Three data-driven subtypes reveal the heterogeneity of youth-onset type 2 diabetes.

Novel data-driven classification can enhance risk stratification and tailor disease management.

Clinically meaningful subtype-peripheral neuropathy associations support criterion validity.

To identify subtypes of newly diagnosed youth-onset T2D using cluster analysis.

A cross-sectional study included participants with T2D (duration ≤1 year) aged 10–19 years from the SEARCH for Diabetes in Youth Study (n = 304; 47.4 %) and aged 10–17 years from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (n = 337; 52.6 %) study before intervention allocation. We examined variables available in routine clinical practice. Main outcomes were data-driven subtypes identified using k-means clustering.

Among 641 participants with youth-onset T2D, 58.2 % were female. The analysis revealed three youth-onset subtypes: 48.5 % had obesity-related T2D (yOD), 18.7 % had insulin deficient T2D (yIDD), and 32.7 % had insulin resistant T2D (yIRD). The yOD subtype was characterized by high BMI and low HbA1c. The yIDD exhibited low fasting C-peptide levels, high HDL cholesterol, and high HbA1c. The yIRD subtype had high BMI, high fasting C-peptide, and high blood pressures compared to other subtypes. A higher prevalence of distal symmetric polyneuropathy was observed at diagnosis among yIDD and yIRD subtypes, relative to the yOD subtype.

Three subtypes of youth-onset T2D were identified with different clinical characteristics. Management of youth-onset T2D may require tailored strategies by subtype.

Precision medicine

Diabetes phenotypes

Beta cell function

Insulin deficiency

Insulin resistance

Michigan Neuropathy Screening Instrument

type 1 diabetes mellitus

diabetes associated antibody

distal symmetric polyneuropathy

youth-onset obesity-related diabetes

Youth-onset Insulin-Deficient Diabetes

Youth-onset Insulin-Resistant Diabetes

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