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Editorial
Diabetes, obesity and metabolism Younger-Onset Diabetes: Is the Age of Onset More Important than the Duration of Diabetes?
Mee Kyoung Kimorcid
Endocrinology and Metabolism 2024;39(1):90-91.
DOI: https://doi.org/10.3803/EnM.2024.102
Published online: February 22, 2024

Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

Corresponding author: Mee Kyoung Kim. Division of Endocrinology and Metabolism, Department of Internal Medicine, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 10 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea Tel: +82-2-3779-1368, Fax: +82-2-595-2534, E-mail: makung@catholic.ac.kr
• Received: January 25, 2024   • Accepted: February 1, 2024

Copyright © 2024 Korean Endocrine Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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].
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.

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.

Fig. 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].
enm-2024-102f1.jpg
  • 1. Emerging Risk Factors Collaboration. Life expectancy associated with different ages at diagnosis of type 2 diabetes in high-income countries: 23 million person-years of observation. Lancet Diabetes Endocrinol 2023;11:731–42.PubMedPMC
  • 2. TODAY Study Group; Bjornstad P, Drews KL, Caprio S, Gubitosi-Klug R, Nathan DM, et al. Long-term complications in youth-onset type 2 diabetes. N Engl J Med 2021;385:416–26.ArticlePubMedPMC
  • 3. Trief PM, Kalichman SC, Wang D, Drews KL, Anderson BJ, Bulger JD, et al. Medication adherence in young adults with youth-onset type 2 diabetes: iCount, an observational study. Diabetes Res Clin Pract 2022;184:109216.ArticlePubMed
  • 4. Weinstock RS, Trief PM, Burke BK, Wen H, Liu X, Kalichman S, et al. Antihypertensive and lipid-lowering medication adherence in young adults with youth-onset type 2 diabetes. JAMA Netw Open 2023;6:e2336964.ArticlePubMedPMC
  • 5. Cho Y, Park HS, Huh BW, Seo SH, Seo DH, Ahn SH, et al. Prevalence and risk of diabetic complications in young-onset versus late-onset type 2 diabetes mellitus. Diabetes Metab 2022;48:101389.ArticlePubMed
  • 6. Chan JC, Lau ES, Luk AO, Cheung KK, Kong AP, Yu LW, et al. Premature mortality and comorbidities in young-onset diabetes: a 7-year prospective analysis. Am J Med 2014;127:616–24.ArticlePubMed
  • 7. Baek HS, Park JY, Yu J, Lee J, Yang Y, Ha J, et al. Characteristics of glycemic control and long-term complications in patients with young-onset type 2 diabetes. Endocrinol Metab (Seoul) 2022;37:641–51.PubMedPMC
  • 8. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020;41:255–323.PubMed
  • 9. Choi JH, Lee KA, Moon JH, Chon S, Kim DJ, Kim HJ, et al. 2023 Clinical practice guidelines for diabetes mellitus of the Korean Diabetes Association. Diabetes Metab J 2023;47:575–94.PubMedPMC

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