Response to: “Insulin Pump Use and Diabetic Ketoacidosis Risk in Type 1 Diabetes: Secular Trends Over Four Decades”

Dear Editor,

It was great to see the positive report by Budhram et al. based on an analysis of the epidemiology of diabetes interventions and complications (EDIC) cohort. ¹ The analysis found that diabetic ketoacidosis (DKA) risk has fallen since 1980. Our own data have also shown that continuous glucose monitoring (CGM) use in type 1 diabetes is also associated with reductions in DKA. ² However exciting, DKA remains problematic for many with diabetes including those with type 2 diabetes. ^2,3 We would like the readers to consider the following points when assessing the original article.

There are limitations with the current study to consider. First, this study compares the rates for DKA between insulin pump users and nonusers. The rates for DKA as seen in Table 1 of the publication show that DKA still occurs and seems to occur at a steady rate of 0.87 and 0.84 events per 100 person-years for insulin pump users and nonusers. So while, the relative risk between users and nonusers has diminished, the overall rates for DKA are not falling further since the 2000s. In addition, EDIC followed up with participants who elected to continue after diabetes control and complications trial (DCCT). In general, study participants tend to be more proactive and engaged. It should be noted that the HbA1c for EDIC participants versus nonparticipants in the intensively treated group was notably lower (7.4% vs. 8.5%, P = 0.0031). ⁴ Even in this highly engaged group, DKA events are occurring. In contrast to the findings by Budhram, a recent study in Lancet Diabetes-Endocrinology, observed increased risk for DKA in young people on hybrid closed loop systems. ⁵

As noted above, CGM has been associated with reductions in DKA risk. However, there remains some risk for DKA. CGM use has increased, especially among those with type 1 diabetes. However, the American Diabetes Association recognizes the “concerning rise in the rate of hyperglycemic crises in people with both type 1 diabetes and type 2 diabetes over the past decade,” with mortality plateauing over the past decade. ² Finally, increasing use of sodium-glucose cotransporter 2 (SGLT2i) inhibitors for their cardiac and renal benefits has led to cases of DKA in both type 1 and type 2 diabetes. ³ Unlike most cases of DKA, SGLT2i use can lead to euglycemic DKA; patients do not have the usual trigger of elevated glucose levels that have elevated ketones without a rise in glucose. As use of these medicine grows, the need for ketone monitoring may also rise.

As mentioned, the findings are exciting, but we want to ensure that readers do not conclude that DKA is no longer an issue we must address.