Beyond Traditional Glycemic Measures: CGM Glycemic Profiles Reveal Associations With Cardiometabolic Risk in Individuals Without Diabetes

OBJECTIVE: Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) may not fully capture the heterogeneity underlying dysglycemia or its associations with cardiometabolic risk factors (CMRFs). We cross-sectionally investigated whether continuous glucose monitoring (CGM) measures and glycemic profiles could reveal 10-year cardiovascular disease (CVD) risk and individual CMRFs among individuals without diabetes. RESEARCH DESIGN AND METHODS: We included 1,356 participants without prevalent diabetes or CVD from the Framingham Heart Study, who wore a blinded Dexcom G6 Pro CGM for up to 10 days. CGM glycemic profiles were characterized using 1) binary classification of glycemic burden and variability and 2) unsupervised clustering of CGM measures. We performed multivariable-adjusted linear and logistic regression models to examine associations of CGM measures and profiles with 10-year CVD risk estimates (PREVENT equations) and individual CMRFs. RESULTS: Participants' mean was age 59.3 years; 55.8% were women, and 92.6% were non-Hispanic White. CGM measures were positively associated with 10-year CVD risk estimates and CMRFs. For example, 1 SD higher percentage of time spent at glucose levels >140 mg/dL (15.4%) was associated with 2% higher 10-year CVD risk estimates and 21-26% higher odds of hypertension and dyslipidemia, even after adjusting for FPG. Glycemic profiles representing higher CGM dysglycemia revealed discordance with traditionally defined glycemic status (FPG and HbA1c). Although 48.1-84.2% of individuals with traditionally defined prediabetes were included in CGM profiles representing higher dysglycemia, such profiles were associated with 6-7% higher 10-year CVD risk estimates, in addition to worse CMRFs. CONCLUSIONS: Glycemic measures reflective of continuous glucose dynamics may provide additional insights into cardiometabolic risk beyond traditional measures.