Exploration of Cardiology

Table 2. Vascular mechanisms shared by SD and PAD in diabetes.

Mechanisms	Pathophysiology	Impact on SD	Impact on PAD	References
Endothelial dysfunction	↓ NO bioavailability, oxidative stress	Impaired penile/clitoral vasodilation	Reduced arterial compliance, atherosclerosis	[10, 23, 24]
Atherosclerosis	Plaque formation, arterial stiffness	Arterial inflow restriction causing ED	Limb ischemia, claudication	[25, 26]
Microangiopathy	Basement membrane thickening, pericyte loss	Reduced genital perfusion	Poor distal limb perfusion	[27]
Inflammation and oxidative stress	↑ CRP, IL-6, TNF-α	Vascular injury, impaired erection	Plaque instability, PAD progression	[28, 29]
Impaired vascular repair	↓ EPCs	Reduced penile vascular recovery	Impaired collateral formation	[30]

Return to article view

NO: nitric oxide; CRP: C-reactive protein; IL-6: interleukin-6; TNF-α: tumor necrosis factor-alpha; EPCs: endothelial progenitor cells; SD: sexual dysfunction; PAD: peripheral artery disease; ED: erectile dysfunction; ↓ indicates decreased/reduced; ↑ indicates increased/elevated.

Declarations

Author contributions

AB: Conceptualization, Investigation, Writing—original draft. MCÇ: Conceptualization, Investigation, Writing—original draft. MK: Conceptualization, Writing—review & editing. MY: Writing—review & editing. LB: Supervision, Validation. YK: Supervision, Validation. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

No financial funding was received for this study.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al.; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9^th edition. Diabetes Res Clin Pract. 2019;157:107843. [DOI] [PubMed]

Wang CCL, Hess CN, Hiatt WR, Goldfine AB. Clinical Update: Cardiovascular Disease in Diabetes Mellitus: Atherosclerotic Cardiovascular Disease and Heart Failure in Type 2 Diabetes Mellitus - Mechanisms, Management, and Clinical Considerations. Circulation. 2016;133:2459–502. [DOI] [PubMed] [PMC]

Maiorino MI, Bellastella G, Esposito K. Diabetes and sexual dysfunction: current perspectives. Diabetes Metab Syndr Obes. 2014;7:95–105. [DOI] [PubMed] [PMC]

Pontiroli AE, Cortelazzi D, Morabito A. Female Sexual Dysfunction and Diabetes: A Systematic Review and Meta-Analysis. J Sex Med. 2013;10:1044–51. [DOI] [PubMed]

Vlachopoulos C, Ioakeimidis N, Terentes-Printzios D, Stefanadis C. The Triad: Erectile Dysfunction - Endothelial Dysfunction-Cardiovascular Disease. Curr Pharm Des. 2008;14:3700–14. [DOI] [PubMed]

Jude EB, Eleftheriadou I, Tentolouris N. Peripheral arterial disease in diabetes—a review. Diabet Med. 2010;27:4–14. [DOI] [PubMed]

Criqui MH, Aboyans V. Epidemiology of Peripheral Artery Disease. Circ Res. 2015;116:1509–26. [DOI] [PubMed]

Johannes CB, Araujo AB, Feldman HA, Derby CA, Kleinman KP, McKinlay JB. Incidence of erectile dysfunction in men 40 to 69 years old: longitudinal results from the Massachusetts male aging study. J Urol. 2000;163:460–3. [PubMed]

Enzlin P, Mathieu C, Van Den Bruel A, Vanderschueren D, Demyttenaere K. Prevalence and Predictors of Sexual Dysfunction in Patients With Type 1 Diabetes. Diabetes Care. 2003;26:409–14. [DOI] [PubMed]

10.

Dilixiati D, Waili A, Tuerxunmaimaiti A, Tao L, Zebibula A, Rexiati M. Risk factors for erectile dysfunction in diabetes mellitus: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2024;15:1368079. [DOI] [PubMed] [PMC]

11.

Mohan G, Mann GS, Sikri T. Sexual Dysfunction in Diabetes Mellitus – An Observational Cohort Study. Apollo Med. 2024;21:41–7. [DOI]

12.

Zhang X, Zhu Z, Tang G, Xu H. Prevalence and predictors of sexual dysfunction in females with type 1 diabetes: a systematic review and meta-analysis. J Sex Med. 2023;20:1161–71. [DOI] [PubMed]

13.

Petolicchio C, Cocchiara F, Spacco G, Delle Chiaie E, Calevo MG, Maggi DC, et al. Erectile and Sexual Function Determinants in Men with Type 1 Diabetes. Diabetology. 2025;6:34. [DOI]

14.

Musicki B, Burnett AL. eNOS function and dysfunction in the penis. Exp Biol Med (Maywood). 2006;231:154–65. [DOI] [PubMed]

15.

Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic Autonomic Neuropathy. Diabetes Care. 2003;26:1553–79. [DOI] [PubMed]

16.

Thompson IM, Tangen CM, Goodman PJ, Probstfield JL, Moinpour CM, Coltman CA. Erectile Dysfunction and Subsequent Cardiovascular Disease. JAMA. 2005;294:2996–3002. [DOI] [PubMed]

17.

Elyasi F, Kashi Z, Tasfieh B, Bahar A, Khademloo M. Sexual Dysfunction in Women with Type 2 Diabetes Mellitus. Iran J Med Sci. 2015;40:206–13. [PubMed] [PMC]

18.

Chen G, Huang L, Lai M, Ran J. Association between erectile dysfunction and the prevalence and prognosis of hyperglycemia in adults in the USA based on NHANES 2001–2004. Sci Rep. 2024;14:17663. [DOI] [PubMed] [PMC]

19.

Nguyen Ngoc Dang H, Viet Luong T, Kiem Pham A, Trung Le T, Duc Le N, Minh Nguyen H, et al. Exploring the bidirectional link between erectile dysfunction and 10-year cardiovascular risk in men with diabetes and hypertension. Sci Rep. 2024;14:28816. [DOI] [PubMed] [PMC]

20.

Li L, Zhang Y, Ma M, Liu F, Shang Y, Yuan Q, et al. Does erectile dysfunction predict cardiovascular risk? A cross-sectional study of clinical characteristics in patients with erectile dysfunction combined with coronary heart disease. Front Cardiovasc Med. 2024;11:1341819. [DOI] [PubMed] [PMC]

21.

American Diabetes Association Professional Practice Committee. 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47:S20–42. [DOI] [PubMed] [PMC]

22.

Aboyans V, Ricco JB, Bartelink MEL, Björck M, Brodmann M, Cohnert T, et al.; ESC Scientific Document Group. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS): Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteriesEndorsed by: the European Stroke Organization (ESO)The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS). Eur Heart J. 2018;39:763–816. [DOI] [PubMed]

23.

Selvin E, Erlinger TP. Prevalence of and Risk Factors for Peripheral Arterial Disease in the United States: Results From the National Health and Nutrition Examination Survey, 1999–2000. Circulation. 2004;110:738–43. [DOI] [PubMed]

24.

Fowkes FG, Murray GD, Butcher I, Heald CL, Lee RJ, Chambless LE, et al.; Ankle Brachial Index Collaboration. Ankle Brachial Index Combined With Framingham Risk Score to Predict Cardiovascular Events and Mortality. JAMA. 2008;300:197–208. [DOI] [PubMed] [PMC]

25.

Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, et al.; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45:S5–67. [DOI] [PubMed]

26.

Aboyans V, Criqui MH, Abraham P, Allison MA, Creager MA, Diehm C, et al. Measurement and Interpretation of the Ankle-Brachial Index: A Scientific Statement From the American Heart Association. Circulation. 2012;126:2890–909. [DOI] [PubMed]

27.

Brooks B, Dean R, Patel S, Wu B, Molyneaux L, Yue DK. TBI or not TBI: that is the question. Is it better to measure toe pressure than ankle pressure in diabetic patients? Diabet Med. 2001;18:528–32. [DOI] [PubMed]

28.

Murphy TP, Dhangana R, Pencina MJ, D’Agostino RB Sr. Ankle-brachial index and cardiovascular risk prediction: an analysis of 11,594 individuals with 10-year follow-up. Atherosclerosis. 2012;220:160–7. [DOI] [PubMed]

29.

Armstrong DG, Boulton AJM, Bus SA. Diabetic Foot Ulcers and Their Recurrence. N Engl J Med. 2017;376:2367–75. [DOI] [PubMed]

30.

Beckman JA, Creager MA, Libby P. Diabetes and Atherosclerosis: Epidemiology, Pathophysiology, and Management. JAMA. 2002;287:2570–81. [DOI] [PubMed]

31.

Vlachopoulos C, Aznaouridis K, Ioakeimidis N, Rokkas K, Vasiliadou C, Alexopoulos N, et al. Unfavourable endothelial and inflammatory state in erectile dysfunction patients with or without coronary artery disease. Eur Heart J. 2006;27:2640–8. [DOI] [PubMed]

32.

Gebeyehu NA, Gesese MM, Tegegne KD, Kebede YS, Kassie GA, Mengstie MA, et al. Global prevalence of sexual dysfunction among diabetic patients from 2008 to 2022: Systematic review and meta-analysis. Metabol Open. 2023;18:100247. [DOI] [PubMed] [PMC]

33.

Bornfeldt KE, Tabas I. Insulin Resistance, Hyperglycemia, and Atherosclerosis. Cell Metab. 2011;14:575–85. [DOI] [PubMed] [PMC]

34.

Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of Cardiovascular Events and All-Cause Mortality With Arterial Stiffness: A Systematic Review and Meta-Analysis. J Am Coll Cardiol. 2010;55:1318–27. [DOI] [PubMed]

35.

Brownlee M. The Pathobiology of Diabetic Complications: A Unifying Mechanism. Diabetes. 2005;54:1615–25. [DOI] [PubMed]

36.

Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, et al. Vascular Risk Factors and Markers of Endothelial Function as Determinants of Inflammatory Markers in Type 1 Diabetes: The EURODIAB Prospective Complications Study. Diabetes Care. 2003;26:2165–73. [DOI] [PubMed]

37.

Libby P. Inflammation in atherosclerosis. Nature. 2002;420:868–74. [DOI] [PubMed]

38.

Foresta C, Caretta N, Lana A, Cabrelle A, Palù G, Ferlin A. Circulating endothelial progenitor cells in subjects with erectile dysfunction. Int J Impot Res. 2005;17:288–90. [DOI] [PubMed]

39.

Pop-Busui R. Cardiac Autonomic Neuropathy in Diabetes: A clinical perspective. Diabetes Care. 2010;33:434–41. [DOI] [PubMed] [PMC]

40.

Grassi G, Seravalle G, Quarti-Trevano F, Dell’Oro R, Arenare F, Spaziani D, et al. Sympathetic and Baroreflex Cardiovascular Control in Hypertension-Related Left Ventricular Dysfunction. Hypertension. 2009;53:205–9. [DOI] [PubMed]

41.

Spallone V, Ziegler D, Freeman R, Bernardi L, Frontoni S, Pop-Busui R, et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev. 2011;27:639–53. [DOI] [PubMed]

42.

Andersson KE. Mechanisms of penile erection and basis for pharmacological treatment of erectile dysfunction. Pharmacol Rev. 2011;63:811–59. [DOI] [PubMed]

43.

Burnett AL, Lowenstein CJ, Bredt DS, Chang TS, Snyder SH. Nitric Oxide: A Physiologic Mediator of Penile Erection. Science. 1992;257:401–3. [DOI] [PubMed]

44.

Freeman R. Autonomic peripheral neuropathy. Lancet. 2005;365:1259–70. [DOI] [PubMed]

45.

Edwards JL, Vincent AM, Cheng HT, Feldman EL. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008;120:1–34. [DOI] [PubMed] [PMC]

46.

Tesfaye S, Boulton AJM, Dyck PJ, Freeman R, Horowitz M, Kempler P, et al.; Toronto Diabetic Neuropathy Expert Group. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria, Estimation of Severity, and Treatments. Diabetes Care. 2010;33:2285–93. [DOI] [PubMed] [PMC]

47.

Dong JY, Zhang YH, Qin LQ. Erectile Dysfunction and Risk of Cardiovascular Disease: Meta-Analysis of Prospective Cohort Studies. J Am Coll Cardiol. 2011;58:1378–85. [DOI] [PubMed]

48.

Zhao B, Hong Z, Wei Y, Yu D, Xu J, Zhang W. Erectile Dysfunction Predicts Cardiovascular Events as an Independent Risk Factor: A Systematic Review and Meta-Analysis. J Sex Med. 2019;16:1005–17. [DOI] [PubMed]

49.

Montorsi P, Ravagnani PM, Galli S, Rotatori F, Briganti A, Salonia A, et al. The Artery Size Hypothesis: A Macrovascular Link Between Erectile Dysfunction and Coronary Artery Disease. Am J Cardiol. 2005;96:19M–23M. [DOI] [PubMed]

50.

Polonsky TS, Taillon LA, Sheth H, Min JK, Archer SL, Ward RP. The association between erectile dysfunction and peripheral arterial disease as determined by screening ankle-brachial index testing. Atherosclerosis. 2009;207:440–4. [DOI] [PubMed]

51.

Wang G, Ni C. Association of erectile dysfunction and peripheral arterial disease in NHANES 2001-2004: a cross-sectional study. Front Endocrinol (Lausanne). 2024;15:1439609. [DOI] [PubMed] [PMC]

52.

Gupta N, Herati A, Gilbert BR. Penile Doppler Ultrasound Predicting Cardiovascular Disease in Men with Erectile Dysfunction. Curr Urol Rep. 2015;16:16. [DOI] [PubMed]

53.

Jung DC, Park SY, Lee JY. Penile Doppler ultrasonography revisited. Ultrasonography. 2018;37:16–24. [DOI] [PubMed] [PMC]

54.

Vlachopoulos C, Ioakeimidis N, Stefanadis C. Biomarkers, erectile dysfunction, and cardiovascular risk prediction: the latest of an evolving concept. Asian J Androl. 2015;17:17–20. [DOI] [PubMed] [PMC]

55.

Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER, Cohen DJ, Reynolds MR, et al.; CLEVER Study Investigators. Supervised Exercise Versus Primary Stenting for Claudication Resulting From Aortoiliac Peripheral Artery Disease: Six-Month Outcomes From the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) Study. Circulation. 2012;125:130–9. [DOI] [PubMed] [PMC]

56.

Murphy TP, Cutlip DE, Regensteiner JG, Mohler ER 3rd, Cohen DJ, Reynolds MR, et al. Supervised Exercise, Stent Revascularization, or Medical Therapy for Claudication Due to Aortoiliac Peripheral Artery Disease: The CLEVER Study. J Am Coll Cardiol. 2015;65:999–1009. [DOI] [PubMed] [PMC]

57.

Dawson DL, Cutler BS, Meissner MH, Strandness DE Jr. Cilostazol Has Beneficial Effects in Treatment of Intermittent Claudication : Results From a Multicenter, Randomized, Prospective, Double-blind Trial. Circulation. 1998;98:678–86. [DOI] [PubMed]

58.

Reilly MP, Mohler ER 3rd. Cilostazol: Treatment of Intermittent Claudication. Ann Pharmacother. 2001;35:48–56. [DOI] [PubMed]

59.

Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JFE, Nauck MA, et al.; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016;375:311–22. [DOI] [PubMed] [PMC]

60.

Neal B, Perkovic V, Matthews DR. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med. 2017;377:2099. [DOI] [PubMed]

61.

Levine GN, Steinke EE, Bakaeen FG, Bozkurt B, Cheitlin MD, Conti JB, et al. Sexual Activity and Cardiovascular Disease: A Scientific Statement From the American Heart Association. Circulation. 2012;125:1058–72. [DOI] [PubMed]

62.

Nehra A, Jackson G, Miner M, Billups KL, Burnett AL, Buvat J, et al. The Princeton III Consensus Recommendations for the Management of Erectile Dysfunction and Cardiovascular Disease. Mayo Clin Proc. 2012;87:766–78. [DOI] [PubMed] [PMC]

63.

Gillett M, Dallosso HM, Dixon S, Brennan A, Carey ME, Campbell MJ, et al. Delivering the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cost effectiveness analysis. BMJ. 2010;341:c4093. [DOI] [PubMed] [PMC]

64.

Davies MJ, Heller S, Skinner TC, Campbell MJ, Carey ME, Cradock S, et al. Effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) programme for people with newly diagnosed type 2 diabetes: cluster randomised controlled trial. BMJ. 2008;336:491–5. [DOI] [PubMed] [PMC]

65.

Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S; EMPA-REG OUTCOME Investigators. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117–28. [DOI] [PubMed]

66.

Gerstein HC, Colhoun HM, Dagenais GR, Diaz R, Lakshmanan M, Pais P, et al.; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394:121–30. [DOI] [PubMed]