Consumption of nutrients and insulin resistance suppress markers of bone turnover in subjects with abdominal obesity

Fuglsang-Nielsen, Rasmus; Rakvaag, Elin; Vestergaard, Peter; Hartmann, Bolette; Holst, Jens Juul; Hermansen, Kjeld; Gregersen, Søren; Starup-Linde, Jakob

Affiliations

¹Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark

²Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark

³Steno Diabetes Center North Jutland, Aalborg University Hospital, Denmark

⁴Department of Endocrinology, Aalborg University Hospital, Denmark

⁵Department of Clinical Medicine, Aalborg University, Denmark

⁶Department of Biomedical Sciences and NNF Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Abstract and keywords

Objective: Abdominal obesity and type 2 diabetes are associated with insulin resistance and low bone turnover along with an increased fracture risk. The mode of action is poorly understood. The bone resorption marker, C-terminal telopeptide type 1 collagen (CTX), and to a lesser extent, the bone formation marker, Procollagen type 1 N-terminal propeptide (P1NP) appear to be inhibited by food consumption. The link between food consumption, insulin resistance and bone turnover remains to be clarified.

Primarily we aimed to compare the postprandial CTX, P1NP and PTH responses by two frequently applied methods in assessing metabolic health; oral glucose tolerance test (OGTT) and mixed meal tolerance test. Secondly, we explored the effect of insulin resistance on bone marker responses.

Methods: We enrolled 64 subjects with abdominal obesity. Following 10 h of fasting, subjects initially underwent a standard OGTT (300 kcal) and approximately one week later a mixed meal tolerance test (1130 kcal). Circulating CTX, P1NP and PTH were assessed on both days at time = 0, after 30 min and after 90 min for comparison of the two interventions. We analyzed glucose and insulin levels for the assessment of insulin resistance. Additionally, we measured plasma calcium levels along with the gut hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 2 (GLP-2) in an attempt to identify possible mediators of the postprandial bone response.

Results: CTX, P1NP and PTH were suppressed by OGTT and the mixed meal; the latter induced a more pronounced suppression after 90 min. Calcium levels were similar between OGTT and meal. GIP and GLP-2 levels increased after both interventions, although only the meal induced a sustained increase after 90 min. Fasting P1NP was inversely associated with insulin resistance. The meal-induced suppression of P1NP (but not CTX or PTH) was inversely associated with level of insulin resistance.

Conclusion: The acute postprandial suppression of bone turnover markers is extended after ingestion of a mixed meal compared to an OGTT. The response appears to be independent of gender and prompted by a reduction in PTH. The study additionally indicates a possible link between the development of insulin resistance and low bone turnover — which may be of key essence in the development of the fragile bone structure and increased fracture risk demonstrated in subjects with abdominal obesity and T2D.

Keywords: Bone turnover; Bone markers; Meal; OGTT; Insulin resistance; CTX; C-terminal cross-linked telopeptide of type-I collagen; P1NP; procollagen type 1 N-terminal propeptide; T2D; type 2 diabetes; OGTT; oral glucose tolerance test; PTH; parathyroid hormone; BMD; bone mineral density; IR; insulin resistance; NIS; normal insulin sensitivity; MIR; moderate insulin resistance; HIR; high insulin resistance; GIP; glucose-dependent insulinotropic polypeptide; GLP-2; glucagon-like peptide-2; 25-OH Vit D; 25-hydroxyvitamin D

Links

DOI: 10.1016/j.bone.2020.115230

PubMed: 31954199

WoS: 000517355400011

History

Received: 2019-09-20

Revised: 2020-01-13

Accepted: 2020-01-13

Online: 2020-01-15

Cited Works (1)

Year	Entry
2015	Evans AL, Paggiosi MA, Eastell R, Walsh JS. Bone density, microstructure and strength in obese and normal weight men and women in younger and older adulthood. J Bone Miner Res. May 2015;30(5):920-928.

Cited By (2)

Year	Entry
2021	Abildgaard J, Ploug T, Pedersen AT, Eiken P, Pedersen BK, Holst JJ, Hartmann B, Lindegaard B. Preserved postprandial suppression of bone turnover markers, despite increased fasting levels, in postmenopausal women. Bone. February 2021;143:115612.
2023	Zahedi B, Daley EJ, Brooks DJ, Bruce M, Townsend RL, Berthoud H-R, Bouxsein ML, Yu EW. The PYY/Y2R-deficient male mouse is not protected from bone loss due to Roux-en-Y gastric bypass. Bone. February 2023;167:116608.