S H Min1, T J Oh2, S-I Baek1, D-H Lee2, K M Kim2, J H Moon2, S H Choi2, K S Park1, H C Jang2, S Lim3. 1. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea. 2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam-city 463-070, South Korea. 3. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea; Department of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital, 300, Gumi-dong, Bundang-gu, Seongnam-city 463-070, South Korea. Electronic address: limsoo@snu.ac.kr.
Abstract
BACKGROUND: Euglycaemic ketoacidosis has been reported after sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. However, the degree of ketonaemia and its metabolic effects have not been well investigated. Our study examined the degree of ketonaemia induced by SGLT2 inhibition and its association with metabolic profiles in type 2 diabetes mellitus (T2DM). METHODS: Biochemical parameters, including insulin, glucagon, free fatty acid (FFA), β-hydroxybutyrate (BHB) and acetoacetate (ACA) levels, were measured in 119 T2DM patients after dapagliflozin treatment for>3 months, and compared with a matched control group. RESULTS: Levels of total ketones, BHB and ACA were significantly higher in the dapagliflozin group than in the control group: 283.7±311.0 vs 119.8±143.8μmol/L; 188.3±226.6 vs 78.0±106.7μmol/L; and 94.1±91.3 vs 41.8±39.1μmol/L, respectively (all P<0.001). After dapagliflozin treatment, BHB was higher than the upper limit of normal (>440μmol/L) in 13 (10.9%) patients who had no relevant symptoms. BHB level after dapagliflozin treatment correlated positively with HbA1c (r=0.280), FFA levels (r=0.596) and QUICKI (r=0.238), and negatively with BMI (r=-0.222), insulin-to-glucagon ratio (r=-0.199) and HOMA-IR (r=-0.205; all P<0.05). On multivariable linear regression analysis, QUICKI was independently associated with BHB level. CONCLUSION: Ketone levels were higher in T2DM patients treated with dapagliflozin than in controls, but with no clinical symptoms or signs of ketonaemia. Low-grade ketonaemia after dapagliflozin treatment may also be associated with improved insulin sensitivity.
BACKGROUND: Euglycaemic ketoacidosis has been reported after sodium-glucose cotransporter 2 (SGLT2) inhibitor treatment. However, the degree of ketonaemia and its metabolic effects have not been well investigated. Our study examined the degree of ketonaemia induced by SGLT2 inhibition and its association with metabolic profiles in type 2 diabetes mellitus (T2DM). METHODS: Biochemical parameters, including insulin, glucagon, free fatty acid (FFA), β-hydroxybutyrate (BHB) and acetoacetate (ACA) levels, were measured in 119 T2DM patients after dapagliflozin treatment for>3 months, and compared with a matched control group. RESULTS: Levels of total ketones, BHB and ACA were significantly higher in the dapagliflozin group than in the control group: 283.7±311.0 vs 119.8±143.8μmol/L; 188.3±226.6 vs 78.0±106.7μmol/L; and 94.1±91.3 vs 41.8±39.1μmol/L, respectively (all P<0.001). After dapagliflozin treatment, BHB was higher than the upper limit of normal (>440μmol/L) in 13 (10.9%) patients who had no relevant symptoms. BHB level after dapagliflozin treatment correlated positively with HbA1c (r=0.280), FFA levels (r=0.596) and QUICKI (r=0.238), and negatively with BMI (r=-0.222), insulin-to-glucagon ratio (r=-0.199) and HOMA-IR (r=-0.205; all P<0.05). On multivariable linear regression analysis, QUICKI was independently associated with BHB level. CONCLUSION:Ketone levels were higher in T2DM patients treated with dapagliflozin than in controls, but with no clinical symptoms or signs of ketonaemia. Low-grade ketonaemia after dapagliflozin treatment may also be associated with improved insulin sensitivity.
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