Association between glycosylated hemoglobin A1c and bone biochemical markers in type 2 diabetic postmenopausal women: a cross-sectional study

Abstract

Background: type 2 diabetes mellitus (T2DM) is a complicated disease that can affect bone health, but the change in bone biochemical markers caused by T2DM was controversial, so the aim of this study was to investigate whether there was a discrepancy in the levels of bone biochemical markers between postmenopausal women with T2DM and non-diabetic women and to explore the relationship between the level of glycosylated hemoglobin A1c (HbA1c) and bone biochemical markers in these subjects.

Methods: A total of 237 type 2 diabetic postmenopausal women visiting the First Affiliated Hospital of Anhui Medical University from January 2017 to October 2018 and 93 healthy postmenopausal women were retrospectively enrolled. The differences in the levels of bone biochemical markers between patients and controls were analyzed by one-way ANOVA or chi-square test. The relationship between HbA1c and bone biochemical markers was analyzed by multivariate regression, forest plot and fitted curve.

Results: Bone formation markers including N-MID osteocalcin and procollagen type 1 amino-terminal pro-peptide (PINP) were decreased in postmenopausal women with T2DM compared to controls (17.42 ± 9.50 vs 23.67 ± 7.58, p < 0.001; 48.47 ± 27.27 vs 65.86 ± 21.06, p < 0.001, respectively), but the bone resorption markers β-crossLaps (β-CTX) was no difference between the two groups (0.57 ± 0.28 vs 0.55 ± 0.21, p = 0.868). Multivariate regression showed that HbA1c was inversely associated with N-MID osteocalcin and PINP after adjusting for age, BMI, menopause^'s years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR. The adjusted coefficients for N-MID osteocalcin and PINP per 1% HbA1c decrease were - 0.71 (- 1.19, - 0.22) and - 1.79 (- 3.30, - 0.28), respectively. A segmentation effect was seen in the fitted curve between HbA1c and β-CTX with an inflection point at 7.4% of HbA1c, the highest quartile of β-CTX (> = 0.74 ng/ml) showed a significantly negative with HbA1c. No significant association was seen between HbA1c and other biochemical markers.

Conclusions: Our study found that bone formation was inhibited in postmenopausal women with T2DM, but bone resorption was not affected, and poor glycemic control was related to lower levels of bone formation, may increase the risk of bone fracture in postmenopausal women with T2DM.

Keywords: 25(oh)D3; HbA1c; N-MID osteocalcin; PINP; PTH; β-CTX.

Fig. 1

Associations of the N-MID osteocalcin with HbA1c in strata of age, menopause years, BMI, diabetic duration, history of fracture, microvascular complication, macrovascular complication, treatment, use of statin medication, and the interaction between subgroup.Data was adjusted for age, BMI, menopause^’s years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR

Fig. 2

Associations of the P1NP with HbA1c in strata of age, menopause years, BMI, diabetic duration, history of fracture, microvascular complication, macrovascular complication, treatment, use of statin medication, and the interaction between subgroup.Data was adjusted for age, BMI, menopause^’s years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA and eGFR

Fig. 3

Smoothing splines of HbA1c and bone biochemical markers generated in generalized additive models. General associations between HbA1c and N-MID osteocalcin (a), and PICP (b); PTH (c), and β-CTX (d); 25(OH)D₃ (e). Adjusted for age, BMI, menopause’s years, diabetic duration, TC, TG, HDL-c, LDL-c, creatinine, UA, and eGFR. The line of dark blue circles indicates 95% confidence intervals