Abstract
Context
In healthy individuals, glucose-dependent insulinotropic polypeptide (GIP) enhances insulin secretion and reduces bone resorption by up to 25% estimated by absolute placebo-corrected changes in carboxy-terminal type 1 collagen crosslinks (CTX) during GIP and glucose administration. In patients with type 2 diabetes (T2D), GIP’s insulinotropic effect is impaired and effects on bone may be reduced.
Objective
To investigate GIP’s effect on bone biomarkers in patients with T2D.
Design
Randomized, double-blinded, crossover study investigating 6 interventions.
Patients
Twelve male patients with T2D.
Interventions
A primed continuous 90-minute GIP infusion (2 pmol/kg/min) or matching placebo (saline) administered at 3 plasma glucose (PG) levels (i.e., paired days with “insulin-induced hypoglycemia” (PG lowered to 3 mmol/L), “fasting hyperglycemia” (mean PG ~8 mmol/L), or “aggravated hyperglycemia” (mean PG ~12 mmol/L).
Main Outcome Measures
Bone biomarkers: CTX, procollagen type 1 N-terminal propeptide (P1NP) and PTH.
Results
On days with insulin-induced hypoglycemia, CTX was suppressed by up to 40 ± 15% during GIP administration compared with 12 ± 11% during placebo infusion (P < 0.0001). On days with fasting hyperglycemia, CTX was suppressed by up to 36 ± 15% during GIP administration, compared with 0 ± 9% during placebo infusion (P < 0.0001). On days with aggravated hyperglycemia, CTX was suppressed by up to 47 ± 23% during GIP administration compared with 10 ± 9% during placebo infusion (P = 0.0005). At all glycemic levels, P1NP and PTH concentrations were similar between paired days after 90 minutes.
Conclusions
Short-term GIP infusions reduce bone resorption by more than one-third (estimated by absolute placebo-corrected CTX reductions) in patients with T2DM, suggesting preserved bone effects of GIP in these patients.
Précis
Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels.
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