Relationship Between the Triglyceride-Glucose Index and Type 2 Diabetic Macroangiopathy: A Single-Center Retrospective Analysis

Figures & data

Figure 1 Flow chart for inclusion of participants in this study.

Notes: A total of 1565 participants were recruited at baseline, and all patients were screened according to exclusion criteria. Of these, 216 participants were diagnosed with diabetes other than type 2 (including type 1 diabetes, gestational diabetes, secondary diabetes), 36 participants had organ insufficiency, and 19 participants had autoimmune disease or blood disease, 27 participants had malignancy, 58 had severe infection within the last three months, 2 had congenital heart disease, 364 had incomplete baseline data, and 75 had incomplete follow-up information. After excluding the above participants, a total of 858 subjects were included in the study.

Table 1 Basic Characteristics of Participants

Variables	Simple T2DM (N=358)	Macrovascular Complications of T2DM (N=500)	P
Age, years	68 (59,76)	70(61,75)	0.164
Male, n%	192 (53.6%)	286 (57.2%)	0.299
Duration of diabetes, years	5 (2,10)	8 (5,12)	<0.001
BMI,kg/m^2	23.58(21.40,25.63)	24.52(22.32,26.36)	<0.001
WBC,10^9/L	6.30 (5.10,7.60)	6.80 (5.50,8.65)	<0.001
RBC,10^12/L	4.39 (3.88,4.78)	4.14 (3.63,4.54)	<0.001
Neutrophils,10^9/L	3.80 (2.90,4.90)	4.50 (3.40,6.40)	<0.001
ALT, U/L	18.00 (12.50,29.53)	16.45 (12.00,26.30)	0.127
AST, U/L	18.00 (14.95,24.93)	19.00 (15.00,27.00)	0.180
Albumin, g/L	40.55 (37.3,43.3)	39.4 (36.60,42.50)	0.004
SCr,μmol/L	67.70 (55.70,83.70)	77.70 (64.20,109.40)	<0.001
BUN, mmol/L	5.65 (4.60,7.23)	6.63 (5.13,9.20)	<0.001
FPG, mmol/L	7.30 (6.11,9.23)	8.47 (6.77,10.32)	<0.001
TG mmol/L	1.27 (0.90,1.78)	1.79 (1.24,2.53)	<0.001
TC, mmol/L	4.58 (3.60,5.27)	4.50 (3.63,5.35)	0.818
HDL-C, mmol/L	2.64 (2.04,3.32)	2.46 (1.85,3.03)	0.001
INR	0.98 (0.91,1.12)	0.99 (0.92,1.13)	0.318
TyG Index	8.91±6.17	9.44±0.74	<0.001
Hypertension, n%	176 (49.2%)	376 (75.2%)	<0.001
Medication history
ACEI/ARB, n%	212(59.2%)	217(43.4%)	<0.001
Statins, n%	276(77.1%)	374(74.8%)	0.439
Metformin, n%	70(19.6%)	124(24.8%)	0.07
Alpha-glucosidase inhibitor, n%	74(20.7%)	127(25.4%)	0.107
Sulfonylurea, n%	66(18.4%)	86(17.2%)	0.64
Dipeptidyl peptidase 4 inhibitor, n%	20(5.6%)	17(3.4%)	0.12
Insulin, n%	80(22.3%)	142(28.4%)	0.046
Aortic calcification, n%	123(14.3%)	325(37.9%)	<0.001

Note: Data are presented as median (IQR) [25th percentile, 75th percentile] or n (%).

Abbreviations: BMI, body mass index; WBC, white blood cell count; RBC, red blood cell count, ALT, alanine aminotransferase; AST, aspartate aminotransferase; Scr, blood creatinine; BUN, blood urea nitrogen; FPG, fasting blood glucose; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; INR, international normalized ratio; TyG Index, triglyceride glucose index; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors.

Table 2 Baseline Characteristics of TyG Index Quartile Groups

Variables	Q1 (n=216)	Q2 (n=215)	Q3 (n=212)	Q4 (n=215)	P
	≤8.70	8.70–9.20	9.20–9.67	≥9.67
Age, years	69(60,77)	69(61,75)	68.5(59,76)	69(60,74.5)	0.908
Male, n%	126(58.3%)	117(54.4%)	126(59.4%)	109(50.7%)	0.248
Duration of diabetes, years	6.5(2,10)	8(5,10)	7(3,10)	8(5,12)	<0.001
BMI, kg/m^2	22.30(21.30,24.19)	22.62(21.36,24.99)	24.85(23.62,26.58)	25.69(24.51,27.25)	<0.001
WBC,10^9/L	6.40(5.20,8.20)	6.30(5.30,7.65)	6.50(5.40,8.00)	7.10(5.55,9.30)	<0.001
RBC,10^12/L	4.11(3.64,4.64)	4.23(3.8,4.58)	4.25(3.73,4.71)	4.27(3.89,4.63)	0.307
Neutrophils,10^9/L	4.30(3.10,5.88)	3.90(3.00,5.20)	4.20(3.30,5.58)	4.60(3.30,6.50)	0.007
ALT, U/L	17.00(12.00,27.60)	16.00(11.60,25.40)	17.00(12.00,27.50)	18.50(13.00,29.90)	0.152
AST, U/L	19.60(15.63,28.00)	17.10(13.30,23.00)	19.00(15.00,24.48)	19.1(15.00,27.70)	0.005
Albumin, g/L	39.30(36.55,42.15)	39.80(37.20,42.35)	40.85(36.80,43.25)	40.00(37.00,43.60)	0.23
SCr,μmol/L	73.20(61.50,101.65)	70.70(58.25,86.7)	76.35(60.95,106.2)	71(59.4,102.95)	0.082
BUN, mmol/L	6.37(5.00,8.81)	5.79(4.79,7.28)	6.2(4.86,8.36)	6.4(5.04,8.67)	0.021
FPG, mmol/L	6.225(5.08,7.33)	7.32(6.21,9.08)	8.495(7.44,9.93)	10.24(8.62,13.04)	<0.001
TG mmol/L	0.855(0.68,1.05)	1.3(1.12,1.54)	1.86(1.58,2.11)	2.83(2.18,3.78)	<0.001
TC, mmol/L	4.03(3.35,4.8)	4.42(3.57,5.14)	4.695(3.75,5.4)	4.9(4.16,5.69)	<0.001
HDL-C, mmol/L	2.32(1.63,2.85)	2.56(1.94,3.07)	2.655(2.05,3.265)	2.67(2.02,3.32)	<0.001
INR	1.02(0.92,1.15)	0.98(0.91,1.08)	0.995(0.925,1.15)	0.97(0.91,1.11)	0.075
Hypertension, n%	136(63.0%)	126(58.6%)	140(66.0%)	150(69.8%)	0.098
Medication history
ACEI/ARB, n%	104(48.1%)	107(49.8%)	105(49.5%)	113(52.6%)	0.83
Statins, n%	169(78.2%)	161(74.9%)	151(71.2%)	171(79.5%)	0.22
Metformin, n%	37(17.1%)	42(19.5%)	53(25%)	62(28.8%)	0.016
Alpha-glucosidase inhibitor, n%	44(20.4%)	43(20.0%)	54(25.5%)	60(27.9%)	0.143
Sulfonylurea, n%	48(22.2%)	38(17.7%)	36(17.0%)	30(14.0%)	0.159
Dipeptidyl peptidase 4 inhibitor, n%	14(6.5%)	10(4.7%)	7(3.3%)	6(2.8%)	0.235
Insulin, n%	41(19%)	50(23.3%)	57(26.9%)	74(34.4%)	0.002
Aortic calcification, n%	74(8.6%)	107(2.5%)	122(14.2%)	145(16.9%)	<0.001
Macrovascular complications, n%	86(39.8%)	98(45.6%)	145(68.4%)	171(79.5%)	<0.001

Note: Data are presented as median (IQR) [25th percentile, 75th percentile] or n (%).

Abbreviations: BMI, body mass index; WBC, white blood cell count; RBC, red blood cell count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Scr, blood creatinine; BUN, blood urea nitrogen; FPG, fasting blood glucose; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; INR, International normalized ratio; TyG Index, triglyceride glucose index; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors.

Table 3 Correlation Between TyG Index and Other Clinical Variables

Variables	r	P
Age, years	0.005	0.875
Duration of diabetes, years	0.136	<0.001
Male	−0.04	0.244
Hypertension	0.069	0.044
Aortic calcification	0.253	<0.001
Statins	0.005	0.894
ACEI/ARB	0.022	0.527
Insulin	0.134	<0.001
TC, mmol/L	0.292	<0.001
HDL-C, mmol/L	0.152	<0.001
Albumin, g/L	0.072	0.035
Macrovascular complications	0.345	<0.001

Abbreviations: TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; TyG Index, triglyceride glucose index; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors.

Table 4 Logistic Regression Analysis of Related Factors with T2DM Complicated with Macrovascular Disease

Variables	Univariate		Multivariate
	OR 95% CI	p	OR 95% CI	p
TyG Index	3.12(2.48–3.93)	<0.001	2.72(1.76–4.21)	<0.001
Hypertension	3.14 (2.35–4.19)	<0.001	3.26(2.32–4.58)	<0.001
Aortic calcification	3.55 (2.667–4.72)	<0.001	2.48(1.77–3.45)	<0.001
ACEI/ARB	0.53 (0.40–0.70)	<0.001	0.40(0.29–0.56)	<0.001
RBC	0.57 (0.47–0.71)	<0.001	0.55(0.43–0.71)	<0.001
TG	2.10 (1.74–2.52)	<0.001	1.33(0.98–1.80)	0.07
HDL-C	0.80 (0.69–0.93)	0.003	0.63(0.52–0.76)	<0.001

Abbreviations: RBC, red blood cell count; TG, triglyceride; HDL-C, high-density lipoprotein cholesterol; TyG Index, triglyceride glucose Index; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors; OR, odds ratio; CI, confidence interval.

Figure 2 Selecting clinical features based on the least absolute shrinkage and selection operator (LASSO) logistic regression.

Notes: (A) Least Absolute Shrinkage and Selection Operator (LASSO) coefficient distribution for each variable. Variables with coefficients close to 0 are removed. Finally, 7 variables were included. (B) Cross-validation of tuning parameters in LASSO models.

Abbreviations: BMI, body mass index; WBC, white blood cell count; RBC, red blood cell count; ALT, alanine aminotransferase; AST, aspartate aminotransferase; Scr, blood creatinine; BUN, blood urea nitrogen; FPG, fasting blood glucose; TG, triglyceride; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; INR, international normalized ratio; TyG Index, triglyceride glucose index; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors.

Figure 3 A nomogram was constructed to predict macrovascular complications in T2DM patients.

Notes: (A) A nomogram for predicting T2DM patients with macrovascular complications. (B) Calibration curve of nomogram risk model for T2DM with macrovascular complications.

Figure 4 ROC curve of TyG index, RBC, and HDL-C in predicting T2DM complicated with macrovascular complications.

Notes: The ROC curve and AUC value of the nomogram. The area under the ROC curve for the TyG index was 0.702 (95% CI 0.67–0.74), the RBC was 0.396 (95% CI 0.36–0.43), and the TG was 0.432 (95% CI 0.39–0.47). The best cut-off value of the TyG index for predicting macrovascular complications was 9.31, with a sensitivity of 59% and a specificity of 74%. The Youden Index was 0.33.

Table 5 Cox Proportional Hazards for All-Cause Mortality in T2DM with or without Macrovascular Complications

Variables	Model 1		Model 2		Model 3
	HR (95% CI)	p-value	HR (95% CI)	p-value	HR (95% CI)	p-value
Age, years	-	-	1.15(1.10–1.20)	<0.001	1.14(1.10–1.19)	<0.001
Duration of diabetes, years	-	-	1.01(0.97–1.05)	0.652	1.01(0.97–1.06)	0.636
Aortic calcification	-	-	0.93(0.51–1.71)	0.811	0.85(0.46–1.58)	0.603
Hypertension	-	-	-	-	0.79(0.44–1.42)	0.430
ACEI/ARB	-	-	-	-	0.52(0.29–0.94)	0.029
Insulin	-	-	-	-	1.47(0.83–2.61)	0.188
Albumin, g/L	-	-	-	-	0.97(0.92–1.02)	0.198
SCr,μmol/L	-	-	-	-	1.00(0.99–1.00)	0.188
BUN, mmol/L	-	-	-	-	1.05(0.99–1.10)	0.080
TyG index	1.87(1.32–2.64)	<0.001	1.99(1.38–2.86)	<0.001	1.89(1.29–2.76)	0.001

Notes: Model 1 was unadjusted; Model 2 was adjusted for age, duration of diabetes, and aortic calcification; Model 3 was adjusted for age, duration of diabetes, aortic calcification, hypertension, history of ACEI/ARB medication, history of insulin medication, albumin, BUN, and SCr.

Abbreviations: Scr, blood creatinine; TyG Index, triglyceride glucose index; BUN, blood urea nitrogen; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors; HR, hazard ratio; CI, confidence interval.

Figure 5 Association of TyG index quartiles with all-cause mortality in T2DM.

Notes: Quartile 1 is used as reference category. Model 1 was adjusted for age, duration of diabetes, hypertension, and aortic calcification; Model 2 was adjusted for age, duration of diabetes, hypertension, aortic calcification, ACEI/ARB medication history, albumin, TG, and TC.

Abbreviations: TyG Index, triglyceride glucose index; RBC, red blood cell count; HDL-C, high-density lipoprotein cholesterol; ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin-converting enzyme inhibitors; TG, triglyceride; TC, total cholesterol; HR, hazard ratio; CI, confidence interval.

Figure 6 Prognostic analysis of patients with T2DM.

Notes: (A) Kaplan-Meier survival curves of all-cause mortality for TyG index quartiles. Q1 group (TyG ≤8.70), Q2 (TyG 8.70–9.20), Q3 (TyG 9.20–9.67), and Q4 (TyG≥9.67). (B) Kaplan-Meier survival curves for all-cause mortality in T2DM with or without macrovascular complications. ^aWithout macrovascular complications; ^bWith macrovascular complications.