Novel Associations of Dyslipidaemia with Vitamin D and Bone Metabolism in Elderly Patients with Diabetes: A Cross-Sectional Study

Figures & data

Table 1 General Characteristics of Elderly Male and Female Patients with T2D

Characteristics	Overall	Male Patients with T2D	Female Patients with T2D	P value
N	2835	1479	1356
Age, year	67.14±7.49	67.25±7.39	67.02±7.61	0.410
BMI, kg/m^2	24.83±3.46	24.97±3.22	24.68±3.69	0.024
FPG, mmol/L	7.79±2.31	7.79±2.21	7.79±2.42	0.931
HbA1c, %	7.49±1.36	7.56±1.39	7.41±1.33	0.004
HOMA2-IR	1.20 (0.90–1.70)	1.2 (0.90–1.60)	1.30 (0.90–1.70)	0.097
Total cholesterol, mmol/L	5.05±1.16	4.77±1.06	5.35±1.19	<0.001
TG, mmol/L	1.81±1.12	1.74±1.14	1.87±1.10	0.002
HDL-C, mmol/L	1.19±0.28	1.11±0.25	1.29±0.29	<0.001
LDL-C, mmol/L	3.13±0.84	2.98±0.78	3.29±0.86	<0.001
eGFR, mL/min/1.73m^2	96.19 (87.15–102.44)	95.33 (86.09–101.28)	97.02 (88.04–103.34)	<0.001
FT3, pmol/L	4.68±0.56	4.82±0.57	4.53±0.52	<0.001
FT4, pmol/L	16.77±2.20	16.96±2.23	16.57±2.15	<0.001
TSH, mIU/L	2.48 (1.75–3.49)	2.33 (1.65–3.20)	2.69 (1.89–3.86)	<0.001
E2, pmol/L	73.67 (31.68–119.00)	116.40 (91.87–139.40)	30.72 (9.18–51.02)	<0.001
Total T, nmol/L	6.71 (0.56–14.36)	14.15 (10.96–18.03)	0.54 (0.32–0.83)	<0.001
FSH, IU/L	23.11 (9.00–51.67)	9.39 (6.35–13.99)	52.62 (39.28–68.12)	<0.001
LH, IU/L	12.58 (6.74–24.40)	7.04 (5.28–9.67)	24.66 (18.36–31.89)	<0.001
25(OH)D, ng/mL	15.57 (12.23–19.44)	16.58 (12.83–20.30)	14.65 (11.54–18.07)	<0.001
P1NP, ng/mL	39.28 (30.00–51.26)	34.30 (27.19–43.76)	44.97 (35.82–58.70)	<0.001
β-CTX, ng/mL	0.19 (0.14–0.26)	0.17 (0.12–0.23)	0.22 (0.16–0.29)	<0.001
Use of statins, n (%)	452 (15.94)	217 (14.67)	235 (17.33)	0.053
Current smoking, n (%)	604 (21.31)	569 (38.47)	35 (2.58)	<0.001
Milk intake				<0.001
Never or rarely (%)	1091 (38.48)	615 (41.58)	476 (35.10)
Often (%)	1744 (61.52)	864 (58.42)	880 (64.90)

Notes: The data are summarized as mean ± SD for continuous variables, whereas skewed variables are presented as the median (first to third quartiles). For the comparison of male patients with female patients with T2D, ANOVA tests were employed for normally distributed variables, while nonparametric Mann–Whitney U-test was performed for skewed parameters. Categorical variables presented as numbers and proportions were compared using chi-square test.

Abbreviations: T2D, type 2 diabetes; BMI, body mass index; FPG, fasting plasma glucose; HbA1c, glycated hemoglobin; HOMA2-IR, homeostasis model assessment 2-insulin resistance; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; FT3, free triiodothyronine; FT4, free thyroxine; TSH, thyrotropin; E2, oestradiol; T, testosterone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; 25(OH)D, 25-hydroxyvitamin D; P1NP, procollagen type I N-terminal propeptide; CTX, C-terminal telopeptide of type I collagen.

Figure 1 Simple correlations between TC, LDL-C, HDL-C, TG and 25(OH)D in male patients (A–D) and female patients (E–H) with T2D.

Abbreviations: TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TG, triglycerides; 25(OH)D, 25-hydroxyvitamin D.

Table 2 Principal Component Regression Analysis of Serum Bone Turnover Markers as Dependent Variables and Parameters of Lipid Profile and 25(OH)D in Subjects with T2D

Variable	LnP1NP (Male)		Lnβ-CTX (Male)
	B (95% CI)	p-value	B (95% CI)	p-value
PC I	0.014 (−0.006–0.033)	0.168	−0.018 (−0.041–0.005)	0.129
PC II	−0.010 (−0.031–0.011)	0.328	−0.038 (−0.063 – −0.012)	0.003
Ln25(OH)D	−0.100 (−0.155 – −0.046)	<0.001	−0.174 (−0.240 – −0.109)	<0.001
Variable	LnP1NP (female)		Lnβ-CTX (female)
	B (95% CI)	p-value	B (95% CI)	p-value
PC I	0.026 (0.005–0.046)	0.015	−0.003 (−0.026–0.020)	0.821
PC II	−0.028 (−0.051 – −0.006)	0.013	−0.034 (−0.059 – −0.010)	0.006
Ln25(OH)D	−0.104 (−0.164 – −0.044)	0.001	−0.207 (−0.273 – −0.141)	<0.001

Notes: Included terms for age, HbA1c, HOMA2-IR, total T, E2, FSH, LH, eGFR, BMI, use of statins, milk intake and current smoking status.

Abbreviations: P1NP, procollagen type I N-terminal propeptide; CTX, C-terminal telopeptide of type I collagen.; 25(OH)D, 25-hydroxyvitamin D; PC I, principal component I; PC II, principal component II.

Figure 2 The conceptual mediation model: “a” indicates the path from PC I and PC II(predictor) to 25(OH)D (mediator), “b” indicates the path from 25(OH)D (mediator) to BTMs (outcome), “c” indicates the path from PC I and PC II(predictor) to BTMs (outcome), and “c’” indicates the path from PC I and PC II(predictor) to BTMs (outcome) when controlled for 25(OH)D (mediator).

Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BTMs, bone turnover markers; PC I, principal component I; PC II, principal component II.

Figure 3 Mediation analysis of the relationship between lipid levels (PC I and PC II) and BTMs by 25(OH)D in male and female patients with T2D (β, 95% CI). Path ab, Path c’ and Path c represent the indirect, direct and total effects of lipid levels on BTMs with 25(OH)D as a mediator in males and females, respectively. (A) and (B) display the mediation effect of 25(OH)D on the association between lipid levels and P1NP and β-CTX, respectively, in male patients with T2D. (C) and (D) display the mediation effect of 25(OH)D on the association between lipid levels and P1NP and β-CTX, respectively, in female patients with T2D. Adjusted for age, BMI, HbA1c, HOMA2-IR, E2 or total T, FSH, eGFR, use of statins, smoking status and milk intake.

Abbreviations: P1NP, procollagen type I N-terminal propeptide; CTX, C-terminal telopeptide of type I collagen; PC I, principal component I; PC II, principal component II; 95% CI, 95% confidence interval.