Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes
Introduction Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in pred...
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BMJ Publishing Group
2025-01-01
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| Series: | BMJ Open Diabetes Research & Care |
| Online Access: | https://drc.bmj.com/content/13/1/e004655.full |
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| author | Desmond Schatz Laura Jacobsen Todd M Brusko Michael J Haller Mark Atkinson MacKenzie D Williams Catherine Ramsey Grace Amanda L Posgai Kieran M McGrail Maigan A Brusko Rhonda Bacher Clive H Wasserfall |
| author_facet | Desmond Schatz Laura Jacobsen Todd M Brusko Michael J Haller Mark Atkinson MacKenzie D Williams Catherine Ramsey Grace Amanda L Posgai Kieran M McGrail Maigan A Brusko Rhonda Bacher Clive H Wasserfall |
| author_sort | Desmond Schatz |
| collection | DOAJ |
| description | Introduction Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in predicting AAb/T1D status.Research design and methods Cross-sectional serum samples (n=154 T1D, n=56 1AAb+, n=77 ≥2AAb+, n=256 AAb−) were assessed for IGF1, IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen (n=543, age range 2.7–30.0 years) using random forest modeling.Results GRS2, age, lipase, trypsinogen, and AAb against ZnT8, GAD65, and insulin were the most informative markers. Notably, these variables were differentially informative according to AAb/T1D status. Higher GRS2 (p<0.001) and lower lipase levels (p=0.002) favored ≥2AAb+ versus AAb− classification. AAb against ZnT8 (p<0.01), GAD65 (p=0.021), or insulin (p=0.01) each independently favored ≥2AAb+ versus 1AAb+ classification. Reduced trypsinogen (p<0.001) and increased lipase levels (p<0.001) favored recent-onset T1D versus ≥2AAb+ classification.Conclusions Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups, with the utility of each enzyme varying according to GRS2 and AAb/T1D status. These data support exocrine pancreas enzymes as candidates for longitudinal follow-up. |
| format | Article |
| id | doaj-art-a607ace1963e43a6a1032780fae57759 |
| institution | Kabale University |
| issn | 2052-4897 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open Diabetes Research & Care |
| spelling | doaj-art-a607ace1963e43a6a1032780fae577592025-01-10T15:05:10ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972025-01-0113110.1136/bmjdrc-2024-004655Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetesDesmond Schatz0Laura Jacobsen1Todd M Brusko2Michael J Haller3Mark Atkinson4MacKenzie D Williams5Catherine Ramsey Grace6Amanda L Posgai7Kieran M McGrail8Maigan A Brusko9Rhonda Bacher10Clive H Wasserfall11Department of Pediatrics, University of Florida, Gainesville, Florida, USADepartment of Pediatrics, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pediatrics, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USADepartment of Biostatistics, University of Florida, Gainesville, Florida, USADepartment of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, Florida, USAIntroduction Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in predicting AAb/T1D status.Research design and methods Cross-sectional serum samples (n=154 T1D, n=56 1AAb+, n=77 ≥2AAb+, n=256 AAb−) were assessed for IGF1, IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen (n=543, age range 2.7–30.0 years) using random forest modeling.Results GRS2, age, lipase, trypsinogen, and AAb against ZnT8, GAD65, and insulin were the most informative markers. Notably, these variables were differentially informative according to AAb/T1D status. Higher GRS2 (p<0.001) and lower lipase levels (p=0.002) favored ≥2AAb+ versus AAb− classification. AAb against ZnT8 (p<0.01), GAD65 (p=0.021), or insulin (p=0.01) each independently favored ≥2AAb+ versus 1AAb+ classification. Reduced trypsinogen (p<0.001) and increased lipase levels (p<0.001) favored recent-onset T1D versus ≥2AAb+ classification.Conclusions Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups, with the utility of each enzyme varying according to GRS2 and AAb/T1D status. These data support exocrine pancreas enzymes as candidates for longitudinal follow-up.https://drc.bmj.com/content/13/1/e004655.full |
| spellingShingle | Desmond Schatz Laura Jacobsen Todd M Brusko Michael J Haller Mark Atkinson MacKenzie D Williams Catherine Ramsey Grace Amanda L Posgai Kieran M McGrail Maigan A Brusko Rhonda Bacher Clive H Wasserfall Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes BMJ Open Diabetes Research & Care |
| title | Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| title_full | Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| title_fullStr | Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| title_full_unstemmed | Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| title_short | Serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| title_sort | serological markers of exocrine pancreatic function are differentially informative for distinguishing individuals progressing to type 1 diabetes |
| url | https://drc.bmj.com/content/13/1/e004655.full |
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