Association of the HLA antigens with early atheromatosis in subjects with type 2 diabetes mellitus.

ABSTRACT

BACKGROUND: Inflammation plays an important role in the pathogenesis of atherosclerosis. The major histocompatibility complex, as expressed by the human leukocyte antigens (HLA) is considered to regulate the immune response. The aim of this study was to investigate the association of the HLA antigens with vascular remodeling estimated by the carotid intima-media thickness (IMT) in subjects with type 2 diabetes mellitus (DM). METHODS: We evaluated 197 patients with type 2 DM, 80 males and 117 females, mean age 61.8+/-7.8 years, with no history of cardiovascular events. The presence of other major cardiovascular risk factors was recorded. The currently identified HLA class I (-A, -B, -Cw) and class II (DR, -DQ) antigens were studied by a classical 2 step microlymphocytotoxic technique in peripheral blood T and B lymphocytes. Measurements of the IMT were performed in the right and left common carotid arteries, 15-20 mm proximal to the dilatation of the carotid bulb in an end-diastolic "frozen" and magnified B-mode ultrasonographic image. Glycosylated hemoglobin A1c (HbA1c) and C-reactive protein (CRP) were also measured. The results are presented as mean +/-1 standard deviation. RESULTS: Regarding the HLA phenotypes in the final analysis we tested a total of 24 HLA antigens that exhibited a frequency of at least 5% in our diabetic population. Only HLA A3 was found to be significantly associated with the carotid IMT. Forty-nine (24.9%) diabetics were HLA A3 positive (group A), while 148 (75.1%) were HLA A3 negative (group B) and had mean IMT of 0.89+/-0.16 mm and 0.98+/-0.21 mm, respectively (p<0.01). Also the two groups differed significantly in respect to CRP, with group A exhibiting lower serum levels (1.1+/-0.4 mg/dl vs 2.6+/-0.7 mg/dl for group A and B, respectively, p<0.05). However, no differences were observed between the two groups as far as blood glucose control, arterial hypertension and dyslipidaemia were concerned. CONCLUSIONS: Human leukocyte antigen A3 is associated with less vascular damage, as expressed by carotid wall thickness, in subjects with type 2 DM. These subjects may be characterized by a milder inflammatory response, as shown by the lower serum levels of CRP.