Profiles of Intraday Glucose in Type 2 Diabetes and Their Association with Complications: An Analysis of Continuous Glucose Monitoring Data

Abstract

Aims: To identify profiles of type 2 diabetes from continuous glucose monitoring (CGM) data using ambulatory glucose profile (AGP) indicators and examine the association with prevalent complications. Methods: Two weeks of CGM data, collected between 2015 and 2019, from 5901 adult type 2 diabetes patients were retrieved from a clinical database in Chennai, India. Non-negative matrix factorization was used to identify profiles as per AGP indicators. The association of profiles with existing complications was examined using multinomial and logistic regressions adjusted for glycated hemoglobin (HbA1c; %), sex, age at onset, and duration of diabetes. Results: Three profiles of glycemic variability (GV) were identified based on CGM data-Profile 1 ["TIR Profile"] (n = 2271), Profile 2 ["Hypo"] (n = 1471), and Profile 3 ["Hyper"] (n = 2159). Compared with time in range (TIR) profile, those belonging to Hyper had higher mean fasting plasma glucose (202.9 vs. 167.1, mg/dL), 2-h postprandial plasma glucose (302.1 vs. 255.6, mg/dL), and HbA1c (9.7 vs. 8.6; %). Both "Hypo profile" and "Hyper profile" had higher odds of nonproliferative diabetic retinopathy ("Hypo": 1.44, 1.20-1.73; "Hyper": 1.33, 1.11-1.58), macroalbuminuria ("Hypo": 1.58, 1.25-1.98; "Hyper": 1.37, 1.10-1.71), and diabetic kidney disease (DKD; "Hypo": 1.65, 1.18-2.31; "Hyper": 1.88, 1.37-2.58), compared with "TIR profile." Those in "Hypo profile" (vs. "TIR profile") had higher odds of proliferative diabetic retinopathy (PDR; 2.84, 1.65-2.88). Conclusions: We have identified three profiles of GV from CGM data. While both "Hypo profile" and "Hyper profile" had higher odds of prevalent DKD compared with "TIR profile," "Hypo profile" had higher odds of PDR. Our study emphasizes the clinical importance of recognizing and treating hypoglycemia (which is often unrecognized without CGM) in patients with type 2 Diabetes Mellitus.

Keywords: Ambulatory glucose profile; Cluster analysis; Glycemic variability; Time in range.

FIG. 1.

Correlation matrix of AGP summary measures (n = 5901). All values are Pearson correlations. We do not use TIR (<70 mg/dL) and time above range (>180 mg/dL) in further analysis since they are not part of the recommended set of AGP indicators. AGP, ambulatory glucose profile; TIR, time below range.

FIG. 2.

Examples of 14-day glycemic profiles derived from non-negative matrix factorization. Examples of 2-week isCGM for individuals belonging to glycemic profiles for (A) “TIR profile,” (B) “Hypo profile,” and (C) “Hyper profile” are shown. Gray polygon represents 70–180 mg/dL (in range). Solid gray lines indicate 54 and 250 mg/dL. (D) Distribution of 2-week hourly median glucose (mg/dL) by GV profile (number of observations; “TIR profile”: 2271, “Hypo profile”: 1471, “Hyper profile”: 2159). GV, glycemic variability; isCGM, intermittently scanned continuous glucose monitoring.

FIG. 3.

Distribution of continuous glucose monitoring indicators for post hoc separation of profiles. A combination of well-characterized GV indicators (Supplementary Note S1) could separate the profiles based on data-derived cut-points.^,, However, the replicability of these cut-points in an independent sample is pending evaluation (Supplementary Table S7). Isoprobability contours at 33rd percentile and 67th percentile are displayed for each panel.