Click to Enlarge: Source: Diabetes Care
INDIANAPOLIS — A new review looked at adult-onset Type 1 diabetes and methods to improve screening and diagnosis.
T1D has been historically regarded as a childhood-onset disease, according to the study team led by the Indiana University School of Medicine and including participation from the Roudebush VAMC in Indianapolis.
The researchers explained that “recent epidemiological data indicate that adult-onset T1D accounts for a substantial proportion of cases worldwide. There is evidence that adult-onset T1D is associated with the classic T1D triad of elevated genetic risk, the presence of islet-specific autoantibodies and progression to severe insulin deficiency.”
The article published in Diabetes, Obesity & Metabolism reviews the understanding of the commonalities and differences between childhood and adult-onset T1D, highlighting significant knowledge gaps in the understanding of the diagnosis, incidence, trajectory and treatment of adult-onset T1D. 1
“Compared to children, adults presenting with T1D exhibit differences in genetic risk, immunologic profiles and metabolic outcomes, including differences in the type and number of autoantibodies present, genetic associations and total genetic burden, rates of C-peptide decline, the persistence of C-peptide in long-duration disease and glycaemic control,” the authors pointed out. “In addition, obesity and metabolic syndrome are increasingly common in adults, which not only blurs the clinical distinction of adult-onset T1D from type 2 diabetes (T2D) but also likely contributes to differences in metabolic outcomes and rates of progression.”
The researchers noted that, because T2D is so prevalent in the adult population, adult-onset T1D is misclassified as T2D in at least 1 in 3 cases. That can lead to delays in appropriate treatment.
Part of the issue, according to the report, is that current diagnostic tools, including autoantibody testing and C-peptide measurement, are underutilized or lack specificity in distinguishing adult-onset T1D from atypical T2D. Complicating the matter is that the impact of different responses to disease-modifying therapy between adults and children is unclear, the study team added.
“Addressing these knowledge gaps requires expanded epidemiological studies, diverse patient registries and refined classification criteria to improve early detection and treatment strategies,” according to the authors. “A deeper understanding of adult-onset T1D will be critical to reduce the burden of misdiagnosis, lead to earlier diagnosis and treatment, and optimize population-based screening approaches in this under-recognized population.”
Background information in the article pointed out that adult-onset T1D accounts for the majority of newly diagnosed T1D cases each year, yet, knowledge gaps exist regarding the diagnosis, classification, treatment and natural history of adult-onset T1D.
Compared to children, adults presenting with T1D have differences across-the-board – in genetic risk, immunologic profiles and metabolic outcomes. Despite that, the authors advised, different diagnostic criteria or treatment plans based upon age at diagnosis have not been developed. They said that raises several key questions for the field:
- Should age be treated as a continuous variable for T1D in biological studies, classification and treatment?
- Is it feasible and preferable to develop different guidelines for T1D diagnosis and treatment for children versus adults?
- Do the newly defined stages of pre-clinical T1D apply equally to children and adults?
- Would adult-specific standards for T1D diagnosis decrease misclassification of diabetes subtype?
A study last year from the national Centers for Disease Control and Prevention and the Atlanta VAMC sought to characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. Researchers noted that characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes from 2011 to 2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%).
“T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend),” the study team wrote in Diabetes Care. “A GRS ≥90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and their characteristics resembled those of individuals with T2D in mean age (64.3 years) and BMI (32.3 kg/m2).”2
The authors advised that, compared with the low-risk group, the highest-risk group was more likely to have:
- diabetic ketoacidosis (low GRS 0.9% vs. highest GRS 3.7%),
- hypoglycemia prompting emergency visits (3.7% vs. 5.8%),
- outpatient plasma glucose <50 mg/dL (7.5% vs. 13.4%),
- a shorter median time to start insulin (3.5 vs. 1.4 years),
- use of a T1D diagnostic code (16.3% vs. 28.1%),
- low C-peptide levels if tested (1.8% vs. 32.4%), and
- glutamic acid decarboxylase antibodies (6.9% vs. 45.2%), all P < 0.001.
“Characteristics associated with T1D were increased with higher genetic risk, and especially with the top 10% of risk,” they concluded. “However, the age and BMI of those participants resemble those of people with T2D, and a substantial proportion did not have diagnostic testing or use of T1D diagnostic codes. T1D genetic screening could be used to aid identification of adult-onset T1D in settings in which T2D predominates.”
- Evans-Molina C, Oram RA. Type 1 diabetes presenting in adults: Trends, diagnostic challenges and unique features. Diabetes Obes Metab. 2025 Apr 15. doi: 10.1111/dom.16402. Epub ahead of print. PMID: 40230204.
- Yang PK, Jackson SL, Charest BR, Cheng YJ, Million Veteran Program, et. Al.. Type 1 Diabetes Genetic Risk in 109,954 Veterans With Adult-Onset Diabetes: The Million Veteran Program (MVP). Diabetes Care. 2024 Jun 1;47(6):1032-1041. doi: 10.2337/dc23-1927. PMID: 38608262; PMCID: PMC11116922.
