1.
Arterial Effects of Canakinumab in Patients With Atherosclerosis and Type 2 Diabetes or Glucose Intolerance.
Choudhury, RP, Birks, JS, Mani, V, Biasiolli, L, Robson, MD, L'Allier, PL, Gingras, MA, Alie, N, McLaughlin, MA, Basson, CT, et al
Journal of the American College of Cardiology. 2016;(16):1769-1780
Abstract
BACKGROUND Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. OBJECTIVES The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. METHODS Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months. They underwent magnetic resonance imaging of the carotid arteries and aorta. RESULTS There were no statistically significant differences between canakinumab compared with placebo in the primary efficacy and safety endpoints. There was no statistically significant change in mean carotid wall area and no effect on aortic distensibility, measured at 3 separate anatomic sites. The change in mean carotid artery wall area was -3.37 mm2 after 12 months with canakinumab versus placebo. High-sensitivity C-reactive protein was significantly reduced by canakinumab compared with placebo at 3 months (geometric mean ratio [GMR]: 0.568; 95% confidence interval [CI]: 0.436 to 0.740; p < 0.0001) and 12 months (GMR: 0.56; 95% CI: 0.414 to 0.758; p = 0.0002). Lipoprotein(a) levels were reduced by canakinumab compared with placebo (-4.30 mg/dl [range: -8.5 to -0.55 mg/dl]; p = 0.025] at 12 months), but triglyceride levels increased (GMR: 1.20; 95% CI: 1.046 to 1.380; p = 0.01). In these patients with type 2 diabetes mellitus or impaired glucose tolerance, canakinumab had no effect compared with placebo on any of the measures assessed by using a standard oral glucose tolerance test. CONCLUSIONS There were no statistically significant effects of canakinumab on measures of vascular structure or function. Canakinumab reduced markers of inflammation (high-sensitivity C-reactive protein and interleukin-6), and there were modest increases in levels of total cholesterol and triglycerides. (Safety & Effectiveness on Vascular Structure and Function of ACZ885 in Atherosclerosis and Either T2DM or IGT Patients; NCT00995930).
2.
The association of dysglycaemia and cardiovascular disease in patients with metabolic syndrome.
Gong, W, Yang, Z, Ye, W, Du, Y, Lu, B, Wang, M, Li, Q, Zhang, W, Pan, Y, Feng, X, et al
The Journal of international medical research. 2009;(5):1486-92
Abstract
The objective of this study was to investigate the relationship between increased prevalence of cardiovascular disease and glucose regulation status in Chinese patients with metabolic syndrome (MetS). All patients underwent an oral glucose tolerance test (2-h post-load plasma glucose) to determine their glucose regulation status and had their brachial-ankle pulse wave velocity (baPWV) measured. Of the 590 patients included in the study, 115 (19.5%) had normal glucose tolerance, 114 (19.3%) had impaired fasting glucose (IFG) alone, 38 (6.4%) had impaired glucose tolerance (IGT) alone, 197 (33.4%) had diabetes mellitus and 126 (21.4%) had combined glucose intolerance (CGI; IFG plus IGT). Patients with diabetes mellitus had a significantly higher baPWV compared with all other groups and patients with CGI had a significantly higher baPWW compared with patients with IFG. Dysglycaemia was common in patients with MetS. An increased prevalence of cardiovascular disease in patients with MetS was related to their glucose regulation status.