Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size

Ross, James J.; Wasserfall, Clive; Bacher, Rhonda; Perry, Daniel J.; McGrail, Kieran; Posgai, Amanda L.; Dong, Xiaoru; Muir, Andrew J.; Li, Xia; Campbell‐Thompson, Martha; Brusko, Todd M.; Schatz, Desmond; Haller, Michael J.; Atkinson, Mark A.

doi:10.2337/figshare.13516922

Cited by 2 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2021, the same team of investigators expanded their studies to trypsinogen, lipase, and amylase in a larger cohort. They showed that trypsinogen and lipase are significantly reduced in subjects with established and recent-onset diabetes, and in individuals with multiple islet autoantibodies compared with single islet autoantibody positive and control subjects (70). In contrast, amylase levels were reduced only in patients with established T1D.…”

Section: Enzymes Of the Exocrine Pancreas As Biomarkers In T1dmentioning

confidence: 99%

The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

Fyvie,

Gillespie

2023

Front. Immunol.

View full text Add to dashboard Cite

Type 1 diabetes (T1D) is an autoimmune condition of children and adults in which immune cells target insulin-producing pancreatic β-cells for destruction. This results in a chronic inability to regulate blood glucose levels. The natural history of T1D is well-characterized in childhood. Evidence of two or more autoantibodies to the islet antigens insulin, GAD, IA-2 or ZnT8 in early childhood is associated with high risk of developing T1D in the future. Prediction of risk is less clear in adults and, overall, the factors controlling the progression rate from multiple islet autoantibody positivity to onset of symptoms are not fully understood. An anti-CD3 antibody, teplizumab, was recently shown to delay clinical progression to T1D in high-risk individuals including adults and older children. This represents an important proof of concept for those at risk of future T1D. Given their role in risk assessment, islet autoantibodies might appear to be the most obvious biomarkers to monitor efficacy. However, monitoring islet autoantibodies in clinical trials has shown only limited effects, although antibodies to the most recently identified autoantigen, tetraspanin-7, have not yet been studied in this context. Measurements of beta cell function remain fundamental to assessing efficacy and different models have been proposed, but improved biomarkers are required for both progression studies before onset of diabetes and in therapeutic monitoring. In this mini-review, we consider some established and emerging predictive and prognostic biomarkers, including markers of pancreatic function that could be integrated with metabolic markers to generate improved strategies to measure outcomes of therapeutic intervention.

show abstract

Section: Enzymes Of the Exocrine Pancreas As Biomarkers In T1dmentioning

confidence: 99%

The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

Fyvie,

Gillespie

2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Serum trypsinogen and lipase levels can successfully categorize individuals as having ≥ 2 islet autoantibodies versus 1 and are an effective indicator of BMI-normalized relative pancreas volume by magnetic resonance imaging (MRI) [17]. Additionally, pancreas volume by MRI is smaller in T1D first degree relatives, islet autoantibody positive, and recent-onset T1D individuals versus controls respectively [5].…”

Section: Using Exocrine Biomarkers In Disease Prediction and Monitoringmentioning

confidence: 99%

Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas

Bruggeman,

Schatz

2023

J Cell Immunol

View full text Add to dashboard Cite

Type 1 diabetes has historically been described as an endocrine (β-cell) specific autoimmune disease. However, a substantial reduction (20-50%) in pancreas organ size and subclinical to symptomatic exocrine pancreatic insufficiency are present at diagnosis and may begin even prior to the development of islet autoimmunity. The mechanisms of exocrine loss in type 1 diabetes are not well understood, but leading hypotheses include developmental defects, β-cell loss resulting in exocrine atrophy, or autoimmune or inflammatory destruction of exocrine cells. Inflammatory changes including acute and chronic pancreatitis, exocrine T cell infiltration and classical complement activation, and serum exocrine autoantibodies within type 1 diabetes individuals suggest that an autoimmune or inflammatory process may contribute to exocrine pancreatic dysfunction. Exocrine pancreas atrophy primarily occurs prior to the onset of clinical disease. Indeed, recent work implicates exocrine-specific alterations in gene and protein expression as key in type 1 diabetes development. Measures of exocrine size and function could be useful additions in the prediction of disease onset and in identifying potential therapeutic responders to disease therapies, however, this is an underdeveloped area of research. Additionally, exocrine pancreatic insufficiency is underdiagnosed in individuals with type 1 diabetes and individualized treatment protocols are lacking. Much work remains to be done in this area, but we can definitively say that type 1 diabetes is a disorder of both the exocrine and endocrine pancreas likely from the start.

show abstract

Exocrine Pancreatic Enzymes Are a Serological Biomarker for Type 1 Diabetes Staging and Pancreas Size

Cited by 2 publications

References 0 publications

The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

The importance of biomarker development for monitoring type 1 diabetes progression rate and therapeutic responsiveness

Type 1 Diabetes: A Disorder of the Exocrine and Endocrine Pancreas

Contact Info

Product

Resources

About