Bone turnover markers during the remission phase in children and adolescents with type 1 diabetes

Abstract

Background and aim: In rodents, osteocalcin (OCN) stimulates insulin production and insulin sensitivity, both important factors during partial remission in humans with type 1 diabetes (T1D). However, decreased OCN has been reported in both adult and pediatric T1D. This study aims at investigating bone turnover and partial remission in children and adolescents with recent onset T1D.Subjects and methods: Ninety-nine individuals (33% girls) were recruited within 3 months of T1D onset and examined three times, 6 months apart. Outcome variables were bone formation markers OCN and procollagen type 1 amino-terminal propeptide (P1NP) and the bone resorption marker C-terminal crosslinked telopeptide of type 1 collagen (CTX). Dependent variables included IDAA1c (surrogate marker of partial remission), total body bone mineral density (BMD) and stimulated C-peptide as representative of endogenous insulin production.Results: OCN-and P1NP Z-scores were significantly decreased throughout the study, whereas CTX Z-scores were increased. None of the bone turnover markers changed significantly between visits. Total body BMD Z-score did not change during the study but was significantly higher than the reference population at visit 2 (P = .035). There were no differences in the bone turnover markers for those in partial remission as defined by either C-peptide or IDAA1c at any visit. The individual Abbreviations: BMD, Bone mineral density; BMI, Body mass index; CSII, Continuous subcutaneous insulin infusion; CTX, C-terminal crosslinked telopeptide of type 1 collagen; DXA, Dual-energy X-ray absorptiometry; fBG, fasting blood glucose; IDAA1c, Insulin dose-adjusted HbA1c; MDI, Multiple daily injections; MMTT, Mixed meal tolerance test; OCN, Osteocalcin; P1NP, Procollagen type 1 amino-terminal propeptide; SD, SD; T1D, Type 1 diabetes mellitus; T2D, Type 2 diabetes mellitus; TDD, Total daily insulin dose.

Differences in insulin sensitivity in the partial remission phase of childhood type 1 diabetes; a longitudinal cohort study

“…They had a total of 3 visits with 6 months apart. In‐ and exclusion criteria have been described previously 15 . Eighty‐two participants were included in the original cohort.…”

“…14 A previous study from our research group found an association between the bone marker C-terminal crosslinked telopeptide of type 1 collagen (CTX) and IDAA 1c in the partial remission phase and hypothesized a mechanism related to improved IS. 15 However, the research in this field is still limited.…”

“…In-and exclusion criteria have been described previously. 15 were included in the original cohort. In this study, we have included all participants that have completed at least one mixed meal tolerance test (MMTT) (n = 78).…”

“…Most studies of IS and T1D have focused on participants beyond the partial remission phase, but in 2020 Niedzwiecki et al addressed remission showing that adults who experienced partial remission had higher IS than non‐remitters seven years after diagnosis 14 . A previous study from our research group found an association between the bone marker C‐terminal crosslinked telopeptide of type 1 collagen (CTX) and IDAA 1c in the partial remission phase and hypothesized a mechanism related to improved IS 15 . However, the research in this field is still limited.…”

Diabetes and Bone Fragility

“…In a study of 99 pediatric patients recently diagnosed with T1D, BMD was unchanged over the first year after diagnosis [42]. Interestingly though, osteocalcin and P1NP (bone formation markers) decreased, while CTX (bone resorption marker) increased during the same period, revealing that bone turnover disturbances are present since very early stages of the disease.…”