Introduction

Type 2 diabetes is a risk factor for cardiovascular disease, this is a known fact but it is less well known that type 1 diabetes and its relative risk for cardiovascular disease can be as much as 10 times greater than the healthy population, especially in women, being even greater than in type 2 diabetes. Consequently, cardiovascular disease is the major cause of mortality in type 1 diabetes.

Diabetes results in an accelerated arteriosclerotic process and early sign of it is arterial stiffness. Arterial stiffness predicts cardiovascular events independently of classical cardiovascular risk factors in several populations. High-sensitivity C-reactive protein (hsCRP) is the most established downstream marker of low-grade inflammation which is one of the factors involved in the pathophysiology of arterial stiffness in type 1 diabetes and has been reported to be a strong predictor of cardiovascular outcomes. Aortic pulse wave velocity (aPWV) independently predicts cardiovascular events and mortality in the general population, in the elderly, in hypertensive individuals, in subjects with end-stage renal failure, and in subjects with type 2 diabetes.

The study is done to evaluate aPWV as a measure of arterial stiffness in a group of subjects with type 1 diabetes without clinical cardiovascular disease and to explore its relationship with biomarkers of low-grade inflammation. 

 

Methodology

Sixty-eight patients with type 1 diabetes and 68 age- and sex-matched healthy subjects were evaluated. Arterial stiffness was assessed by aortic pulse wave velocity (aPWV). Serum concentrations of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, and soluble fractions of tumour necrosis factor-α receptors 1 and 2 (sTNFαR1 and sTNFαR2, respectively) were measured. All statistical analyses were stratified by sex.

 

Results

Subjects with diabetes had a higher aPWV compared with healthy control subjects (men: 6.9 vs. 6.3 m/s, P < 0.001; women: 6.4 vs. 6.0 m/s, P = 0.023). These differences remained significant after adjusting for cardiovascular risk factors.

Men with diabetes had higher concentrations of hsCRP (1.2 vs. 0.6 mg/L; P = 0.036), IL-6 (0.6 vs. 0.3 pg/mL; P = 0.002), sTNFαR1 (2,739 vs. 1,410 pg/mL; P < 0.001), and sTNFαR2 (2,774 vs. 2,060 pg/mL; P < 0.001).

Women with diabetes only had higher concentrations of IL-6 (0.6 vs. 0.4 pg/mL; P = 0.039). In men with diabetes, aPWV correlated positively with hsCRP (r = 0.389; P = 0.031) and IL-6 (r = 0.447; P = 0.008), whereas in women with diabetes no significant correlation was found.

In men, multiple linear regression analysis showed that the following variables were associated independently with aPWV: age, BMI, type 1 diabetes, and low-grade inflammation (R2 = 0.543). In women, these variables were age, BMI, mean arterial pressure, and type 1 diabetes (R2 = 0.550).

 

Conclusion

Arterial stiffness assessed as aPWV is increased in patients with type 1 diabetes without clinical cardiovascular disease, independently of classical cardiovascular risk factors. The exact mechanisms responsible for the increase in arterial stiffness in type 1 diabetes are not fully understood but are likely to reflect a complex interaction between structural and functional changes in the arterial wall. Low-grade inflammation has been associated with the presence of a worse cardiovascular profile and the presence of micro- and macrovascular complications in subjects with type 1 diabetes.

Men with type 1 diabetes have higher aPWV and higher concentrations of inflammatory-related serum proteins than control subjects.  In men with type 1 diabetes, low-grade inflammation is independently associated with arterial stiffness.

Finally, the study shows, for the first time, that arterial stiffness is associated with an increase in inflammatory-related serum proteins in men with type 1 diabetes. Findings of the study suggest that arterial stiffness measurement is a useful tool for detecting subclinical arteriosclerosis and making a better cardiovascular prediction in type 1 diabetes. 

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