Signs of subclinical atherosclerosis in asymptomatic patients at increased risk of type 2 diabetes mellitus
Introduction
The prevalence of type 2 diabetes mellitus (T2DM) in adults is around 8.3% worldwide and 7.9% in Europe, and shows an increasing tendency according to the estimates of Shaw JE et al.1 Pre-diabetic states such as IGT and IFG are similarly common with a prevalence of 38% in the USA.2 As the prevalence of diabetes continues to increase, the incidence of diabetes-related complications is also predicted to increase.
The Finnish Diabetes Risk Score (Findrisc, FR)3 was designed to evaluate the 10-year risk for developing T2DM. FR is a simple, validated screening tool, which has been successfully used in previous studies for risk estimation in various populations.4., 5., 6., 7. It focuses on general, globally prevalent risk factors. FR is composed of 8 parameters: age, body-mass index (BMI), waist circumference, physical activity, diet, antihypertensive drug use, history of high blood glucose and family history of diabetes. FR risk assessment is proved to be a useful tool for identifying those with impaired glucose metabolism, as it shows high predictive value for a positive oral glucose tolerance test (OGTT).8 It is, therefore, widely used for screening.
According to the recent Scientific Statement from the American Heart Association and the American Diabetes Association, T2DM can be detected by measuring the glycated hemoglobin (HbA1c) level, even in non-fasting peripheral blood. This technique is highly cost-effective and a more simple method than the OGTT; therefore, it has been recommended for population screening of individuals for unidentified T2DM or prediabetes. According to the statement, HbA1c% ≥ 6.5 refers to diabetes and a value of 5.7%–6.4% to prediabetes.9
Cardiovascular disease (CVD) is the largest single cause of death in the European Union, accounting for over 4 million deaths per year.10 CVD has many risk factors, of which obesity, hypertension, hypercholesterolemia, smoking and diabetes are the most important.11 The prevalence of T2DM shows a strong correlation with CVD as 70%–80% of the mortality among patients with T2DM is related to the micro- and macrovascular complications.12., 13. According to the literature, at the time of diagnosis 12% of patients with T2DM have macro- and 30% have microvascular lesions already.14 These data imply that patients with elevated Findrisc score also have higher risk for atherosclerosis. Silventoinen et al. found an association of an elevated FR score (> 12) with cardiovascular events in a follow-up study.15 Similarly, Fizelova et al. presented in a recent study that FR performs reasonably well in predicting coronary heart disease, stroke and mortality.16 Raiko et al. reported that Findrisc has a similar performance to CVD risk scores in predicting subclinical atherosclerosis in young adults.17
Carotid intima–media thickness (CIMT) is an accepted indicator of subclinical atherosclerosis. CIMT measurement is a potential complementary method in cardiovascular risk assessment of patients with diabetes according to the ESC-EASD guidelines.18
The association between diabetes and atherosclerosis has been extensively investigated. A few studies have analyzed the relationship between risk of diabetes or pre-diabetic state according to HbA1c level and signs of subclinical atherosclerosis in asymptomatic patients.19., 20. In two recent moderate sample size studies, DiPino et al. and Sciali et al. found higher CIMT in pre-diabetic subjects compared to the control subjects, in addition to a significant association of HbA1c with CIMT.21., 22.
In this cross-sectional study, our aim was to assess the CIMT in patients with increased risk of T2DM or at pre-diabetic state and to analyze the association of CIMT and these dysmetabolic conditions in a primary preventional Central-European population.
Section snippets
Participants and study design
A cross-sectional study named Budakalász Health Examinaton Survey was performed in the form of a voluntary cardiovascular screening program targeting the adult population (> 20 years, ~ 8000 inhabitants) of a Central-Hungarian town (Budakalász) in 2011–2013. The study protocol included the completion of the European Health Indicators Monitoring survey and information on basic socio-economic status, smoking, physical activity and dietary habits. Medical history, cardiovascular risk factors and
Results
The study flowchart is presented in Fig. 1. Overall, 1475 asymptomatic participants were included. Mean age was 51.8 ± 14.4 years (age range was 20–88 years); 40.8% of participants were male.
Discussion
In our asymptomatic study population 51.7% of the participants had an elevated HbA1c% level (≥ 5.7), Findrisc score (≥ 12) or both. Both HbA1c% and Findrisc score showed a significant positive correlation with maximum and mean CIMT. Carotid findings in participants who had FR ≥ 12 or elevated HbA1c% level were about two times more frequent than in the control group. Moreover, patients with both elevated Findrisc score and HbA1c% level had five times higher chance for developing pathological CIMT.
Conclusions
In our study, carotid findings were more frequent in participants with prediabetes or high diabetes risk. Findrisc score assessment in addition to HbA1c levels better discriminates prediabetes subjects with higher cardiovascular risk profile. Having both high FR score and elevated HbA1c% level means a five times higher chance for developing pathological CIMT.
According to these results, subclinical atherosclerosis is present in a high rate of patients with prediabetes and also in those at high
Limitations
Our study sample is not representative as participation was voluntary.
When diagnosing prediabetes, only HbA1c% levels were considered; OGTT was not performed due to the circumstances (set-up) of the study.
Ethics approval and consent to participate
Ethical approval was acquired from the Hungarian Scientific and Ethics Committee (TUKEB 8424-0/2011-EKU). The study was performed in accordance with the Declaration of Helsinki. Written informed consent was obtained from all participants of the study.
Funding
This study was supported by the Hungarian Scientific Research Fund, OTKA K-105555.
Author contributions
LK, ZsB, ZsSz, PS, DB and BM contributed to the conception and design of the study. LK, ZsB, RV, ZsSz, LP, AL, EÉ and OSz contributed to the acquisition of the work. LK, ZB, and RV contributed to the analysis and interpretation of the work. DB, ZsSz, GyJ and BM also contributed to the interpretation of the data. LK, ZB and RV drafted the manuscript. SP, ZsSz, LP, AL, EÉ, OSz, DB, GyJ and BM critically revised the manuscript. All gave final approval.
Acknowledgment
We thank Éva Fórizs, Erika Vargáné and Anikó Grinyi for assistance with performing laboratory tests and Nóra Abonyi for assistance with data collection.
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Competing interests: The authors declare that they have no competing interests.