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The American Journal of Managed Care June 2018
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Prevalence and Predictors of Hypoglycemia in South Korea
Sun-Young Park, PhD; Eun Jin Jang, PhD; Ju-Young Shin, PhD; Min-Young Lee, PhD; Donguk Kim, PhD; and Eui-Kyung Lee, PhD
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Prevalence and Predictors of Hypoglycemia in South Korea

Sun-Young Park, PhD; Eun Jin Jang, PhD; Ju-Young Shin, PhD; Min-Young Lee, PhD; Donguk Kim, PhD; and Eui-Kyung Lee, PhD
The prevalence and predictors of hypoglycemia in South Korean patients with type 2 diabetes were evaluated using a nationwide healthcare database.

Objectives: This study aimed to identify the prevalence and predictors of hypoglycemia in patients with type 2 diabetes (T2D) using South Korea’s nationwide healthcare database.

Study Design: Retrospective cohort and nested case-control analyses were conducted to estimate the prevalence and predictors of hypoglycemia, respectively.

Methods: A cohort of 2,273,481 patients with T2D was followed to estimate the 1-year prevalence of hypoglycemia. Total hypoglycemia was identified using outpatient, inpatient, or emergency department visit data containing a diagnosis code for hypoglycemia. Severe hypoglycemia was defined as an event with inpatient admission or emergency care. Within the T2D cohort, cases with hypoglycemia were identified, and up to 4 controls were randomly selected after matching by sex, age, and cohort entry date. Possible predictive factors included insurance type, medical institution type, hypoglycemic history, antidiabetic drugs, Charlson Comorbidity Index score, and diabetic complications. We conducted conditional logistic regression analyses to estimate adjusted odds ratios (aORs) and 95% CIs to identify predictors of hypoglycemia.

Results: The prevalences of total and severe hypoglycemia were 1.38% and 0.96%, respectively. Those with a history of hypoglycemia had the highest risk for a further hypoglycemic event (aOR, 16.71; 95% CI, 15.62-17.88). Use of combination therapy with insulin and sulfonylurea was highly associated with severe hypoglycemia (aOR, 15.09; 95% CI, 13.60-16.74). Among diabetic complications, the presence of nephropathy was the greatest predictive factor (aOR, 1.79; 95% CI, 1.73-1.85).

Conclusions: Patients with a history of hypoglycemia or receiving combined antidiabetic therapy must be appropriately managed to achieve optimal glycemic control without significant risk of hypoglycemia.

Am J Manag Care. 2018;24(6):278-286
Takeaway Points

Our study evaluated the prevalence and predictors of hypoglycemia among patients with type 2 diabetes (T2D) using the nationwide South Korean healthcare database.
  • The prevalence of total and severe hypoglycemia in patients with T2D was 1.38% and 0.96%, respectively.
  • A history of hypoglycemia was a strong predictive factor, approximately 16.71 times higher, for a further hypoglycemic event, and combination therapy of insulin and sulfonylurea was highly associated with severe hypoglycemia.
  • Patients with hypoglycemic history or having combined antidiabetic therapy need to be appropriately managed to achieve optimal glycemic control without significant risk of hypoglycemia.
Maintaining adequate glycemic control in patients with diabetes is essential for preventing micro- and macrovascular complications and premature death. However, intensive glycemic control can increase the risk of hypoglycemia.1 Aggressively achieving an optimal glycated hemoglobin (A1C) level is associated with a 3-fold increased risk of hypoglycemia.2 Hypoglycemia is a potentially severe adverse effect of antidiabetic treatment and can negatively impact physical, mental, and social aspects of a patient’s life. Short-term effects of hypoglycemia include an increased risk of accidents or falls and decreased cognitive function. Long-term consequences include decreased productivity, increased risk for cardiovascular diseases, and fear of future episodes.3 Furthermore, hypoglycemia can lead to a significant cost burden on healthcare systems and society.4,5 Patients who experience hypoglycemia are less satisfied with, and less likely to adhere to, antidiabetic treatment, which threatens the efficacy of treatment.6,7 Therefore, preventing hypoglycemia is important in diabetes management.

Previous studies’ results have documented possible predictors of hypoglycemia, including a past history of hypoglycemic events, antidiabetic drugs, and diabetic complications. A history of hypoglycemia is known as the most important risk factor for subsequent hypoglycemic events.8 Hypoglycemia can occur as a side effect of some antidiabetic drugs that increase insulin production.9 Associated comorbidities (eg, liver or kidney disorders and micro- or macrovascular complications), behavioral risk factors (eg, alcohol consumption, exercise, and missed meals), and diabetes duration are also common risk factors for hypoglycemia.4,10

Hypoglycemia is a well-recognized complication in patients with type 1 diabetes (T1D), but it is often underestimated in patients with type 2 diabetes (T2D).11,12 Previous studies on T2D have focused on patients using insulin or specific oral medications or who visited specific medical institutions, rather than on the population as a whole.10,13-15 Furthermore, heterogeneity of study design, data collection methods, and target population make comparison of findings difficult across studies. Therefore, it is necessary to identify the risk of hypoglycemia in the entire population with T2D to provide an efficient management plan for optimal glycemic control with the lowest possible risk of hypoglycemia. This study aimed to evaluate the prevalence and predictive factors of hypoglycemia among patients with T2D using nationwide claims data.


Data Source

We utilized the nationwide healthcare database of the Health Insurance Review and Assessment Service (HIRA; Seoul, South Korea) between January 1, 2011, and December 31, 2013. HIRA is a governmental agency established to evaluate the accuracy of claims for National Health Insurance (covers approximately 96.7% of the overall population in South Korea) and National Medical Aid (covers approximately 3.3% of the population).16 The HIRA database is generated during claim reimbursement for healthcare services. This database is representative of the total population in South Korea and has advantages for generalization to the population. It includes information regarding demographic variables; all medical services provided, along with diagnostic codes (Korean Classification of Diseases version 7 [KCD-7]); and all prescription medications dispensed.

Patient records and information were anonymized and deidentified before the analysis. This study was approved by the institutional review board of Sungkyunkwan University. Informed consent was waived by the board.

Study Design and Patient Selection Criteria

Two methods were used to evaluate the prevalence and predictors of hypoglycemia among patients with T2D. First, a retrospective cohort study was used to estimate the 1-year prevalence of hypoglycemia in these patients. The study population included patients 20 years or older and diagnosed with T2D, defined as having a T2D diagnosis code (KCD-7 code E11) and receiving treatment with antidiabetic drugs. The index period for selecting patients was January 1, 2011, to December 31, 2012, to ensure a 1-year follow-up period for estimating the prevalence. We excluded patients diagnosed with T1D (KCD-7 code E10) or gestational diabetes (KCD-7 code O24).

Second, a nested case-control study was conducted to identify the predictors of hypoglycemia within the cohort with T2D. The cohort entry date was defined as the first date of receiving antidiabetic drugs, with a diagnosis of T2D between July 1, 2011, and December 31, 2013. A 6-month period was applied to assess possible predictive factors. Within the eligible cohort, we identified cases with hypoglycemia that occurred after the cohort entry date. For each case, we defined the index date as the date of the first eligible claim for a hypoglycemia-related visit. Controls were selected using individual matching. For each case, up to 4 controls matched for sex, age (±5 years), and cohort entry date were randomly selected without replication from patients with T2D without a diagnosis of hypoglycemia after the cohort entry date. The index date for each control was considered equal to the index date of their matched case.

Prevalence of Hypoglycemia

The 1-year prevalence of hypoglycemia was defined as the percentage of patients who experienced 1 or more hypoglycemic episode during the 1-year follow-up period after being screened for T2D. Total hypoglycemia was identified on the basis of the first medical encounter for hypoglycemia (outpatient, inpatient, or emergency department [ED] visits) containing any of the following KCD-7 diagnosis codes: E11.63 (T2D, with hypoglycemia), E12.63 (malnutrition-related diabetes mellitus, with hypoglycemia), E13.63 (other specified diabetes mellitus, with hypoglycemia), E14.63 (unspecified diabetes mellitus, with hypoglycemia), E16.0 (drug-induced hypoglycemia without coma), E16.1 (other hypoglycemia), or E16.2 (hypoglycemia, unspecified). Also, the setting of hypoglycemia diagnosis was used to capture information on the severity of hypoglycemia. Severe hypoglycemia was defined as an event with inpatient admission or emergency care. Annual prevalence was also presented from 2011 to 2013.

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