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.

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