Trial | NCT02673554  Report issue

Title

The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of GIP
The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of Glucose-dependent Insulinotropic Polypeptide (GIP) in Patients With Type 2 Diabetes is Not Caused by Rapid Tachyphylaxis

  • Phase

    Phase 1

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    30
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:

Oral glucose challenge;
hyperglycemic clamp (8.5 mmol/l) with two repeated GIP bolus administrations (50 pmol/kg body weight at 30 and 120 min); and
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.
Study Started
May 31
2004
Primary Completion
Dec 31
2008
Last Update
Feb 04
2016
Estimate

Drug GIP Bolus

bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp

Drug GIP Clamp

hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min

Procedure Oral glucose tolerance test (OGTT)

an oral glucose challenge (75 g)

Procedure hyperglycemic clamp

a hyperglycemic clamp (capillary venous glucose concentration ~ 8.5 mmol/l)

Oral glucose tolerance test Experimental

An oral glucose challenge (75 g)

GIP Bolus Active Comparator

Hyperglycemic clamp (capillary venous glucose concentration ~ 8.5 mmol/l) with two repeated intravenous bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp

GIP Infusion Active Comparator

Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min

Criteria 

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
No Results Posted