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

Phase 1

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: GIP Clamp; Procedure: Oral glucose tolerance test (OGTT); Drug: GIP Bolus; Procedure: hyperglycemic clamp

• Registration Number: NCT02673554
• Lead Sponsor: Diabeteszentrum Bad Lauterberg im Harz

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2004-05
• Primary Completion: 2008-12
• Study First Submitted: 2016-01-28
• Status Verified: 2016-02
• Study First Submitted QC: 2016-02-01
• Last Update Submitted: 2016-02-01
• Study First Posted: 2016-02-04
• Last Update Posted: 2016-02-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
GIP Infusion	GIP Clamp	Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min
GIP Infusion	hyperglycemic clamp	Hyperglycemic clamp with the continuous intravenous infusion of 2 pmol.kg-1.min-1 synthetic human GIP between 30 and 180 min
Oral glucose tolerance test	Oral glucose tolerance test (OGTT)	An oral glucose challenge (75 g)
GIP Bolus	hyperglycemic clamp	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 Bolus	GIP Bolus	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

Primary Outcome Measures

Name	Time	Method
Insulin secretory response after GIP bolus or infusion.	210 minutes