The Reduced Insulinotropic Effect of a Continuous Infusion Relative to a Bolus Injection of GIP

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02673554
• Other study ID #: GIP and Tachyphylaxis
• Status: Completed
• Phase: Phase 1
• First received: January 28, 2016
• Last updated: February 1, 2016
• Start date: May 2004

Study information

• Verified date: February 2016
• Source: Diabeteszentrum Bad Lauterberg im Harz
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. primary completion date: December 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• GIP Bolus
bolus injections of synthetic human GIP (50 pmol/kg body weight) administered 30 and 120 min after commencing the hyperglycemic clamp
• 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)
• hyperglycemic clamp
a hyperglycemic clamp (capillary venous glucose concentration ~ 8.5 mmol/l)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Diabeteszentrum Bad Lauterberg im Harz

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin secretory response after GIP bolus or infusion.		210 minutes	No