Glycemic variability and coronary plaque progression in statin-treated type 2 diabetic patients with coronary artery disease: a prespecified sub-analysis of the OPTIMAL Randomized Controlled Trial

Background Patients with type 2 diabetes mellitus (T2DM) are at high risk of atherosclerotic cardiovascular disease (ASCVD), necessitating optimal strategies to attenuate coronary disease progression. Although achieving HbA1c <7.0% is recommended to reduce macrovascular risk, it does not capture short-term glycemic variability or hypoglycemia, both of which have been implicated in adverse cardiovascular outcomes. Continuous glucose monitoring (CGM) enables assessment of these fluctuations. However, whether longitudinal changes in CGM-derived metrics are associated with progression of coronary athersoclerosis remains uncertain. Purpose To determine whether CGM-derived glycemic variability is associated with coronary plaque progression and whether these measures provide incremental value beyond HbA1c in statin-treated T2DM patients with coronary artery disease. Method The OPTIMAL trial was a prospective, randomized controlled study comparing HbA1c-guided and CGM-guided glycemic management using serial intravascular ultrasound (IVUS). In this prespecified sub-analysis, statin-treated T2DM patients with paired CGM and IVUS data at baseline and 48 weeks were included. CGM-derived measures included hypoglycemia frequency, percent coefficient of variance [%CV], and average glucose. Associations between serial changes in these indices and change in percent atheroma volume (PAV) were evaluated. PAV regression was defined as any reduction in PAV at 48 weeks. Results Patients were predominantly male (78.2%) with a high prevalence of hypertension (74.4%), and dyslipidemia (88.5%) (Table 1). Mean baseline HbA1c was 7.6 ± 0.9%, and 51.3% of participants achieved HbA1c<7.0% by week 48 (Table 1). Changes in CGM-derived measured were not associated with change in PAV or PAV regression. In contrast, achievement of HbA1c <7.0% at week 48 was was independently associated with PAV reduction (OR 0.35, 95% CI [0.18, 0.71], p=0.004). Conclusions Changes in glycemic variability did not necessarily predict progression of coronary atherosclerosis in statin-treated T2DM patients with CAD. Our findings support the recommendation in the current guidelines to achieve HbA1c <7.0% for the secondary prevention of ASCVD. Further studies are warranted to explore whether another measure reflecting glycemic variability better predicts subsequent disease progression in T2DM patients with CAD.