Younger-Onset Diabetes: Is the Age of Onset More Important than the Duration of Diabetes?
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A recent paper published in The Lancet Diabetes & Endocrinology [1] reported a linear dose-response relationship between the age at diabetes diagnosis and the risk of all-cause mortality. Their public health modeling using data from the United States found that individuals who lived to 50 years of age and were diagnosed with diabetes at 30 years of age died 14 years earlier than those without diabetes. Similarly, those diagnosed at 40 years of age died 10 years earlier, and those diagnosed at 50 years of age died 6 years earlier (Fig. 1). Each decade of earlier diagnosis of type 2 diabetes mellitus was linked to a 3- to 4-year decrease in life expectancy. The most significant associations with early diabetes diagnosis were observed for vascular and other non-neoplastic causes of death, which primarily included respiratory, neurological, and infectious diseases, as well as external causes. The authors observed that the relative impact of diabetes was most pronounced in the age group with the lowest underlying mortality risk in the general population [1]. In contrast, the proportional impact of diabetes diminished in older adults, who have a higher baseline mortality risk [1].
Estimates of reduced life expectancy by age at diagnosis of type 2 diabetes compared with people without diabetes. Schematic illustration showing that at the age of 50 years, individuals who were diagnosed with diabetes when they were 30 years old died about 14 years earlier than individuals without diabetes; those diagnosed at the age of 40 years died around 10 years earlier, and those diagnosed at the age of 50 years died around 6 years earlier [1].
In my view, young-onset diabetes is not a distinct type of diabetes; instead, it is associated with a natural increase in all-cause mortality due to the extended duration of the disease. The increased mortality and diabetes-related complications observed in individuals diagnosed with diabetes in their 20s and 30s may stem from psychosocial factors, such as a limited understanding of the disease at a younger age, a lower perceived significance of the condition, and suboptimal medication adherence. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was a randomized clinical trial that compared three interventions—metformin alone, metformin combined with rosiglitazone, and metformin paired with an intensive lifestyle intervention—in participants aged 10 to 17 years with newly diagnosed type 2 diabetes [2]. Following the trial, the study shifted to an observational phase, during which participants sought diabetes care within their communities. In this phase, researchers noted a significant issue with adherence to oral hypoglycemic agents and insulin among the participants [3]. Nearly 70% of those prescribed oral hypoglycemic agents were considered to have low adherence, defined as taking less than 80% of the prescribed pills. Although the high-adherence group had a lower hemoglobin A1c (HbA1c) level (9.2% vs. 10.0%, P<0.04), the average HbA1c for the subjects was 9.7%, indicating the challenges of achieving glycemic control in this demographic [3]. Additionally, adherence to antihypertensive and lipid-lowering medications was notably poor within this group, with nearly 80% displaying poor adherence to their medication regimens [4].
Several recent papers have reported on young-onset diabetes, highlighting concerns about the increased risk of complications in these patients [5-7]. However, it remains unclear whether the age at which diabetes begins is the critical factor, or if the heightened risk is due to the longer duration of the disease, as an earlier diagnosis naturally results in a longer disease course. A Korean study found that young-onset diabetes (diagnosed before 40 years of age) was associated with a higher risk of microvascular complications than late-onset diabetes (diagnosed at 40 years or older) [5]. However, this association was significantly weakened and became statistically insignificant after adjusting for the duration of diabetes. In the Hong Kong Diabetes Registry, which includes data on over 9,000 Chinese patients with type 2 diabetes, young-onset diabetes was initially associated with a 30% to 50% higher risk for cardiovascular-renal events than late-onset diabetes when only age was adjusted for [6]. However, this risk association disappeared after further adjustment for the duration of the disease. The Emerging Risk Factors Collaboration Study and the UK Biobank [1], which collectively analyzed data from more than 1,500,000 individuals from Europe and North America, examined the relationship between the age of diabetes diagnosis and mortality. Notably, these studies did not consider the duration of diabetes. Thus, the results of previous studies have varied depending on whether adjustments were made for both the age of onset and the duration of diabetes.
The European Society of Cardiology guidelines acknowledge the importance of diabetes duration, categorizing patients as high or moderate risk based on this factor [8]. Similarly, the Korean Diabetes Association’s guidelines recognize the duration of diabetes as a risk factor for cardiovascular diseases [9]. Therefore, in assessing the risks associated with diabetes, it is important to consider not only the age of onset but also the duration of the condition.
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CONFLICTS OF INTEREST
Mee Kyoung Kim is a deputy editor of the journal. But she was not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.