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Development of a model to predict 5-year risk of severe hypoglycemia in patients with type 2 diabetes
  1. Lisa S Chow1,
  2. Rachel Zmora2,
  3. Sisi Ma3,
  4. Elizabeth R Seaquist1,
  5. Pamela J Schreiner2
  1. 1 Division of Diabetes, Endocrinology and Metabolism, University of Minnesota Medical School, Minneapolis, Minnesota, USA
  2. 2 Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Saint Paul, Minnesota, USA
  3. 3 Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota, USA
  1. Correspondence to Dr Lisa S Chow; chow0007{at}


Objective We constructed a predictive model of long-term risk for severe hypoglycemia (SH: hypoglycemia requiring assistance) in patients with type 2 diabetes (T2DM).

Research design and methods Data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (original n=10 251, n=5135 used in the current analysis), a randomized, multicenter, double 2×2 factorial design study examining the effect of glycemic, blood pressure, and lipid control on cardiovascular outcomes in patients with diagnosed T2DM, were used. Over the follow-up (3.76±1.12 years), the ACCORD participants experienced 607 incident SH events. Cox regression was used to identify the SH risk prediction model.

Results We identified 17 predictors—glycemic management, age, race, education, waist circumference, medications (insulin, antihypertensive, HMG-CoA reductase inhibitors, sulfonylurea, biguanide and meglitinide), years since diabetes diagnosis, history of hypoglycemia in the last week, systolic blood pressure, diastolic blood pressure, serum creatinine, and urinary albumin creatinine ratio—to construct a prediction model for SH (c-statistic=0.782). Using this information, we derived point scores to estimate the 5-year risk for SH in individual patients with T2DM. After adjusting for other variables in the model, the three strongest predictors for SH over 5 years were intensive glycemic management (HR=2.37, 95% CI 1.99 to 2.83), insulin use (HR=2.14, 95% CI 1.77 to 2.59), and antihypertensive medication use (HR=1.90, 95% CI 1.26 to 2.86).

Conclusion Using the ACCORD data, we identified attributes to predict 5-year risk of SH in patients with T2DM, which warrant evaluation in broader populations to determine applicability.

  • Hypoglycemia
  • Prediction
  • Type 2 Diabetes

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  • Contributors RZ, SM, ERS, PJS, LSC designed the study. PJS, RZ, SM performed the data analysis. RZ, SM, ERS, PJS, LSC all critically reviewed the manuscript and provided intellectual content and feedback. All authors reviewed the manuscript before submission. LSC is the guarantor of the study and takes responsibility for the content of the article.

  • Funding The study is supported by funding from the University of Minnesota Academic Health Center. The ACCORD study was supported by contracts from the National Heart, Lung, and Blood Institute (N01-HC-95178, N01-HC-95179, N01-HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01-HC-95184, IAA-Y1-HC-9035, and IAA-Y1-HC- 1010), by other components of the National Institutes of Health—including the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, and the National Eye Institute—by the Centers for Disease Control and Prevention, and by the General Clinical Research Centers. The following companies provided study medications, equipment, or supplies: Abbott Laboratories, Amylin Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare, GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk, Omron Healthcare, Sanofi Aventis, and Schering-Plough.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement This manuscript was prepared using the ACCORD Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center and does not necessarily reflect the opinions or views of the ACCORD or the NHLBI. The data can be obtained directly from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center.

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