TY - JOUR

T1 - Glucose-Dependent Insulinotropic Polypeptide (GIP) Reduces Bone Resorption in Patients With Type 2 Diabetes

AU - Christensen, Mikkel B.

AU - Lund, Asger B.

AU - Jørgensen, Niklas R.

AU - Holst, Jens J.

AU - Vilsbøll, Tina

AU - Knop, Filip K.

PY - 2020

Y1 - 2020

N2 - 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 pmollkg/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 similar to 8 mmol/L), or "aggravated hyperglycemia" (mean PG similar to 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 PHI 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.Precis: Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels. (C) Endocrine Society 2020.

AB - 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 pmollkg/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 similar to 8 mmol/L), or "aggravated hyperglycemia" (mean PG similar to 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 PHI 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.Precis: Short-term GIP infusions reduce the bone resorption marker CTX by one-third in patients with type 2 diabetes independent of glycemic levels. (C) Endocrine Society 2020.

KW - Gastric inhibitory polypeptide

KW - glucose-dependent insulinotropic polypeptide (GIP)

KW - bone markers

KW - procollagen type 1 N-terminal propeptide (P1NP)

KW - carboxy-terminal collagen type 1 crosslinks (CTX)

KW - PEPTIDE

KW - SECRETION

KW - TURNOVER

KW - GLUCAGON

U2 - 10.1210/jendso/bvaa097

DO - 10.1210/jendso/bvaa097

M3 - Journal article

C2 - 32904711

VL - 4

JO - Journal of the endocrine society

JF - Journal of the endocrine society

SN - 2472-1972

IS - 9

M1 - 097

ER -