Diabetes is a complex disease associated with a significantly increased risk of cardiovascular morbidity and mortality. Other chronic conditions such as hypertension, dyslipidemia and heart failure often coexist with diabetes, further increasing the complexity of the disease and its management. Serious complications, including micro- and macrovascular conditions, such as retinopathy, atherosclerosis, peripheral artery disease and diabetic autonomic failure can also arise from diabetes.

Central hemodynamic measures of wave reflection and aortic pulse wave velocity (PWV, the most commonly used surrogate of arterial stiffness) have been shown to be significantly associated with both Type 1 and Type 2 diabetes, as well as earlier pre-diabetic states. Moreover, arterial stiffness is also associated with comorbidities and complications associated with diabetes.38,56,57

Arterial stiffness may play an important role in risk stratification and be a key component in the management strategy for diabetic patients.58,59 Central arterial pressure waveform analysis and arterial stiffness assessments can provide additional information to aid individualized therapeutic decisions and, importantly, allow for treatment effects to be monitored.

Strategies to reduce the high cardiovascular risk in individuals with diabetes include better glycaemic control and reduction of cardiovascular risk factors, including hypertension and dyslipidemia.  The significant association of central blood pressure waveform parameters with diabetes provides a foundation for therapeutic targets and modalities to investigate the impact of various treatment strategies.

Insulin therapy has been shown to improve AIx in patients with Type 2 diabetes48 and reduce aortic PWV in patients with Type 1 diabetes49.

Angiotensin receptor blockers (ARB) are recommend in diabetic patients with hypertension, and two ARB’s, Valsartan and Telmisartan, have been shown to reduce aortic PWV in patients with Type 2 diabetes50, 51. In a cohort of patients with impaired glucose tolerance, treatment with rosiglitazone significantly reduced aortic PWV and AIx, and ramipril resulted in a significant reduction in AIxs52.

Ascorbic acids have been shown to reduce AIx over a 4-week treatment period in Type 2 diabetes,53 and the sugar substitute, erythritol, significantly reduced central aortic pressure after a daily intake for a 4-week period in Type 2 diabetes54. Daily intake for one year of flavinoids have also been shown to reduce aortic PWV in patients with Type 2 diabetes55.

  1. Ben-Shlomo, Y. et al. Aortic pulse wave velocity improves cardiovascular event prediction: an individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol 2014;63(7):636-646.
  2. Vlachopoulos, C. et al. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 2010;31(15):1865-1871.
  3. Sharman, J. E. et al. Rationale and design of a randomized study to determine the value of central Blood Pressure for GUIDing managEment of hypertension: the BP GUIDE study. Am Heart J 2012;163(5):761-767.
  4. WHO, “Diabetes. Fact Sheet No 312.” 2015.
  5. Mozaffarian, D. et al. Heart Disease and Stroke Statistics-2016 Update: A Report From the American Heart Association. Circulation 2015;
  6. Dokken, B. B. The pathophysiology of cardiovascular disease and diabetes: beyond blood pressure and lipids. Diabetes Spectrum 2008;21(3):161-165.
  7. Laugesen, E. et al. Assessment of central blood pressure in patients with type 2 diabetes: a comparison between SphygmoCor and invasively measured values. Am J Hypertens 2014;27(2):169-176.
  8. Laugesen, E. et al. Reproducibility of pulse wave analysis and pulse wave velocity in patients with type 2 diabetes. Scand J Clin Lab Invest 2013;73(5):428-435.
  9. Bjornstad, P. et al. Achieving International Society for Pediatric and Adolescent Diabetes and American Diabetes Association clinical guidelines offers cardiorenal protection for youth with type 1 diabetes. Pediatr Diabetes 2015;16(1):22-30.
  10. Wilkinson, I. B. et al. Increased augmentation index and systolic stress in type 1 diabetes mellitus. QJM 2000;93(7):441-448.
  11. Sommerfield, A. J. et al. Vessel wall stiffness in type 1 diabetes and the central hemodynamic effects of acute hypoglycemia. Am J Physiol Endocrinol Metab 2007;293(5):E1274-E1279.
  12. Westerbacka, J. et al. Insulin-induced decrease in large artery stiffness is impaired in uncomplicated type 1 diabetes mellitus. Hypertension 2000;35(5):1043-1048.
  13. Wilhelm, B. et al. Endothelial function and arterial stiffness in uncomplicated type 1 diabetes and healthy controls and the impact of insulin on these parameters during an euglycemic clamp. J Diabetes Sci Technol 2007;1(4):582-589.
  14. Brooks, B. A. et al. Augmentation of central arterial pressure in Type 2 diabetes. Diabet Med 2001;18(5):374-380.
  15. Lacy, P. S. et al. Increased pulse wave velocity is not associated with elevated augmentation index in patients with diabetes. J Hypertens 2004;22(10):1937-1944.
  16. Theilade, S. et al. Arterial stiffness is associated with cardiovascular, renal, retinal, and autonomic disease in type 1 diabetes. Diabetes Care 2013;36(3):715-721.
  17. Sveen, K. A. et al. Glucosepane and oxidative markers in skin collagen correlate with intima media thickness and arterial stiffness in long-term type 1 diabetes. J Diabetes Complications 2015;29(3):407-412.
  18. Fukui, M. et al. Augmentation of central arterial pressure as a marker of atherosclerosis in patients with type 2 diabetes. Diabetes Res Clin Pract 2003;59(2):153-161.
  19. Gomez-Marcos, M. A. et al. Relationship between intima-media thickness of the common carotid artery and arterial stiffness in subjects with and without type 2 diabetes: a case-series report. Cardiovasc Diabetol 2011;10(1):3-
  20. Rahman, S. et al. Early manifestation of macrovasculopathy in newly diagnosed never treated type II diabetic patients with no traditional CVD risk factors. Diabetes Res Clin Pract 2008;80(2):253-258.
  21. Hansen, M. L. et al. Associations between plasma fibulin-1, pulse wave velocity and diabetes in patients with coronary heart disease. J Diabetes Complications 2015;29(3):362-366.
  22. Bagherzadeh, A. et al. Association of cardiac autonomic neuropathy with arterial stiffness in type 2 diabetes mellitus patients. J Diabetes Metab Disord 2013;12(1):55-
  23. Cruickshank, K. et al. Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation 2002;106(16):2085-2090.
  24. Schram, M. T. et al. Increased central artery stiffness in impaired glucose metabolism and type 2 diabetes: the Hoorn Study. Hypertension 2004;43(2):176-181.
  25. Ravikumar, R. et al. Comparison of carotid intima-media thickness, arterial stiffness, and brachial artery flow mediated dilatation in diabetic and nondiabetic subjects (The Chennai Urban Population Study [CUPS-9]). Am J Cardiol 2002;90(7):702-707.
  26. Wilhelm, B. et al. Increased arterial augmentation and augmentation index as surrogate parameters for arteriosclerosis in subjects with diabetes mellitus and nondiabetic subjects with cardiovascular disease. J Diabetes Sci Technol 2007;1(2):260-263.
  27. Heilman, K. et al. Arterial stiffness, carotid artery intima-media thickness and plasma myeloperoxidase level in children with type 1 diabetes. Diabetes Res Clin Pract 2009;84(2):168-173.
  28. Haller, M. J. et al. Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes Care 2004;27(12):2911-2917.
  29. Urbina, E. M. et al. Prevalence of increased arterial stiffness in children with type 1 diabetes mellitus differs by measurement site and sex: the SEARCH for Diabetes in Youth Study. J Pediatr 2010;156(5):731-7, 737.
  30. Urbina, E. M. et al. Increased arterial stiffness is found in adolescents with obesity or obesity-related type 2 diabetes mellitus. J Hypertens 2010;28(8):1692-1698.
  31. Wadwa, R. P. et al. Measures of arterial stiffness in youth with type 1 and type 2 diabetes: the SEARCH for diabetes in youth study. Diabetes Care 2010;33(4):881-886.
  32. Strazhesko, I. et al. Association of Insulin Resistance, Arterial Stiffness and Telomere Length in Adults Free of Cardiovascular Diseases. PLoS One 2015;10(8):e0136676-
  33. Mohan, V. et al. Association of Indian Diabetes Risk Score with arterial stiffness in Asian Indian nondiabetic subjects: the Chennai Urban Rural Epidemiology Study (CURES-84). J Diabetes Sci Technol 2010;4(2):337-343.
  34. Ghiadoni, L. et al. Metabolic syndrome and vascular alterations in normotensive subjects at risk of diabetes mellitus. Hypertension 2008;51(2):440-445.
  35. Schillaci, G. et al. Metabolic syndrome is associated with aortic stiffness in untreated essential hypertension. Hypertension 2005;45(6):1078-1082.
  36. Holewijn, S. et al. The metabolic syndrome and its traits as risk factors for subclinical atherosclerosis. J Clin Endocrinol Metab 2009;94(8):2893-2899.
  37. Vagovicova, P. et al. Differential effect of metabolic syndrome on various parameters of arterial stiffness. Blood Press 2015;24(4):206-211.
  38. Theilade, S. et al. Pulse wave reflection is associated with diabetes duration, albuminuria and cardiovascular disease in type 1 diabetes. Acta Diabetol 2014;51(6):973-980.
  39. Westerbacka, J. et al. Increased augmentation of central blood pressure is associated with increases in carotid intima-media thickness in type 2 diabetic patients. Diabetologia 2005;48(8):1654-1662.
  40. Dziedzic-Oleksy, H. et al. Evaluation of arterial stiffness in patients with coronary atherosclerosis, cardiac syndrome X and systemic lupus erythematosus (RCD code: I-3C.1). JRCD 2015;2(2):43-51.
  41. Bruno, R. M. et al. Type 2 diabetes mellitus worsens arterial stiffness in hypertensive patients through endothelial dysfunction. Diabetologia 2012;55(6):1847-1855.
  42. Pradeepa, R. et al. Prevalence of peripheral vascular disease and its association with carotid intima-media thickness and arterial stiffness in type 2 diabetes: the Chennai urban rural epidemiology study (CURES 111). Diab Vasc Dis Res 2014;11(3):190-200.
  43. Shah, A. S. et al. Insulin sensitivity and arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study. J Diabetes Complications 2015;29(4):512-516.
  44. Dabelea, D. et al. Cardiovascular risk factors are associated with increased arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study. Diabetes Care 2013;36(12):3938-3943.
  45. Liatis, S. et al. Cardiac autonomic function correlates with arterial stiffness in the early stage of type 1 diabetes. Exp Diabetes Res 2011;2011(957901-
  46. Jaiswal, M. et al. Reduced heart rate variability is associated with increased arterial stiffness in youth with type 1 diabetes: the SEARCH CVD study. Diabetes Care 2013;36(8):2351-2358.
  47. Secrest, A. M. et al. Pulse wave analysis and cardiac autonomic neuropathy in type 1 diabetes: a report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Technol Ther 2011;13(12):1264-1268.
  48. Tamminen, M. K. et al. Insulin therapy improves insulin actions on glucose metabolism and aortic wave reflection in type 2 diabetic patients. Eur J Clin Invest 2003;33(10):855-860.
  49. Rosenlund, S. et al. Treatment with continuous subcutaneous insulin infusion is associated with lower arterial stiffness. Acta Diabetol 2014;51(6):955-962.
  50. Asmar, R. et al. Effects of telmisartan on arterial stiffness in Type 2 diabetes patients with essential hypertension. J Renin Angiotensin Aldosterone Syst 2002;3(3):176-180.
  51. Karalliedde, J. et al. Valsartan Improves Arterial Stiffness in Type 2 Diabetes Independently of Blood Pressure Lowering. Hypertension 2008;51(6):1617-1623.
  52. Rahman, S. et al. Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study. Eur J Clin Pharmacol 2007;63(8):733-741.
  53. Mullan, B. A. et al. Ascorbic acid reduces blood pressure and arterial stiffness in type 2 diabetes. Hypertension 2002;40(6):804-809.
  54. Flint, N. et al. Effects of erythritol on endothelial function in patients with type 2 diabetes mellitus: a pilot study. Acta Diabetol 2014;51(3):513-516.
  55. Curtis, P. J. et al. Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial. Am J Clin Nutr 2013;97(5):936-942.
  56. Prenner S, Chirinos J. Atherosclerosis 2015;238:370-379.
  57. Smulyan H et al. Am J Hypertens. 2016 Jan;29(1):5-13
  58. Yeboah et al. JAMA 2012;308(8):788-95
  59. Ben-Shlomo Y et al. J Am Coll Cardiol 2014;63(7):636-646.