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

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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

GIP Bolus

Drug

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

GIP Clamp

Drug

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 (OGTT)

Procedure

an oral glucose challenge (75 g)

Hyperglycemic clamp

Procedure

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

Primary outcomes

Insulin secretory response after GIP bolus or infusion.

Time frame: 210 minutes

Sponsors and collaborators

Lead sponsor

Diabeteszentrum Bad Lauterberg im Harz

Other

Registry information

Official study 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

Important dates

Study start: 2004
Primary completion: 2008
First posted: Feb 4, 2016
Registry last updated: Feb 4, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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