Impact of long-term glucose variability on coronary atherosclerosis progression in patients with type 2 diabetes: a 2.3 year follow-up study

Abstract

Background Glycemic variability (GV) confers a risk of cardiovascular events. In this study, we aimed to investigate whether long-term GV has an impact on coronary atherosclerosis progression in patients with type 2 diabetes mellitus (T2DM). Methods A total of 396 patients with T2DM who had coronary computed tomography angiography and laboratory data available at baseline and for follow-up evaluations [median 2.3 (1.8–3.1) years] were included. Fasting plasma glucose (FPG) was measured every 1–3 months, and HbA1c was measured quarterly. The coefficient of variation (CV) of HbA1c and FPG were calculated as measures of GV. Quantitative assessment of coronary plaques was performed by measuring the annual change and progression rate of total plaque volume (TPV). Significant progression was defined as annual TPV progression ≥ 15%. Multivariable regression analyses were used to assess the effects of GV on atherosclerosis progression. Results In the 396 patients, the annual change in TPV was 12.35 ± 14.23 mm3, and annual progression rate was 13.36 ± 12.69%. There were 143 (36.11%) patients with significant progression, and they had a significantly higher CV-HbA1c (P < 0.001) and CV-FPG (P < 0.001) than those without significant progression. In multivariable regression analyses, both CV-HbA1c and CV-FPG were independent predictors of annual change in TPV [CV-HbA1c: β = 0.241 (0.019–0.462), P = 0.034; CV-FPG: β = 0.265 (0.060–0.465), P = 0.012], annual TPV progression [CV-HbA1c: β = 0.214 (0.023–0.405), P = 0.029; CV-FPG: β = 0.218 (0.037–0.399), P = 0.019], and significant atherosclerosis progression [CV-HbA1c: odds ratio [OR] = 1.367 (1.149–1.650), P = 0.010; CV-FPG: OR = 1.321 (1.127–1.634), P = 0.013]. Conclusions Long-term GV is associated with accelerated progression of coronary atherosclerosis independent of conventional risk factors in patients with T2DM. Trial registration ClinicalTrials.gov (NCT02587741), October 27, 2015; retrospectively registered

Comprehensive elaboration of glycemic variability in diabetic macrovascular and microvascular complications

“…The study enrolled 420 T2DM patients and suggested that visit-to-visit HbA1c variability expressed as SD, CV and VIM was independently associated with incidence of in-stent restenosis in patients with T2DM after stent implantation [ 61 ]. Of note, several studies disclosed that long-term GV including both HbA1c and FPG variability (calculated by CV) was associated with peripheral artery disease risk and accelerated progression of coronary atherosclerosis in patients with T2DM [ 62 , 63 ]. These clinical results addressed the essential role of GV in diabetic macrovascular complications (Table 2 ), and paved the way for the research on relevant mechanisms.…”

Bioinformatic Reconstruction and Analysis of Gene Networks Related to Glucose Variability in Diabetes and Its Complications

“…In the ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) clinical trial visit-to-visit, GV was associated with both macro- and microvascular complications in type 2 diabetic subjects [ 5 ]. It has been shown that in patients with type 2 diabetes, increased GV predicts a decline in renal function [ 6 ], proliferative diabetic retinopathy and diabetic macular oedema [ 7 ], accelerated progression of coronary atherosclerosis [ 8 ], left ventricular adverse remodeling after myocardial infarction [ 9 ], major cardiovascular events, cardiovascular, and all-cause death [ 10 ]. The relationship between GV and mortality was described in the Verona Diabetes Study: in elderly type 2 diabetic subjects, the coefficient of variation of fasting plasma glucose turned out to be an independent predictor of total, cardiovascular, and cancer mortality [ 11 ].…”

Diabetic heart disease: A clinical update

“…There are various possible explanations for this phenomenon, including a high prevalence of microvascular dysfunction, rapid atherosclerosis progression, high atherosclerotic disease burden, and high-risk plaque composition (bigger necrotic core and larger calcium content) among the diabetic population[ 41 ]. In patients with DM, various risk factors related to atherosclerotic plaque progression include hypertension, male sex, mean plaque burden > 75% at baseline, and glycaemic variability[ 42 ]. The atherosclerotic burden can be measured invasively with the gold standard intravascular ultrasound or noninvasively with the coronary computed tomography angiography and coronary artery calcium (CAC) score.…”