Review
Copyright ©The Author(s) 2023.
World J Diabetes. Jun 15, 2023; 14(6): 724-740
Published online Jun 15, 2023. doi: 10.4239/wjd.v14.i6.724
Table 1 Epicardial adipose tissue expansion in patients with glucose metabolism disorders
Ref.
Participants, n
Amount of EAT in the observation group
Amount of EAT in the control group
P value
EAT thickness (mm) measured by echocardiography thickness on the right ventricular free wall
Baloglu et al[21], 2019 T2DM patients: 128; healthy controls: 323.53 ± 0.794.64 ± 1.39< 0.001
Akbas et al[22], 2014 T2DM patients: 156; healthy controls: 504.66 ± 1.503.91 ± 1.600.005
Chen et al[23], 2017 T2DM patients: 167; healthy controls: 824.00 (3.00-5.00)2.00 (1.00-3.00)< 0.001
Philouze et al[24], 2017 T2DM patients: 44; healthy controls: 356.40 ± 1.703.30 ± 1.10< 0.001
Cetin et al[25], 2013 T2DM patients: 139; age- and sex-matched controls: 406.00 ± 1.504.42 ± 1.00< 0.001
Yafei et al[26], 2019 T2DM patients: 76; age- and sex-matched controls: 306.23 ± 1.274.60 ± 1.03< 0.001
Christensen et al[27], 2019 T2DM patients: 770; age- and sex-matched controls: 2344.60 ± 1.803.40 ± 1.20< 0.0001
Wang et al[28], 2017 T2DM with duration ≤ 10 yr: 35; T2DM with duration > 10 yr: 334.47 ± 1.905.45 ± 1.40< 0.05
Altin et al[29], 2016 Patients with IR: 113; age- and sex-matched controls: 1127.34 ± 1.965.22 ± 1.75< 0.001
Iacobellis et al[30], 2008 Patients with IFG: 65; non-diabetic controls: 50Males: 8.00 ± 3.006.00 ± 2.00< 0.001
Females: 7.10 ± 4.005.80 ± 3.00
EAT volume (cm3) measured by computed tomography
Wang et al[31], 2008 T2DM patients: 49; non-diabetic controls: 78166.1 ± 60.6123.4 ± 41.8< 0.0001
Akyürek et al[32], 2014 T2DM patients: 93; non-diabetic controls: 8540.1 ± 23.9 16.9 ± 7.7< 0.001
Gullaksen et al[33], 2019 T2DM patients: 44; non-diabetic controls: 59119.0 ± 49.086.0 ± 40.0< 0.001
Groves et al[34], 2014 T2DM patients: 92; non-diabetic controls: 59118.6 ± 43.070.0 ± 44.0< 0.0001
Versteylen et al[35], 2012 Patients with IFG: 118; non-diabetic controls: 20992.0 ± 39.075.0 ± 34.0< 0.001
EAT volume (cm3) or area (cm2) measured by cardiac magnetic resonance
Huang et al[36], 2022 T2DM with duration ≤ 5 yr: 56; T2DM with duration > 5 yr: 5748.4 ± 13.4 cm358.4 ± 17.3 cm3< 0.001
Evin et al[37], 2016 T2DM patients: 20; healthy controls: 19135.0 ± 31.0 cm390.0 ± 30.0 cm3< 0.001
Al-Talabany et al[38], 2018 T2DM patients: 54; non-diabetic controls: 2913.5 ± 3.5 cm211.8 ± 4.1 cm2< 0.05
Rado et al[39], 2019 Prediabetes patients: 100; healthy controls: 2009.2 cm27.7 cm2< 0.001
Table 2 Relationship between increased epicardial adipose tissue and clinical characteristics of heart failure with preserved ejection fraction
Ref.
Participants, n
Imaging method
Relationship between increased EAT and clinical characteristics of HFpEF
Pathological changes
Clinical manifestations
Prognosis
van Woerden et al[48], 2018 64 HF patients with LVEF > 40%CMRMyocardial injury: increased creatine kinase-MB and TnTDecreased quality of life (KCCQ score)
Wang et al[49], 2022 53 HF patients with LVEF > 50%CMRInflammation: increased CRP; LV hypertrophy: increased LVmass index; LV diastolic dysfunction: increased E/e' and tricuspid regurgitation velocity
Venkateshvaran et al[50], 2022 182 HF patients with LVEF > 50%EchoInflammation; endothelial dysfunction; LV hypertrophy: increased LV septal wall thickness; LV diastolic dysfunction: increased E peak deceleration timeDecreased quality of life (KCCQ score)
Koepp et al[51], 2020 169 HF patients with LVEF > 50%EchoIncreased cardiac filling pressures, pulmonary hypertension, and pericardial restraintDecreased exercise capacity (VO2, AVO2 diff)
Haykowsky et al[52], 2018 100 HF patients with LVEF > 50%CMRDecreased exercise capacity (VO2, 6-min walk test, leg power)
Gorter et al[53], 2020 75 HF patients with LVEF > 45%EchoDecreased exercise capacity (VO2)
Pugliese et al[54], 2021 188 HF patients with LVEF > 50%EchoMyocardial injury: increased TnT; inflammation: increased CRPDecreased exercise capacity (peak VO2 and AVO2 diff)Increased risk of the composite endpoint of HF hospitalization and cardiovascular deaths
van Woerden et al[55], 2022 105 HF patients with LVEF > 40%CMRIncreased risk of HF hospitalization, all-cause death, and the composite endpoint
Table 3 Pharmacological interventions targeting epicardial adipose tissue
Ref.
Imaging method
Participants, n
Intervention method and duration
Change of EAT
Other findings
Park et al[74], 2010Echo145 coronary artery stenosis patientsAtorvastatin: n = 82, 20 mg/d; simvastatin: n = 63, 10 mg/d; for 6-8 moAtorvastatin decreased EAT thickness (0.47 ± 0.65 mm) more than simvastatin (EAT 0.12 ± 0.52 mm, P = 0.001)Decreased TC, TG, and LDL-C
Soucek et al[75], 2015CT38 atrial fibrillation patients Atorvastatin: 80 mg/d, for 3 moEAT volume decreased from 86.9 (64.1-124.8) mL to 92.3 (62.0- 133.3) mL (P < 0.05)Decreased CRP, TC, and LDL-C
Alexopoulos et al[76], 2013 CT 420 hyperlipidemic post-menopausal womenAtorvastatin: n = 194, 80 mg/d; pravastatin: n = 226, 40 mg/d; for 12 moAtorvastatin decreased EAT volume (3.38%) more than pravastatin (0.83%, P = 0.025)Decreased TC, TG, and LDL-C
Rivas Galvez et al[78], 2020 Echo41 patients treated with PCSK9 inhibitorsEvolocumab: n = 16; alirocumab: n = 8; twice in 6 moEAT thickness decreased by 20.39% (P = 0.0001).Decreased BMI, TC, and LDL-C
Iacobellis et al[82], 2017Echo41 patients T2DM Metformin: 500 mg-1000 mg, twice daily, for 6 moEAT thickness changed from 7.4 ± 1.6 mm to 7.5 ± 1.5 mm and 6.9 ± 1.3 mm at 3 and 6 mo, respectivelyDecreased BMI
Ziyrek et al[83], 2019Echo40 T2DM patientsMetformin: 1000 mg, twice daily, for 3 moEAT thickness decreased from 5.07 ± 1.33 mm to 4.76 ± 1.32 mm (P < 0.001)
Iacobellis et al[84], 2020 Echo51 T2DM patientsMetformin: 500 mg-1000 mg, twice daily, for 6 moEAT thickness decreased from 8.0 ± 2.5 mm to 7.4 ± 2.5 mm and 7.5 ± 2.4 mm at 3 and 6 mo, respectively (compared with baseline P < 0.016)
Moody et al[90], 2014 CMR12 T2DM patientsPioglitazone: 15 mg/d, for 2 wk, then increase to 45 mg/d, for 22 wkEAT area decreased from 15.3 ± 3.9 cm2 to 14.0 ± 3.9 cm2 (P = 0.03)Decreased paracardial adipose tissue; improved left ventricular diastolic function
Lima-Martínez et al[94], 2015 Echo26 T2DM patientsCombination of sitagliptin (50 mg) and metformin (1000 mg), twice daily, for 24 wkEAT thickness reduction of 15% (P = 0.001)
van Eyk et al[99], 2019CMR22 T2DM patientsLiraglutide: 0.6 mg/d gradually increased to 1.8 mg/d in 2 wk, for 26 wkEAT area reduction of 0 ± 2 cm2Decreased visceral fat volume
Bizino et al[100], 2020CMR23 T2DM patientsLiraglutide: 0.6 mg/d gradually increased to 1.8 mg/d in 2 wk, 26 wkEAT area reduction of 1.1 ± 6.0 cm2Decreased body weight and subcutaneous fat
Iacobellis et al[82], 2017 Echo54 T2DM patientsCombination of liraglutide (increased to 1.8 mg/once daily) and metformin (1000 mg, twice daily), for 12 wkEAT thickness reduction of 29% and 36% at 3 and 6 mo, respectivelyDecreased BMI and HbA1c
Zhao et al[101], 2021Echo21 T2DM patientsLiraglutide: 0.6 mg/d gradually increased to 1.2 mg/d in 3-5 d, for 3 moEAT decreased from 5.00 (5.0-7.0) mm to 3.95 ± 1.43 mm (P < 0.001)Decreased weight, HbA1c, TC, TG, and LDL-C
Dutour et al[102], 2016 CMR22 T2DM patientsExenatide: 5 mg twice daily, for 4 wk, then increase to 10 mg twice daily, for 22 wkEAT volume reduction of 8.8 ± 2.1%Decreased weight, HbA1c, and hepatic triglyceride content
Morano et al[103], 2015 Echo25 T2DM patientsCombination of exenatide (5 mg twice daily, for 1 mo, and then increase to 10 mg twice daily, for 2 mo) and liraglutide (1.2 mg/d), for 3 moEAT thickness decreased from 9.4 ± 1.6 mm to 8.0 ± 1.9 mm (P = 0.003)Decreased MRI; improved renal resistive index
Iacobellis et al[104], 2020 Echo6 T2DM patientsSemaglutide: n = 30, 1 mg weekly; dulaglutide: n = 30, 1.5 mg weekly; for 12 wkEAT thickness reduction of 20% in both semaglutide and dulaglutide groupsDecreased BMI and HbA1c
Requena et al[108], 2021 CMR84 non-diabetic patients with HFrEFEmpagliflozin: 10 mg/d, for 6 moEAT volume reduction of 5.14 mL, P < 0.05Decreasing subcutaneous fat and matrix volume
Ardahanlı et al[109], 2021 Echo37 T2DM patientsEmpagliflozin: 10 mg/d, for 6 moEAT thickness decreased from 7.6 ± 1.7 mm to 6.7 ± 1.3 mm (P < 0.001)Decreased BMI, waist circumference, HbA1c, uric acid, systolic and diastolic blood pressure, and carotid intima-media thickness
Iacobellis et al[84], 2020 Echo51 T2DM patientsCombination of dapagliflozin (5 to 10 mg/d) and metformin (500 to 1000 mg, twice daily), for 24 moEAT thickness decreased by 15% from baseline to 12 wk and 20% after 24 wk (compared with baseline P < 0.01)Decreased weight and HbA1c
Sato et al[110], 2018 CT20 T2DM patientsDapagliflozin: 10 mg/d, for 6 moEAT volume reduction of 16.4 ± 8.3 mL (P < 0.05)Decreased HbA1c, TNF-α, TG, insulin resistance, and left atrial dimension
Sato et al[111], 2020CT18 T2DM patients with coronary artery diseaseDapagliflozin: 5 mg/d, for 6 moEAT volume reduction of 15.2 ± 12.8 mL (P < 0.05)Decreased HbA1c, TNF-α, and insulin resistance
Braha et al[112], 2021CT52 T2DM patientsDapagliflozin: 10 mg/d, for 6 moEAT volume reduction of 17.1% (P < 0.001)Decreased BMI, triglyceride glucose index, and HbA1c
Yagi et al[113], 2017 Echo13 T2DM patientsCanagliflozin: 100 mg/d, for 6 moEAT thickness decreased from 9.3 ± 2.5 to 8.1 ± 2.3 mm (P < 0.01) and to 7.3 ± 2.0 mm (P < 0.001) at 3 mo and 6 mo, respectivelyDecreased BMI
Fukuda et al[114], 2017 CMR9 T2DM patientsIpragliflozin: 50 mg/d, 12 wkEAT volume decreased from 102 (79-126) mL to 89 (66-109) mL (P = 0.008)Decreased weight, BMI, HbA1c, TG, leptin, fasting plasma glucose, and insulin resistance
Bouchi et al[115], 2017CMR19 T2DM patientsLuseogliflozin: 2.5-5.0 mg/d for 12 wkEAT volume decreased from 117 (96-136) mL to 111 (88-134) mL (P = 0.048)Decreased weight, BMI, systolic and diastolic blood pressure, HbA1c, fasting plasma glucose, insulin resistance, and CRP
Gaborit et al[116], 2021CMR26 T2DM patientsEmpagliflozin: 10 mg/d, 12 wkEAT volume decreased from 108.5 ± 31.8 mL to 106.9 ± 31.8 mL (P = 0.09)Decreased BMI, TG, HbA1c, fasting blood glucose, liver fat content, and visceral fat volume