Effect of cilostazol on carotid plaque volume measured by three‐dimensional ultrasonography in patients with type 2 diabetes: The
            FANCY
            study

Objective: GLP-1 receptor agonists (GLP-1RAs) improved multiple proatherogenic risk factors and reduced cardiovascular events in recent clinical trials, suggesting that they may slow progression of atherosclerosis. We tested whether exenatide once weekly reduces carotid plaque progression in individuals with type 2 diabetes mellitus. Research Design and Methods: In a double-blind, pragmatic trial, 163 participants were randomized (2:1) to exenatide (n=109) or placebo (n=54). Changes in carotid plaque volume and composition were measured at 9 and 18 months by multi-contrast 3T-MRI. Fasting and post high-fat meal plasma glucose and lipids, and endothelial function responses were measured at 3, 9 and 18 months. Results: Exenatide reduced hemoglobin A1c (estimated difference vs. placebo 0.55%, p=0.0007), and fasting and post-meal plasma glucose (19 mg/dl, p=0.0002 and 25 mg/dl, p<0.0001). Change in plaque volume in the exenatide group (mean 0.3% ± SD 12%) was not different from the placebo group (-2.2 ± 8%) (p=0.4). The change in plaque volume in the exenatide group was associated with changes in hemoglobin A1c (r=0.38, p=0.0004), body weight and overall plasma glucose (r=0.29, p=0.007 both). There were no differences in changes in plaque composition, body weight, blood pressure, fasting and post-meal plasma triglycerides and endothelial function between the groups. Conclusions: Exenatide once weekly for up to 18 months improved fasting and postprandial glycemic control but did not modify change in carotid plaque volume or composition. This study raises the possibility that short term anti-atherosclerotic effects may not play a central role in the cardiovascular benefits of GLP-1RAs.

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

10.21203/rs.3.rs-35204/v1 ◽

2020 ◽

Author(s):

Chen Botvin ◽

Salo Haratz ◽

Ramit Ravona-Springer ◽

Anthony Heymann ◽

Andrew Levy ◽

...

Keyword(s):

Type 2 Diabetes ◽

Elderly Patients ◽

Carotid Plaque ◽

Regression Models ◽

Carotid Atherosclerosis ◽

Ordinal Regression ◽

Plaque Volume ◽

Large Plaque ◽

Carotid Distensibility

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.

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