Impact of SGLT2 on Glucosuria in HNF1A-MODY

H-21066984

Maturity onset diabetes of the young (MODY) is a subtype of diabetes which is caused by mutations in specific genes leading to diabetes. The most common cause of MODY is due to mutations in the gene hepatocyte nuclear factor 1 alpha (HNF1A) and is consequently named HNF1A-MODY (or MODY3). HNF1A-MODY is associated with urinary excretion of glucose at lower blood glucose levels compared to other types of diabetes. Normally, glucose is reabsorbed by sodium-glucose cotransporter 2 (SGLT2), but SGLT2 is downregulated due to the mutation in HNF1A. Investigators aim to evaluate the impact of the decreased expression of SGLT2 on glucosuria in patients with HNF1A-MODY compared to patients with type 2 diabetes (T2D) using a single dose of an SGLT2 inhibitor during a glucose clamp experiment.

2022-06-22

2023-06-14

2023-06-14

Completed

21

Inclusion Criteria: * Age ≥18 years * HNF1A-MODY verified by genetic testing (only patients with HNF1A-MODY) * Type 2 diabetes diagnosis according to World Health Organization (only patients with type 2 diabetes) * Treatment with diet and/or a glucose-lowering drug (only patients with HNF1A-MODY) * Normal haemoglobin (males 8.3-10.5 mmol/l, females 7.3-9.5 mmol/l) * Informed consent Exclusion Criteria: * Nephropathy (estimated GFR \<60 ml/min/1.73m2 and/or albuminuria) * Known significant liver disease and/or plasma alanine aminotransferase (ALT) and/or plasma aspartate aminotransferase (AST) above 2 × normal values) * Pregnancy or breastfeeding * Treatment with SGLT2 inhibitor * Fasting plasma glucose \> 10 mmol/l * Family history of HNF1A-MODY (only patients with type 2 diabetes)

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2023-07-27