Postprandial plasma glucose is an independent risk factor for increased carotid intima-media thickness in non-diabetic individuals
Introduction
Recently, hyperglycemia was suggested to be a risk factor for macrovascular disease also in the non-diabetic range [1], [2], [3], [4], [5]. This was one of the reasons to bring down the cut-off limit for diabetes diagnosis from 7.8 to 7.0 mmol/l plasma glucose in the fasting state [6]. Impaired glucose tolerance (IGT) is an established risk factor for diabetes as well as for cardiovascular disease (CVD) [3], [7]. Several epidemiological trials with non-diabetic populations, such as the Whitehall Study [2], [3], the Framingham Study [4], [5], the Chicago Heart Study [8] and the Helsinki Policemen Study [9] demonstrated the particular importance of postprandial (pp) hyperglycemia for B-cell function and coronary risk. In the Diabetes Intervention Study (DIS) [10], a prospective trial with newly detected diet controlled type 2 diabetic patients pp blood glucose but not fasting blood glucose was an independent risk factor for both incidence of myocardial infarction and all-cause mortality.
The intima-media thickness (IMT) of the common carotid artery (CCA), measured by B-mode ultrasound, is a generally accepted marker of early atherosclerosis [11], [12]. This noninvasive method for the direct examination of the vessel status was shown to be highly reproducible and with low inter/intraindividual variability [13], [14], [15]. Recently, increased carotid IMT was reported in both type 2 and type 1 diabetic patients [16], [17], [18]. HbA1c levels in the absence of diabetes were found to correlate to intima media thickening [19]. In a previous study we established only a weak correlation to exist between fasting plasma glucose and IMT in non-diabetic individuals [20]. So far, there are no data available on the relationship of pp hyperglycemia, standard risk factors and insulin secretion anomalies to carotid IMT in non-diabetic subjects, defined according to the new ADA diabetes classification [6]. Therefore, we analysed the following:
- 1.
relationship of carotid IMT to pp glucose, insulin and coronary risk factors
- 2.
relationship between pp glucose, insulin secretion and coronary risk factors
Section snippets
Research design and methods
A total of 403 middle-aged nondiabetic subjects (147 male and 256 female) were examined within the RIAD Study. RIAD is a prospective, 3 years follow-up survey on the development of diabetes and atherosclerosis in subjects with IGT in comparison to subjects with normal glucose tolerance. Details of the study design and participants have been previously described [20]. Briefly, middle-aged subjects (40–70 years) from the city of Dresden and its surroundings with risk factors for diabetes, such as
Laboratory examination
Standard OGTT with 75 g glucose (Glucodex, Rougier, Chambly, Que., Canada) was conducted in the RIAD participants according to a strict protocol. Venous blood was obtained after an overnight fast of at least 10 h as well as postprandially at 30, 60, 90 and 120 min. EDTA plasma and serum were separated by centrifugation (4000 rpm for 8 min at 4°C). Aliquots of plasma and serum were immediately frozen with liquid nitrogen and were stored at −80°C until analysis. Plasma glucose and HbA1c were
Ultrasound measurement
Ultrasonography of the common carotid artery (CCA) was conducted bilaterally with an Acuson 128XP computed sonography system using a 10 MHz linear array transducer, as previously described [20]. Briefly, we measured the IMT of the far wall of the distal CCA, as originally described by Pignoli et al. [21]. The images were frozen in the end diastolic phase to avoid variability during the cardiac cycle. All scans were conducted by only two physicians to reduce intraindividual variability. The
Statistics
Data evaluation was conducted using the SPSS/PC+ programme. Quintiles for pp plasma glucose were built and IMT as well as metabolic parameters corresponding to these five groups were compared by one-way ANOVA. The distribution of values was assessed by the Levene test for homogeneity of variances, and the Mann–Whitney U test was performed if necessary. The level of significance was determined by P<0.05. Data are presented as mean±S.E.M. and 95% confidence interval (CI) for the mean. The partial
Results
A continuous rise in body mass index, triglycerides and a decrease in HDL-cholesterol was observed along the quintiles of 2 h pp plasma glucose, whereas waist to hip ratio and albuminuria were only considerably enhanced in the top quintile (Table 2). The average levels of blood pressure and total cholesterol were not related to glucose level in this non-diabetic group. The results with respect to blood pressure may be biased by the fact that the majority of subjects with hypertension were
Discussion
Increased IMT of the CCA is a generally accepted good marker of early atherosclerosis [11], [12]. The high reproducibility of this noninvasive method for visualizing the vessel wall and its close correlation to the atherosclerotic changes of the coronary arteries has led to its frequent application for the direct assessment of the vessel status at present. A variety of risk factors, such as dys/hyperlipidemia [22], [23], hypertension [23], [24], impaired fibrinolysis [23], [25],
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