|Year : 2018 | Volume
| Issue : 1 | Page : 57-61
Assessment of endothelial function among patients with type 2 diabetes mellitus
Saadealdeen Majeed Hassoon1, AS Kalid Mahdi Al Bermani2
1 Department of Medicine, College of Medicine, Al-Mustansiriya University, Baghdad, Iraq
2 Department of Internal Medicine and Cardiology, Al-Karama Teaching Hospital, Baghdad, Iraq
|Date of Web Publication||25-Jul-2018|
Prof. Saadealdeen Majeed Hassoon
Department of Medicine, College of Medicine, Almustensyriah University, Baghdad
Source of Support: None, Conflict of Interest: None
Background: Endothelial dysfunction is an initial key step in the pathogenesis of atherosclerosis. Many tests developed to measure endothelial function, most of which are either invasive or semi-invasive. The unique nature of brachial artery reactivity test of being a noninvasive, quantitative, and repeatable procedure is gaining increasing interest as an index in assessing endothelial cell function. Aim of Study: The aim is to study the assessment of endothelial function among a group of patients with type 2 diabetes mellitus (DM), using brachial artery reactivity test. Patients and Methods: In a case control study enrolling 35 patients with type 2 DM matched against a similar number of nondiabetic participants of related genders and age groups to trace the brachial artery diameter both at rest and in response to reactive hyperemia using a commercially available U/S machine equipped with a high-resolution linear probe (7.5 MHz) following an already defined U/S protocol. Results: The diabetic participants revealed a statistically significant attenuation in brachial artery dilatation in response reactive hyperemia when compared with nondiabetic group (mean ± standard deviation) (4.63 ± 0.4 mm vs. 5.61 ± 0.47 mm). Comparing the two groups, a statistically significant impairment of the brachial artery dilatation is traced in relation to the atherosclerotic risk factors both in isolation and in clusters. Moreover, strict glycemic control (HbA1c ≤6%) significantly altered the response to vasodilatation (0.74 ± 0.17 mm vs. 0.43 ± 0.14 mm, P = 0.0001). Age, gender difference, and duration of diabetes did not significantly alter the results. Conclusions: Endothelial dysfunction is not uncommon among patients with type 2 DM. Brachial artery reactivity test is a well-accepted, noninvasive, repeatable, and a quantitatively reproducible index to trace endothelial function.
Keywords: Endothelial function, reactive hyperemia, type 2 diabetes
|How to cite this article:|
Hassoon SM, Kalid Mahdi Al Bermani A S. Assessment of endothelial function among patients with type 2 diabetes mellitus. Mustansiriya Med J 2018;17:57-61
|How to cite this URL:|
Hassoon SM, Kalid Mahdi Al Bermani A S. Assessment of endothelial function among patients with type 2 diabetes mellitus. Mustansiriya Med J [serial online] 2018 [cited 2020 Jun 2];17:57-61. Available from: http://www.mmjonweb.org/text.asp?2018/17/1/57/237547
| Introduction|| |
Appreciation of the central role of the endothelium throughout the atherosclerotic disease process had led to the development of a range of methods to test different aspects of its function which include measures of both endothelial injury and repair. These tests have provided not only novel insights into pathophysiology of atherosclerosis but also a clinical opportunity to detect early disease, quantify risk, judge the response to intervention designed to prevent progression of early disease, and reduce later adverse events. Ideally, such tests should be safe, noninvasive, reproducible, repeatable, cheap, and standardized between laboratories; the results should also reflect the dynamic biology of the endothelium throughout the natural history of atherosclerosis, define the subclinical disease processes, as well as provide prognostic information for risk stratification in the later clinical phase.
Endothelium-dependent vasomotion has been the most widely used clinical endpoint for the assessment of endothelial function. Testing involves pharmacological and/or physiological stimulation of endothelial release of nitric oxide (NO) and other vasoactive compounds and often a comparison of vascular response to endothelium-independent vasodilators such as nitroglycerine. Determination of local (NO) bioavailability not only reflects its influence on the vascular tone but also traces other important functions of this molecule such as thromboregulation, cell adhesion, and proliferation.
Aim of the study
The aim is to study the assessment of endothelial function among a sample of adult patients with type 2 diabetes mellitus (DM), using brachial artery reactivity test.
| Patients and Methods|| |
An observational analytic case–control study is conducted in Al-Yarmouk Teaching Hospital/Department of Medicine with the assistance of Department of Radiology/Ultrasound Unit, in the period from April 2010 to October 2010, whereby (35) patients with type 2 DM were tested against (35) nondiabetic persons of related gender and age as a control group after getting their agreement to be enrolled in the study, proceeded by discussing the aim and the procedure for each volunteer. A brief history and physical examination were conducted looking for a previous or present cardiovascular disease defined as cardiac, coronary, cerebrovascular, peripheral arterial, and venous diseases and risk factors (smoking, arterial hypertension as is defined by JNC VII, dyslipidemia, and obesity). Body mass index as a measure of total body fat was extracted from participant weight in kilogram to his height in meter squared. Three-milliliter anticoagulated blood sample was aspirated from each participant to assess HbA1c fraction; a glycemic control represents HbA1c of 6% and less American association of clinical endocrinology(AACE). An extra fasting 10 ml was aspirated to measure plasma lipid profile. All the participants were tested using an already defined ultrasound protocol to trace brachial artery reactivity using a commercially available machine (Kontron/Voluson 530D of Kretz/Austria) equipped with a high-resolution linear probe (7.5MHz).
The participant is positioned supine with the arm extended in a comfortable position to measure the brachial artery diameter. The artery is imaged above the antecubital fossa in a longitudinal plane; a segment with clear anterior and posterior intimal interface between the lumen and the vessel wall is selected for continuous two-dimensional grayscale imaging [Figure 1].
|Figure 1: High-resolution ultrasound image of brachial artery at baseline (a), and 1 min. after upper-arm occlusion cuff inflation release and subsequent flow-mediated vasodilatation (b)|
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A baseline resting image is acquired, and the brachial artery diameter is measured. To create a flow stimulus in the brachial artery, a blood pressure cuff is placed above the antecubital fossa and is inflated to at least 50 mmHg above the systolic pressure to occlude arterial blood flow for a standardized length of time (3 min), and this causes ischemia and consequent dilatation of downstream resistance vessels through autoregulatory mechanisms. Subsequent cuff deflation induces a brief high flow state through the brachial artery (reactive hyperemia) to accommodate the dilated resistant vessels. The resulting increase in shear stress causes the brachial artery to dilate. The longitudinal image of the artery is recorded continuously from 30 s before to 2 min after cuff deflation. At least 10 min of rest is needed after reactive hyperemia (flow-mediated diameter) before another image is acquired to reflect the reestablished baseline condition.
An exogenous (NO) donor (0.4 mg. GTN) sublingual tablet has been given to determine the maximum obtainable vasodilatation response which serves as a measure of endothelium-independent vasodilatation reflecting the vascular smooth muscle function.
History and/or presence of cardiovascular disease defined as cardiac, coronary, cerebrovascular, peripheral arterial, and venovascular diseases.
Raw data from the two groups were collected and analyzed using software statistical package SPSS version 8, SPSS UK Ltd, St. Andrew~s House, West Street, Woking, Surrey GU21 1EB, applying Pearson's Chi-square test and Student's t-test, and results were tabulated, blotted, and graphically represented in the form of mean and standard deviation, and the degree of difference between two measured variables was traced to be significant when P < 0.05 using Student's t-test.
| Results|| |
[Table 1] shows age- and gender-distribution among diabetic and nondiabetic groups in relation to the changes in mean values of brachial artery diameter at rest and in response to reactive hyperemia.
|Table 1: Mean brachial artery diameter and the range in millimeters at rest, flow-mediated response, and in response to GTN among diabetics and nondiabetics|
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[Table 2] is referring to mean brachial artery diameter among the two studied groups both at rest and in response to reactive hyperemia (intrinsic NO release) once and in response to GTN (extrinsic NO release) once again.
|Table 2: Age and gender distribution among diabetic and nondiabetic groups in relation to mean degree increase in brachial artery diameter from baseline in response to reactive hyperemia|
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The mean difference in brachial artery diameter among both groups in relation to conventional risk factors for atherosclerosis is followed in [Table 3]. The nonalliance in relation to duration of diabetes is demonstrated in [Table 4]; on the other hand, [Table 5] shows the influence of the strict diabetic control among diabetic group on the brachial artery diameter, whereby a significant difference in brachial artery diameter is traced, suggesting a better endothelial function under the umbrella of tight control.
|Table 3: The mean increase in brachial artery diameter in relation to clinical characteristics among the diabetics and controls|
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|Table 4: Impact of duration of diabetes on degree of mean increase in brachial artery diameter from baseline level in response to reactive hyperemia|
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|Table 5: Effect of strict diabetic control on mean increase of brachial artery diameter from baseline in response to reactive hyperemia|
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| Discussion|| |
Although is not yet clinically applicable tool, brachial artery vasomotion test as an index to trace endothelial function is a well-known noninvasive research tool over the previous two decades, and is preferred on other techniques used for the same reason, which are either invasive or semi-invasive procedures and are dependent on the assessment of coronary endothelial cell function and/or assessing different biomarkers in blood plasma, reflecting the interaction between a shear stress and endothelial cell response, they are found to be subjected to variation in the level and/or interacting with other substances, besides they might be released from other sources other than endothelial cells, making them less sensitive and less specific index that would only add to the cost and complexity of the issue.
Brachial artery flow-mediated diameter measurement has been shown to correlate with the measures of coronary endothelial cell function with a high index of sensitivity and specificity. A unique advantage of this test is the noninvasive nature, being quantitative, and ability to repeat it in the same patient, making it more cost-effective and easy to handle, reasons that make it more rational to be adopted in our study.
When tested against a matched group of controls of related gender and age [Table 1], the diabetic patients had shown a significant impairment in the flow-mediated diameter (endothelial cell-dependent vasodilatation) (P = 0.0001), in contrast to the baseline and GTN-mediated (smooth muscle cell-dependent vasodilatation) brachial artery caliber, reflecting the role of oxidative stress induced by diabetic state and associated metabolic derangement on a cellular level, a result which came consistent with many met analytic studies,,, suggesting impaired intrinsic NO release in response to shear stress of brachial artery hyperemia and pointing to an early endothelial cell dysfunction irrespective of the patient age [Table 2],, a key step in initiating atherosclerosis,, and providing an evidence based clue to the fact that DM is an atherosclerosis equivalent problem which starts at an earlier age than the nondiabetic subjects [Table 2].,
Moreover, when adjusted for gender, a significant attenuation is traced in brachial artery diameter in response to reactive hyperemia between the two major tested groups (diabetic and control), suggesting that the unique protection provided by female gender probably through the positive add-on effect of estrogen on endothelial cell  is omitted in the presence of diabetes and its detrimental metabolic effect on cellular biology. The unexpected relationship in gender variable within the same group may in part be related to the small size studied population sample.
Although diabetes carries a greater burden of additional cardiovascular risk factors,, there still remains a significant risk in attenuating brachial artery reactivity when diabetes is the sole clinical characteristic [Table 3], suggesting that diabetes is independent and a powerful predictor for endothelial cell dysfunction and that the effects of other risk factors are augmented in its presence [Table 3].
On the other hand, duration of diabetes did not influence the flow-mediated brachial artery diameter significantly [Table 4], a step that came in agreement with results mentioned in many studies (Janka 1985; Hsueh and Anderson 1992; Bloomgarden 1998; De Mattia et al. 1998; Neri et al. 1998; Watts and Playford, 1998; and Gazis et al. 1999). Hyperglycemia whether acute or chronic is a major causal factor in the development of endothelial dysfunction in DM, and the mechanism underlying this phenomenon is likely to be multifactorial through influencing several metabolic pathways leading to increase oxidative stress contributing to endothelial dysfunction, while a tight control represented by HbA1c of 6% or less [Table 5] reverses the metabolic and cellular derangement induced by hyperglycemia and the associated released cytokines (e.g., monocyte adhesion molecules, interleukin-6, and tumor necrosis factor) which are negatively influencing cellular biology including endothelial dysfunction; hence, strict control of diabetes will undoubtedly reverse the detrimental metabolic derangement of the disease.
The fluctuation in laboratory facilities concerning the availability of HbA1c kits had limited the size of the studied sample enrolled in the study. Inability to overcome the add-on effect of the drugs used by the patients and controls, which are known to influence the endothelial function, for example, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, statins, B-blockers, and salicylate.
| Conclusions|| |
Brachial artery reactivity test as an index to trace endothelial function is a noninvasive, easy to handle, acceptable, quantitative test which can be used repeatedly in the same patient and/or applied over a large number as a screening tool. Endothelial dysfunction is not uncommon among patients with type 2 diabetes and is traced irrespective of the associated cardiovascular risk factors and duration of diabetes. Significant changes were traced among the diabetics when compared with the control group in respect to age, gender, and the degree of glycemic control. We recommend a more extended prospective study with larger sample to trace the influence of the previously mentioned variables on the clinical course of diabetes in order to risk stratify the patients and/or tracing the endothelial dysfunction in preclinical stage and to assess the influence of applying different pharmacological and nonpharmacological interventions to reverse it.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]