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Observational Study
. 2023 Mar 30;24(7):6474.
doi: 10.3390/ijms24076474.

Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes

Sara Dule  1 , Ilaria Barchetta  1 , Flavia Agata Cimini  1 , Giulia Passarella  1 , Arianna Dellanno  1 , Tiziana Filardi  1 , Vittorio Venditti  1 , Enrico Bleve  1 , Diego Bailetti  2 , Elisabetta Romagnoli  1 , Susanna Morano  1 , Marco Giorgio Baroni  2   3 , Maria Gisella Cavallo  1
Affiliations
Observational Study

Reduced High-Density Lipoprotein Cholesterol Is an Independent Determinant of Altered Bone Quality in Women with Type 2 Diabetes

Sara Dule et al. Int J Mol Sci. .

Abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased fracture risk. Our study aimed to explore differences in bone alterations between T2DM women and controls and to assess clinical predictors of bone impairment in T2DM. For this observational case control study, we recruited 126 T2DM female patients and 117 non-diabetic, age- and BMI-comparable women, who underwent clinical examination, routine biochemistry and dual-energy X-ray absorptiometry (DXA) scans for bone mineral density (BMD) and trabecular bone score (TBS) assessment-derived indexes. These were correlated to metabolic parameters, such as glycemic control and lipid profile, by bivariate analyses, and significant variables were entered in multivariate adjusted models to detect independent determinants of altered bone status in diabetes. The T2DM patients were less represented in the normal bone category compared with controls (5% vs. 12%; p = 0.04); T2DM was associated with low TBS (OR: 2.47, C.I. 95%: 1.19-5.16, p = 0.016) in a regression model adjusted for age, menopausal status and BMI. In women with T2DM, TBS directly correlated with plasma high-density lipoprotein cholesterol (HDL-c) (p = 0.029) and vitamin D (p = 0.017) levels. An inverse association was observed with menopausal status (p < 0.001), metabolic syndrome (p = 0.014), BMI (p = 0.005), and waist circumference (p < 0.001). In the multivariate regression analysis, lower HDL-c represented the main predictor of altered bone quality in T2DM, regardless of age, menopausal status, BMI, waist circumference, statin treatment, physical activity, and vitamin D (p = 0.029; R2 = 0.47), which likely underlies common pathways between metabolic disease and bone health in diabetes.

Keywords: fracture risk; insulin resistance; lipid metabolism; metabolic syndrome; osteopenia; osteoporosis; trabecular bone score.

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Conflict of interest statement

The authors declare no conflict of interest. The funder had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
CONSORT flow-chart of the study. Abbreviations: BMI: body mass index, HbA1c: glycosylated hemoglobin.
Figure 2
Figure 2
Molecular mechanisms that link low HDL-c levels to bone alterations. For full description, see text. Abbreviations: HDL: high-density lipoprotein cholesterol; APC: antigen presenting cell; MSC: multipotent mesenchymal stem cell.
See this image and copyright information in PMC

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