Hypoglycemia-associated Mortality Is Not Drug-associated but Linked to Comorbidities

Abstract

Objective Although tight glucose control is widely used in hospitalized patients, there is concern that medication-induced hypoglycemia may worsen patient outcomes. We sought to determine if the mortality risk associated with hypoglycemia in hospitalized non-critically ill patients is linked to glucose-lowering medications (drug-associated hypoglycemia) or if it is merely an association mediated by comorbidities (spontaneous hypoglycemia). Methods Retrospective cohort of patients admitted to the general wards of an academic center during 2007. The in-hospital mortality risk of a hypoglycemic group (at least one blood glucose ≤ 70 mg/dl) was compared to that of a normoglycemic group using survival analysis. Stratification by subgroups of patients with spontaneous and drug-associated hypoglycemia was performed. Results Among 31,970 patients, 3,349 (10.5%) had at least one episode of hypoglycemia. Patients with hypoglycemia were older, had more comorbidities, and received more antidiabetic agents. Hypoglycemia was associated with increased in-hospital mortality (HR: 1.67, 95% CI, 1.33 to 2.09, p<0.001). However, this greater risk was limited to patients with spontaneous hypoglycemia (HR: 2.62, 95% CI, 1.97 to 3.47, p<0.001), not to those with drug-associated hypoglycemia (HR: 1.06, 95% CI, 0.74 to 1.52, p=0.749). After adjustment for patient comorbidities, the association between spontaneous hypoglycemia and mortality was eliminated (HR: 1.11, 95% CI, 0.76 to 1.64, p=0.582). Conclusions Drug-associated hypoglycemia was not associated with increased mortality risk in patients admitted to the general wards. The association between spontaneous hypoglycemia and mortality was eliminated after adjustment for comorbidities, suggesting that hypoglycemia may be a marker of disease burden rather than a direct cause of death.

Management of hospitalized type 2 diabetes mellitus patients

“…[22] However, other studies suggest that the increased mortality rate associated with hypoglycemia is only with spontaneous hypoglycemia rather than drug-associated hypoglycemia. [23] The causes of hypoglycemia in hospitalized T2DM patients include continued hypoglycemic therapy, such as sulfonylureas, when caloric intake is stopped or reduced, use of standard sliding-scale insulin inadequately, [24] errors in insulin dosing, and implementation of intensive insulin therapy in critically ill patients. [25] Prolonged QT interval, ischemic electrocardiogram changes, arrhythmias, and sudden death are also associated with hypoglycemia.…”

Prediction and Prevention of Treatment-Related Inpatient Hypoglycemia

“…Hypoglycemia has been associated with mortality in multiple intensive care unit studies, but this association is not as clear on the medical wards. [1][2][3][4] Hypoglycemia in the outpatient setting is a recognized risk factor for mortality and morbidity including cardiovascular, cerebrovascular, and patient fall events. 5,6 The prevalence of hypoglycemia (<70 mg/dl) was reported to be 5.7% of all point-of-care blood glucose (BG) tests in a 2009 survey of 575 hospitals.…”

The clinical impact of hypoglycemia in hospitalized patients

“…A retrospective study of a large cohort of patients with or without diabetes, admitted to Departments of Internal Medicine, showed that mortality was higher among patients who had spontaneous hypoglycemias. 17 After adjustment for comorbidities, hypoglycemia was no longer an independent risk factor for mortality, thereby reinforcing the concept that hypoglycemia acts as a marker of severe underlying disease, rather than as a direct cause of death. Similar results were found in patients with AMI, about 50% of them diabetics.…”

“…Risk factors for spontaneous hypoglycemia are septic shock, comorbidities (as defined by the Charlson comorbidity index), drug interactions in polypharmacy, renal failure, liver or adrenal disease, severe heart failure and neoplasms. 17,18 We have always to remember that during hospitalization, patients undergo changes of their insulin sensitivity and counter-regulatory hormone, secondary to the disease, procedures and treatment carried out. 19,20 Older patients also have often organ dysfunction age related, which alters insulin sensitivity and drug metabolism, resulting in the enhancement of hypoglycemic events.…”

“…Although diabetes and the subsequent use of hypoglycemic drugs is the most common risk factor, only 50% of hypoglycemic events occurs in diabetic patients or in those receiving insulin. 17,18 The spontaneous hypoglycemia, which occurs without any clear precipitating cause, must be distinguished from that one drug-induced, even as it has a poor prognosis and a different pathogenesis. Risk factors for spontaneous hypoglycemia are septic shock, comorbidities (as defined by the Charlson comorbidity index), drug interactions in polypharmacy, renal failure, liver or adrenal disease, severe heart failure and neoplasms.…”