Age at T2DM diagnosis a major factor for subsequent adverse outcomes

For individuals with type 2 diabetes mellitus (T2DM), the earlier the age at diagnosis, the higher the likelihood of subsequent coronary heart disease (CHD), stroke, cancer, and all-cause death, as shown in a study.

In a cohort of 549,959 individuals with T2DM from the Zhejiang province in China, the risk of all outcomes diminished progressively with increasing age at diagnosis (p<0.001), and those in the youngest age group (30–39 years) had higher risks of all adverse outcomes compared with those in the oldest age group (≥80 years), the investigators reported.

The standardized incidence ratios (SIRs) were 5.93 (95 percent confidence [CI], 3.46–10.14) for CHD, 5.45 (95 percent CI, 3.72–7.99) for stroke, and 1.85 (95 percent CI, 1.38–2.49) for cancer in the youngest age group. In comparison, the SIRs for the respective outcomes in the oldest age group were 1.32 (95 percent CI, 1.08–1.60), 1.25 (95 percent CI, 1.08–1.44), and 0.78 (95 percent CI, 0.56–1.09). [Diabetes Res Clin Pract 2024;doi:10.1016/j.diabres.2024.111870]

The standardized mortality ratios (SMRs) for all-cause death were 3.15 (95 percent CI, 1.69–5.84) in the youngest age group and 1.12 (95 percent CI, 0.88–1.43) in the oldest age group.

“As an indicator for assessing relative risk, the higher SIR or SMR of early-onset T2DM is partly due to the low background incidence of complications which are age-related in young individuals in the general population, making the impact of diabetes in young individuals more noticeable. In contrast, elderly patients without diabetes also have a higher risk of these complications due to age-related factors, which may reduce the prominence of T2DM as a risk factor over time,” the investigators explained.

Nevertheless, the findings suggest the importance of intensified care for individuals with early-onset T2DM, necessitating the development of tailored follow-up strategies, they added.

Biological mechanisms

According to the investigators, obesity may explain the observed association between early-onset T2DM and adverse outcomes. Apart from being a significant risk factor for T2DM, obesity is also linked to a higher risk of cardiovascular disease and cancer, they said. This association is driven by multiple mechanisms, including elevated growth factors, hormonal imbalances, and chronic inflammation. Individuals with early-onset T2DM often present with higher body mass indices and poorer metabolic control, further exacerbating these adverse effects. [Pediatr Diabetes 2019;20:5-9; Circulation 2021;143:e984-e1010; Ann NY Acad Sci 2014;1311:57-76]

Individuals with early-onset T2DM have also been shown to have poorer glycaemic and lipid control, as well as higher levels of glycosylated haemoglobin and triglyceride, which may be attributed to a combination of suboptimal adherence to drugs and diabetes self-care, as the investigators pointed out. [Circulation 2019;139:2228-2237; Diabetes Res Clin Pract 2024;208:111098; Diabetologia 2013;56:2593-2600; J Diabetes 2022;13:260-271]

Furthermore, some individuals with early-onset T2DM may have a more physiologically aggressive form of diabetes, insulin insufficiency, and insulin resistance, they added. [JAMA Netw Open 2022;5:e2232766]

“There is an urgent need to clarify the mechanisms linking age at diagnosis of T2DM and increased risk of adverse outcomes to better prevent the adverse effects and reduce the burden of T2DM,” the investigators said.