The landscape of type 2 diabetes (T2D) has changed with an increasing number of people being diagnosed under age 40 years. The principal concern with young-onset T2D is the early development of complications, with associated morbidity and premature mortality. In view of the potential impact on the working-age population and the associated personal, societal and economic ramifications, it is important to understand the factors that drive the pathogenesis of these complications in order to mitigate or prevent their occurrence. Few studies have investigated the impact of young-onset T2D on microvascular disease such as retinopathy. As one of the leading causes of blindness and visual impairment in adults under age 40 years,1 this is a feared complication among people with diabetes and merits further investigation.

In this issue of the journal, Tibballs et al2 report that young adult-onset T2D, diagnosed between the ages of 18 and 39 years and constituting 10% of the overall population with T2D, had a higher burden of retinopathy and a greater risk of developing this complication, including severe retinal disease, compared with those diagnosed with T2D later in life. Young-onset male subjects were particularly susceptible to this complication. Despite receiving more intensive diabetes treatment, including insulin, the young-onset cohort exhibited more rapid deterioration in glycemic control. Compared with females with T2D, the young-onset males had higher HbA1c at diagnosis and this difference in glycemic control persisted throughout the study observation period.

The findings from Tibballs et al confirmed the adverse biological phenotype of young-onset T2D, with a faster progression to pancreatic beta cell failure compared with the older-onset group. An inverse relationship exists between age of diabetes onset and the rate of decline in beta cell function, which progresses more rapidly when diagnosed below age 40 years,3 leading to accelerated deterioration in glycemic control, reduced glycemic durability, and a poorer response to non-insulin therapies, thus necessitating earlier insulin treatment. This study highlights the clinical challenge of trying to achieve a level of glycemic control that will minimize the risk of developing microvascular complications.

Importantly, this study adds to accumulating evidence that young-onset T2D represents a more adverse phenotype for the development of retinopathy than in people who are diagnosed later in life. A recent meta-analysis and systematic review of studies in diverse ethnic populations from different parts of the world has demonstrated that a lower age of T2D onset was associated with a higher risk of retinopathy,4 the magnitude of which was similar to that reported in the present study. Additionally, the observed propensity for more severe retinal disease in the young-onset cohort is consistent with previously published work. Current evidence indicates that subjects with young-onset T2D are likely to incur a substantial burden of severe retinopathy after more than 10 years of diabetes.5 6

The excess risk of retinopathy observed in male subjects with young-onset T2D, which persisted even after adjustment for traditional risk factors such as diabetes duration and glycemic control, suggests that sexual dimorphism may be an important factor in the development of diabetic retinopathy. A study by Middleton et al also demonstrated excess retinopathy risk among young-onset male subjects.5 However, the study by Tibballs et al provides additional and novel insights into the clinical characteristics related to the sex difference. Exposure to glycemic load was higher among male patients at diagnosis and persisted despite receiving diabetes treatment of similar intensity to the female cohort. It is not fully understood why the males are more susceptible to retinopathy, and the authors speculate that delayed diabetes diagnosis in young men may contribute to the greater glycemic exposure and retinopathy risk. The observation of a higher risk of undiagnosed diabetes among men aged below 40 years7 supports this speculation. Another plausible explanation is a greater decline in beta cell function among males with young-onset T2D. The persistence of higher HbA1c level after diagnosis in the male cohort supports this notion, raising the hypothesis that sexual dimorphism influences the pathophysiological mechanisms causing beta cell dysfunction in young adult-onset T2D.

Evidence for the rapidly rising incidence of young-onset T2D is well established,8 but data on its proportion in relation to the overall population with T2D remain scarce. The prevalence of 10% for the young-onset population in the study by Tibballs et al is a worrying statistic. In the UK, the National Diabetes Audit of young people with T2D reported around 5% of the population with T2D in England were aged between 18 and 39 years, and this group represented the overall majority (98.7%) of those diagnosed below age 40 years, with ethnic minority groups being over-represented.9 Most of these patients were under the care of general practitioners in the community. Given that the population characteristics described in this audit are similar to those reported by Tibballs et al in Norway, these informative data provide insight into the absolute magnitude of the burgeoning population with young-onset T2D in Western European countries.

Clinical management of young-onset T2D presents a unique challenge because the biological and psychosocial characteristics differ from the older-onset population with T2D. In addition to the accelerated progression of beta cell dysfunction and failure, these young individuals are more obese at diagnosis. Weight management to induce diabetes remission or prevent the onset of this disorder is of paramount importance. From the psychosocial perspective, socioeconomic deprivation and mental health conditions are prevalent in this young population, constituting barriers to self-care and engagement with health services. The current health system is not providing the care required to improve the long-term outcomes.9 10

The study by Tibballs et al has provided direction for future research to improve care and outcomes of young people living with T2D. Of the microvascular complications, young-onset T2D appears to be most at risk of developing retinopathy.4 Apart from investigating the potential influence of biological sex on complication risk and addressing strategies for effective glycemic control, as highlighted by the authors, ascertainment of appropriate healthcare models to deliver care that is culturally sensitive and clinically responsive to the complex needs of this young population is imperative. More evidence is needed to formulate guidelines that will inform clinical practice and healthcare policy. Engagement from relevant stakeholders, including healthcare providers, researchers and policymakers, is crucial to achieving these objectives.

No data are available. Not applicable.

Not required.

Not applicable.