Large, Controlled Cohort Study. J Clin Endocrinol Metab 2016;101(2):461–469.CrossRefGoogle Scholar
  17. 17.
    Lipska KJ, Ross JS, Wang Y, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med 2014;174(7):1116–1124.CrossRefGoogle Scholar
  18. 18.
    Geller AI, Shehab N, Lovegrove MC, et al. National estimates of insulin-related hypoglycemia and errors leading to emergency department visits and hospitalizations. JAMA Intern Med 2014;174(5):678–686.CrossRefGoogle Scholar
  19. 19.
    American Diabetes Association. Standards of medical care in diabetes--2016. Diabetes Care 2016;39 Suppl 1:S1–112.Google Scholar
  20. 20.
    Levy AR, O’Brien BJ, Sellors C, Grootendorst P, Willison D. Coding accuracy of administrative drug claims in the Ontario Drug Benefit database. Can J Clin Pharmacol= J Can Pharmacol Clin 2003;10(2):67–71.Google Scholar
  21. 21.
    Deyo RA, Cherkin DC, Ciol MA. Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. J Clin Epidemiol 1992;45(6):613–619.CrossRefGoogle Scholar
  22. 22.
    Schneeweiss S, Seeger JD, Maclure M, Wang PS, Avorn J, Glynn RJ. Performance of comorbidity scores to control for confounding in epidemiologic studies using claims data. Am J Epidemiol 2001;154(9):854–864.CrossRefGoogle Scholar
  23. 23.
    van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ 2010;182(6):551–557.CrossRefGoogle Scholar
  24. 24.
    van Walraven C, Wong J, Forster AJ. LACE+ index: extension of a validated index to predict early death or urgent readmission after hospital discharge using administrative data. Open Med 2012;6(3):e80–90.Google Scholar
  25. 25.
    Leong A, Berkowitz SA, Triant VA, et al. Hypoglycemia in Diabetes Mellitus as a Coronary Artery Disease Risk Factor in Patients at Elevated Vascular Risk. J Clin Endocrinol Metab 2016;101(2):659–668.CrossRefGoogle Scholar
  26. 26.
    Juurlink DN, Mamdani MM, Lee DS, et al. Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study. N Engl J Med 2004;351(6):543–551.CrossRefGoogle Scholar
  27. 27.
    Healy SJ, Black D, Harris C, Lorenz A, Dungan KM. Inpatient diabetes education is associated with less frequent hospital readmission among patients with poor glycemic control. Diabetes Care 2013;36(10):2960–2967.CrossRefGoogle Scholar
  28. 28.
    Wexler DJ, Beauharnais CC, Regan S, Nathan DM, Cagliero E, Larkin ME. Impact of inpatient diabetes management, education, and improved discharge transition on glycemic control 12 months after discharge. Diabetes Res Clin Pract 2012;98(2):249–256.CrossRefGoogle Scholar
  29. 29.
    Braithwaite SS, Magee M, Sharretts JM, et al. The case for supporting inpatient glycemic control programs now: the evidence and beyond. J Hosp Med 2008;3(5 Suppl):6–16.CrossRefGoogle Scholar
  30. 30.
    Peyrot M, Rubin RR, Lauritzen T, et al. Resistance to insulin therapy among patients and providers: results of the cross-national Diabetes Attitudes, Wishes, and Needs (DAWN) study. Diabetes Care 2005;28(11):2673–2679.CrossRefGoogle Scholar
  31. 31.
    Phillips CO, Wright SM, Kern DE, Singa RM, Shepperd S, Rubin HR. Comprehensive discharge planning with postdischarge support for older patients with congestive heart failure: a meta-analysis. JAMA 2004;291(11):1358–1367.CrossRefGoogle Scholar
  32. 32.
    Laverty AA, Elkin SL, Watt HC, et al. Impact of a COPD discharge care bundle on readmissions following admission with acute exacerbation: interrupted time series analysis. PLoS One 2015;10(2):e0116187.CrossRefGoogle Scholar
  33. 33.
    Goncalves-Bradley DC, Lannin NA, Clemson LM, Cameron ID, Shepperd S. Discharge planning from hospital. Cochrane Database Syst Rev 2016(1):CD000313.Google Scholar
  34. 34.
    LaManna JB, Bushy A, Norris AE, Chase SK. Early and Intermediate Hospital-to-Home Transition Outcomes of Older Adults Diagnosed With Diabetes. The Diabetes Educator 2016;42(1):72–86.CrossRefGoogle Scholar
  35. 35.
    Jack BW, Chetty VK, Anthony D, et al. A reengineered hospital discharge program to decrease rehospitalization: a randomized trial. Ann Intern Med 2009;150(3):178–187.CrossRefGoogle Scholar
  36. 36.
    Coleman EA, Parry C, Chalmers S, Min SJ. The care transitions intervention: results of a randomized controlled trial. Arch Intern Med 2006;166(17):1822–1828.CrossRefGoogle Scholar
  37. 37.
    Hansen LO, Young RS, Hinami K, Leung A, Williams MV. Interventions to reduce 30-day rehospitalization: a systematic review. Ann Intern Med 2011;155(8):520–528.CrossRefGoogle Scholar
  38. 38.
    Seggelke SA, Hawkins RM, Gibbs J, Rasouli N, Wang C, Draznin B. Transitional care clinic for uninsured and medicaid-covered patients with diabetes mellitus discharged from the hospital: a pilot quality improvement study. Hosp Pract 2014;42(1):46–51.CrossRefGoogle Scholar
  39. 39.
    Dungan K, Lyons S, Manu K, et al. An individualized inpatient diabetes education and hospital transition program for poorly controlled hospitalized patients with diabetes. Endocr Pract : Off J Am Coll Endocrinol Am Assoc Clin Endocrinol 2014;20(12):1265–1273.Google Scholar
  40. 40.
    Rubin DJ, Donnell-Jackson K, Jhingan R, Golden SH, Paranjape A. Early readmission among patients with diabetes: a qualitative assessment of contributing factors. J Diabetes Complicat 2014;28(6):869–873.CrossRefGoogle Scholar
  41. 41.
    Lipska KJ, Ross JS, Miao Y, Shah ND, Lee SJ, Steinman MA. Potential overtreatment of diabetes mellitus in older adults with tight glycemic control. JAMA Intern Med 2015;175(3):356–362.CrossRefGoogle Scholar
  42. 42.
    McCoy RG, Lipska KJ, Yao X, Ross JS, Montori VM, Shah ND. Intensive Treatment and Severe Hypoglycemia Among Adults With Type 2 Diabetes. JAMA Intern Med 2016;176(7):969–978.CrossRefGoogle Scholar
  43. 43.
    Rodriguez-Gutierrez R, Lipska KJ, McCoy RG. Intensive Glycemic Control in Type 2 Diabetes Mellitus-A Balancing Act of Latent Benefit and Avoidable Harm: A Teachable Moment. JAMA Intern Med 2016;176(3):300–301.CrossRefGoogle Scholar
  44. 44.
    Jackevicius CA, Mamdani M, Tu JV. Adherence with statin therapy in elderly patients with and without acute coronary syndromes. JAMA 2002;288(4):462–467.CrossRefGoogle Scholar

Copyright information

© Society of General Internal Medicine 2019

Authors and Affiliations

  • Zoe Lysy
    • 1
    • 2
  • Kinwah Fung
    • 3
  • Vasily Giannakeas
    • 1
    • 3
  • Hadas D. Fischer
    • 3
  • Chaim M. Bell
    • 2
    • 3
    • 4
    • 5
  • Lorraine L. Lipscombe
    • 1
    • 2
    • 3
    • 4
    Email author
  1. 1.Women’s College HospitalWomen’s College Research InstituteTorontoCanada
  2. 2.Department of MedicineUniversity of TorontoTorontoCanada
  3. 3.Institute for Clinical Evaluative SciencesTorontoCanada
  4. 4.Institute of Health Policy, Management and EvaluationUniversity of TorontoTorontoCanada
  5. 5.Sinai Health SystemTorontoCanada

Personalised recommendations