A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 dia
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ORIGINAL ARTICLE
A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1A-MODY than in type 2 diabetes mellitus J. Hohendorff1,2 M. Szopa1,2 J. Skupien1,2 M. Kapusta3 B. Zapala3 T. Platek3 S. Mrozinska1,2 T. Parpan4 W. Glodzik5 A. Ludwig-Galezowska6 B. Kiec-Wilk1,2 T. Klupa1,2 M. T. Malecki1,2 ●
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Received: 26 February 2017 / Accepted: 1 June 2017 © The Author(s) 2017. This article is an open access publication
Abstract Aims SGLT2 inhibitors are a new class of oral hypoglycemic agents used in type 2 diabetes (T2DM). Their effectiveness in maturity onset diabetes of the young (MODY) is unknown. We aimed to assess the response to a single dose of 10 mg dapagliflozin in patients with Hepatocyte Nuclear Factor 1 Alpha (HNF1A)-MODY, Glucokinase (GCK)-MODY, and type 2 diabetes. Methods We examined 14 HNF1A-MODY, 19 GCKMODY, and 12 type 2 diabetes patients. All studied individuals received a single morning dose of 10 mg of dapagliflozin added to their current therapy of diabetes. To assess the response to dapagliflozin we analyzed change in urinary glucose to creatinine ratio and serum 1,5-Anhydroglucitol (1,5-AG) level. Results There were only four patients with positive urine glucose before dapagliflozin administration (one with HNF1A-MODY, two with GCK-MODY, and one with T2DM), whereas after SGLT-2 inhibitor use, glycosuria
occurred in all studied participants. Considerable changes in mean glucose to creatinine ratio after dapagliflozin administration were observed in all three groups (20.51 ± 12.08, 23.19 ± 8.10, and 9.84 ± 6.68 mmol/mmol for HNF1AMODY, GCK-MODY, and T2DM, respectively, p < 0.001 for all comparisons). Post-hoc analysis revealed significant differences in mean glucose to creatinine ratio change between type 2 diabetes and each monogenic diabetes in response to dapagliflozin (p = 0.02, p = 0.003 for HNF1-A and GCK MODY, respectively), but not between the two MODY forms (p = 0.7231). Significant change in serum 1,5-AG was noticed only in T2DM and it was −6.57 ± 7.34 mg/ml (p = 0.04). Conclusions A single dose of dapagliflozin, an SGLT-2 inhibitor, induces higher glycosuria in GCK- and HNF1AMODY than in T2DM. Whether flozins are a valid therapeutic option in these forms of MODY requires long-term clinical studies. Keywords HNF1A GCK MODY SGLT2 Dapagliflozin ●
* M. T. Malecki [email protected] 1
Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, Poland
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Department of Metabolic Diseases, University Hospital, Krakow, Poland
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Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
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Brothers Hospitallers’ of St. John of God Hospital, Krakow, Poland
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Sanatio Medical Center, Krakow, Poland
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Center for Medical Genomics OMICRON, Jagiellonian University Medical College, Krakow, Poland
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Abbreviations 1,5-AG 1,5-Anhydroglucitol apo-M Apolipoprotein M BMI Body mass index CKD-EPI Chronic kidney disease epidemiology collaboration eGFR Estimated glomerular fi
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