Maturity-Onset Diabetes of the Young, Type 3 Clinical Trial
Official title:
The Effect of GIP and GLP-1 on Insulin and Glucagon Secretion in Patients With HNF1A-diabetes Treated With or Without Sulphonylurea
The most prevalent monogenetic diabetic subtype is named maturity onset diabetes of the young type (MODY3) or hepatocyte nuclear factor 1α (HNF1A)-diabetes. The aim of this study is to evaluate the effects of supra-physiological levels of GIP and GLP-1, respectively, on insulin and glucagon secretion at fasting plasma glucose (FPG) and "post-prandial" PG levels (1.5 × FPG) in patients with HNF1A-diabetes and matched healthy controls treated with or without a low dose of glimepiride (sulphonylurea). In addition, we will evaluate the maximal insulin and glucagon secretory capacity in both groups.
A total of 6 experimental days will be performed. The following is an outline of an
experimental day:
Participants will meet after a 10-hour fast. A tablet of glimepiride 1.0 mg or placebo will
be administered 90 minutes before the initiation of the experiment (-90 minutes) The mean FPG
will be calculated from blood samples -105, -100 and -90 minutes. Two intravenous cannulas
will be inserted in a cubital vein of each arm. One intravenous cannula will be used for
infusions of glucose, arginine and GIP and the other will be used to collect venous blood.
The forearm from which blood samples are drawn will be placed in a heating pad (50°C)
throughout the experiment for arterialisation of venous blood.
At time 0 minutes, a glucose clamp will be established at the FPG level for 60 minutes and
hereafter a post-prandial clamp period of 1.5 × FPG for another 60 minutes. At time 120
minutes, a bolus of 5g of L-arginine (given as 50% arginine HCl) will be infused during 30
seconds. The post-prandial clamp will be maintained for another 10 minutes until time 130
minutes to prevent reactive hypoglycaemia. Throughout the experiment (0-130 minutes) a
continuous infusion of either GIP (1.5 pmol/kg/min), GLP-1 (0.5 pmol/kg/min) or placebo
(saline) will be administered.
During the experiment PG will be kept stable by a continuous 20%-glucose infusion. The rate
of infusion will be regulated according to PG determined by bed-site measurements every 5
minutes. After 60 minutes, a post-prandial clamp will be established by a bolus infusion over
one minute using 50%-glucose to target 1.5 × FPG (the amount of glucose to be administered
will calculated as follows: (1.5 × FPG - FPG) × 35 mg glucose × weight in kilogram).
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT05417646 -
Impact of SGLT2 on Glucosuria in HNF1A-MODY
|
N/A | |
| Enrolling by invitation |
NCT04239586 -
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|
Phase 4 |