Protocol of a Prospective Observational Study on the Relationship Between Glucose Fluctuation and Cardiovascular Events in Patients with Type 2 Diabetes

Abstract

IntroductionA recent study demonstrated that large glucose fluctuations were associated with an increased incidence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) and acute myocardial infarction. However, it is unknown whether glucose fluctuations are related to the incidence of CVD or the progression of atherosclerosis in patients with T2DM with no apparent history of CVD. In this protocol, we will be investigating the relationships of glucose fluctuations evaluated by continuous glucose monitoring (CGM) to the incidence of composite cardiovascular events and the progression of atherosclerosis in patients with T2DM who had no apparent history of CVD.MethodsThis is a prospective, multicenter, 5-year follow-up observational study. Between April 2018 and October 2019, 1000 participants are expected to be recruited at 34 medical institutions. CGM using FreeStyle Libre Pro is useful for evaluating glucose fluctuations by continuously monitoring glucose levels in interstitial fluid for up to 14 days. The primary study outcome is the relationship between fluctuations in glucose levels evaluated by CGM and the incidence of composite cardiovascular events. Secondary outcomes include the relationships of fluctuations in glucose levels evaluated by CGM to changes in carotid intima media thickness evaluated by echography or grayscale median (an index of tissue characteristics of the carotid wall), brachial–ankle pulse wave velocity, development or progression of diabetic retinopathy or nephropathy, quality-of-life-related diabetes therapy, quality of sleep, development of dementia, and autonomic nerve function.Planned OutcomeThis protocol is designed to investigate the relationship between glucose fluctuations and the incidence of composite cardiovascular events. We completed the registration of 1000 participants in March 2019. Thus, results will be available in 2024. We expect that evaluating glucose fluctuations will aid the identification of patients with a high probability of developing CVD.Trial RegistrationClinicalTrials.gov identifier, UMIN000032325.Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-019-0665-8) contains supplementary material, which is available to authorized users.

Associations Between Continuous Glucose Monitoring-derived Metrics and Diabetic Retinopathy and Albuminuria in Patients With Type 2 Diabetes

“…This study is an exploratory sub-analysis of an ongoing, observational, prospective cohort study that aims to investigate the relationships between glucose uctuations evaluated with CGM and the incidence of composite cardiovascular events over a 5-year follow-up period as described previously [20]. This study used baseline study from the cohort study.…”

“…The FreeStyle Libre Pro (FLP) (Abbott Japan, Tokyo, Japan) CGM (FLP-CGM) device, which measures glucose levels every 15 minutes for up to 14 days, was used in this study as previously reported [20]. Other than wearing FLP-CGM, there were no restrictions on participants' daily lives.…”

“…CV (%) was calculated by dividing SD by the mean of the corresponding glucose readings. The original statistical analysis plan (SAP) for this study was reported in the initial study protocol [20]. We added some CGM-derived metrics in this study since the ATTD Congress proposed some CGM-derived metrics as useful clinical targets that complement HbA1c [15].…”

Associations Between Continuous Glucose Monitoring-derived Metrics and Arterial Stiffness in Patients with Type 2 Diabetes

“…This study is an exploratory sub-analysis of an ongoing, observational, prospective cohort study that aims to investigate the relationship between glucose variability evaluated with CGM and the incidence of composite cardiovascular events over a 5-year follow-up period, as described previously [12]. This study used baseline data from the cohort study.…”

“…The study population consists of Japanese patients with type 2 diabetes who regularly attend the outpatient diabetes clinics of 34 institutions shown in Supplementary Table 1. The study design, inclusion criteria, and exclusion criteria were published previously [12]. Brie y, consecutive subjects were screened.…”