Clinical trial NCT02673554: The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of GIP
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Glucose-dependent Insulinotropic Polypeptide (GIP)
Glucagon-Like Peptide 1 (GLP-1)
Incretin
Insulin secretion
Tachyphylaxis
Lead sponsor: Diabeteszentrum Bad Lauterberg im Harz
Sponsor class: OTHER
First posted: 2016-02-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Insulin secretory response after GIP bolus or infusion.
timeFrame: 210 minutes
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Diabeteszentrum Bad Lauterberg
name: Michael A. Nauck, Prof.
role: PRINCIPAL_INVESTIGATOR
References: