OLDER adults with Type 2 diabetes and chronic kidney disease (CKD) who maintained low-density lipoprotein cholesterol (LDL-C) levels within the therapeutic range had a lower risk of all-cause mortality, according to a multicentre cohort study examining long-term glycaemic and lipid control. The findings also suggested an interaction between glycaemic and lipid control, although this association was inconsistent across sensitivity analyses.
Researchers analysed data from the Tianjin Health Big Data Platform to investigate whether sustained attainment of glycated haemoglobin (HbA1c) and LDL-C targets was associated with mortality in adults with Type 2 diabetes mellitus and CKD. The retrospective cohort included 2,005 older adults aged 65 years and above and 5,973 younger adults aged under 65 years.
Time in therapeutic range (TTR) was calculated using the Rosendaal method, which estimates the proportion of time spent within a specified target range. The thresholds were HbA1c below 7.0% and LDL-C below 1.8 mmol/L. Researchers used multivariable Cox regression models, alongside subgroup analyses and sensitivity analyses, to assess associations with all-cause mortality.
Over a median follow-up of 4.56 years, 211 older adults died, representing 10.5% of this group. In adjusted analyses without an interaction term, each ten-percentage point increase in LDL-C TTR was associated with lower mortality (hazard ratio [HR]: 0.934; p=0.003). HbA1c TTR was not independently associated with mortality in the same model (HR: 0.983; p=0.459).
When an interaction term was introduced, the interaction between HbA1c TTR and LDL-C TTR was statistically significant (HR: 1.016; p=0.006). This suggested that the inverse association between either measure and mortality was attenuated at higher levels of the other measure. Restricted cubic spline analysis also identified a significant nonlinear association between LDL-C TTR and mortality (p for nonlinearity=0.020), whereas the overall association for HbA1c TTR was not significant (p=0.231).
Among younger adults, both TTR measures showed significant main effects, but their interaction was not statistically significant (p=0.124).
The interaction remained significant in a time varying covariate model (HR: 1.013; p=0.019), but not in the landmark analysis (p=0.968). It was also absent when an alternative HbA1c target of 6.5–8.0% was applied, although the association between LDL-C TTR and mortality remained significant.
The researchers concluded that higher LDL-C TTR was associated with lower mortality in older adults with Type 2 diabetes and CKD. However, the exploratory nature of the findings and inconsistent sensitivity analyses mean they do not justify changes to current management targets. Prospective studies are needed to validate these associations and clarify the clinical significance of the observed interaction.
Reference
Wang X et al. 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. Clin Interv Aging. 2026;21:646150.
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