Association between lncRNA H19 and osteoporosis in postmenopausal patients with type 2 diabetes mellitus

Abstract

Background: This study aimed to assess the expression level of long non-coding RNA H19 (lncRNA H19) in peripheral blood mononuclear cells (PBMCs) of postmenopausal patients with type 2 diabetes mellitus (T2DM) with comorbid osteoporosis (T2DM-OP), and to evaluate its diagnostic value and its role in the pathogenesis of T2DM-OP.

Methods: A total of 150 postmenopausal patients with T2DM were recruited from the First People's Hospital of Lianyungang City, China. Based on the bone mineral density (BMD) results measured by dual-energy X-ray absorptiometry (DXA), the patients were stratified into the T2DM-OP group (n = 108) and the T2DM group (n = 42). Clinical data and laboratory parameters were collected, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to quantitatively determine the expression of lncRNA H19 in PBMCs.

Results: When compared with the T2DM group, the expression level of lncRNA H19 in PBMCs of T2DM-OP patients was significantly lower (P < 0.001). The results of bivariate analysis revealed that lncRNA H19 was positively correlated with albumin (ALB, R = 0.311) and BMD (R = 0.696), while negatively correlated with age (R = -0.514), glycated hemoglobin A1c (HbA1c, R = -0.272), fasting blood glucose (FBG, R = -0.275), and transforming growth factor-β1 (TGF-β1, R = -0.392). All of these correlations were statistically significant (R < 0.001). Binary logistic regression analysis identified age, body mass index (BMI), HbA1c, TGF-β1, and lncRNA H19 as independent risk factors for T2DM-OP. Additionally, multiple linear regression analysis demonstrated that age, HbA1c, FBG, TGF-β1, and BMD were key determinants of the expression of lncRNA H19. Receiver operating characteristic (ROC) curve analysis indicated that lncRNA H19 had high diagnostic accuracy for postmenopausal T2DM-OP, with an area under the curve (AUC) of 0.833.

Conclusions: The expression level of lncRNA H19 in PBMCs of postmenopausal T2DM-OP patients was significantly reduced. This reduction could contribute to the pathogenesis of T2DM-OP through the regulation of modulating glucose metabolism and the lncRNA H19/TGF-β1 signaling pathway. Moreover, its expression level may serve as a highly promising non-invasive biomarker with high diagnostic accuracy for the early detection of postmenopausal T2DM-OP.

Trial registration: Retrospectively registered (ChiCTR2300074807).

Keywords: LncRNA H19; Osteoporosis; Peripheral blood mononuclear cells; Postmenopausal; TGF-β1; Type 2 diabetes mellitus.

Fig. 1

Differential expression of lncRNA H19 between the T2DM group and the T2DM-OP group visualized by box plots. Abbreviations: T2DM, type 2 diabetes mellitus; T2DM-OP, type 2 diabetes mellitus with comorbid osteoporosis; lncRNA H19, long non-coding RNA H19. Notes: The box represents the IQR (25th-75th percentiles) with a midline at the median. Whiskers extend to extreme values within 1.5×IQR. ****P < 0.0001

Fig. 2

Bivariate correlations between lncRNA H19 expression and other variables. Abbreviations: lncRNA H19, long non-coding RNA H19; ALB, albumin; HbA1c, glycated hemoglobin A1c; FBG, fasting blood glucose; BMD, bone mineral density; TGF-β1, transforming growth factor-β1

Fig. 3

ROC curve analysis: diagnostic performance of lncRNA H19 for T2DM-OP. Abbreviations: lncRNA H19, long non-coding RNA H19; AUC, area under the curve; CI, confidence interval; ROC, receiver operating characteristic