Here’s a shocking truth: despite common assumptions, lower kidney function levels—measured by eGFR rates—do not appear to increase the risk of diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D). But here’s where it gets controversial: this finding challenges the notion that reduced kidney function alone is a significant risk factor for DKA, even without the use of kidney-protective medications like SGLT inhibitors. And this is the part most people miss: while SGLT inhibitors have proven effective in reducing late-stage kidney issues in type 2 diabetes, they also come with an elevated DKA risk—a trade-off that’s been hotly debated in medical circles.
In a groundbreaking study published in Diabetes Care, researchers led by Abdulmohsen Bakhsh, MD, an endocrinologist at Mount Sinai Hospital in Toronto, Canada, analyzed 35 years of data from the DCCT/EDIC study. Their goal? To determine whether reduced kidney function, as measured by eGFR, independently increases DKA risk in T1D patients. The study included 1,441 adults with T1D, with a mean age of 26.8 years and a diabetes duration of approximately 6 years. Over a 34-year follow-up, 297 participants experienced at least one DKA event, totaling 488 episodes.
Surprisingly, the data revealed no significant difference in DKA rates between individuals with eGFR levels between 30 and 90 mL/min/1.73 m² and those in the reference range of 90 to 120 mL/min/1.73 m². Even in the lowest eGFR category (<30 mL/min/1.73 m²), the incidence rate of the first DKA event was not statistically higher. Boldly put, this suggests that kidney function alone may not be the DKA culprit we once thought it was.
However, the study wasn’t without limitations. The cohort was relatively young and healthy, and the analysis lacked data on confounding factors like socioeconomic status and alcohol intake. Yet, the large sample size and long-term follow-up strengthened the findings, paving the way for clinical trials to explore SGLT inhibitors as kidney-protective agents in T1D.
But here’s the twist: these results contradict earlier findings from the FinnDiane study, which reported higher DKA risk in individuals with baseline eGFR ≤60 mL/min/1.73 m². Bakhsh and his team argue that their time-updated analysis—which assessed eGFR levels immediately before each DKA event—may provide a more accurate risk estimate than FinnDiane’s baseline measurements. Still, the debate rages on: is this enough to reconsider SGLT inhibitors for T1D patients with kidney issues?
Looking ahead, experts like Charles Leonard, PharmD, MSCE, MPH, emphasize the need for further research. “Distinguishing causation from correlation is critical,” he notes, urging caution before concluding that low eGFR is harmless in this context. And this is the part that sparks debate: while the study’s findings are compelling, they’re “less than convincing at present,” according to Leonard, who calls for rigorously designed prospective studies to clarify the kidney-benefit vs. DKA-risk balance in T1D, especially in advanced kidney disease.
So, what’s your take? Do these findings challenge your understanding of DKA risk in T1D? Or do you think more research is needed before we can confidently prescribe SGLT inhibitors for kidney protection in this population? Let’s keep the conversation going in the comments!
