Clinical value of high-density lipoprotein-mediated cholesterol efflux capacity in diabetes mellitus_West China Medical Journal

Authors：

YU Ting ^1,2,3 , GAN Wei ^1,2,3 , YU Xingzhi ^1,2,3 , DING Fei ^1,2,3 ,  ZHAO Yanhua ^1,2,3

1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
2. Clinical Laboratory Medicine Research Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P. R. China;
3. Sichuan Provincial Clinical Research Center for Laboratory Medicine, Chengdu, Sichuan 610041, P. R. China;

Corresponding?author：

ZHAO Yanhua, Email: zhaoyanhua527@163.com

Keywords：

High-density lipoprotein; cholesterol efflux capacity; type 2 diabetes mellitus; cardiovascular disease

DOI：

10.7507/1002-0179.202607128

Video：

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Objective To investigate the changes and clinical significance of high-density lipoprotein (HDL)-mediated cholesterol efflux capacity (CEC) in patients with diabetes mellitus. Methods Patients with diabetes attending West China Hospital of Sichuan University between January 2022 and June 2024 and healthy physical examination subjects during the same period (serving as the control group) were selected. The diabetic group was further divided into high glycated hemoglobin (HbA1c) with normal fasting plasma glucose (FPG) group and high HbA1c with high FPG group. CEC levels were compared among groups, correlations between CEC and glucose/lipid metabolism indices were analyzed, and binary logistic regression was used to assess the independent association between CEC and diabetes. Results A total of 260 patients with diabetes were enrolled, and 203 patients in the control group. Among them, there were 88 cases in the high HbA1c with normal FPG group and 172 cases in the high HbA1c with high FPG group. Compared with the control group [30.52% (26.99%, 32.25%)], CEC levels in the high HbA1c with normal FPG group [26.01% (23.81%, 28.21%)] and the high HbA1c with high FPG group [24.02% (17.40%, 27.49%)] were significantly lower (P<0.001). At the same HbA1c stratum, higher FPG was associated with lower CEC; at the same FPG stratum, higher HbA1c was associated with lower CEC. Correlation analysis showed that CEC was negatively correlated with FPG (r=?0.434, P<0.001) and HbA1c (r=–0.444, P<0.001), positively correlated with apolipoprotein A-Ⅰ (r=0.363, P<0.001), positively correlated with HDL-cholesterol (r=0.103, P=0.028). Multivariate logistic regression analysis showed that CEC was still associated with diabetes [odds ratio=0.785, 95% confidence interval (0.732, 0.842), P<0.001]. Conclusions HDL-mediated CEC is significantly impaired in patients with diabetes, and the degree of impairment worsens with increasing blood glucose and HbA1c levels. Routine lipid parameters cannot reflect HDL function, and CEC may serve as an independent indicator for evaluating the risk of diabetes and its cardiovascular complications.

Citation： YU Ting, GAN Wei, YU Xingzhi, DING Fei, ZHAO Yanhua. Clinical value of high-density lipoprotein-mediated cholesterol efflux capacity in diabetes mellitus. West China Medical Journal, 2026, 41(8): 1265-1270. doi: 10.7507/1002-0179.202607128 Copy

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2.	Paneni F, Cosentino F, Marrara F, et al. The clinical relevance of dysfunctional HDL in patients with coronary artery disease: a 3-year follow-up study[J]. Int J Cardiol, 2012, 158(1): 158-160.
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12.	Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis[J]. N Engl J Med, 2011, 364(2): 127-135.
13.	He Y, Ronsein GE, Tang C, et al. Diabetes impairs cellular cholesterol efflux from ABCA1 to small HDL particles[J]. Circ Res, 2020, 127(9): 1198-1210.
14.	Ahmed MO, Byrne RE, Pazderska A, et al. HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study[J]. Diabetologia, 2021, 64(3): 656-667.
15.	Zhang X, van der Vorst EPC. High-density lipoprotein modifications: causes and functional consequences in type 2 diabetes mellitus[J]. Cells, 2024, 13(13): 1113.
16.	Passarelli M, Tang C, McDonald TO, et al. Advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cells[J]. Diabetes, 2005, 54(7): 2198-2205.
17.	Lui DTW, Tan KCB. High-density lipoprotein in diabetes: structural and functional relevance[J]. J Diabetes Investig, 2024, 15(7): 805-816.
18.	Orozco Morales JA, Medina Urrutia AX, Tamayo MT, et al. Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes[J/OL]. Front Pediatr, 2024, 12: 1462406. DOI: 10.3389/fped.2024.1462406.
19.	Uruska A, Mietkiewska-Dolecka M, Grzelka-Wozniak A, et al. Clinical remission in newly diagnosed type 1 diabetes mellitus and HDL function on cholesterol efflux capacity: prospective InLipoDiab1 study[J/OL]. Endocr Connect, 2025, 14(6): e240704. DOI: 10.1530/EC-24-0704.
20.	Yamashita M, Tamasawa N, Matsuki K, et al. Insulin suppresses HDL-mediated cholesterol efflux from macrophages through inhibition of neutral cholesteryl ester hydrolase and ATP-binding cassette transporter G1 expressions[J]. J Atheroscler Thromb, 2010, 17(11): 1183-1189.
21.	Brunham LR, Kruit JK, Pape TD, et al. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment[J]. Nat Med, 2007, 13(3): 340-347.
22.	Genest J, Choi HY. The cholesterol uptake capacity: the search for scalable HDL function tests continues[J]. Atherosclerosis, 2022, 345: 39-40.
23.	Harada A, Toh R, Murakami K, et al. Cholesterol uptake capacity: a new measure of HDL functionality for coronary risk assessment[J]. J Appl Lab Med, 2017, 2(2): 186-200.

1. The AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy[J]. N Engl J Med, 2011, 365(24): 2255-2267.
2. Paneni F, Cosentino F, Marrara F, et al. The clinical relevance of dysfunctional HDL in patients with coronary artery disease: a 3-year follow-up study[J]. Int J Cardiol, 2012, 158(1): 158-160.
3. Briel M, Ferreira-Gonzalez I, You JJ, et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: systematic review and meta-regression analysis[J]. BMJ, 2009, 338: b92.
4. Rohatgi A, Westerterp M, von Eckardstein A, et al. HDL in the 21st century: a multifunctional roadmap for future HDL research[J]. Circulation, 2021, 143(23): 2293-2309.
5. Smith JD, Le Goff W, Settle M, et al. ABCA1 mediates concurrent cholesterol and phospholipid efflux to apolipoprotein A-I[J]. J Lipid Res, 2004, 45(4): 635-644.
6. Rohatgi A, Khera A, Berry JD, et al. HDL cholesterol efflux capacity and incident cardiovascular events[J]. N Engl J Med, 2014, 371(25): 2383-2393.
7. Saleheen D, Scott R, Javad S, et al. Association of HDL cholesterol efflux capacity with incident coronary heart disease events: a prospective case-control study[J]. Lancet Diabetes Endocrinol, 2015, 3(7): 507-513.
8. Marx N, Federici M, Schütt K, et al. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes: developed by the task force on the management of cardiovascular disease in patients with diabetes of the European Society of Cardiology (ESC)[J]. Eur Heart J, 2023, 44(39):4043-4140.
9. Liu M, Pei J, Zeng C, et al. Association of non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio with cardiovascular outcomes in patients with type 2 diabetes mellitus: evidence from the ACCORD cohort[J]. Diabetes Obes Metab, 2025, 27(1): 300-311.
10. Cochran BJ, King TW, Chemello K, et al. HDL metabolism and function in diabetes mellitus[J]. Nat Rev Endocrinol, 2026, 22(1): 36-49.
11. 中華醫學會糖尿病學分會. 中國 2 型糖尿病防治指南(2020 年版)[J]. 中華糖尿病雜志, 2021, 41(5): 482-548.
12. Khera AV, Cuchel M, de la Llera-Moya M, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis[J]. N Engl J Med, 2011, 364(2): 127-135.
13. He Y, Ronsein GE, Tang C, et al. Diabetes impairs cellular cholesterol efflux from ABCA1 to small HDL particles[J]. Circ Res, 2020, 127(9): 1198-1210.
14. Ahmed MO, Byrne RE, Pazderska A, et al. HDL particle size is increased and HDL-cholesterol efflux is enhanced in type 1 diabetes: a cross-sectional study[J]. Diabetologia, 2021, 64(3): 656-667.
15. Zhang X, van der Vorst EPC. High-density lipoprotein modifications: causes and functional consequences in type 2 diabetes mellitus[J]. Cells, 2024, 13(13): 1113.
16. Passarelli M, Tang C, McDonald TO, et al. Advanced glycation end product precursors impair ABCA1-dependent cholesterol removal from cells[J]. Diabetes, 2005, 54(7): 2198-2205.
17. Lui DTW, Tan KCB. High-density lipoprotein in diabetes: structural and functional relevance[J]. J Diabetes Investig, 2024, 15(7): 805-816.
18. Orozco Morales JA, Medina Urrutia AX, Tamayo MT, et al. Impact of metabolic-associated fatty liver disease on the cholesterol efflux capacity of high-density lipoproteins in adolescents with type 2 diabetes[J/OL]. Front Pediatr, 2024, 12: 1462406. DOI: 10.3389/fped.2024.1462406.
19. Uruska A, Mietkiewska-Dolecka M, Grzelka-Wozniak A, et al. Clinical remission in newly diagnosed type 1 diabetes mellitus and HDL function on cholesterol efflux capacity: prospective InLipoDiab1 study[J/OL]. Endocr Connect, 2025, 14(6): e240704. DOI: 10.1530/EC-24-0704.
20. Yamashita M, Tamasawa N, Matsuki K, et al. Insulin suppresses HDL-mediated cholesterol efflux from macrophages through inhibition of neutral cholesteryl ester hydrolase and ATP-binding cassette transporter G1 expressions[J]. J Atheroscler Thromb, 2010, 17(11): 1183-1189.
21. Brunham LR, Kruit JK, Pape TD, et al. Beta-cell ABCA1 influences insulin secretion, glucose homeostasis and response to thiazolidinedione treatment[J]. Nat Med, 2007, 13(3): 340-347.
22. Genest J, Choi HY. The cholesterol uptake capacity: the search for scalable HDL function tests continues[J]. Atherosclerosis, 2022, 345: 39-40.
23. Harada A, Toh R, Murakami K, et al. Cholesterol uptake capacity: a new measure of HDL functionality for coronary risk assessment[J]. J Appl Lab Med, 2017, 2(2): 186-200.

West China Medical Journal

Clinical value of high-density lipoprotein-mediated cholesterol efflux capacity in diabetes mellitus

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