“Younger Age is Associated with Treatment and Complication Outcomes Among Type 2 Diabetes Mellitus Patients in Kigali University Teaching Hospital” [Letter]

Dear editor

We read with interest the study by Alagbonsi et al reporting that, after multivariable adjustment, age was the only factor independently associated with treatment and complication outcomes among T2DM patients in Rwanda.¹ While the question is important, we believe several methodological issues limit the causal interpretation the authors draw.

Firstly, diabetes duration was not measured, and it is a well-established confounder of the age–complication relationship. The complications outcome was defined only cross-sectionally (presence/absence of microvascular and macrovascular events), with no adjustment for time since diagnosis. Large cohort and registry studies have repeatedly shown that diabetes duration, not age per se, is the dominant independent predictor of microvascular complications, with its effect actually strongest in younger patients.^2–4 The ADVANCE trial analysis by Zoungas et al, for example, found that age (or age at diagnosis) predicted macrovascular events and death, but only duration independently predicted microvascular events.² A comparable Australian cohort of 3419 T2DM patients found the same pattern.³ Without duration data, the age effect reported here cannot be distinguished from an unmeasured duration effect, and the biological explanations offered in the Discussion (vascular ageing, nephron reserve) are speculative in the absence of this adjustment.

Second, mortality is embedded in the “treatment outcome”, which may bias the age association mechanically rather than biologically. Patients who died during follow-up were classified as “not improved”. Since all-cause mortality rises steeply with age independent of glycaemic response, coding death as treatment failure will tend to disadvantage the ≥65-year reference group regardless of any true difference in glycaemic response, inflating the apparent protective effect of younger age. The paper does not report how many deaths occurred by age group, making it impossible to assess how much of the reported prevalence ratio reflects mortality rather than HbA1c change.

The “improved” outcome definition is vulnerable to regression to the mean. Improvement was defined as HbA1c < 7.0% or a ≥1.0-point drop from baseline. Patients presenting with higher baseline HbA1c mechanically have more room to register a ≥1-point fall, independent of any real treatment effect. Baseline HbA1c by age group was not reported, so it is unclear whether younger patients simply started with more severe hyperglycaemia (plausible, given more aggressive disease progression noted by the authors themselves)⁵ and thus were more likely to be classified as “improved” by this criterion alone.

Implausible HbA1c values were not queried, despite equivalent scrutiny of the creatinine outlier. HbA1c values as high as 30% are reported (Table 1). Most certified assays have a linear/reportable range up to roughly 16–20%, and laboratory guidelines recommend verification of any HbA1c result >15% for possible hemoglobin variant interference.^6,7 The authors explicitly verified and justified their most extreme creatinine value but applied no comparable scrutiny to this equally implausible HbA1c figure, raising a data-quality concern that could affect both the descriptive statistics and outcome classification.

The central claim that age, independent of therapy type and lifestyle factors, drives treatment and complication outcomes in this population is plausible but insufficiently supported without accounting for diabetes duration, mortality misclassification, and outcome-definition artifacts. We would encourage the authors, in any follow-up work, to report diabetes duration, baseline HbA1c by age stratum, and death counts by age group, which would allow readers to judge how much of the reported “age effect” is attributable to age itself vs these correlated but distinct variables.

Funding Statement

This communication did not receive any funding.

Generative Artificial Intelligence

During the preparation of this work the authors used Claude Ai (version sonnet 5) in order to paraphrase the work. After using this tool/service, the authors reviewed and edited the content as needed and takes full responsibility for the content of the published article.

Data Sharing Statement

No dataset was used in the communication.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, and execution, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agreed to be accountable for all aspects of the work.

Disclosure

The authors declared that they have no conflicts of interest regarding this communication.