Discussion
In this large observational single-center study of 786 DKA episodes, we show that DKA more commonly affects people with type 1 diabetes; however, we also noted a trend toward ethnic minorities preponderance and those of an older age, especially in type 2 diabetes. Importantly, however, nearly a quarter of admission with DKA were in people with a clinical diagnosis of type 2 diabetes. Wang et al13 reported type 2 diabetes accounted a third of overall DKA cases in Swedish population. However, the results were limited by a small study population. The most common precipitants were intercurrent illness and suboptimal compliance, although no clear precipitating etiology could be ascertained for 16.5% of our cohort. There was no difference between type 1 and type 2 diabetes in DKA severity at presentation, insulin requirements for DKA treatment or complications of DKA treatment. South Asian or black ethnicities admitted with DKA were more likely to have type 2 diabetes, while those of white Caucasian ethnicity with DKA were more likely to have type 1 diabetes. People with type 2 diabetes were found to have a significantly longer hospital stay than those with type 1 diabetes. We noted a graded difference in length of hospitalization as age increased, which plateaued after 70 years.
The strengths of this study are that this is a single-center study of long duration with comprehensive data collection of demographics, presentation and outcome of DKA management. To our knowledge, our cohort is the largest consecutive DKA episodes ever reported, with inclusion of all people with DKA over a 6-year time period. However, we note lack of ketone measurement data, intensive care unit admission and mortality data, which limit our assessment between those with type 1 and type 2 diabetes. Previous studies showed higher mortality in type 2 diabetes with DKA compared with type 1 diabetes14 15 and mortality is reported to relate to the precipitating cause of DKA. Additionally, antibody and C peptide data were also unavailable and thus we relied on a clinical diagnosis of type 1 diabetes and type 2 diabetes.
Our findings on the precipitating etiology are similar to previous studies which have found that intercurrent illness and suboptimal compliance were the two most common presentations.16 No identifiable precipitating factor could be found in half of patients with type 2 diabetes for DKA in a similar study in the past, akin to our study.11 Identifying the precipitating factor is important in order to avoid future episodes. We also identified a small proportion of DKA related to SGLT2 inhibitors, in line with building evidence in this drug class,17 18 as well as increasing contribution with time from causes such as checkpoint inhibitor cancer therapy and COVID-19 virus infection. We recently reported that in people with type 1 diabetes, those with COVID-19 presented more hyperglycemic episodes, and in those with type 2 diabetes those with COVID-19 were more likely to require intensive care support and had higher mortality rates.19 Other studies have also identified changes in presenting characteristics of patients with DKA during the COVID-19 pandemic, most notably an increase in presentation of DKA in patients with type 2 diabetes.20 21
Our analysis did not show any differences in serum osmolality between DKA in type 1 and type 2 diabetes. We do show however that higher calculated osmolality across the cohort, driven by higher glucose, lactate and urea, indicated more severe dehydration and a longer length of hospitalization, but not longer DKA duration. However, those with higher serum osmolality and type 1 diabetes had an increased DKA duration and longer hospital stay when compared with those with a lower serum osmolality and type 1 diabetes.
The longer hospital stay we observed in those with type 2 diabetes may be indicative of a more complex requirement for care in this cohort. People with type 2 diabetes tend to have more comorbidities, experience macrovascular and/or microvascular complications, and have worse diabetic control compared with people with type 1 diabetes, which will add to disease burden and recovery from DKA.14 22–25 On the other hand, those with type 2 diabetes who experience DKA may represent a more complex cohort, as studies have identified increased risk of complications, such as stroke, in this group in comparison with patients with type 2 diabetes who do not experience DKA.26 Although our analyses did not find a significant difference in clinical parameters, multiple studies have indicated greater severity and mortality of DKA in patients with type 2 diabetes in comparison with those with type 1 diabetes.14–16
Balasubramanyam et al11 reported a high proportion of DKA episodes in non-Caucasian adults occur in persons with type 2 diabetes, similar to our findings.11 These findings may be representative of the population diagnosed with these diseases, as minority ethnic groups are at a higher risk of type 2 diabetes.27 However, this may also be in part due to the fact that those who are South Asian or black are more likely to have worse diabetes control, have a genetic predisposition or to be of a lower socioeconomic and/or educational status, all factors which associate with an increased risk of DKA.28–30 It is also increasingly recognized that non-Caucasian ethnics are more likely to be diagnosed with ketosis-prone type 2 diabetes and this may contribute to some of the DKA episodes seen.31
Over the years, our analysis identified a reduction in DKA duration but an increase in length of hospitalization. During this time period, multiple changes to DKA management have been implemented in our hospital trust as part of an ongoing quality improvement.32 33 These interventions have been effective at reducing DKA duration and have included development of a real-time audit tool, automatic referral to a specialist team, electronic surveillance of blood gas results, education and redesigning of local guidelines, and monthly feedback meetings. Nevertheless, an increase in length of hospitalization was seen which contradicts reports from other centers.9 We are still not clear of the reasons for the increased median length of stay, although this has been stable for a number of years.
The findings of this study can help inform policy and practice to reduce morbidity and mortality associated with DKA. Patient education among at-risk groups, particularly those of non-Caucasian ethnicity, can increase awareness of the potential of DKA as a complication of both type 1 and type 2 diabetes. Increasing awareness will prevent DKA occurrence and enable rapid identification of warning signs to reduce DKA-associated morbidity. Furthermore, although no differences were observed in management requirements, it is important to consider factors which may affect length of hospitalization in those with type 2 diabetes. Additionally, our subgroup analysis which confirmed that those with a higher serum osmolality are sicker may inform medical practice to alert front-line workers to patients who are likely to require more care.