Correlation Between Mean Amplitude of Glycemic Excursion and Bone Turnover Markers in Patients with Type 2 Diabetes: A Cross-Sectional Study

Figures & data

Table 1 Patient Characteristics

Characteristics	Female (n=142)	Male (n=108)	P value
Age (years)	68.8±10.97	66.62±11.29	0.205
Waist–hip ratio	0.91±0.065	0.94±0.064	0.011
Body mass index (kg/m^2)	25.27±4.14	24.36±3.18	0.126
Diabetes duration ≥5 years	100 (70.10%)	(31.08%)	0.868
Smoking
No smoking	118 (83.10%)	32 (23.63%)	0.021
Previous or current smoker	24 (16.90%)	96 (88.89%)
Physical activity
No	49 (34.51%)	37 (34.26%)	0.164
Yes	93 (65.49%)	71 (65.74%)
Antidiabetics
Metformin	(44.33%)	(41.89%)
Sulfonylurea	(16.49%)	(18.92%)
Non-sulfonylurea	(6.18%)	(5.40%)
TZDs	(8.25%)	(5.40%)
Α-glycosidase inhibitors	(9.27%)	(17.57%)	0.843
DPP-4	(18.56%)	(13.51%)
SGLT-2	(15.46%)	(12.16%)
GLP-1	(2.06%)	(1.35%)
Insulin	(43.30%)	(36.49%)
Glycemic markers
HbA1c (%)	9.42±2.29	9.79±2.17	0.334
Plasma fasting glucose (mmol/L)	9.05±2.40	9.73±3.13	0.117
Fasting insulin levels (pmol/L)	103 (63.30, 146.82)	81.00 (58.00,111.60)	0.474
TC (mmol/L)	4.65±1.23	4.35±1.15	0.123
TG (mmol/L)	1.61±1.05	1.64±1.17	0.898
HDL-C (mmol/L)	1.24±0.33	1.07±0.24	<0.001
LDL-C (mmol/L)	2.52±0.85	2.44±0.83	0.569
eGFR (mL/min/1.73m^2)	102.04±37.90	99.91±28.85	0.701
Vitamin D (mmol/L)	47.30±12.19	48.49±12.04	0.529
PTH (pmol/L)	3.72±2.06	3.67±1.77	0.881
Calcium (mmol/L)	2.27±0.12	2.22±0.09	0.479
Β-CTX (ng/mL)	0.45±0.24	0.40±0.28	0.216
P1NP (ng/mL)	44.45±22.66	35.33±25.57	0.015
MAGE (mmol/L)	3.94±1.58	4.05±1.65	0.665

Abbreviations: TZDs, thiazolidinediones; DPP-4, dipeptidyl peptidase-4 inhibitor; SGLT-2, sodium-dependent glucose transporter 2 inhibitor; GLP-1, glucagon-like peptide-1 receptor agonist; HbA1c, glycosylated hemoglobin; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; β-CTX, β-C-terminal cross-linked telopeptide of type-I collagen; P1NP, procollagen type 1 amino terminal propeptide; MAGE, mean amplitude of glycemic excursions. The results are presented as the mean ± SD or number (percentage).

Figure 1 Flow chart of the study. A total of 396 patients with type 2 diabetes mellitus (T2DM) were recruited. After applying the inclusion and exclusion criteria, 146 patients were excluded. Finally, 250 patients with T2DM (142 female and 108 male patients) were included in the analysis.

Table 2 Univariable Regression Analysis of the Correlation Between Bone Markers and Demographic/Biochemical Datas

	Female				Male
	Β-CTX		P1NP		Β-CTX		P1NP
	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P
Age (years)	0.005 (0.001,0.010)	0.015	0.468 (0.058,0.877)	0.026	−0.003 (−0.009,0.003)	0.359	−0.143 (−0.690,0.404)	0.604
Waist–hip ratio	0.276 (−0.476,1.028)	0.468	47.730 (−24.352,119.811)	0.192	−0.649 (−1.705,0.407)	0.224	−78.213 (−172.780,16.355)	0.104
Body mass index (kg/m^2)	0.005 (−0.007,0.017)	0.396	1.215 (0.100,2.330)	0.033	−0.015 (−0.037,0.006)	0.151	−1.322 (−3.236,0.592)	0.173
Menopause or not	0.195 (0.011,0.380)	0.038	18.384 (0.726, 36.042)	0.041	-	-	-	-
Diabetes duration ≥5 years	−0.011 (−0.116,0.093)	0.829	4.030 (−5.966, 14.026)	0.426	−0.028 (−0.171,0.115)	0.696	6.271 (−6.580,19.122)	0.334
HbA1c (%)	−0.011 (−0.034,0.013)	0.366	−2.759 (−4.932, −0.586)	0.013	0.013 (−0.007,0.034)	0.208	−2.318 (−4.999,0.364)	0.089
HOMA-IR	−0.011 (−0.030,0.002)	0.168	−0.113 (−0.256, 0.031)	0.122	−0.001 (−0.003,0.001)	0.306	−0.078 (−0.261,0.105)	0.396
TC (mmol/L)	−0.027 (−0.069,0.014)	0.197	−3.798 (−7.788, 0.193)	0.062	−0.027 (−0.089,0.035)	0.390	−4.249 (−9.639,1.196)	0.124
TG (mmol/L)	−0.049 (−0.097, −0.001)	0.047	−3.225 (−7.931,1.480)	0.177	−0.020 (−0.080,0.041)	0.517	−3.590 (−8.914,1.734)	0.183
HDL-C (mmol/L)	0.110 (−0.044,0.264)	0.160	−0.085 (−15.142,14.972)	0.991	−0.077 (−0.377,0.223)	0.610	12.416 (−14.213,39.044)	0.355
LDL-C (mmol/L)	−0.063 (−0.122, −0.003)	0.039	−6.443 (−12.181, −0.705)	0.028	−0.048 (−0.133,0.038)	0.269	−7.109 (−14.624,0.405)	0.063
eGFR (mL/min/1.73m^2)	−0.001 (−0.003, 0.000)	0.064	−0.112 (−0.237,0.014)	0.080	−0.002 (−0.005,0.000)	0.055	−0.081 (−0.301,0.139)	0.466
Vitamin D (mmol/L)	−0.003 (−0.007, 0.001)	0.133	−0.299 (−0.673,0.074)	0.115	−0.002 (−0.008,0.003)	0.378	0.010 (−0.492,0.512)	0.969
Calcium (mmol/L)	−0.020 (−0.298, 0.258)	0.886	1.124 (−2.136, 5.143)	0.679	0.098 (−0.149,0.204)	0.529	0.149 (−0.894,0.593)	0.614
MAGE (mmol/L)	−0.025 (−0.036, 0.005)	0.073	−2.516 (−5.389,0.356)	0.085	−0.043 (−0.082,0.003)	0.034	−2.895 (−6.521, −0.731)	0.096

Abbreviations: HbA1c, glycosylated hemoglobin; TC, total cholesterol; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; PTH, parathyroid hormone; β-CTX, β-C-terminal cross-linked telopeptide of type-I collagen; P1NP, procollagen type 1 amino terminal propeptide; MAGE, mean amplitude of glycemic excursions. The results are presented as the mean (95% CI).

Figure 2 Scatterplot and regression line of C-terminal telopeptide fragments of type-I collagen (β-CTX) and N-terminal propeptide of type 1 collagen (P1NP) levels by the mean amplitude of glycemic excursions (MAGE). (A) The β-CTX by MAGE in female patients with T2DM, (B) P1NP by MAGE in female patients with T2DM, (C) β-CTX by MAGE in male patients with T2DM, and (D) P1NP by MAGE in male patients with T2DM.

Table 3 Multivariable Regression Analysis of the Correlation Between Bone Markers and Glycemic Variability

	Female				Male
	Β-CTX		P1NP		Β-CTX		P1NP
	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P	Β Coefficient (95% CI)	P
Age (years)	0.005 (0.001,0.010)	0.029	0.580 (−0.186,1.346)	0.135	-	-	-	-
Body mass index (kg/m^2)	-	-	0.518 (−1.068,2.103)	0.517	-	-	-	-
Menopause or not	0.062 (−0.216,0.340)	0.658	−5.109 (−35.440,25.222)	0.738	-	-	-	-
HbA1c (%)	-	-	−1.850 (−4.620,0.921)	0.187	-	-	−1.962 (−4.879,0.955)	0.183
TC (mmol/L)	-	-	1.267 (−9.894,12.427)	0.821	-	-	-	-
TG (mmol/L)	−0.033 (−0.089,0.023)	0.243	-	-	-	-	-	-
LDL-C (mmol/L)	−0.028 (−0.099,0.044)	0.447	−5.532 (−22.395,11.331)	0.515	-	-	−1.962 (−4.879,0.955)	0.183
eGFR (mL/min/1.73m^2)	-	-	0.001 (−0.197,0.199)	0.993	−0.002 (−0.005,0.000)	0.036	-	-
MAGE (mmol/L)	−0.036 (−0.198, −0.030)	0.042	−2.864 (−6.516,0.788)	0.122	−0.048 (−0.089, −0.007)	0.022	0.800 (−3.801,4.681)	0.681

Abbreviations: HbA1c, glycosylated hemoglobin; TC, total cholesterol; TG, triglyceride; LDL-C, low-density lipoprotein cholesterol; eGFR, estimated glomerular filtration rate; β-CTX, β-C-terminal cross-linked telopeptide of type-I collagen; P1NP, procollagen type 1 amino terminal propeptide; MAGE, mean amplitude of glycemic excursions. The results are presented as the mean (95% CI).