Predictive Effect of Triglyceride-Glucose Index on Adverse Prognostic Events in Patients with Type 2 Diabetes Mellitus and Ischemic Cardiomyopathy

Figures & data

Figure 1 Flow chart of the study population enrollment.

Abbreviations: TyG, triglyceride glucose; FPG, fasting plasma glucose; TG, triglycerides; OGTT, Oral Glucose Tolerance Test; T2DM, type 2 diabetes mellitus; MACCEs, Major adverse cardiac and cerebral events.

Table 1 Baseline Characteristics of the Study Population According to the Occurrence of MACCEs

Characteristic	Total (n=1514)	NO-MACCEs (n=837)	MACCEs (n=677)	P
Male, n (%)	1119 (73.9%)	633 (75.6%)	486 (71.8%)	0.091
Ethnicity, n (%)
Han	791 (52.2%)	453 (54.1%)	338 (49.9%)	0.262
Uyghur	537 (35.5%)	292 (34.9%)	245 (36.2%)
Kazah	48 (3.2%)	24 (2.9%)	24 (3.6%)
Other	138 (9.1%)	68 (8.1%)	70 (10.3%)
Smoking, n (%)	620 (40.9%)	319 (38.1%)	301 (44.5%)	0.013
Drinking, n (%)	401 (26.5%)	228 (27.2%)	173 (25.6%)	0.460
HT his, n (%)	1024 (67.6%)	558 (66.7%)	466 (68.8%)	0.370
TyG-Index	7.53 (7.06–8.13)	7.22 (6.76–7.79)	8.04 (7.43–8.51)	<0.001
Age, years	66 (58–73)	65 (57–73)	67 (59–74)	<0.001
BMI, kg/m^2	25.71 (23.38–28.44)	25.81 (23.44–28.53)	25.61 (23.14–28.38)	0.403
SBP, mmHg	122 (110–139)	120 (110–138)	125 (111–140)	0.048
DBP, mmHg	74 (66–81)	74 (66–82)	75 (66–80)	0.995
WBC, 10^9/L	7.27 (5.91–8.77)	7.13 (5.81–8.61)	7.45 (6.07–9.10)	<0.001
Neutrophil, 10^9/L	4.67 (3.68–5.95)	4.56 (3.57–5.75)	4.86 (3.80–6.29)	<0.001
Lymphocyte, 10^9/L	1.62 (1.20–2.09)	1.64 (1.20–2.10)	1.58 (1.17–2.07)	0.114
RBC, 10^9/L	4.40 (3.93–4.81)	4.40 (3.98–4.83)	4.40 (3.90–4.81)	0.427
PLT, 10^9/L	201.0 (162.0–249.0)	195.0 (158.0–247.0)	208.0 (166.5–252.0)	0.010
Cr, umol/L	91.0 (73.0–118.3)	87.0 (71.0–114.0)	97.5 (77.0–126.7)	<0.001
UA, umol/L	379.20 (301.00–480.03)	369.50 (297.76–465.00)	393.00 (303.38–495.00)	0.039
FPG, mmol/L	8.10 (5.98–11.97)	6.67 (5.27–9.29)	10.32 (7.57–14.38)	<0.001
TG, mmol/L	1.31 (0.96–1.83)	1.16 (0.82–1.60)	1.58 (1.15–2.27)	<0.001
HDL-C, mmol/L	0.88 (0.71–1.07)	0.89 (0.72–1.09)	0.87 (0.70–1.04)	<0.001
LDL-C, mmol/L	2.16 (1.65–2.76)	2.09 (1.58–2.66)	2.22 (1.73–2.84)	<0.001
TC, mmol/L	3.44 (2.78–4.11)	3.28 (2.68–3.95)	3.57 (2.98–4.34)	<0.001
TBil, umol/L	13.50 (9.50–19.61)	14.3 (9.84–20.25)	12.6 (9.31–18.68)	<0.001
Albumin, g/L	36.60 (32.70–40.20)	36.82 (33.10–40.48)	36.22 (32.30–40.00)	0.051
ALT, U/L	19.70 (15.10–28.80)	19.80 (15.00–28.10)	19.60 (15.20–29.83)	0.317
AST, U/L	19.50 (13.48–30.08)	19.30 (13.40–29.75)	19.80 (13.69–31.02)	0.233
LDH, U/L	199.85 (167.00–242.7)	198.00 (167.00–236.64)	202.00 (166.86–254.12)	0.288
GGT, U/L	32.1 (21.0–59.0)	32.0 (20.2–58.06)	32.7 (22.0–60.9)	0.182
ALP, U/L	75.0 (60.0–97.0)	72.0 (58.0–94.0)	79.0 (62.0–102.1)	<0.001
CK, U/L	70.65 (46.00–107.00)	71.00 (47.90–107.23)	70.05 (44.91–106.95)	0.717
LVEF	42.0 (36.8–47.0)	43.0 (37.0–48.0)	40.3 (36.0–46.0)	<0.001
Medication, n (%)
Antiplatelet agent	493 (32.5%)	290 (34.6%)	203 (29.9%)	0.054
ACEI/ARB	465 (30.7%)	246 (29.3%)	219 (32.3%)	0.215
Beta-blocker	211 (13.9%)	109 (13.0%)	102 (15.0%)	0.254
Statins	342 (22.6%)	186 (22.2%)	156 (23.0%)	0.704
Oral hypoglycemic agents	1026 (67.7%)	566 (67.6%)	460 (67.9%)	0.893
Insulin	509 (33.6%)	277 (33.1%)	232 (34.2%)	0.631

Notes: Data are expressed as n (%) and median (25 and 75 interquartile). p values in bold are < 0.05.

Abbreviations: TyG index, triglyceride-glucose index; BMI, body mass index; HT his, history of hypertension; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; PLT, platelet; Cr, creatinine; UA, uric acid; FPG, fasting plasma glucose; TG, triglyceride; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol; TBil, total bilirubin; ALT, alanine transferase; AST, aspartate transferase; LDH, lactate dehydrogenase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; CK, creatine kinase; LVEF, left ventricle ejection fraction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MACCEs, Major adverse cardiac and cerebral events.

Table 2 Baseline Characteristics of the Study Population According to the Tertiles of the TyG Index

Characteristic	Tertile1 (n=509)	Tertile 2 (n=500)	Tertile 3 (n=505)	P
Male, n (%)	397 (78%)	374 (74.8%)	348 (68.9%)	0.004
Ethnicity, n (%)
Han	295 (57.9%)	248 (49.6%)	248 (49.1%)	0.019
Uyghur	157 (30.8%)	179 (35.8%)	201 (39.8%)
Kazah	18 (3.5%)	17 (3.4%)	13 (2.6%)
Other	39 (7.7%)	56 (11.2%)	43 (8.5%)
Smoking, n (%)	196 (38.5%)	204 (40.8%)	220 (43.5%)	0.261
Drinking, n (%)	138 (27.1%)	141 (28.2%)	122 (24.2%)	0.323
HT his, n (%)	329 (64.6%)	349 (69.8%)	346 (68.5%)	0.188
TyG-Index	6.83 (6.54–7.07)	7.53 (7.37–7.72)	8.39 (8.13–8.71)	< 0.001
Age, years	68 (61–74)	65 (58–73)	65 (57–73)	< 0.001
BMI, kg/m^2	25.21 (22.86–27.92)	26.15 (23.56–28.74)	25.78 (23.53–28.72)	< 0.001
SBP, mmHg	121 (110–137)	121.5 (110–139)	125 (111–140)	0.079
DBP, mmHg	73 (65–81)	74.5 (67–82)	75 (68–80)	0.280
WBC, 10^9/L	7.05 (5.66–8.28)	7.22 (5.95–8.8)	7.57 (6.14–9.38)	< 0.001
Neutrophil, 10^9/L	4.43 (3.47–5.65)	4.71 (3.73–6.01)	4.93 (3.84–6.54)	< 0.001
Lymphocyte, 10^9/L	1.54 (1.16–1.99)	1.64 (1.22–2.12)	1.67 (1.22–2.13)	0.084
RBC, 10^9/L	4.36 (3.87–4.78)	4.4 (3.95–4.82)	4.45 (3.96–4.84)	0.177
PLT, 10^9/L	191 (155–238)	201.5 (161–248)	210 (170–257)	< 0.001
Cr, umol/L	90.0 (72.0–116.8)	89.0 (72.1–117.3)	94.8 (75.0–122.1)	0.114
UA, umol/L	390.4 (315.1–491.0)	384.5 (300.8–471.8)	367.0 (291.5–474.0)	0.013
FPG, mmol/L	5.74 (4.76–6.85)	8.09 (6.64–10.13)	13.03 (10.07–16.83)	< 0.001
TG, mmol/L	0.89 (0.71–1.13)	1.32 (1.06–1.63)	2.02 (1.58–2.94)	< 0.001
HDL-C, mmol/L	0.92 (0.72–1.09)	0.87 (0.71–1.07)	0.85 (0.7–1.05)	0.015
LDL-C, mmol/L	1.91 (1.47–2.47)	2.17 (1.76–2.68)	2.38 (1.83–3.11)	< 0.001
TC, mmol/L	3.06 (2.51–3.71)	3.38 (2.84–3.95)	3.68 (2.91–4.70)	< 0.001
TBil, umol/L	14.9 (10.4–21)	13.3 (9.4–19.3)	12.4 (9.1–18.2)	< 0.001
Albumin, g/L	36.7 (33.1–39.7)	36.6 (32.8–40.8)	36.5 (32.2–40.3)	0.657
ALT, U/L	20.3 (15.7–28.3)	19.7 (14.9–28.9)	19.1 (15.0–28.9)	0.613
AST, U/L	18.1 (12.9–29.8)	20.3 (13.5–29.6)	19.6 (14.1–31.6)	0.064
LDH, U/L	199.7 (172.9–241.0)	202.6 (167.0–242.8)	197.4 (160.0–243.7)	0.444
GGT, U/L	35.6 (21.0–63.0)	31.3 (20.6–55.3)	31.0 (21.8–58.1)	0.185
ALP, U/L	75.0 (59.0, 99.0)	71.0 (58.2–90.9)	80.0 (63.1–101.5)	< 0.001
CK, U/L	68.4 (46.0–102.0)	72.6 (47.0–109.0)	69.8 (45.0–109.1)	0.493
LVEF	43.0 (37.3–48.9)	41.0 (36.8–47.0)	40.3 (35.0–46.0)	< 0.001
Medication, n (%)
Antiplatelet agent	184 (36.1%)	175 (35.0%)	134 (26.5%)	0.002
ACEI/ARB	152 (29.8%)	154 (30.8%)	159 (31.5%)	0.854
Beta-blocker	92 (18.0%)	60 (12.0%)	59 (11.7%)	0.004
Statins	104 (20.4%)	120 (24.0%)	118 (23.3%)	0.351
Oral hypoglycemic agents	368 (72.2%)	323 (64.6%)	335 (66.3%)	0.023
Insulin	189 (37.1%)	149 (29.8%)	171 (33.9%)	0.048

Notes: Data are expressed as n (%) and median (25 and 75 interquartile). p values in bold are < 0.05.

Abbreviations: TyG index, triglyceride-glucose index; BMI, body mass index; HT his, history of hypertension; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; PLT, platelet; Cr, creatinine; UA, uric acid; FPG fasting plasma glucose; TG, triglyceride; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol; TBil, total bilirubin; ALT, alanine transferase; AST, aspartate transferase; LDH, lactate dehydrogenase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; CK, creatine kinase; LVEF, left ventricle ejection fraction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MACCEs, Major adverse cardiac and cerebral events.

Table 3 Correlations Between the TyG Index and Cardiovascular Risk Factors

Characteristic	Correlation Coefficient	p values
Age	−0.099	<0.001
BMI	0.076	0.003
SBP	0.051	0.045
DBP	0.044	0.087
WBC	0.130	<0.001
Neutrophil	0.123	<0.001
Lymphocyte	0.059	0.021
RBC	0.059	0.022
PLT	0.119	<0.001
Cr	0.045	0.079
UA	−0.055	0.034
HDL-C	−0.076	0.003
LDL-C	0.242	<0.001
TC	0.338	<0.001
TBil	−0.111	<0.001
Albumin	0.024	0.343
ALT	−0.020	0.436
AST	0.063	0.014
LDH	−0.037	0.151
GGT	−0.001	0.961
ALP	0.055	0.033
CK	0.011	0.671
LVEF	−0.100	<0.001

Note: p values in bold are < 0.05.

Abbreviations: TyG index, triglyceride-glucose index; BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; WBC, white blood cell; RBC, red blood cell; PLT, platelet; Cr, creatinine; UA, uric acid; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol; TBil, total bilirubin; ALT, alanine transferase; AST, aspartate transferase; LDH, lactate dehydrogenase; GGT, glutamyl transpeptidase; ALP, alkaline phosphatase; CK, creatine kinase; LVEF, left ventricle ejection fraction.

Table 4 Independent Predictors of Composite MACCEs

	Univariate Cox Regression			Multivariate Cox Regression
	HR	95% CI	p	HR	95% CI	p
TyG-Index	2.043	(1.871–2.230)	<0.001	2.204	(1.997–2.443)	<0.001
Male, gender	0.946	(0.800–1.119)	0.518
Age	1.015	(1.008–1.023)	<0.001	1.023	(1.014–1.031)	<0.001
BMI, kg/m^2	0.990	(0.973–1.007)	0.254
Neutrophil, 10^9/L	1.059	(1.033–1.087)	<0.001	1.008	(0.979–1.038)	0.602
Lymphocyte, 10^9/L	0.943	(0.852–1.042)	0.250
PLT, 10^9/L	1.002	(1.001–1.003)	<0.001	1.002	(1.001–1.003)	<0.001
UA, umol/L	1.001	(1.000–1.001)	0.002	1.001	(1.000–1.001)	0.003
HDL-C, mmol/L	0.842	(0.682–1.039)	0.109
LDL-C, mmol/L	1.069	(0.991–1.154)	0.084
TC, mmol/L	1.053	(0.996–1.114)	0.068
TBil, umol/L	0.997	(0.990–1.004)	0.404
ALP, U/L	1.002	(1.000–1.003)	0.013	1.002	(1.001–1.003)	0.048
LVEF, %	0.996	(0.989–1.004)	0.326
Antiplatelet agent	0.872	(0.740–1.028)	0.102
ACEI/ARB	1.042	(0.887–1.224)	0.617
Beta-blocker	1.185	(0.960–1.463)	0.114
Statins	1.022	(0.854–1.222)	0.813
Oral hypoglycemic agents	1.000	(0.851–1.175)	0.998
Insulin	1.022	(0.872–1.198)	0.788

Notes: Adjusted factors included TyG-Index, Age, neutrophil, PLT, UA, ALP, HDL-C, LDL-C, TC. p values in bold are < 0.05.

Abbreviations: TyG index, triglyceride-glucose index, BMI, body mass index; PLT, platelet; UA, uric acid; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol; TBil total bilirubin; ALP, alkaline phosphatase; LVEF, left ventricle ejection fraction; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; MACCEs, Major adverse cardiac and cerebral events.

Figure 2 Kaplan–Meier survival curve for MACCEs across the TyG index tertiles.

Table 5 Cox Proportional Hazards Regression Models of MACCEs

Characteristic	n (%)	Univariate Cox Regression		Multivariate Cox Regression
		HR (95% CI)	p	Adjusted HR (95% CI)	p
MACCEs
TyG≤7.21	100 (19.6)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	199 (39.8)	1.996 (1.570–2.538)	<0.001	2.152 (1.684–2.751)	<0.001
TyG≥7.89	378 (74.9)	4.383 (3.515–5.465)	<0.001	4.856 (3.842–6.136)	<0.001
Chest-pain
TyG≤7.21	9 (1.8)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	11 (2.2)	1.218 (0.505–2.939)	0.661	1.167 (0.477–2.854)	0.735
TyG≥7.89	71 (14.1)	9.336 (4.661–18.699)	<0.001	9.056 (4.370–18.767)	<0.001
Acute-myocardial infarction
TyG≤7.21	4 (0.8)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	15 (3)	3.737 (1.240–11.262)	0.019	4.236 (1.368–13.179)	0.012
TyG≥7.89	15 (3)	4.313 (1.430–13.008)	<0.009	4.437 (1.420–13.869)	0.010
Heart failure
TyG≤7.21	8 (1.6)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	22 (4.4)	2.758 (1.228–6.195)	0.014	2.657 (1.162–6.072)	0.021
TyG≥7.89	56 (11.1)	8.025 (3.824–16.843)	<0.001	7.334 (3.424–15.708)	<0.001
Cardiogenic-shock
TyG≤7.21	5 (0.9)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	8 (1.6)	1.563 (0.511–4.780)	0.433	1.957 (0.617–6.325)	0.252
TyG≥7.89	12 (2.3)	2.779 (0.977–7.905)	0.055	3.707 (1.207–11.384)	0.022
Malignant-arrhythmia
TyG≤7.21	8 (1.5)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	19 (3.8)	2.353 (1.030–5.376)	0.042	2.554 (1.100–5.931)	0.029
TyG≥7.89	35 (6.9)	5.128 (2.376–11.065)	<0.001	5.309 (2.367–11.908)	<0.001
Cerebral-infarction
TyG≤7.21	14 (2.7)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	17 (3.4)	1.223 (0.603–2.481)	0.577	1.269 (0.614–2.624)	0.520
TyG≥7.89	33 (6.5)	2.857 (1.526–5.348)	<0.001	3.127 (1.596–6.128)	<0.001
Gastrointestinal bleeding
TyG≤7.21	6 (1.1)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	10 (2)	1.688 (0.614–4.646)	0.310	2.117 (0.748–5.996)	0.158
TyG≥7.89	17 (3.3)	3.351 (1.318–8.517)	0.011	4.326 (1.612–11.613)	0.004
All-cause death
TyG≤7.21	85 (16.7)	Ref	‑/‑	Ref	‑/‑
7.21 < TyG <7.89	157 (31.4)	1.854 (1.424–2.414)	<0.001	2.022 (1.543–2.649)	<0.001
TyG≥7.89	287 (56.8)	3.945 (3.096–5.027)	<0.001	4.502 (3.478–5.827)	<0.001

Notes: Adjusted factors included Age, BMI, neutrophil, lymphocyte, PLT, UA, HDL-C, LDL-C, ALP, LVEF, gender, TC, HT his, Ethnicity, Medication (Antiplatelet agent, ACEI/ARB, Beta-blocker, Statins, Oral hypoglycemic agents, Insulin). p values in bold are < 0.05.

Abbreviations: TyG index, triglyceride-glucose index; BMI, body mass index; PLT, platelet; UA, uric acid; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; ALP, alkaline phosphatase; LVEF, left ventricle ejection fraction; TC, total cholesterol; HT his, history of hypertension; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker, MACCEs Major adverse cardiac and cerebral events; HR, hazard ratio; CI, confidence interval; Ref, reference.

Table 6 Evaluate the Incremental Predictive Value and Predictive Power of Various Models with NRI, IDI and C-Index

Characteristic	C-Index	p	Continuous NRI	p	IDI	p
Original model	0.588 (0.565–0.610)	<0.001		Ref		Ref
+TG	0.622 (0.600–0.644)	<0.001	0.173 (0.057–0.282)	0.004	0.027 (0.010–0.043)	0.004
+FPG	0.662 (0.641–0.683)	<0.001	0.278 (0.171–0.384)	0.004	0.089 (0.061–0.116)	<0.001
+TyG-Index	0.678 (0.658–0.698)	<0.001	0.361 (0.253–0.454)	0.002	0.138 (0.098–0.175)	0.002

Notes: Baseline risk model including age, PLT, UA, ALP. p values in bold are < 0.05.

Abbreviations: NRI, net reclassification improvement; IDI, integrated discrimination improvement; FPG, fasting plasma glucose; TG, triglyceride; TyG, triglyceride-glucose index; UA, uric acid; ALP, alkaline phosphatase; PLT, platelet; Ref, reference.

Figure 3 Time-dependent ROC curves of the TyG index for the prediction of MACCEs.

Figure 4 Forest plot of composite MACCEs according to different subgroups.

Notes: Adjusted model included Age, gender, smoking, HT his, BMI, Neutrophil, lymphocyte, HDL-C, LDL-C, TC, UA, PLT, ALP, LVEF, Medication (Anti platelet agent, ACEI/ARB, Beta blocker, Statins, Oral hypoglycemic agents, Insulin).

Abbreviations: MACCEs, Major adverse cardiac and cerebral events; TyG, triglyceride‑glucose index; BMI, body mass index; HT his, history of hypertension; LDL-C, low-density lipoprotein-cholesterol; HDL-C, high-density lipoprotein-cholesterol; TC, total cholesterol; UA, uric acid; PLT, platelet; ALP, alkaline phosphatase; ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; HR, hazard ratio; CI, confidence interval; Ref., reference (TyG ≤ 7.21 group).