Response to the Letter: Comment to letter by Segar L.

Dr Segar's letter cites relevant papers from the literature, which may be of interest to the readership of JCEM. We have two specific comments:

Dr Segar's letter cites relevant papers from the literature, which may be of interest to the readership of the Journal of Clinical Endocrinology and Metabolism. We have two specific comments. First, Dr Segar states that there is no tubular maximum for ketone bodies, suggesting that ketone body transporters do not become saturated under physiological conditions. This represents an oversimplification of the data in the literature. Indeed, in the paper by Owen et al (1) cited as reference 5 in the letter, the data suggest that there are two ketone body transport systems: a high-affinity/low-capacity transporter that becomes saturated at a blood β-hydroxybutyrate concentration of approximately 2 mmol/L; and a low-affinity/high-capacity transporter that does not appear to become saturated at physiologically relevant concentrations of ketone bodies. In any case, published data provide evidence that renal clearance of ketone bodies increases (and fractional reabsorption of ketone bodies decreases) when blood ketone body levels increase. Similar conclusions have been reached based on data from patients with diabetic ketoacidosis or with starvation ketosis.

Second, Dr Segar cites American Diabetes Association guidelines to the effect that physicians should be measuring ketonemia rather than ketonuria. We certainly agree that this would be ideal. However, recent publications (eg, Peters et al, Diabetes Care, 2015) have recommended that ketonuria is an appropriate approach to monitoring sodium-glucose cotransporter-2 inhibitor-treated patients. Accordingly, it is useful to educate physicians and patients that sodium-glucose cotransporter-2 inhibitors may decrease renal excretion of ketone bodies, thus, rendering measurements of ketonuria even less useful than in other causes of ketosis/ketoacidosis.

Disclosure Summary: S.I.T. was previously employed by and currently owns stock in Bristol-Myers Squibb Company, and has served as a paid consultant or advisor for Aegerion Pharmaceuticals, Agios Pharmaceuticals, Calibrium, and Isis Pharmaceuticals. J.E.B. and K.I.R. declare no competing interests.

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