Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors

Abstract

Background: The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM).

Methods: We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations.

Results: GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (γ=0.209, P=0.009) and MAG (γ=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk.

Conclusion: GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM.

Keywords: 10-year atherosclerotic cardiovascular disease risk; Cardiovascular risk factors; Diabetes mellitus, type 2; Glycemic variability; Oral hypoglycemic agents.

Fig. 1. Diagram of schedule for 7-point self-monitoring of blood glucose (SMBG) and glycated hemoglobin (HbA1c) measurements.

Fig. 2. Differences in standard deviation (A) and mean absolute glucose change (B) grouped according to the use of individual oral hypoglycemic agents. SU, sulfonylurea; DPP4i, dipeptidyl peptidase-4 inhibitor; AGI, α-glucosidase inhibitor; MET, metformin; TZD, thiazolidinedione. ^aP<0.05 by Student t test.

Fig. 3. Differences in standard deviation (A) and mean absolute glucose change (B) according to oral hypoglycemic agent groups. Group 1: dipeptidyl peptidase-4 inhibitor (DPP4i) or α-glucosidase inhibitor (AGI)-use/sulfonylurea (SU)-non-use; group 2: DPP4i or AGI-non-use/SU-non-use; group 3: DPP4i or AGI-use/SU-use; and group 4: DPP4i or AGI-non-use/SU-use. On grouping, the administration of thiazolidinedione and metformin was not considered. ANOVA, analysis of variance.

Fig. 4. Differences in standard deviation (A) and mean absolute glucose change (B) according to quartiles of 10-year atherosclerotic cardiovascular disease (ASCVD) risk. Quartiles of 10-year ASCVD risk: first quartile range ≤7.9%, second quartile range 8% to 13.9%, third quartile range 14% to 23.9%, and fourth quartile range ≥24%. ANOVA, analysis of variance.