Type 2 Diabetes
Conditions
Keywords
Glucose-dependent Insulinotropic Polypeptide (GIP), Glucagon-Like Peptide 1 (GLP-1), Incretin, Insulin secretion, Tachyphylaxis
Brief summary
In patients with type 2 diabetes, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) has lost its insulinotropic activity, but more so after continuous versus bolus administration. The design was a two-way crossover design comparing repeated bolus injection and continuous infusion of GIP under hyperglycaemic clamp conditions. Patients were age- gender- and weight-matched with type 2 diabetes, first degree relatives of such patients, and healthy subjects. Investigators performed a: 1. Oral glucose challenge; 2. hyperglycemic clamp (8.5 mmol/l) with two repeated GIP bolus administrations (50 pmol/kg body weight at 30 and 120 min); and 3. hyperglycemic clamp with continuous administration of GIP (2 pmol.kg-1.min-1 from 30-180 min). To answer the question, whether rapid tachyphylaxis occurs with regard to the insulinotropic action of GIP, investigators studied type 2-diabetic patients, their first-degree relatives, and healthy controls under hyperglycaemic clamp conditions with two GIP bolus injections 90 min apart, and compared this to a continued intravenous infusion of GIP.
Interventions
DRUGGIP Bolus
bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp
DRUGGIP Clamp
hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min
PROCEDUREOral glucose tolerance test (OGTT)
an oral glucose challenge (75 g)
PROCEDUREhyperglycemic clamp
a hyperglycemic clamp (capillary venous glucose concentration \ 8.5 mmol/l)
Sponsors
Diabeteszentrum Bad Lauterberg im Harz
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Exclusion of pregnancy * Exclusion of impaired glucose tolerance or type 2 diabetes in metabolical healthy subjects * current diagnosis of type 2 diabetes according to the guidelines of the German Diabetes Association (DDG) ( Kerner et al . 2001) in subjects of diabetes group * fasting glucose ≤ 150 mg/dl * Body-mass-index ≥ 20 kg/m² * Written consent
Exclusion criteria
* Type 1 diabetes * Impaired glucose tolerance or Type 2 diabetes in metabolical healthy subjects * Ketone bodies urine diagnostics at least ++ * Acidosis * Fasting blood glucose \> 150 mg/dl * Body-mass-index \< 20 kg/m² * No written consent * Pregnancy or unsafe contraception in women before menopause * Active malignancy * Angina as current, unsolved clinical problem * Inadequately treated or untreated arterial hypertension ( \> 160 mmHg systolic and / or \> 95 mmHg diastolic ) * Infection / fever \> 37.5 ° C * Treatment with glucocorticoids * Insulin therapy within the last three months * Anemia with a hemoglobin level \< 12 g/dl * Liver function limitations * Renal impairment ( serum creatinine \> 1.5 mg/dl ) * Alcohol or drug abuse * Participation in clinical trials in the last 3 months * Inability or unwillingness to comply with the requirements of the Protocol * Known hypersensitivity to GIP
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Insulin secretory response after GIP bolus or infusion. | 210 minutes |
Outcome results
None listed