Glucose-dependent Insulinotropic Polypeptide: Blood Glucose Stabilizing Effects in Patients with Type 2 diabetes

Context. Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). Objective. To evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses of glucagon and insulin and glucose disposal in patients with T2DM. Design. A placebo-controlled, cross-over, experimental study. Settings. Copenhagen University hospital Gentofte. Patients. Twelve patients with T2DM (age: 62±1 years (mean±SEM), BMI: 29±1 kg/m(2); HbA1c: 6.5±0.1% (48±2 mmol/mol)). Intervention. Iv infusions of physiological amounts of GIP (2 pmol×kg(-1)×min(-1)) or saline. Main Outcome Measures. Plasma concentrations of glucagon, glucose, insulin, C-peptide, intact GIP and amounts of glucose needed to maintain glucose clamps. Results. During fasting glycemia (plasma glucose ∼8 mmol/l), GIP elicited significant increments in both insulin and glucagon levels resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/l), GIP elicited a minor early-phase insulin response and increased glucagon levels during the initial 30 minutes resulting in less glucose needed to be infused to maintain the clamp (29±8 vs. 49±12 mg×kg(-1), p