Serum sclerostin and glucose homeostasis: No association in healthy men. Cross-sectional and prospective data from the EGIR-RISC study

Bone. 2021 Feb:143:115681. doi: 10.1016/j.bone.2020.115681. Epub 2020 Oct 7.

Abstract

Introduction: Sclerostin, an inhibitor of bone formation, has emerged as a potential negative regulator of glucose homeostasis. We aimed to investigate if serum sclerostin associates with insulin sensitivity, beta cell function, prediabetes or metabolic syndrome in healthy men.

Materials and methods: Serum sclerostin was measured in basal and insulin-stimulated samples from 526 men without diabetes from the RISC cohort study. An OGTT was performed at baseline and after 3 years. An IVGTT and a hyperinsulinaemic-euglycaemic clamp were performed at baseline. Insulin sensitivity was estimated by the oral glucose sensitivity index (OGIS) and the M-value relative to insulin levels. Beta cell function was assessed by the acute and total insulin secretion (ISRtot) and by beta cell glucose sensitivity.

Results: Serum sclerostin levels correlated positively with age but were similar in individuals with (n = 69) and without (n = 457) prediabetes or the metabolic syndrome. Serum sclerostin was associated with measures of neither insulin sensitivity nor beta cell function at baseline in age-adjusted analyses including all participants. However, baseline serum sclerostin correlated inversely with OGIS at follow-up in men without prediabetes (B: -0.29 (-0.57, -0.01) p = 0.045), and inversely with beta cell glucose sensitivity in men with prediabetes (B: -13.3 (-26.3, -0.2) p = 0.046). Associations between serum sclerostin and 3-year changes in measures of glucose homeostasis were not observed. Acute hyperinsulinemia suppressed serum sclerostin (p = 0.02), and this reduction correlated with OGIS and ISRtot.

Conclusions: Overall, serum sclerostin was not associated with prediabetes, insulin sensitivity or insulin secretion in healthy men. The inverse relationship between serum sclerostin and insulin sensitivity at follow-up was weak and likely not of clinical relevance. The ability of insulin to reduce sclerostin, possibly promoting bone formation, needs to be clarified.

Keywords: Bone-glucose interactions; Insulin secretion; Insulin sensitivity; Prediabetes; Sclerostin; Wnt/β-catenin/LRP5.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Glucose*
  • Cohort Studies
  • Cross-Sectional Studies
  • Glucose
  • Glucose Tolerance Test
  • Homeostasis
  • Humans
  • Insulin
  • Insulin Resistance*
  • Male
  • Prospective Studies

Substances

  • Blood Glucose
  • Insulin
  • Glucose