Novel markers of coronary inflammation in patients with type 2 diabetes

Abstract

Atherosclerotic cardiovascular disease (CVD) is a leading cause of death in type 2 diabetics with myocardial infarction and stroke responsible for twice as many deaths in type 2 diabetics than non-diabetics. The primary mechanism responsible for myocardial infarction and stroke is atherosclerotic plaque rupture. Systemic inflammation is closely linked to atherosclerotic inflammation and increases cardiovascular event risk. Histologically, ruptured plaques display a metabolically active lipid cores with a large inflammatory component. Conventional plaque imaging methods such as ultrasound, invasive, CT, and MR angiography focus on morphological plaque features of vulnerability but cannot directly assess the metabolic activity of the plaque. 18F-FDG PET/CT is a hybrid imaging technique using a radiolabeled analog of glucose (18-Fluorine labeled to Fluorodeoxyglucose/18F-FDG) to provide anatomical (CT) and metabolic (PET) information on atherosclerotic plaque. Uptake of FDG has been shown in numerous studies to correlate closely with plaque macrophage burden. Recent large-scale studies suggest that modulation of systemic and atherosclerotic inflammation reduces cardiovascular events. In patients with type 2 diabetes, Pioglitazone (but not Glimepiride) reduces atherosclerotic inflammation as assessed by 18F-FDG PET/CT independent of its hypoglycaemic effect. Therefore, identification of those most likely to benefit from an anti-inflammatory response to pioglitazone is likely to be beneficial. In a cohort study of 38 reasonably well-controlled type 2 diabetics on standard oral hypoglycaemic agents (OHAs), Tahara et al. aimed to identify clinical variables that predicted reduction of coronary inflammation after a 4-month treatment period with add-on Pioglitazone (n = 16) or Glimepiride (n = 22). At baseline and 4 months post add-on therapy, all patients underwent a 75 g oral glucose tolerance test (OGTT), fasting plasma glucose (FPG) and insulin, 30-min, 60-min, 90-min, and 120-min postload plasma glucose, serum levels of pigment epithelium-derived factor [PEDF (a novel marker of insulin resistance)], and an 18F-FDG PET/CT. Coronary inflammation was assessed through calculation of standardized uptake values (SUV) within the left main trunk (LMT) and divided by the SUV within the superior vena cava to give a target-to-background ratio (TBR) of atherosclerotic plaque to blood pool uptake (LMT-TBR). As glucose is a competitive antagonist of FDG, serum levels affect cellular uptake therefore a correction was made for fasting plasma glucose (FPG) on the day on scanning. Add-on therapy reduced fasting, 30-, 60-, 90-, and 120-minute postload glucose along with HBA1c levels and LMT-TBR. There was a significant and independent correlation of baseline non-use of aspirin (p = 0.03), baseline-elevated PEDF (R = -0.378, p = 0.019), D PEDF (R = 0.379, p = 0.016), and D120-min glucose (R = 0.436, p = 0.006) with an 11% reduction in overall mean LMT-TBR values (2.17 ± 0.53 to 1.93 ± 0.55). The authors suggest baseline PEDF, DPEDF and D120 min post prandial glucose and as potential therapeutic targets to reduce coronary inflammation in type 2 diabetics and that aspirin may reduce the anti-inflammatory effect of pioglitazone. Reprint requests: J. P. M. Andrews, MD, British Heart Foundation, Centrefor Cardiovascular Science, University of Edinburgh, Edinburgh EH16 4SB, UK; [email protected] J Nucl Cardiol 2020;27:1365–7. 1071-3581/$34.00 Copyright 2019 The Author(s)