ODP101 In Men with Type 2 Diabetes Mellitus, Poor Glycemic Control is Associated with Diminished Circulating Osteoblast Progenitors

BACKGROUND: An emerging field of research concerns the deleterious effects of type 2 diabetes mellitus (T2DM) on bone. Our group has previously reported a hemoglobin A1c (A1c) threshold of 7% where bone impairment occurs as reflected by reduction in bone turnover markers and deterioration in bone microarchitecture and strength. However, whether poor glycemic control is also associated with underlying derangements in cellular flux remains unclear. METHODS: Analysis of the baseline data from 42 consecutive men aged 35-65 enrolled in a clinical trial (NCT03887936) at the Michael E DeBakey VA Medical Center, Houston, TX, who were able to provide the outcomes of interest. Inclusion criteria were average fasting morning testosterone from 2 measurements of <300 ng/dl, T2DM and BMI<35 kg/m2. The following variables were assessed: A1c by high performance liquid chromatography; testosterone and estradiol by LC/MS; bone turnover markers and sex hormone binding globulin by ELISA; quantification of osteoblast (OB) progenitors and osteoclast (OC) precursors by flow cytometry; areal bone mineral density (aBMD) and body composition by DXA; and bone microarchitecture and strength by high resolution peripheral quantitative computerized tomography. RESULTS: Participants with poorly controlled T2DM (A1c>7%) had significantly lower percent of OB progenitors in circulation than those with A1c≤7% (1.12 ± 0. 079% v 1.47 ± 0.11% of non-B non-T non-NK cells, p=0. 02) when controlling for age, duration of T2DM, free testosterone, and 25-hydroxyvitamin D levels. Higher levels of free testosterone were associated with smaller percentage of OB progenitors (r = -0.31, p = 0. 05). Although the percent of OC precursors in circulation (cells that were dual CD14CD11b+, CD14MCSFR+, or CD14CD120b+) was not significantly related to A1c, it was positively associated with percent of OB progenitors in peripheral blood (r = 0.34, p = 0. 03; r = 0.35, p = 0. 02; r = 0.39, p = 0. 01) respectively. There was a significant positive association between OB progenitors and visceral adipose tissue (VAT) volume (r=0.41, p=0. 009). Although there was no association between osteoblast progenitors and osteocalcin levels (product of mature OBs), osteocalcin negatively correlated with VAT (r=-0.47, p=0. 002). There was no association between OB progenitors and OC precursors with aBMD or bone microarchitecture parameters. CONCLUSIONS: Poor glycemic control is associated with fewer circulating OB progenitors, as was higher free testosterone levels while the converse was true for VAT. It is possible that the former harms cell viability, while the latter two affect differentiation of OB progenitors into mature OB's; with testosterone promoting, and visceral adipose tissue (via unknown mediators) retarding maturation as suggested by the negative association between osteocalcin and VAT. The positive association between OB progenitors with circulating OC precursors is consistent with the physiologic crosstalk between OB and OC which appears to be preserved in patients with T2D. Presentation: No date and time listed