Diabetes Mellitus, Hyperglucagonemia, Hyperglycemia
Conditions
Brief summary
In order to evaluate the potential role of the gastrointestinal (GI) tract in the postprandial hyperglucagonemia, which characterizes type 1 diabetes mellitus (T1DM) (as well as type 2 diabetes mellitus (T2DM)), we wish to investigate the secretion of glucagon in patients with T1DM without residual beta-cell function during 50-g oral glucose tolerance test (OGTT) and during isoglycemic iv glucose infusion. By evaluating C-peptide negative patients with T1DM we aim to describe the glucagon response to glucose (+/-stimulation of the GI tract) independently of the potentially very important regulation of glucagon secretion by endogenous insulin secretion. A more detailed understanding of the inappropriate glucagon secretion in T1DM is highly needed in order to establish new intervention strategies in the future treatment of the growing numbers of T1DM patients.
Interventions
OTHEROral glucose tolerance test
50 g of waterfree glucose dissolved in 300 ml water is ingested over 5 minutes following a 10-h fast including liquids and medication (if any).
OTHERIsoglycemic iv glucose infusion
The plasma glucose curve obtained during a 50 g-OGTT (performed on a separate day) is copied using an adjustable iv glucose infusion (20% w/v) performed following a 10-h fast including liquids and medication (if any). The iv catheter is inserted into a peripheral vein in the hand/forearm.
Sponsors
University Hospital, Gentofte, Copenhagen
Study design
Observational model
CASE_CONTROL
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Caucasian over 18 years with T1DM (diagnosed according to WHO's criteria) treated with long-acting insulin * No residual beta-cell function (arginine test without increment in plasma C-peptide - see below) * BMI \<30 kg/m2 * Normal haemoglobin * Informed consent
Exclusion criteria
* Residual beta-cell function (increment in plasma C-peptide during arginine test - see below) * Known liver disease or affected liver enzymes (ALAT/ASAT \> 2 x upper normal limit) * Diabetic nephropathy (se-creatinin \> 130 µM and/or albuminuria) * Proliferative diabetic retinopathy (anamnestic) * Treatment with medication that cannot be discontinued for 14 hours
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Glucagon responses (as assessed by area under curve (AUC)) during 50-g oral glucose tolerance test (OGTT) and isoglycemic iv glucose infusion, respectively. | months |
Secondary
| Measure | Time frame |
|---|---|
| Responses of glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) as assessed by AUC during 50-g OGTT and isoglycemic iv glucose infusion, respectively. | months |
| GI-mediated glucose tolerance as assessed by the amount of glucose ingested as compared to the amount of glucose needed to mimic the OGTT curve during the iv glucose infusion. | Months |
Countries
Denmark
Outcome results
None listed