Association between insulin resistance and left ventricular remodeling after STEMI in patients without a history of diabetes mellitus

doi:10.3969/j.issn.1674-8115.2025.03.005

Abstract

Abstract:

Objective ·To investigate the association of insulin resistance with left ventricular (LV) remodeling after ST-segment elevation myocardial infarction (STEMI) in patients without a history of diabetes mellitus. Methods ·This study consecutively enrolled STEMI patients without a history of diabetes mellitus who underwent percutaneous coronary intervention in the Department of Cardiology of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from January 2014 to December 2022. The patients were followed up for 6 months. Age, gender, smoking status, blood pressure, body mass index, biochemical indexes (liver function, kidney function, lipid profiles, glycemic levels and peak troponin levels, etc.) and pharmacological treatment were recorded. Homeostasis model assessment of insulin resistance (HOMA-IR) was used to evaluate insulin resistance and mean values of visit-to-visit HOMA-IR were calculated. Patients were divided into 4 groups (low-level group, low-to-medium-level group, medium-to-high-level group, and high-level group) according to the quartiles of mean HOMA-IR levels. Echocardiography was performed at baseline and during follow-up. Then the association between mean values of insulin resistance and post-infarction LV remodeling was analyzed. Results ·A total of 219 patients were finally included, with an average age of (62.7±11.9) years, and male patients accounted for 85.4% (187 cases). The average follow-up time was (6.4±1.8) months. During follow-up, the average number of HOMA-IR measurements was (4.32±2.18), and the mean value of visit-to-visit HOMA-IR was 2.41 (1.58, 3.98), which was higher than normal range. The results showed that post-infarction LV end-diastolic diameter (P=0.027) and LV end-diastolic volume index (P=0.013) generally showed a trend for dilation with increasing mean HOMA-IR levels. Pearson correlation analysis revealed the mean values of visit-to-visit HOMA-IR were positively correlated to changes in LV dimensions (Δ LV end-diastolic volume index: r=0.20, P=0.003; Δ LV end-diastolic diameter: r=0.21, P=0.002). Multivariate regression analysis demonstrated that higher HOMA-IR was independently associated with greater LV dilation after STEMI, even after adjusting for age, gender, traditional risk factors (history of hypertension, body mass index, smoking status, renal function and lipid profiles), pharmacological treatment, baseline LV ejection fraction and peak troponin levels. Compared with patients with the lowest quartile of HOMA-IR, those with the highest HOMA-IR quartile exhibited a 7.727 mL/m² increase in LV end-diastolic volume index (P<0.001). Conclusion ·This study reveals that insulin resistance is prevalent in STEMI patients without a history of diabetes mellitus. Insulin resistance is an independent predictor of adverse LV remodeling in this population.

Key words: insulin resistance, myocardial infarction, left ventricular dilation, remodeling

CLC Number:

R543.3

YANG Chendie, HU Changqing, YUAN He, TAY Guan Poh, AMUTI Abulikemu, ZHANG Ruiyan, WANG Xiaoqun. Association between insulin resistance and left ventricular remodeling after STEMI in patients without a history of diabetes mellitus[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(3): 292-300.

Figures/Tables 6

TrendMD

References 24

1	JENČA D, MELENOVSKÝ V, STEHLIK J, et al. Heart failure after myocardial infarction: incidence and predictors[J]. ESC Heart Fail, 2021, 8(1): 222-237.
2	FRANTZ S, HUNDERTMARK M J, SCHULZ-MENGER J, et al. Left ventricular remodelling post-myocardial infarction: pathophysiology, imaging, and novel therapies[J]. Eur Heart J, 2022, 43(27): 2549-2561.
3	YAP J, IREI J, LOZANO-GERONA J, et al. Macrophages in cardiac remodelling after myocardial infarction[J]. Nat Rev Cardiol, 2023, 20(6): 373-385.
4	QUIJADA P, PARK S, ZHAO P, et al. Cardiac pericytes mediate the remodeling response to myocardial infarction[J]. J Clin Invest, 2023, 133(10): e162188.
5	BULLUCK H, CARBERRY J, CARRICK D, et al. Redefining adverse and reverse left ventricular remodeling by cardiovascular magnetic resonance following ST-segment-elevation myocardial infarction and their implications on long-term prognosis[J]. Circ Cardiovasc Imaging, 2020, 13(7): e009937.
6	BOSTAN M M, STĂTESCU C, ANGHEL L, et al. Post-myocardial infarction ventricular remodeling biomarkers-the key link between pathophysiology and clinic[J]. Biomolecules, 2020, 10(11): 1587.
7	YANG C D, SHEN Y, DING F H, et al. Visit-to-visit fasting plasma glucose variability is associated with left ventricular adverse remodeling in diabetic patients with STEMI[J]. Cardiovasc Diabetol, 2020, 19(1): 131.
8	LEE S H, PARK S Y, CHOI C S. Insulin resistance: from mechanisms to therapeutic strategies[J]. Diabetes Metab J, 2022, 46(1): 15-37.
9	DI PINO A, DEFRONZO R A. Insulin resistance and atherosclerosis: implications for insulin-sensitizing agents[J]. Endocr Rev, 2019, 40(6): 1447-1467.
10	ROKICKA D, HUDZIK B, WRÓBEL M, et al. The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes[J]. Cardiovasc Diabetol, 2024, 23(1): 147.
11	JIANG H D, LIU Y T, GUO H Y, et al. The association between the triglyceride-glucose index and in-stent restenosis in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis[J]. BMC Cardiovasc Disord, 2024, 24(1): 234.
12	SUNDSTRÖM J, LIND L, NYSTRÖM N, et al. Left ventricular concentric remodeling rather than left ventricular hypertrophy is related to the insulin resistance syndrome in elderly men[J]. Circulation, 2000, 101(22): 2595-2600.
13	PARIZO J, MAHAFFEY K W. Diabetes and heart failure post-acute myocardial infarction: important associations and need for evidence-based interventions[J]. Eur J Prev Cardiol, 2020, 27(17): 1887-1889.
14	INGELSSON E, SUNDSTRÖM J, ARNLÖV J, et al. Insulin resistance and risk of congestive heart failure[J]. JAMA, 2005, 294(3): 334-341.
15	SHAH R V, ABBASI S A, HEYDARI B, et al. Insulin resistance, subclinical left ventricular remodeling, and the obesity paradox: MESA (Multi-Ethnic Study of Atherosclerosis)[J]. J Am Coll Cardiol, 2013, 61(16): 1698-1706.
16	QIAO T T, LUO T, PEI H L, et al. Association between abdominal obesity indices and risk of cardiovascular events in Chinese populations with type 2 diabetes: a prospective cohort study[J]. Cardiovasc Diabetol, 2022, 21(1): 225.
17	LIU Y K, LING S S, LUI L M W, et al. Prevalence of type 2 diabetes mellitus, impaired fasting glucose, general obesity, and abdominal obesity in patients with bipolar disorder: a systematic review and meta-analysis[J]. J Affect Disord, 2022, 300: 449-461.
18	WAN H, WANG Y Y, XIANG Q, et al. Associations between abdominal obesity indices and diabetic complications: Chinese visceral adiposity index and neck circumference[J]. Cardiovasc Diabetol, 2020, 19(1): 118.
19	MOHAMMADI H, OHM J, DISCACCIATI A, et al. Abdominal obesity and the risk of recurrent atherosclerotic cardiovascular disease after myocardial infarction[J]. Eur J Prev Cardiol, 2020, 27(18): 1944-1952.
20	POWELL-WILEY T M, POIRIER P, BURKE L E, et al. Obesity and cardiovascular disease: a scientific statement from the American heart association[J]. Circulation, 2021, 143(21): e984-e1010.
21	DALE ABEL E. Insulin signaling in the heart[J]. Am J Physiol Endocrinol Metab, 2021, 321(1): E130-E145.
22	TRIFUNOVIC D, STANKOVIC S, SOBIC-SARANOVIC D, et al. Acute insulin resistance in ST-segment elevation myocardial infarction in non-diabetic patients is associated with incomplete myocardial reperfusion and impaired coronary microcirculatory function[J]. Cardiovasc Diabetol, 2014, 13: 73.
23	THAKKER G D, FRANGOGIANNIS N G, BUJAK M, et al. Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction[J]. Am J Physiol Heart Circ Physiol, 2006, 291(5): H2504-H2514.
24	MENG Z J, ZHANG Z, ZHAO J L, et al. Nitrative modification of caveolin-3: a novel mechanism of cardiac insulin resistance and a potential therapeutic target against ischemic heart failure in prediabetic animals[J]. Circulation, 2023, 147(15): 1162-1179.

Item	Mean HOMA-IR level				P value
Item	Low (≤1.58) (n=55)	Low-medium (>1.58 and ≤2.41) (n=56)	Medium-high (>2.41 and ≤3.98) (n=54)	High (>3.98) (n=54)	P value
Demographic characteristics and clinical assessment
Gender (male)/n (%)	48 (87.3)	46 (82.1)	47 (87.0)	46 (85.2)	0.862
Age/year	63.40±12.28	66.04±10.56	60.39±10.45	60.70±13.47	0.042
Hypertension/%	27 (49.1)	25 (44.6)	28 (51.9)	39 (72.2)	0.020
Current smoker/%	27 (49.1)	22 (39.3)	27 (50.0)	30 (55.6)	0.386
BMI/(kg·m^-2)	23.24±3.48	23.67±3.27	25.80±2.74	27.27±6.61	<0.001
Systolic blood pressure/mmHg	121.89±22.83	121.36±16.63	121.72±20.59	127.48±17.38	0.305
Diastolic blood pressure/mmHg	73.78±13.63	76.68±12.50	74.61±14.66	77.39±13.11	0.460
Laboratory measurement
HbA1c/%	5.61±0.32	5.66±0.38	5.87±0.84	6.19±1.22	0.001
Fasting glucose/(mmol·L^-1)	5.60 (4.96‒7.53)	6.68 (5.34‒8.48)	5.84 (4.78‒7.50)	6.54 (5.62‒9.00)	0.073
2 h Postprandial blood glucose/(mmol·L^-1)	8.61 (7.46‒12.40)	8.72 (7.37‒10.40)	8.30 (7.01‒10.59)	8.61 (7.46‒12.40)	0.587
Fasting insulin/(μIU·mL^-1)	6.69(5.02‒9.12)	9.27 (7.22‒12.45)	14.29 (11.31‒17.47)	16.67 (12.83‒21.80)	<0.001
Alanine transaminase/(IU·L^-1)	34.80±26.54	42.71±39.29	37.28±22.18	46.44±31.00	0.188
Triglyceride/(mmol·L^-1)	1.08 (0.77‒1.60)	1.43 (1.00‒1.80)	1.82 (1.31‒2.41)	1.90 (1.35‒2.45)	<0.001
Total cholesterol/(mmol·L^-1)	4.68±1.39	4.60±1.29	4.77±1.05	4.86±1.05	0.700
LDL-C/(mmol·L^-1)	3.04±1.36	2.91±1.01	3.01±1.00	3.01±0.85	0.928
HDL-C/(mmol·L^-1)	1.14±0.28	1.09±0.24	1.03±0.20	1.02±0.20	0.030
Serum creatine/(μmol·L^-1)	79.42±17.26	82.36±16.11	84.83±22.32	84.24±25.95	0.521
Blood urea nitrogen/(mmol·L^-1)	5.81±1.58	5.74±1.52	5.52±1.63	5.61±1.60	0.775
eGFR/[mL·min^-1·(1.732 m)^-2]	97.50±21.38	91.00±12.33	98.45±25.65	97.94±22.95	0.208
NT-proBNP/(pg·mL^-1)	355.50 (148.40‒1 525.00)	493.25 (192.78‒1 364.50)	602.15 (135.18‒1 861.00)	253.20 (110.62‒1 069.00)	0.285
Peak cTnI level/(ng·mL^-1)	41.20 (5.47‒87.67)	54.70 (15.42‒104.85)	44.64 (9.69‒110.19)	31.40 (25.61‒95.52)	0.389
Medication use
Aspirin/n (%)	50 (90.9)	56 (100.0)	54 (100.0)	51 (94.4)	0.025
P2Y12 inhibitor/n (%)	55 (100.0)	52 (92.9)	54 (100.0)	50 (92.6)	0.041
β blocker/n (%)	53 (96.4)	40 (71.4)	47 (87.0)	50 (92.6)	0.001
ACEI/ARB/n (%)	36 (65.5)	39 (69.6)	39 (72.2)	47 (87.0)	0.061
ARNI/n (%)	15 (27.3)	12 (21.4)	16 (29.6)	17 (31.5)	0.661
SGLT2 inhibitor/n (%)	2 (3.6)	2 (3.6)	2 (3.7)	7 (13.0)	0.096
MRA/n (%)	4 (7.3)	6 (10.7)	7 (13.0)	6 (11.1)	0.806
Diuretics/n (%)	1 (1.8)	6 (10.7)	7 (13.0)	4 (7.4)	0.164

Item	Mean HOMA-IR level				P value
Item	Low (≤1.58) (n=55)	Low-medium (>1.58 and ≤2.41) (n=56)	Medium-high (>2.41 and ≤3.98) (n=54)	High (>3.98) (n=54)	P value
Demographic characteristics and clinical assessment
Gender (male)/n (%)	48 (87.3)	46 (82.1)	47 (87.0)	46 (85.2)	0.862
Age/year	63.40±12.28	66.04±10.56	60.39±10.45	60.70±13.47	0.042
Hypertension/%	27 (49.1)	25 (44.6)	28 (51.9)	39 (72.2)	0.020
Current smoker/%	27 (49.1)	22 (39.3)	27 (50.0)	30 (55.6)	0.386
BMI/(kg·m^-2)	23.24±3.48	23.67±3.27	25.80±2.74	27.27±6.61	<0.001
Systolic blood pressure/mmHg	121.89±22.83	121.36±16.63	121.72±20.59	127.48±17.38	0.305
Diastolic blood pressure/mmHg	73.78±13.63	76.68±12.50	74.61±14.66	77.39±13.11	0.460
Laboratory measurement
HbA1c/%	5.61±0.32	5.66±0.38	5.87±0.84	6.19±1.22	0.001
Fasting glucose/(mmol·L^-1)	5.60 (4.96‒7.53)	6.68 (5.34‒8.48)	5.84 (4.78‒7.50)	6.54 (5.62‒9.00)	0.073
2 h Postprandial blood glucose/(mmol·L^-1)	8.61 (7.46‒12.40)	8.72 (7.37‒10.40)	8.30 (7.01‒10.59)	8.61 (7.46‒12.40)	0.587
Fasting insulin/(μIU·mL^-1)	6.69(5.02‒9.12)	9.27 (7.22‒12.45)	14.29 (11.31‒17.47)	16.67 (12.83‒21.80)	<0.001
Alanine transaminase/(IU·L^-1)	34.80±26.54	42.71±39.29	37.28±22.18	46.44±31.00	0.188
Triglyceride/(mmol·L^-1)	1.08 (0.77‒1.60)	1.43 (1.00‒1.80)	1.82 (1.31‒2.41)	1.90 (1.35‒2.45)	<0.001
Total cholesterol/(mmol·L^-1)	4.68±1.39	4.60±1.29	4.77±1.05	4.86±1.05	0.700
LDL-C/(mmol·L^-1)	3.04±1.36	2.91±1.01	3.01±1.00	3.01±0.85	0.928
HDL-C/(mmol·L^-1)	1.14±0.28	1.09±0.24	1.03±0.20	1.02±0.20	0.030
Serum creatine/(μmol·L^-1)	79.42±17.26	82.36±16.11	84.83±22.32	84.24±25.95	0.521
Blood urea nitrogen/(mmol·L^-1)	5.81±1.58	5.74±1.52	5.52±1.63	5.61±1.60	0.775
eGFR/[mL·min^-1·(1.732 m)^-2]	97.50±21.38	91.00±12.33	98.45±25.65	97.94±22.95	0.208
NT-proBNP/(pg·mL^-1)	355.50 (148.40‒1 525.00)	493.25 (192.78‒1 364.50)	602.15 (135.18‒1 861.00)	253.20 (110.62‒1 069.00)	0.285
Peak cTnI level/(ng·mL^-1)	41.20 (5.47‒87.67)	54.70 (15.42‒104.85)	44.64 (9.69‒110.19)	31.40 (25.61‒95.52)	0.389
Medication use
Aspirin/n (%)	50 (90.9)	56 (100.0)	54 (100.0)	51 (94.4)	0.025
P2Y12 inhibitor/n (%)	55 (100.0)	52 (92.9)	54 (100.0)	50 (92.6)	0.041
β blocker/n (%)	53 (96.4)	40 (71.4)	47 (87.0)	50 (92.6)	0.001
ACEI/ARB/n (%)	36 (65.5)	39 (69.6)	39 (72.2)	47 (87.0)	0.061
ARNI/n (%)	15 (27.3)	12 (21.4)	16 (29.6)	17 (31.5)	0.661
SGLT2 inhibitor/n (%)	2 (3.6)	2 (3.6)	2 (3.7)	7 (13.0)	0.096
MRA/n (%)	4 (7.3)	6 (10.7)	7 (13.0)	6 (11.1)	0.806
Diuretics/n (%)	1 (1.8)	6 (10.7)	7 (13.0)	4 (7.4)	0.164

Item	Mean HOMA-IR level				P value
Item	Low(≤1.58)	Low-medium (>1.58 and ≤2.41)	Medium-high (>2.41 and ≤3.98)	High (>3.98)	P value
LVEDV index/(mL·m^-2)
Baseline	71.41±20.42	68.22±15.72	73.52±18.68	63.09±11.13	0.009
Follow-up	68.69±21.54	69.11±16.91	71.99±14.54	66.85±12.42	0.455
Δ	-2.73±12.30	0.88±9.58	-1.52±12.01	3.77±9.93	0.013
LVESV index/(mL·m^-2)
Baseline	30.01±15.62	27.96±12.03	31.20±14.04	24.48±6.23	0.032
Follow-up	28.45±16.11	28.33±12.47	28.74±10.16	25.67±8.75	0.528
Δ	-1.56±6.22	0.37±5.87	-2.46±9.57	1.19±8.10	0.047
LVEDD/mm
Baseline	50.56±6.50	49.84±6.06	52.46±5.45	49.87±4.01	0.051
Follow-up	49.76±6.99	50.00±5.93	52.07±4.41	50.91±4.13	0.118
Δ	-0.80±3.46	0.16±3.03	-0.39±3.49	1.04±3.31	0.027
LVESD/mm
Baseline	34.44±7.14	33.88±6.55	35.91±6.33	33.39±4.15	0.168
Follow-up	33.64±7.40	33.91±6.31	35.00±4.67	33.72±4.64	0.599
Δ	-0.80±2.59	0.04±2.91	-0.91±3.67	0.33±4.11	0.147
IVST/mm
Baseline	9.36±1.01	9.32±1.16	9.93±1.53	9.46±1.30	0.050
Follow-up	9.33±1.02	9.11±1.14	9.54±1.22	9.46±1.19	0.216
Δ	-0.04±0.90	-0.21±0.99	-0.39±1.17	0±1.17	0.204
LVPWT/mm
Baseline	8.93±0.63	8.66±0.84	9.33±0.95	9.00±1.18	0.002
Follow-up	8.87±0.75	8.79±0.85	9.13±0.97	8.91±0.96	0.216
Δ	-0.05±0.65	0.12±0.72	-0.20±0.88	-0.09±1.15	0.255
LVMI/(g·mm^-2)
Baseline	96.11±24.27	90.16±18.38	103.38±28.52	86.74±18.06	0.001
Follow-up	92.94±24.73	90.57±21.50	97.43±22.24	89.89±20.66	0.288
Δ	-3.17±15.22	0.42±12.82	-5.95±14.79	3.15±15.28	0.008
LVEF/%
Baseline	57.85±8.97	58.20±8.85	56.69±9.80	59.31±8.09	0.500
Follow-up	58.44±9.98	57.91±9.55	58.33±8.33	60.24±7.33	0.531
Δ	0.58±4.89	-0.29±4.77	1.65±3.89	0.93±7.08	0.285

Item	Mean HOMA-IR level				P value
Item	Low(≤1.58)	Low-medium (>1.58 and ≤2.41)	Medium-high (>2.41 and ≤3.98)	High (>3.98)	P value
LVEDV index/(mL·m^-2)
Baseline	71.41±20.42	68.22±15.72	73.52±18.68	63.09±11.13	0.009
Follow-up	68.69±21.54	69.11±16.91	71.99±14.54	66.85±12.42	0.455
Δ	-2.73±12.30	0.88±9.58	-1.52±12.01	3.77±9.93	0.013
LVESV index/(mL·m^-2)
Baseline	30.01±15.62	27.96±12.03	31.20±14.04	24.48±6.23	0.032
Follow-up	28.45±16.11	28.33±12.47	28.74±10.16	25.67±8.75	0.528
Δ	-1.56±6.22	0.37±5.87	-2.46±9.57	1.19±8.10	0.047
LVEDD/mm
Baseline	50.56±6.50	49.84±6.06	52.46±5.45	49.87±4.01	0.051
Follow-up	49.76±6.99	50.00±5.93	52.07±4.41	50.91±4.13	0.118
Δ	-0.80±3.46	0.16±3.03	-0.39±3.49	1.04±3.31	0.027
LVESD/mm
Baseline	34.44±7.14	33.88±6.55	35.91±6.33	33.39±4.15	0.168
Follow-up	33.64±7.40	33.91±6.31	35.00±4.67	33.72±4.64	0.599
Δ	-0.80±2.59	0.04±2.91	-0.91±3.67	0.33±4.11	0.147
IVST/mm
Baseline	9.36±1.01	9.32±1.16	9.93±1.53	9.46±1.30	0.050
Follow-up	9.33±1.02	9.11±1.14	9.54±1.22	9.46±1.19	0.216
Δ	-0.04±0.90	-0.21±0.99	-0.39±1.17	0±1.17	0.204
LVPWT/mm
Baseline	8.93±0.63	8.66±0.84	9.33±0.95	9.00±1.18	0.002
Follow-up	8.87±0.75	8.79±0.85	9.13±0.97	8.91±0.96	0.216
Δ	-0.05±0.65	0.12±0.72	-0.20±0.88	-0.09±1.15	0.255
LVMI/(g·mm^-2)
Baseline	96.11±24.27	90.16±18.38	103.38±28.52	86.74±18.06	0.001
Follow-up	92.94±24.73	90.57±21.50	97.43±22.24	89.89±20.66	0.288
Δ	-3.17±15.22	0.42±12.82	-5.95±14.79	3.15±15.28	0.008
LVEF/%
Baseline	57.85±8.97	58.20±8.85	56.69±9.80	59.31±8.09	0.500
Follow-up	58.44±9.98	57.91±9.55	58.33±8.33	60.24±7.33	0.531
Δ	0.58±4.89	-0.29±4.77	1.65±3.89	0.93±7.08	0.285

Mean HOMA-IR level	Model 1	Model 2	Model 3	Model 4	Model 5
Low (≤1.58)	Reference	Reference	Reference	Reference	Reference
Low-medium (>1.58 and ≤2.41)
Coefficient (95%CI)	3.608 (-0.515‒7.730)	3.506 (-0.645‒7.657)	4.036 (-0.206‒8.279)	5.541 (1.169‒9.914)	3.036 (-1.373‒7.445)
Standardized β	0.141	0.137	0.157	0.216	0.118
P value	0.086	0.097	0.062	0.013	0.176
Medium-high (>2.41 and ≤3.98)
Coefficient (95%CI)	1.201 (-2.959‒5.361)	1.199 (-2.990‒5.388)	1.918 (-2.434‒6.270)	2.386 (-1.915‒6.688)	2.674 (-1.492‒6.839)
Standardized β	0.046	0.046	0.074	0.092	0.103
P value	0.570	0.573	0.386	0.275	0.207
High (>3.98)
Coefficient (95%CI)	6.492 (2.332‒10.652)	6.453 (2.266‒10.641)	7.348 (2.786‒11.910)	8.028 (3.530‒12.526)	7.727 (3.317‒12.136)
Standardized β	0.250	0.248	0.283	0.309	0.298
P value	0.002	0.003	0.002	<0.001	<0.001