Haptoglobin 1-1 is Associated with Larger Carotid Plaque Volume Among Elderly with Type 2 Diabetes: The IDCD Study.

Abstract Background and aims: The haptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with type 2 diabetes complications. The Hp2-2 genotype has been linked to elevated CHD risk while the 1-1 genotype has been recently related to cerebral small vessel disease. This study investigated whether Hp phenotype is associated with carotid atherosclerotic structure and function among type 2 diabetes elderly patients participating in the Israel Diabetes and Cognitive Decline (IDCD) study. Methods: IDCD participants (n=472) underwent a battery of carotid atherosclerosis ultrasound assessments with measurements of carotid intima media thickness (cIMT), distensibility, elastography, and carotid plaque volume. Ordinal regression models adjusting for demographic and cardiovascular risk factors assessed the associations of categorical measures of carotid plaque volume with Hp phenotype . Logistic regression models were used to assess the association of Hp phenotype with impaired cIMT, carotid distensibility and elastography. Results: Participants averaged 76.4±4.4 years old, 42% were female, mean HbA1c was 6.7±0.7% (50±7.7 mmol/mol). Hp phenotype distribution was 46 (10.4%) Hp 1-1, 186 (40.7%) Hp 2-1 and 209 (45.7%) Hp 2-2 carriers. Carotid plaque volume was categorized into 4 groups: including no plaque (n=128) and tertiles of plaque volume: small plaque (volume ≤122 mm³,n=110), medium plaque (volume 122-273 mm³, n=106) and large plaque (volume≥274 mm³, n=104). The prevalence of Hp 1-1 phenotype increased with greater carotid plaque volume (6.5%, 10.6%, 8.8% and 16.5% in the no, small, medium, and large plaque groups respectively; p=0.027). Compared to Hp-1 carriers, non-carriers (i.e. Hp 2-1 and Hp 2-2) had approximately 30% lower risk for large carotid plaque volume, as estimated using ordinal regression (OR: 0.713 [0.496, 1.03], 0.694 [0.484, 0.997] for Hp 2-1, Hp 2-2 respectively). No associations were found between Hp phenotype and level of carotid stenosis, cIMT, carotid distensibility and carotid elastography.Conclusion: Our findings suggest that among non-demented elderly patients with type 2 diabetes, the Haptoglobin 1-1 phenotype is associated with greater carotid atherosclerosis. These findings add evidence for the involvement of the Hp 1-1 phenotype in the pathophysiology of cerebrovascular disease.