Risk factors associated with glycated hemoglobin A1c trajectories progressing to type 2 diabetes

BACKGROUND AND OBJECTIVE: The notion of prediabetes, defined by the ADA as glycated hemoglobin A1c (HbA1c) of 5.7–6.4%, implies increased vascular inflammatory and immunologic processes and higher risk for developing diabetes mellitus and major cardiovascular events. We aimed to determine the risk factors associated with rapid progression of normal and prediabetes patients to type 2 diabetes mellitus (T2DM). METHODS: Retrospective cohort study in a single 8-hospital health system in southeast Michigan, between 2006 and 2020. All patients with HbA1c <6.5% at baseline and at least 2 other HbA1c measurements were clustered in five trajectories encompassing more than 95% of the study population. Multivariate linear regression analysis was performed to examine the association of demographic and comorbidities with HbA1c trajectories progressing to diabetes. RESULTS: A total of 5,347 prediabetic patients were clustered based on their HbA1c progression (C1: 4,853, C2: 253, C66: 102, C12: 85, C68: 54). The largest cluster (C1) had a baseline median HbA1c value of 6.0% and exhibited stable HbA1c levels in prediabetic range across all subsequent years. The smallest cluster (C68) had the lowest median baseline HbA1c value and also remained stable across subsequent years. The proportion of normal HbA1c in each of the pre-diabetic trajectories ranged from 0 to 12.7%, whereas 81.5% of the reference cluster (C68) were normal HbA1c at baseline. The C2 (steady rising) trajectory was significantly associated with BMI (adj OR 1.10, 95%CI 1.03–1.17), and family history of DM (adj OR 2.75, 95%CI 1.32–5.74). With respect to the late rising trajectories, baseline BMI was significantly associated with both C66 and C12 trajectory (adj OR 1.10, 95%CI 1.03–1.18) and (adj OR 1.13, 95%CI 1.05–1.23) respectively, whereas, the C12 trajectory was also significantly associated with age (adj OR 1.62, 95%CI 1.04–2.53) and history of MACE (adj OR 3.20, 95%CI 1.14–8.93). CONCLUSIONS: We suggest that perhaps a more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c, whether they have normal hemoglobin A1c or they have prediabetes. KEY MESSAGES: Progression to diabetes from normal or prediabetic hemoglobin A1c within four years is associated with baseline BMI. A steady rise in HbA1c during a four-year period is associated with age and family history of T2DM, whereas age and personal history of MACE are associated with a rapid rise in HbA1c. A more aggressive preventative approach should be considered in patients with a family history of T2DM who have high BMI and year-to-year increase in HbA1c.