Maturity-Onset Diabetes of the Young, Type 3, Type 2 Diabetes
Conditions
Keywords
Sodium-Glucose Transporter 2, Sodium-Glucose Transporter 2 Inhibitors, Glycosuria
Brief summary
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.
Detailed description
Participants: Patients with HNF1A-MODY (n=12) and patients with T2D (n=12)
Interventions
OTHERHyperglycaemic clamp
Three-hour, three-step glucose clamp with plasma glucose targets 10, 14 and 18 mmol/l (each one hour)
DRUGPlacebo
Placebo comparator to empagliflozin
DRUGEmpagliflozin
Single-dose, 25 mg, two hours before clamp
Sponsors
University of Copenhagen
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Urinary glucose excretion | Assesed during 3 hour hyperglycaemic clamp |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infused amount of glucose | Assesed during 3 hour hyperglycaemic clamp | — |
| Urine volume | Assesed during 3 hour hyperglycaemic clamp | — |
| Glucose tissue disposal | Assesed during 3 hour hyperglycaemic clamp | difference between infused and excreted glucose |
| Urinary glucose excretion adjusted for glomerular filtration rate (GFR) | Assesed during 3 hour hyperglycaemic clamp | GFR: 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) plasma clearance |
| Concentration of plasma c-peptide | Assesed during 3 hour hyperglycaemic clamp | Summarized as area under the curve (AUC) |
| Concentration of plasma glucagon | Assesed during 3 hour hyperglycaemic clamp | Summarized as AUC |
| Renal threshold of glucose excretion | Assesed during 3 hour hyperglycaemic clamp | Estimated using plasma glucose concentrations, urinary glucose excretion and GFR |
| Urinary creatinine clearance | Assesed during 3 hour hyperglycaemic clamp | Urinary creatinine clearance calculated by plasma creatinine concentration and urinary creatinine excretion |
Countries
Denmark
Outcome results
None listed