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Multicenter Study
. 2017 Oct 1;177(10):1461-1470.
doi: 10.1001/jamainternmed.2017.3844.

Development and Validation of a Tool to Identify Patients With Type 2 Diabetes at High Risk of Hypoglycemia-Related Emergency Department or Hospital Use

Affiliations
Multicenter Study

Development and Validation of a Tool to Identify Patients With Type 2 Diabetes at High Risk of Hypoglycemia-Related Emergency Department or Hospital Use

Andrew J Karter et al. JAMA Intern Med. .

Abstract

Importance: Hypoglycemia-related emergency department (ED) or hospital use among patients with type 2 diabetes (T2D) is clinically significant and possibly preventable.

Objective: To develop and validate a tool to categorize risk of hypoglycemic-related utilization in patients with T2D.

Design, setting, and participants: Using recursive partitioning with a split-sample design, we created a classification tree based on potential predictors of hypoglycemia-related ED or hospital use. The resulting model was transcribed into a tool for practical application and tested in 1 internal and 2 fully independent, external samples. Development and internal testing was conducted in a split sample of 206 435 patients with T2D from Kaiser Permanente Northern California (KPNC), an integrated health care system. The tool was externally tested in 1 335 966 Veterans Health Administration and 14 972 Group Health Cooperative patients with T2D.

Exposures: Based on a literature review, we identified 156 candidate predictor variables (prebaseline exposures) using data collected from electronic medical records.

Main outcomes and measures: Hypoglycemia-related ED or hospital use during 12 months of follow-up.

Results: The derivation sample (n = 165 148) had a mean (SD) age of 63.9 (13.0) years and included 78 576 (47.6%) women. The crude annual rate of at least 1 hypoglycemia-related ED or hospital encounter in the KPNC derivation sample was 0.49%. The resulting hypoglycemia risk stratification tool required 6 patient-specific inputs: number of prior episodes of hypoglycemia-related utilization, insulin use, sulfonylurea use, prior year ED use, chronic kidney disease stage, and age. We categorized the predicted 12-month risk of any hypoglycemia-related utilization as high (>5%), intermediate (1%-5%), or low (<1%). In the internal validation sample, 2.0%, 10.7%, and 87.3% were categorized as high, intermediate, and low risk, respectively, with observed 12-month hypoglycemia-related utilization rates of 6.7%, 1.4%, and 0.2%, respectively. There was good discrimination in the internal validation KPNC sample (C statistic = 0.83) and both external validation samples (Veterans Health Administration: C statistic = 0.81; Group Health Cooperative: C statistic = 0.79).

Conclusions and relevance: This hypoglycemia risk stratification tool categorizes the 12-month risk of hypoglycemia-related utilization in patients with T2D using only 6 inputs. This tool could facilitate targeted population management interventions, potentially reducing hypoglycemia risk and improving patient safety and quality of life.

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Conflict of interest statement

Conflict of Interest Disclosures: The National Institutes of Health supplied additional funding for our hypoglycemia-related research (NIDDK R01DK103721, R01DK081796). Drs Karter and Huang are also supported by the NIDDK Centers for Diabetes Translational Research (P30 DK092924 and P30 DK092949, respectively). Dr Huang was supported by K24 DK105340. Dr Lipska receives support from the Centers for Medicare & Medicaid Services to develop and maintain publicly reported quality measures, and from the Yale Claude D. Pepper Older Americans Independence Center (P30AG021342) and the National Institute on Aging through the Paul Beeson Career Development Award (K23AG048359). No other disclosures are reported.

Figures

Figure 1.
Figure 1.. Classification Tree for Hypoglycemia-Related Emergency Department (ED) or Hospital Use
Hypoglycemic-related utilization was defined by having any ED visit with a primary diagnosis of hypoglycemia or a hospitalization with a principal diagnosis of hypoglycemia. Hypoglycemia cases were ascertained with any of the following International Classification of Diseases, Ninth Revision, codes: 251.0, 251.1, 251.2, 962.3, or 250.8, without concurrent 259.8, 272.7, 681.XX, 682.XX, 686.9X, 707.1-707.9, 709.3, 730.0-730.2, or 731.8 codes. The classification tree was developed using the 808 out of 165 148 T2D adults (derivation sample) from Kaiser Permanente who had such utilization (4.9 events per 1000 person-years) in 2014. The classification is based on 6 predictor variables from the electronic medical record and resulted in 10 mutually exclusive leaf nodes. The criterion for each node is displayed with the corresponding number of individuals (n) who met that criterion. The 12-month observed rate of any hypoglycemia-related ED or hospital use is displayed in each leaf node and categorized as high (>5% risk), intermediate (1%-5% risk), or low risk (<1% risk). CKD indicates chronic kidney disease.
Figure 2.
Figure 2.. Hypoglycemia Risk Stratification Tool
aHypoglycemia cases were ascertained with any of the following International Classification of Diseases, Ninth Revision, codes: 251.0, 251.1, 251.2, 962.3, or 250.8, without concurrent 259.8, 272.7, 681.XX, 682.XX, 686.9X, 707.1-707.9, 709.3, 730.0-730.2, or 731.8 codes. bHypoglycemic-related utilization was defined by having any emergency department (ED) visit with a primary diagnosis of hypoglycemia or a hospitalization with a principal diagnosis of hypoglycemia.
Figure 3.
Figure 3.. Calibration Plots Comparing the Expected vs Observed 12-Month Rate of Having Any Hypoglycemia-Related Utilizationa for the Interval Derivation Sample From Kaiser Permanente Northern California (KPNC) (n = 165 148), the KPNC Internal Validation Sample (n = 41 287), the External Validation Sample From Group Health (GH) (n = 14 972), and the External Validation Sample From the Veterans Administration (VA) (n = 1 335 966)
aHypoglycemic-related utilization was defined by having any emergency department visit with a primary diagnosis of hypoglycemia or a hospitalization with a principal diagnosis of hypoglycemia. Hypoglycemia cases were ascertained with any of the following International Classification of Diseases, Ninth Revision, codes: 251.0, 251.1, 251.2, 962.3, or 250.8, without concurrent 259.8, 272.7, 681.XX, 682.XX, 686.9X, 707.1-707.9, 709.3, 730.0-730.2, or 731.8 codes.

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References

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