Context: The gut hormone glucose-dependent insulinotropic polypeptide (GIP) causes postprandial insulin release and inhibits bone resorption assessed by carboxy-terminal collagen crosslinks (CTX).

Objective: To study if GIP affects bone homeostasis biomarkers independently of insulin release and glycemic level.

Design: Randomized, double-blinded, crossover study with 5 study days.

Patients: Ten male C-peptide-negative patients with type 1 diabetes.

Interventions: On 3 matched days with "low glycemia" (plasma glucose in the interval 3 to 7 mmol/L for 120 minutes), we administered intravenous (IV) GIP (4 pmol × kg-1 × min-1), glucagon-like peptide 1 (1 pmol × kg-1 × min-1), or placebo (saline), and on 2 matched days with "high glycemia" (plasma glucose 12 mmol/L for 90 minutes), we administered either GIP or saline.

Main Outcome Measures: CTX, procollagen type 1 N-terminal propeptide (P1NP), and parathyroid hormone (PTH).

Results: During low glycemia: GIP progressively suppressed CTX from baseline by up to 59 ± 18% compared with 24 ± 10% during saline infusion (P < 0.0001). Absolute values of P1NP and PTH did not differ between days. During high glycemia: GIP suppressed CTX from baseline by up to 59 ± 19% compared with 7 ± 9% during saline infusion (P < 0.0001). P1NP did not differ between days. GIP suppressed PTH after 60 minutes compared with saline (P < 0.01), but this difference disappeared after 90 minutes.

Conclusions: Short-term GIP infusions robustly reduce bone resorption independently of endogenous insulin secretion and during both elevated and low plasma glucose, but have no effect on P1NP or PTH after 90 minutes.