The effect of hyperinsulinaemic-euglycaemic clamp and exercise on bone remodeling markers in obese men

Abstract

Bone remodelling markers (BRMs) are suppressed following a glucose load and during glucose infusion. As exercise increases indices of bone health and improves glucose handling, we hypothesised that, at rest, hyperinsulinaemiceuglycaemic clamp will suppress BRMs in obese men and that exercise prior to the clamp will prevent this suppression. Eleven obese nondiabetic men (age 58.1 ± 2.2 years, body mass index ¼ 33.1 ± 1.4 kg m À 2 mean ± s.e.m.) had a hyperinsulinaemic-euglycaemic clamp (HEC) at rest (Control) and 60 min post exercise (four bouts  4 min cycling at 95% of hazard ratio peak ). Blood samples were analysed for serum insulin, glucose, bone formation markers, total osteocalcin (tOC) and procollagen type 1 N-terminal propeptide (P1NP), and the bone resorption marker, b-isomerised C-terminal telopeptides (b-CTx). In the control trial (no exercise), tOC, P1NP and b-CTx decreased with HEC by 410% compared with baseline (Po0.05). Fasting serum glucose, but not insulin, tended to correlate negatively with the BRMs (b range À 0.57 to À 0.66, p range 0.051-0.087). b-CTx, but not OC or P1NP, increased within 60 min post exercise (B16%, Po0.01). During the post-exercise HEC, the glucose infusion rate was B30% higher compared with the no exercise trial. Despite this, BRMs were only suppressed to a similar extent as in the control session (10%). HEC suppressed BRMs in obese men. Exercise did not prevent this suppression of BRMs by HEC but improved glucose handling during the trial. It remains to be tested whether an exercise intervention of longer duration may be able to prevent the effect of HEC on bone remodelling.

Glucocorticoid-Induced Insulin Resistance in Men Is Associated With Suppressed Undercarboxylated Osteocalcin

“…The suppression of bone remodeling markers, including tOC, ucOC, P1NP, and β‐CTx, has previously been reported following nutrient intake such as an oral glucose tolerance test or a mixed meal or glucose infusion during an euglycemic‐hyperinsulinemic clamp . In support of previous findings, we report that tOC, ucOC, P1NP, and β‐CTx are suppressed in healthy men after insulin and glucose infusion, supporting the bidirectional feed‐forward loop between osteocalcin and glucose.…”

The influence of α-actinin-3 deficiency on bone remodelling markers in young men

“…Even a single bout of exercise can increase circulating levels of BRMs and ucOC, and can improve insulin sensitivity [6][7][8]. However, we, and others, have reported large individual variability for the changes in BRMs and ucOC in response to similar exercise [9,6,7,10,8,11]. Indeed, some individuals are 'low-responders' (do not increase some aerobicrelated traits in response to exercise training), while others respond well or very well ('highresponders') to similar exercise, and this is, at least partly, likely due to genetic variability [12].…”

Glucose Tolerance Tests and Osteocalcin Responses in Healthy People

“…Insulin infused at high, intermediate and low doses neither affected the level of undercarboxylated osteocalcin in participants with type 2 diabetes nor in healthy individuals ( 9 ). Furthermore, OGTT has previously been shown to decrease osteocalcin as well as undercarboxylated osteocalcin ( 10 , 11 ) and osteocalcin levels decreased during a hyperinsulinemic, euglycemic clamp in obese people ( 12 ). Antiresorptive therapies are hypothesized to increase undercarboxylated osteocalcin and thereby decrease diabetes incidence, however, in a post-hoc analysis of three randomized controlled trials the antiresorptive therapy did not affect fasting plasma glucose, weight loss, or diabetes risk ( 13 ).…”