Renal Handling of Ketones in Response to Sodium–Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes
OBJECTIVE Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes.
RESEARCH DESIGN AND METHODS We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min−1 · 1.73 m−2) and in control subjects without diabetes at baseline and following empagliflozin treatment.
RESULTS With chronic (4 weeks) sodium–glucose cotransporter 2 inhibition, baseline fractional glucose excretion (<2%) rose to 38 ± 12% and 46 ± 11% (fasting vs. postmeal, respectively; P < 0.0001) over a range of BMIs (range 23–41 kg/m2) and creatinine clearance (65–168 mL · min−1 · m−2). Excretion of β-HB (median [interquartile range]: 0.08 [0.10] to 0.31 [0.43] µmol · min−1), lactate (0.06 [0.06] to 0.28 [0.25] µmol · min−1), and sodium (0.27 [0.22] to 0.36 [0.16] mEq · min−1) all increased (P ≤ 0.001 for all) and were each positively related to glycosuria (P ≤ 0.001). These parameters changed in the same direction in subjects without diabetes, but changes were smaller than in the patients with diabetes. Although plasma N-terminal pro–B-type natriuretic peptide levels were unaltered, plasma erythropoietin c Continue reading