Original articleImpaired endothelial function is not associated with arterial stiffness in adults with type 1 diabetesLa dysfonction endothéliale n’est pas associée à la rigidité artérielle chez les adultes diabétiques de type 1
Introduction
The relative risk of cardiovascular (CV) disease in type 1 diabetes can be as much as ten times greater than in the non-diabetic population, especially in women [1], and is even greater than the risk in type 2 diabetes [2]. In fact, CV disease is the major cause of mortality in type 1 diabetes [2], representing around 40–47% of deaths in certain cohorts [3], [4]. Diabetes results in an accelerated arteriosclerotic process that is not fully explained by classical CV risk factors. The pathophysiological mechanisms underlying CV events in type 1 diabetes are complex and still not fully understood, but are known to involve endothelial dysfunction (ED) as an important factor in the arteriosclerotic process.
ED is characterized by reduced bioavailability of certain vasodilators such as nitric oxide and increased production of certain vasoconstrictors [5]. Endothelial function can be estimated indirectly by measuring endothelium-dependent vasodilatation and by determining ED serum markers such as adhesion molecules [5]. Reactive hyperaemia peripheral arterial tonometry (RH-PAT) is a novel and promising non-invasive technique for assessing peripheral microvascular endothelial function. It measures changes in digital pulse volume during reactive hyperaemia [6]. In adults, it has shown excellent correlation with measures of coronary and peripheral ED [6], [7]. Furthermore, RH-PAT has been associated with CV risk factors [8], [9] and has recently been shown to be an independent predictor of late CV events [10]. In paediatric patients with type 1 diabetes, lower RH-PAT scores have been described compared with their respective controls, but no data are available in adults [11], [12].
Arterial stiffness (AS) is an early sign of arteriosclerosis [13] and is therefore a highly promising method for detecting patients at risk of arteriosclerosis long before a CV event occurs. Indeed, AS has emerged as an independent determinant of CV events and mortality beyond the classical CV risk factors in several populations [14]. Previously, our group was able to demonstrate that AS is increased in patients with type 1 diabetes and no clinical CV disease [15].
Although the precise mechanisms responsible for the increase in AS are not yet fully understood, ED could be involved, leading to functional stiffening of the arterial wall [16]. In fact, ED has been associated with measures of AS in healthy subjects [17], [18] and in patients with CV disease [19] or CV risk factors [20], [21]. Also, type 1 diabetes has been associated with ED [22], thought to be an important factor in the pathogenesis of micro- and macrovascular complications [23], [24], [25]. However, the relationship between ED and AS in patients with type 1 diabetes remains unclear. For this reason, it was hypothesized that, in type 1 diabetes, ED (as assessed by RH-PAT and ED serum markers) would be increased and associated with AS. Thus, the present study was carried out in patients with type 1 diabetes without clinical CV disease and in age- and gender-matched healthy (non-diabetic) subjects.
Section snippets
Patients and methods
A total of 68 patients with type 1 diabetes (34 men and 34 women) aged 18–65 years and 68 age- and gender-matched healthy subjects were included. None of them had any condition associated with an inflammatory response (such as acute or chronic infectious diseases) or had received anti-inflammatory treatment within the previous 6 months, and none had experienced any previous clinical CV event. Patients with type 1 diabetes were consecutively recruited from our outpatients clinic and all had
Baseline characteristics
Altogether, 68 patients with type 1 diabetes and 68 age- and gender-matched healthy (non-diabetic) subjects (n = 136) were evaluated. Their main clinical and analytical characteristics are shown in Table 1 (men) and Table 2 (women). Their baseline characteristics have been described elsewhere [15].
The initial non-adjusted analyses found no differences in RH-PAT index scores between patients with type 1 diabetes and the healthy controls (men: 1.55% [1.38–1.98] versus 1.61% [1.40–2.17], P = 0.556;
Discussion
It is accepted that generalized ED precedes the development of arteriosclerosis and that hyperglycaemia promotes vascular damage, thereby raising the risk of CV events. Thus, early detection of ED is important in patients with type 1 diabetes before the development of overt CV disease. The present study has revealed for the first time that adults with type 1 diabetes and no signs of CV disease show evidence of ED as determined by the RH-PAT index. Furthermore, type 1 diabetes abrogated gender
Conclusion
Our study has demonstrated that ED is increased in type 1 diabetes patients with no previous clinical CV events compared with age-matched healthy (non-diabetic) subjects, and that gender differences for ED are lost in this population. However, ED was not associated with AS. These findings suggest that ED arises earlier than AS in type 1 diabetes.
Disclosure of interest
The authors declare that they have no conflicts of interest concerning this article.
Acknowledgements
Financial support was provided by:
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Fundació la Marató de TV3-2008 (TV3 Marathon Foundation 2008; Project N° 081410);
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FIS PS09/01360, Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo (Carlos III Institute of Health, Ministry of Health and Consumer Affairs), Spain;
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Intensification Grant to José Miguel González-Clemente (Carlos III Institute of Health, Ministry of Health and Consumer Affairs, Spain).
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