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Euglycemic SGLT2i DKA vs Type 1 Diabetes DKA

May 9, 2024

Written by Nickolas Srica

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Sodium-glucose cotransporter 2 inhibitor (SGLT2i)-associated ketoacidosis (DKA) had delayed resolution compared to type 1 diabetes (T1D)-associated DKA despite often being “milder”. This could be due to significantly lower insulin doses given in the setting of the lower plasma glucose levels often seen in this population.

Sugar, sugar how you get so high… or normal…
The pathophysiology of T1D DKA is different than that of SGLT2i DKA. The former is driven by an insulin deficiency, while the latter is due to an overall reduction in plasma glucose (PG) concentration from urinary glucose losses, leading to reduced insulin secretion and increased glucagon, which leads to ketosis and often normal or only mildly elevated PG levels. Despite this difference, multiple endocrinology associations recommend treatment with the same protocols, but are we adequately dosing insulin in SGLT2i DKA?

This was a retrospective cohort study comparing ketone and bicarbonate level changes after 24 hours of treatment in cases of SGLT2i DKA and T1D DKA between two tertiary hospitals in South Australia. Despite the SGLT2i DKA group having milder DKA comparatively (median [IQR] ketone peak:  5.3 [4.2-5.9] vs 6.5 [4.7-7.2] mmol/L; p=0.02), they also had delayed resolution (median [IQR] time: 36 [24-72] vs 18 [12-27] hours; p=0.002), which is suspected to be related to lower admission PG levels (12.5 vs 36.8 mmol/L; p<0.001) leading to significantly lower insulin doses in the first 24 hours (median [IQR] dose: 44.0 [27.0-82.5] vs 87.0 [63.0-124.0] units; p=0.01).

How will this change my practice?
Based on the above, these authors conclude it would be reasonable to increase dextrose infusion rates and concentrations to allow for increased insulin doses to suppress ketosis more quickly in SGLT2i DKA. Though this was a smaller retrospective study and more prospective randomized trial data is needed to fully understand the risks (i.e., hypoglycemic events) versus benefits of this approach, I agree this might be a reasonable approach to get our patients improving faster.

SGLT2 Inhibitor-Associated Ketoacidosis vs Type 1 Diabetes-Associated Ketoacidosis. JAMA Netw Open. 2024 Mar 18;7(3):e242744. doi: 10.1001/jamanetworkopen.2024.2744. PMID: 38497966

What are your thoughts?