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<p>Fibrocalculous pancreatic diabetes mellitus (FCPD) is characterised by pancreatic calcification, intraductal calculi and severe insulin deficiency, yet abnormalities in glucagon regulation and incretin hormone responses remain incompletely understood. We evaluated the glucagon, incretins and oxyntomodulin secretory responses to oral and intravenous glucose administration in participants with FCPD. Participants with FCPD (cases; <i>n</i> = 9; mean age 34 ± 7.2 years) and healthy individuals (controls; <i>n</i> = 6; mean age 29.8 ± 7.7 years) underwent an extended oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI). Serial measurements of plasma glucose, insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM), and pancreatic polypeptide (PP) were done. Serial hormone responses were analysed using linear mixed-effects models, with area-under-the-curve analyses using trapezoidal rule, performed as secondary summaries. On primary mixed-model analysis, the participants with FCPD exhibited significantly higher fasting and post-OGTT glucagon concentrations with glucagon exposure being greater following OGTT than IIGI in the group with FCPD, whereas no route-dependent difference was observed in control participants. GLP-1 and OXM responses were similarly increased in participants with FCPD, particularly following, oral glucose tolerance test, while GIP responses were attenuated. In contrast, C-peptide and pancreatic polypeptide responses were profoundly suppressed during both OGTT and IIGI in FCPD, consistent with severe pancreatic endocrine failure. Despite matched glycaemic exposure, the incretin effect and gastrointestinal glucose disposal were reduced in the FCPD group. These findings demonstrate persistent hyperglucagonemia accompanied by a distinctive pattern of incretin secretion in FCPD, characterised by exaggerated L-cell–derived hormone secretion with attenuated K-cell (GIP) response and impaired pancreatic peptide responses, highlighting altered entero-pancreatic hormonal regulation in this condition.</p>

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Distinctive patterns of glucagon and incretin responses to oral and isoglycaemic intravenous glucose load in fibrocalculous pancreatic diabetes

  • 期刊论文

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  • 发表日期：

    2026年6月19日

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  • Shivendra Verma,
  • Riddhi Dasgupta,
  • Shajith Anoop,
  • Felix K. Jebasingh,
  • Sudipta Dhar Chowdury,
  • Arun Jose,
  • Gracy Varghese,
  • Pamella Christudoss,
  • Padmanaban Venkatesan,
  • Grace Rebekah,
  • Michael Horowitz,
  • Nihal Thomas

摘要

Fibrocalculous pancreatic diabetes mellitus (FCPD) is characterised by pancreatic calcification, intraductal calculi and severe insulin deficiency, yet abnormalities in glucagon regulation and incretin hormone responses remain incompletely understood. We evaluated the glucagon, incretins and oxyntomodulin secretory responses to oral and intravenous glucose administration in participants with FCPD. Participants with FCPD (cases; n = 9; mean age 34 ± 7.2 years) and healthy individuals (controls; n = 6; mean age 29.8 ± 7.7 years) underwent an extended oral glucose tolerance test (OGTT) and isoglycaemic intravenous glucose infusion (IIGI). Serial measurements of plasma glucose, insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), oxyntomodulin (OXM), and pancreatic polypeptide (PP) were done. Serial hormone responses were analysed using linear mixed-effects models, with area-under-the-curve analyses using trapezoidal rule, performed as secondary summaries. On primary mixed-model analysis, the participants with FCPD exhibited significantly higher fasting and post-OGTT glucagon concentrations with glucagon exposure being greater following OGTT than IIGI in the group with FCPD, whereas no route-dependent difference was observed in control participants. GLP-1 and OXM responses were similarly increased in participants with FCPD, particularly following, oral glucose tolerance test, while GIP responses were attenuated. In contrast, C-peptide and pancreatic polypeptide responses were profoundly suppressed during both OGTT and IIGI in FCPD, consistent with severe pancreatic endocrine failure. Despite matched glycaemic exposure, the incretin effect and gastrointestinal glucose disposal were reduced in the FCPD group. These findings demonstrate persistent hyperglucagonemia accompanied by a distinctive pattern of incretin secretion in FCPD, characterised by exaggerated L-cell–derived hormone secretion with attenuated K-cell (GIP) response and impaired pancreatic peptide responses, highlighting altered entero-pancreatic hormonal regulation in this condition.