The present study describes the clinical characteristics of patients with hyperglycemic crises using data obtained from multiple institutions in Japan. The mortality rate of patients with DKA and HHS was 2.8% and 7.1%, respectively. No linear relationship was found between the severity of DKA and mortality. Major precipitating factors of acute episodes were poor adherence to treatment regimens, infections, and intake of excessive sugar-sweetened beverages. The rate of ICU admission varied among institutions.
The mortality rate of patients with DKA and HHS varies among countries and has changed over time. In recent publications, the mortality rate of patients with DKA has been reported from 0.16–4.1%[6],[7],[8] whereas that of HHS was between 10 to 20%[3],[11]. The results of the present study are similar to previous reports for DKA but the mortality rate of patients with HHS in the present study was lower. The reason for this difference is unclear but could be explained by global trends in improving diabetes care. A report based on a US national survey showed that the mortality rate of patients with DKA was decreasing while hospitalization was increasing[7]. This improvement might be attributed to increased awareness of the disease and adaption of established guidelines for the treatment of patients with DKA.
It is unclear if severity of DKA correlates with mortality or not. While some studies indicated an association between them[8],[16], other studies found that other factors were more important than DKA severity. For example, a previous study of a prediction model for the prognosis of patients with DKA concluded that coexisting severe diseases are the most significant predictor for mortality[17]. Another study suggested that advanced age and altered levels of consciousness were important predictors of mortality as well as electrolyte disturbances[18]. In the present study, the severe DKA group was younger and the prevalence of comorbidities such as stroke was lower compared with the other DKA groups. Considering the findings of the present study and previous reports, the severity of DKA may be less important than other factors such as patient age or comorbidities.
Treatment in the ICU has been considered appropriate for patients with hyperglycemic crises for decades as indicated in the guidelines[19], [20]. The essentials of treatment for hyperglycemic crises are fluid resuscitation, electrolyte replacement, and insulin infusion, which require close monitoring of vital signs, electrolytes, and blood glucose levels. However, recent studies have shown that DKA can be safely managed in the emergency department[21] or even in general wards[22]. We found that differences in ICU utilization for these patients by institution was quite varied, ranging from 0–100%. Such a discrepancy may reflect variations in practice and setting of each hospital. A study including 159 hospitals in the United States also reported ICU admission rates from 2.1 to 87.7% but no association was found between the rates of ICU utilization and mortality or length of hospital stay[13]. Another large retrospective study involving 15,022 patients with DKA showed that institutions that utilized ICUs more frequently had higher costs but had no improvement in hospital mortality[23]. As far as proper triage and management are provided, where care is provided for these patients could be less important. Nevertheless, it should be emphasized that patients who need organ support or have severe comorbidities are suitable for management in the ICU[15]. As the present study suggests, a considerable number of patients required mechanical ventilation, vasopressor use, and renal replacement therapy. Patient profile and conditions also affect prognosis, which should be considered. Past reports suggested that older age, sepsis, coma and lower levels of activity of daily living, and severe comorbidities were risk factors for mortality[17],[24]. Accordingly, the use of organ support as well as patient background should be taken into account for the selection of providing care in the ICU.
In the present study, more than 20% of the patients reported excessive consumption of sugar-sweetened beverages prior to hyperglycemic emergencies. Both patients’ behavior and medical illnesses are important triggers for hyperglycemic emergencies[25],[26]. Previous reports identified poor adherence and infection as common precipitants[2], [27], [28]. Recent studies demonstrated that increased consumption of sweet soft drinks worsens insulin resistance and impairs pancreatic beta-cell function[29], [30], which is related to the pathophysiology of decompensated hyperglycemia. Although the exact prevalence was not documented in previous studies, the results of the present study suggest that excessive consumption of sugar-sweetened beverages may be a significant trigger for developing DKA and HHS.
The present study shows the proportion of patients who were taking medications that could worsen diabetes. Several types of medication, e.g., corticosteroids[31], beta blockers[32], anti-psychotics[33], thiazides[34], quinolones[35] and phenytoin[5], have been reported to be associated with deterioration of diabetes control. Although the overall prevalence of drug-induced diabetes is unknown, approximately 15 to 50% of patients taking corticosteroids and 10% of people taking anti-psychotic medications develop diabetes[36], [37]. Some studies have also described patients with drug-induced DKA and HHS[38], [39]. We reviewed prescriptions for the patients with diabetes requiring emergency admission and found that a few patients were taking such medications. Although corticosteroids were prescribed in 6% of patients with HHS, only a small number of patients were taking other medications which could affect diabetes. Given that other precipitating factors are more frequent, the impact of these drugs may be less important in the context of the overall acute critical episodes.
To the best of our knowledge, this is one of the largest and most detailed epidemiological studies of hyperglycemic crises in the medical literature. The strengths of this study are the large sample size and comprehensive description of patient characteristics including precipitating factors, medical resources used, and complications during hospitalization. However, the present study has also acknowledged limitations. First, multivariable regression analysis could not be conducted due to the low incidence of mortality. As a result, predictors of mortality or association between ICU admission and outcomes were not investigated. Considering the low mortality rate, studies with a much larger population such as a nationwide database will be needed to conduct multivariable regression analysis. Second, since the inclusion criteria included hyperglycemia, the present study did not enroll patients with euglycemic DKA which is currently an emerging problem[40]. However, this may be a minor issue because most of the study period was before the widespread use of sodium-glucose cotransporter 2 inhibitors in Japan.