Impact of Hypoglycemia Associated With Antihyperglycemic Medications on Vascular Risks in Veterans With Type 2 Diabetes

School of Pharmacy, Saint Joseph College, Hartford, Connecticut, USA.
Diabetes care (Impact Factor: 8.42). 03/2012; 35(5):1126-32. DOI: 10.2337/dc11-2048
Source: PubMed


Hypoglycemia is associated with failure to show cardiovascular benefit and increased mortality of intensive glycemic control in randomized clinical trials. This retrospective cohort study aimed to examine the impact of hypoglycemia on vascular events in clinical practice.
Patients with type 2 diabetes were identified by ICD-9-CM codes (250.xx except for 250.x1 and 250.x3) between 1 January 2004 and 1 September 2010 from the Veterans Integrated Service Network 16. Index date was defined as the first date of new antihyperglycemic medications (index treatment). Patients with 1-year preindex records of hypoglycemia, cardiovascular, and microvascular diseases were excluded. The hypoglycemia group was identified by ICD-9-CM codes (250.8, 251.0, 251.1, and 251.2) within the index treatment period. A propensity score-matched group was used as control subjects. Cardiovascular events, microvascular complications, and all-cause death were compared using Kaplan-Meier analysis and Cox proportional hazards regression model.
Among the unmatched sample (N = 44,261), the hypoglycemia incidence rate was 3.57/100 patient-years. The matched sample (hypoglycemia group: n = 761; control group: n = 761) had a median follow-up of 3.93 years, mean age of 62.6 ± 11.0 years, and preindex HbA(1c) of 10.69 ± 2.61%. The 1-year change in HbA(1c) was similar (hypoglycemia group -0.51 vs. control group -0.32%, P = 0.7244). The hypoglycemia group had significantly higher risks of cardiovascular events (hazard ratio 2.00 [95% CI 1.63-2.44]) and microvascular complications (1.76 [1.46-2.11]) but no statistical mortality difference. Patients with at least two hypoglycemic episodes were at higher risks of vascular events than those with one episode (1.53 [1.10-1.66]).
Hypoglycemia is associated with higher risks of incident vascular events. Patients with hypoglycemia should be monitored closely for vascular events.

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    • "As in other studies (Bullano, Fisher, Grochulski, Menditto, & Willey, 2006; Zhao, Campbell, Fonseca, & Shi, 2012), hypoglycemia was defined as having an ICD-9-CM code 250.8 (Diabetes with other specified manifestations; applies to diabetic hypoglycemia NOS and hypoglycemic shock NOS), 251.0 (Hypoglycemic coma), 251.1 (Other specified hypoglycemia), and 251.2 (Hypoglycemia, unspecified). The hypoglycemia was categorized as primary if it was the primary cause of admission and secondary if it occurred during the hospital stay. "
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    ABSTRACT: We aimed to evaluate the frequency of hypoglycemia and its impact on the length of stay and all-cause in-hospital mortality in hospitalized patients with diabetes. We used data from the Basic Minimum Data Set of the Spanish National Health System. Hypoglycemia was defined as having an ICD-9-CM code 250.8, 251.0, 251.1, and 251.2, and categorized as primary if it was the main cause of admission and secondary if it occurred during the hospital stay. The association between hypoglycemia and the study outcomes was evaluated in two cohorts - with and without secondary hypoglycemia - matched by propensity scores and using multivariate models. Among the 5,447,725 discharges with a diagnosis of diabetes recorded from January 1997 to December 2010, there were 92,591 (1.7%) discharges with primary hypoglycemia and 154,510 (2.8%) with secondary hypoglycemia. The prevalence of secondary hypoglycemia increased from 1.1% in 1997 to a peak of 3.8% in 2007, while the prevalence of primary hypoglycemia remained fairly stable. Primary hypoglycemia was associated with reduced in-hospital mortality (Odds ratio [OR] 0.06; 95% Confidence interval [CI], 0.03-0.10) and a significant decrease in time to discharge (Hazard ratio [HR] 2.53; 95% CI, 2.30-2.76), while secondary hypoglycemia was associated with an increased likelihood of in-hospital mortality (OR 1.12; 95% CI, 1.09-1.15) and a significant increase in time to discharge (HR 0.80; 95% CI, 0.79-0.80). In conclusion, the prevalence of secondary hypoglycemia is increasing in patients with diabetes and is associated with an increased likelihood of in-hospital mortality and a longer hospital stay. Copyright © 2015. Published by Elsevier Inc.
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    • "In a large nationwide cohort study from Taiwan, even mild symptomatic hypoglycemia was associated with increased cardiovascular risk, all-cause hospitalization, and all-cause mortality [23]. Furthermore, Zhao et al reported that patients with hypoglycemia had a significantly higher risk of cardiovascular events (hazard ratio [HR] 2.00) and microvascular complications (HR 1.76) [24]. In addition to these serious effects, This article is protected by copyright. "
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