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From the Journals

Pancreatic Enzymes and Autoantibodies Signal T1D Progression

Lipase and trypsinogen levels were differentially informative for distinguishing clinical groups in type 1 diabetes, researchers reported.

Conexiant

A recent study identified lipase and trypsinogen levels as key biomarkers for distinguishing clinical groups in type 1 diabetes, suggesting their potential for guiding risk stratification and monitoring disease progression.

The cross-sectional study, published in BMJ Open Diabetes Research & Care, evaluated serum biomarkers from 543 participants aged 2.7 to 30 years. Participants were categorized into four groups: Type 1 diabetes (T1D) (n=154), individuals with ≥2 islet autoantibodies (AAb+) without T1D (n=77), 1AAb+ (n=56), and AAb− (n=256). Researchers employed random forest modeling to analyze seven biomarkers—insulin-like growth factor 1 (IGF1), IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen—alongside genetic risk scores (GRS2) and AAb status.

“Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups,” the authors reported.

Key findings include:

  • Lipase and Trypsinogen: These enzymes exhibited distinct patterns based on T1D status. Lower lipase levels (P=0.002) and higher genetic risk scores (P<0.001) were associated with progression from AAb− to ≥2 islet autoantibodies. Notably, lower lipase levels were particularly significant in younger participants with high GRS2 values.

  • Autoantibodies: AAb against ZnT8 (P<0.01), GAD65 (P=0.021), and insulin (P=0.01) independently differentiated ≥2 islet autoantibodies from 1AAb+ individuals.

  • T1D Onset: Compared with participants with ≥2 islet autoantibodies, those with recent-onset T1D exhibited reduced trypsinogen (P<0.001) and elevated lipase (P<0.001).

The study highlighted the importance of combining enzymatic markers with genetic and immunologic data to enhance predictive models. Random forest modeling incorporated GRS2, age, lipase, trypsinogen, and AAb status as key variables, while recognizing the limitation of using AAb status rather than titer levels.

“Reduced trypsinogen and increased lipase levels favored recent-onset T1D versus ≥2AAb+ classification," noted study authors, emphasizing the dynamic interplay between exocrine pancreatic function and T1D progression.

The findings suggest that incorporating lipase and trypsinogen levels into clinical practice, alongside genetic and autoantibody data, could refine risk stratification and inform early detection and intervention strategies. Longitudinal studies are needed to confirm the utility of these markers over time.

No conflicts of interest were disclosed in the report.