In this large retrospective cohort study of >4,000 admissions, we have focused on patients with known diabetes admitted to the general hospital ward. Mortality among hypoglycemic patients in this population was 3%, significantly lower than the 22–48% observed in the previously published investigations that included critically ill patients (18
). Nevertheless, we have found a similarly strong relationship between hypoglycemia and in-hospital mortality as well as LOS. Unlike in some studies of the general hospital population (18
), this relationship was dose dependent: both LOS and inpatient mortality increased gradually as the number of hypoglycemic episodes rose. A greater degree of hypoglycemia was also associated with an increase in inpatient mortality. Furthermore, an analysis of a data subset that contained only one admission per patient revealed a strong association between the number of episodes of hypoglycemia and outpatient mortality at 1 year after discharge from the hospital.
Although the retrospective nature of our analysis does not allow a direct inference of causality, several explanations of this relationship can be hypothesized. On the one hand, hypoglycemia could affect outcomes directly by leading to falls, seizures, or death. It could also have an indirect effect by requiring adjustments of the patients' antihyperglycemic regimen or delays of tests and procedures, consequently leading to an extension of the hospital stay.
On the other hand, hypoglycemia could be a marker for disease severity. Studies in the general hospital population, including patients in the ICU, showed that decreased caloric intake, which could be related to disease-induced anorexia, was a significant contributor to hypoglycemia (5
). Although our study design excluded critically ill patients, malnutrition is well described in less severely ill patients as well (22
). The marker hypothesis is further supported by the strong association between hypoglycemia and outpatient mortality, a finding that is difficult to explain by a direct effect of inpatient hypoglycemia on survival.
Several recommendations can be made on the basis of our results. Sicker diabetic patients in the general ward should be monitored closely for the occurrence of hypoglycemia. Extra care should be taken to prevent hypoglycemic events in this population already at high risk for adverse events, with particular attention being paid to matching the antihyperglycemic regimen to the nutritional intake. At the same time, hypoglycemia among diabetic patients in the general ward could be interpreted as a warning sign of an impending clinical deterioration. It could therefore serve as a useful indicator for the necessity of increased monitoring, more aggressive treatment of infections, transitioning to a more intensive care setting, and case management.
Our study has a number of strengths. It is the first study to focus on patients with diabetes hospitalized in the general ward, by far the largest group of inpatients at high risk for hypoglycemia. It is one of the largest analyses of the phenomenon of inpatient hypoglycemia, encompassing >4,300 admissions of 2,582 individual patients. In addition, it included both inpatient and outpatient outcomes, thus helping to differentiate possible immediate effects of hypoglycemia from a noncausal association.
This analysis has several limitations. The study included only patients admitted to a single academic hospital in Boston, Massachusetts, which could limit its generalizability to other geographic and health care settings. It was impossible to differentiate between type 1 and type 2 diabetes from the available data; therefore, it cannot be stated with certainty whether our findings apply to one or both conditions. However, statistically, most patients in the hospital have type 2 diabetes. Lack of nutrition information for individual patients has hindered the analysis of the causes of hypoglycemia. Furthermore, our data did not include descriptions of the types and severity of the immediate clinical sequelae (changes in mental status, loss of consciousness, or seizures) of the hypoglycemic episodes. We used point-of-care blood glucose levels in this study, the accuracy of which may have been limited, particularly at the lower glucose levels. On the other hand, central laboratory glucose levels used in many other studies are typically obtained much less frequently, possibly leading to an underestimation of the frequency and severity of hypoglycemia. In addition, unless blood samples for glucose measurement are routinely collected into tubes with a glycolysis inhibitor, the measured blood glucose level may be falsely lowered in patients with high white cell counts (23
), precisely the patients at high risk for adverse outcomes. Finally, the retrospective nature of the study does not allow us to draw conclusions about causal relationships and may have led to a bias if missing data were distributed unevenly with respect to the outcomes analyzed.
In summary, hypoglycemia in diabetic patients hospitalized in the general ward was associated with increased inpatient and postdischarge mortality as well as with a prolonged LOS. Further studies are needed to establish a causal relationship. In the meantime, care should be taken to prevent hypoglycemia in this high-risk patient population.