Diabetes Mellitus, Type 1
Conditions
Keywords
Diabetes Mellitus, Type 1, Hypoglycemia, Gastric Inhibitory Polypeptide, Glucagon, Incretin
Brief summary
In the present project the investigators will evaluate whether glucagonotropic properties of the gut-derived incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may be utilized as a safeguard against hypoglycemia in patients with T1D.
Interventions
DRUGglucose-dependent insulinotropic peptide
Infusion of GIP
DRUGGlucose-Dependent Insulin-Releasing Hormone[3-30]
Infusion of GIP antagonist GIP\[3-30\]
DRUGSaline Solution
Infusion of Saline
Sponsors
Steno Diabetes Center Copenhagen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
The peptides/placebo is prepared, in a randomized fashion, by a laboratory assistant..
Intervention model description
Double blinded, randomized, cross-over study
Eligibility
Sex/Gender
MALE
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Caucasian men * Body mass index between 20-27 kg/m\^2 * T1D (diagnosed according to the criteria of the World Health Organization) with HbA1c\<69 mmol/l (\<8,5%) * T1D duration between 2-20 years * Stimulated C-peptide ≤ 100 pmol/mL) * Treatment with a stable basal bolus or insulin pump regimen ≥ 3 months * Informed consent
Exclusion criteria
* Anemia (hemoglobin below normal range) * Liver disease (ALAT and/or ASAT \>2 times normal values) or history of hepatobiliary disorder * Nephropathy (serum creatinine above normal range and/or albuminuria) * Allergy or intolerance to ingredients included in the standardized meals * Prior myocardial infarction or other cardiac events * Any physical or psychological condition that the investigator fells would interfere with trial participation * Treatment with any glucose-lowering drugs beside insulin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| plasma glucose concentration | At times (minute): - 30, - 15, 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180, 195, 210, 225, 240 on study days | plasma glucose excursions and plasma glucose nadir |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incretin hormones | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Incretin hormones GLP-1 and GIP. Incremental and total area under the Concentration-Time Curve |
| GIP[3-30] | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | GIP\[3-30\]. Incremental and total area under the Concentration-Time Curve |
| Free fatty acids (FFA) | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Free fatty acids(FFA). Incremental and total area under the Concentration-Time Curve |
| Blood analysis of paracetamol as an assessment of gastric emptying | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Assessment of gastric emptying |
| Fat mRNA | At time 240 minute on study days | Fat biopsy to evaluate changes in fat mRNA |
| Fat Lipoprotein lipase (LPL) | At time 240 minute on study days | Fat biopsy to evaluate LPL changes in fat |
| Glucose regulatory hormones | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Counter regulatory hormones: glucagon, noradrenalin, cortisol, somatotropin, and insulin/c-peptide. Incremental and total area under the Concentration-Time Curve |
| Fat Fatty acid binding protein 4 (FABP4) | At time 240 minute on study days | Fat biopsy to evaluate Fatty acid binding protein 4 (FABP4) changes in fat |
| Fat Hormonse-sensitive lipase (HSL) | At time 240 minute on study days | Fat biopsy to evaluate Hormonse-sensitive lipase (HSL) changes in fat |
| Fat Vascular endothelial growth factor 4 (VEGF-A) | At time 240 minute on study days | Fat biopsy to evaluate Vascular endothelial growth factor 4 (VEGF-A) changes in fat |
| Fat GIP receptor (GIPR) | At time 240 minute on study days | Fat biopsy to evaluate GIP receptor (GIPR) changes in fat |
| Blood pressure | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Changes in blood pressure, mm Hg |
| Pulse | At times (minute): - 30, 0, 15, 30, 60, 90, 120, 150, 180, 210, 240 on study days | Changes in pulse, beats per minute |
| Fat Perilipin 4 | At time 240 minute on study days | Fat biopsy to evaluate Perilipin 4 changes in fat |
Countries
Denmark
Outcome results
None listed