Update on Measuring Ketones

Abstract

Ketone bodies are an energy substrate produced by the liver and used during states of low carbohydrate availability, such as fasting or prolonged exercise. High ketone concentrations can be present with insulin insufficiency and are a key finding in diabetic ketoacidosis (DKA). During states of insulin deficiency, lipolysis increases and a flood of circulating free fatty acids is converted in the liver into ketone bodies—mainly beta-hydroxybutyrate and acetoacetate. During DKA, beta-hydroxybutyrate is the predominant ketone in blood. As DKA resolves, beta-hydroxybutyrate is oxidized to acetoacetate, which is the predominant ketone in the urine. Because of this lag, a urine ketone test might be increasing even as DKA is resolving. Point-of-care tests are available for self-testing of blood ketones and urine ketones through measurement of beta-hydroxybutyrate and acetoacetate and are cleared by the US Food and Drug Administration (FDA). Acetone forms through spontaneous decarboxylation of acetoacetate and can be measured in exhaled breath, but currently no device is FDA-cleared for this purpose. Recently, technology has been announced for measuring beta-hydroxybutyrate in interstitial fluid. Measurement of ketones can be helpful to assess compliance with low carbohydrate diets; assessment of acidosis associated with alcohol use, in conjunction with SGLT2 inhibitors and immune checkpoint inhibitor therapy, both of which can increase the risk of DKA; and to identify DKA due to insulin deficiency. This article reviews the challenges and shortcomings of ketone testing in diabetes treatment and summarizes emerging trends in the measurement of ketones in the blood, urine, breath, and interstitial fluid.

A Randomized Crossover Trial of Mixed Meal Tolerance Test Response in People with Type 1 Diabetes on Insulin Pump Therapy and YG1699 or Dapagliflozin

“…YG1699 is not intended to solve the DKA problem and should be viewed as a potential therapeutic option only in the setting of ketone monitoring. Some safety experience in Europe with dapagliflozin in T1D suggests that ketone monitoring can be implemented effectively, and the results of this study are of interest because continuous ketone monitoring devices may soon become an option in diabetes care 29,30 …”

“…Some safety experience in Europe with dapagliflozin in T1D suggests that ketone monitoring can be implemented effectively, and the results of this study are of interest because continuous ketone monitoring devices may soon become an option in diabetes care. 29,30 This study has some limitations, mainly the short exposure (1 week) and the small sample size. Safety results cannot be extrapolated to longer exposures, and the ability of YG1699 to produce normal post-prandial glucose values should not be generalized to T1D populations with much higher baseline A1C.…”

Hyperglycaemic crises in adults with diabetes: a consensus report

“…Compared with a laboratory measurement, the convenience of testing and rapidity of results from POCT can reduce the time for assessment, duration of admission and time to recovery from DKA [2,12,110]. A systematic review of nine studies on the accuracy of capillary β-hydroxybutyrate measurement for identifying DKA, compared with multiple other analytical and clinical tests, reported high sensitivity, specificity, and positive and negative predictive values [111]. However, there is concern about how accurate POCT instruments are compared with laboratory instruments for measuring β-hydroxybutyrate levels ≥5 mmol/l [108,112].…”

From Sweet to Sour: SGLT-2-Inhibitor-Induced Euglycemic Diabetic Ketoacidosis

“…Urine ketone measurements in patients taking SGLT-2 inhibitors may be misleading, which is why blood ketone testing is recommended in these cases [50]. A continuous ketone-monitoring technology that detects interstitial fluid β-hydroxybutyrate levels may also be a promising innovative solution for enabling the safer use of SGLT-2 inhibitors in high-risk patients or aiding in early EDKA detection during hospitalisation, perioperative periods, and during transitional care following hospital discharge [51,52].…”