Circadian Oscillatory Pattern of Glycemic Control in Patients With Diabetes Mellitus

Abstract

Diabetes mellitus (DM) is one of the major public health problems. Glucose variability is of such relevance that vascular complications occurrences in DM patients has been attributed to hyperglycemia and dysglycemia event. Therefore, glycemia variability may be considered a health issue; however, whether glycemia variability is represented by a given pattern oscillation, is yet to be determined. Then, we sought to determine whether glycemic variability, assessed with continuous glucose monitoring (CGM), display a stationary pattern of oscillation with characteristics of circadian rhythm in patients with diabetes mellitus (DM) type I (DM-I) and type II (DM-II). The CGM data was assessed every 5 minutes x 24 hours x 6 days. Patients (n=196; age, 18-80 years) were assigned to DM-I (n=144, Males: 79), DM-II (n=24, Males 14) and Control (i.e., healthy; n=28, Males: 6) groups. Circadian rhythm of glycemia was assessed during day (08:00-20:00 h) and night (20:00-08:00 h) phases. Anthropometry, pharmacologic treatments, glycosylated hemoglobin (HbA1c), and years of evolution were determined. Participants with DM-I and DM-II had greater HbA1c and standard deviation of glycemia compared to Controls, independent of sex. CGM revealed a predominant stationary oscillatory pattern of glycemic control in all experimental groups. Moreover, maximum energy oscillation of glycemia revealed oscillations between 2-6 days. Between 10:00-14:00 h DM-I females displayed greater increase of glycemia compared to DM-I males and Control females (p<0.05). Females DM-II patients, between 13:00–19:00 h showed an increase (p<0.05) of glycemia vs. Control females. The DM-I and DM-II males, between 02:00-10:00 h and 22:00-24:00 h, increased glycemia compared to Control males. The magnitude of interindividual variability of hyperglycemia was similar during day and night phases in DM-I and DM-II patients, although in DM-I male patients hyperglycemia was greater at night compared to day phase (p<0.05). This study demonstrates that the DM-I and -II Female group has a stationary pattern that is characterized by having a circadian pattern. Therefore, the oscillatory pattern reveal that exist a sensitive daily time, which could help to develop new therapeutic strategies to improve the outcome of this critical population.