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

Diabeteszentrum Bad Lauterberg im Harz

Status and phase: Completed; Phase 1

Conditions: Type 2 Diabetes

Treatments: Procedure: Oral glucose tolerance test (OGTT); Drug: GIP Bolus; Drug: GIP Clamp; Procedure: hyperglycemic clamp

Study type: Interventional

Funder types: Other

Identifiers

NCT02673554

GIP and Tachyphylaxis

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

Oral glucose tolerance test

Experimental group

Description:

An oral glucose challenge (75 g)

Treatment:

Procedure: Oral glucose tolerance test (OGTT)

GIP Bolus

Active Comparator group

Description:

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

Treatment:

Drug: GIP Bolus

Procedure: hyperglycemic clamp

GIP Infusion

Active Comparator group

Description:

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

Treatment:

Drug: GIP Clamp

Procedure: hyperglycemic clamp