Real Life HbA1c variability profiles and association with ASCVD risk in T2DM

Alon Lapidus, Limor Adler

Keywords: diabetes millitus, HbA1c, variability profiles, ASCVD

Background:

Hyperglycemia correlates with the risk of atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. However, unequivocal correlations between HbA1c levels and the development of ASCVD have not been demonstrated.

Research questions:

We examined the association between intrapersonal dynamics in HbA1c and development ASCVD, hypothesizing that higher variability is associated with greater ASCVD risk.

Method:

A retrospective observational study on T2DM patients in the electronic registry of Maccabi HCS diagnosed Jan. 1st 2005 – Dec. 31st 2019. Inclusion criteria required: >3 years of follow-up, with at least four discrete HbA1c measurements per every 3 years. Prior ASCVD were excluded. The clinical endpoint was development of ASCVD. Intrapersonal HbA1c variables were calculated, descriptive statistics and Cox multivariate regression models were used to determine hazard ratios (HR).

Results:

Of 59,364 patients included, 4670 patients (7.9%) developed ASCVD with a follow-up of 7.1±2.8 years (cardiovascular (CV) cohort). The majority (63%) had an intrapersonal HbA1c profile of mean <7% & standard deviation (SD) <1. The basic Cox regression showed increased HRs for increased HbA1c mean and baseline CV risk factors, but not for rise in HbA1c SD. A second Cox regression model analyzing the highly variable (HbA1c SD >1) sub-population showed significantly increased HRs for increase in intrapersonal HbA1c mean range (HbA1c mean >8%, HR 5.3, p=0.004) and SD >2 (HR 1.17, p<0.05). Finally, 2959 patients developed ASCVD within 3 years, and were excluded.

Conclusions:

We identified three patterns of ASCVD in diabetes. First, ASCVD within 3 years, not included and deserves further investigation. Second, stable and well managed glycemic control (63% of CV cohort), suggesting that baseline risk factors are paramount in developing ASCVD, regardless of optimal glycemic management. For the remainder, both HbA1c mean and SD are ASCVD risk factors. Baseline risks notwithstanding, the more variable the intrapersonal HbA1c measurements are, the greater the risk of developing ASCVD.

Points for discussion:

#155