HbA1c and LDL-C Time in Therapeutic Range: A Study on All-Cause Mortality in Older Adults with Type 2 Diabetes Mellitus and Chronic Kidney Disease.

Authors

Xiaolong Wang, Jian Yang, Qian Wang, Zhenglin Ye, Zhe Feng, Zheyi Dong

Published in

Clinical interventions in aging. Volume 21. Pages 646150. Epub Oct 20, 2026.

Abstract

Whether long-term attainment of glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) targets improves prognosis in older adults with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remains unclear. We used time in therapeutic range (TTR) to quantify sustained glycemic and lipid control and examined its association, and interaction, with all-cause mortality.
This retrospective multicenter cohort study, based on the Tianjin Health Big Data Platform, included 2005 older (≥65 years) and 5973 younger (<65 years) adults with T2DM-CKD. HbA1c-TTR (target <7.0%) and LDL-TTR (target <1.8 mmol/L) were calculated using the Rosendaal method. After Cox-LASSO covariate selection, multivariable Cox models with and without an interaction term were built, supplemented by RCS, subgroup analyses, and landmark and time-varying covariate sensitivity analyses.
Over a median follow-up of 4.56 years, 211 older adults (10.5%) died. Without an interaction term, LDL-TTR (per 10-percentage-point increase) was associated with lower mortality (HR 0.934, P=0.003), while HbA1c-TTR was not (HR 0.983, P=0.459); with the interaction term, the HbA1c-TTR × LDL-TTR interaction was significant (HR 1.016, P=0.006). Adjusted RCS showed a significant nonlinear association for LDL-TTR (P nonlinear=0.020) but not for HbA1c-TTR overall (P=0.231). In the younger cohort, both main effects were significant, but the interaction was not (P=0.124). The interaction remained significant in the time-varying covariate model (HR 1.013, P=0.019) but not in the landmark analysis or under the alternative 6.5-8.0% HbA1c definition, under which LDL-TTR's main effect remained significant.
In older adults with T2DM and CKD, higher LDL-TTR was independently associated with lower mortality, and a significant HbA1c-TTR × LDL-TTR interaction suggested that the inverse association of one TTR measure with mortality was attenuated at higher levels of the other. This interaction was absent in the younger cohort and under an alternative HbA1c target (6.5-8.0%), and was inconsistent across sensitivity analyses (significant with time-varying covariates, HR 1.013, P=0.019; non-significant in a landmark analysis, P=0.968). These exploratory findings do not support changing current management targets and require prospective validation.

PMID:
42927069
Bibliographic data and abstract were imported from PubMed on 25 Oct 2026.

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