Abstract
BackgroundPrediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Our aim was to characterize atheromatous plaque burden by the number of affected territories and the total plaque area in the prediabetes stage.MethodsAtheromatous plaque burden (quantity of plaques and total plaque area) was assessed in 12 territories from the carotid and femoral regions using ultrasonography in 6688 non-diabetic middle-aged subjects without cardiovascular disease. Prediabetes was defined by glycosylated hemoglobin (HbA1c) between 5.7 and 6.4% according to the American Diabetes Association guidelines.ResultsPrediabetes was diagnosed in 33.9% (n = 2269) of the ILERVAS participants. Subjects with prediabetes presented a higher prevalence of subclinical atheromatous disease than participants with HbA1c < 5.7% (70.4 vs. 67.5%, p = 0.017). In the population with prediabetes this was observed at the level of the carotid territory (p < 0.001), but not in the femoral arteries. Participants in the prediabetes stage also presented a significantly higher number of affected territories (2 [1;3] vs. 1 [0;3], p = 0.002), with a positive correlation between HbA1c levels and the number of affected territories (r = 0.068, p < 0.001). However, atheromatosis was only significantly (p = 0.016) magnified by prediabetes in those subjects with 3 or more cardiovascular risk factors. The multivariable logistic regression model showed that the well-established cardiovascular risk factors together with HbA1c were independently associated with the presence of atheromatous disease in participants with prediabetes. When males and females were analyzed separately, we found that only men with prediabetes presented both carotid and femoral atherosclerosis, as well as an increase of total plaque area in comparison with non-prediabetic subjects.ConclusionsThe prediabetes stage is accompanied by an increased subclinical atheromatous disease only in the presence of other cardiovascular risk factors. Prediabetes modulates the atherogenic effect of cardiovascular risk factors in terms of distribution and total plaque area in a sex-dependent manner.Trial registration NCT03228459 (clinicaltrials.gov)
Highlights
Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population
The prevalence of subclinical atheromatous disease in the entire population was significantly higher in subjects with prediabetes than in control participants (70.4% vs. 67.5%, p = 0.017)
When only women were analyzed, the increased prevalence of subclinical atheromatous disease detected in postmenopausal control women when compared to premenopausal control women appeared to be attenuated among those with prediabetes (Additional file 1: Table S2)
Summary
Prediabetes has recently been associated with subclinical atheromatous disease in the middle-aged population. Cardiovascular (CV) disease is the main comorbidity of diabetes and is estimated to affect 32.2% of all subjects and is responsible for 27% of the total cost of treating diabetes [2, 3]. Many patients with type 2 diabetes have one or more additional classical risk factors for macrovascular disease and many have evidence of overt atherosclerosis [4]. Symptoms are not always present, and the term “unrecognized diabetic cardiac impairment” has been proposed for individuals that develop CV disease without the classic angina-related or heart failure symptoms [6]. Compared with subjects without diabetes, atheromatous disease in diabetes has special characteristics, such as its being more extensive, and affecting multiple and more peripheral blood vessels, that makes it more serious and aggressive [7]
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