Blood Ketones: Measurement, Interpretation, Limitations, and Utility in the Management of Diabetic Ketoacidosis

Abstract

■ AbstractDiabetic ketoacidosis (DKA) remains a common medical emergency. Over the last few years, new national guidelines have changed the focus in managing the condition from being glucose-centered to ketone-centered. With the advent of advancing technology and the increasing use of hand-held, point-of-care ketone meters, greater emphasis is placed on making treatment decisions based on these readings. Furthermore, recent warnings about euglycemic DKA occurring in people with diabetes using sodium-glucose co-transporter 2 (SGLT-2) inhibitors urge clinicians to inform their patients of this condition and possible testing options. This review describes the reasons for a change in treating DKA, and outlines the benefits and limitations of using ketone readings, in particular highlighting the difference between urine and capillary readings.

Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients

“…Glucagon accelerates the generation of ketonemia and hyperglycemia in the insulin deficient state, but as previously mentioned it is not essential for development of diabetic ketoacidosis. In addition to ketone body overproduction, clearance is also decreased in diabetic ketoacidosis 2536…”

Sodium‐glucose co‐transporter inhibitors, their role in type 1 diabetes treatment and a risk mitigation strategy for preventing diabetic ketoacidosis: The STOP DKA Protocol

“…Despite the price differential which is often an important consideration, we recommend avoiding urine ketone monitoring and relying only on blood ketone monitoring for the following reasons: Unlike blood ketone monitoring which measures β‐hydroxybutyrate, urine ketone monitoring only measures acetoacetate which is unstable and unreliable for DKA diagnosis (see below) Unlike urine ketone monitoring, blood ketone monitoring has better sensitivity and specificity for DKA; acetoacetate levels rise with the duration of DKA and may be undetectable in urine samples during the early phases of DKA There is poor correlation between urine ketone and plasma ketone levels; notably, ketone estimates from urine samples represent bladder ketone levels since the last void and not current urine ketone levels Resolution of DKA may be missed since treatment‐triggered β‐hydroxybutyrate oxidation would elevate urine acetoacetate levels and present a false‐positive signal indicating persistent DKA …”

Systematic literature review and network meta‐analysis of sodium‐glucose co‐transporter inhibitors vs metformin as add‐on to insulin in type 1 diabetes

“…While the use of lower SGLT inhibitor doses, blood ketone testing and following sick‐day rules have been suggested as ways for patients with T1DM to independently manage their DKA risk, one study involving 2995 patients with T1DM found that more than 30% did not engage in routine ketone testing . Concerns have also been raised about the costs associated with these tests and potentially inaccurate results . Therefore, to determine the risk–benefit ratio and cost‐effectiveness of SGLT inhibitors in T1DM patients, the DKA risk associated with their use requires further investigation, along with examination of other commonly associated side effects such as urinary tract infections (UTIs) …”

“…23 Concerns have also been raised about the costs associated with these tests and potentially inaccurate results. 24 Therefore, to determine the riskbenefit ratio and cost-effectiveness of SGLT inhibitors in T1DM patients, the DKA risk associated with their use requires further investigation, along with examination of other commonly associated side effects such as urinary tract infections (UTIs). 25,26 In the absence of head-to-head clinical trials directly comparing SGLT inhibitors and metformin in the T1DM population, their efficacy and safety as adjunctive therapies needs examining indirectly.…”