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A Method for Mouse Pancreatic Islet Isolation and Intracellular cAMP Determination
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The Transition From a Compensatory Increase to a Decrease in C-peptide During the Progression to Type 1 Diabetes and

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Researchers tracked glucose and C-peptide levels in individuals at risk for type 1 diabetes (T1D). A specific marker, Index60, showed a transition point approximately 1.5 years before diagnosis, indicating increased T1D risk.

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Area of Science:

  • Endocrinology
  • Immunology
  • Diabetes Research

Background:

  • Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing beta cells.
  • Understanding the progression of T1D is crucial for developing effective prevention and early intervention strategies.

Purpose of the Study:

  • To define the relationship between glucose and C-peptide levels during the progression to type 1 diabetes (T1D).
  • To identify predictive markers for T1D development.

Main Methods:

  • Longitudinal study of glucose and C-peptide response curves (GCRCs) using oral glucose tolerance tests (OGTTs).
  • Analysis of area under the curve (AUC) for glucose and C-peptide, and the integrated Index60 value.
  • Inclusion of data from the Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Pathway to Prevention Study (TNPTP) cohorts.

Main Results:

  • AUC glucose consistently increased from baseline to 0.5 years prediagnosis.
  • AUC C-peptide increased until approximately 1.5 years prediagnosis, then decreased, particularly the late response (60-120 min).
  • Median Index60 values at 1.5 years prediagnosis served as thresholds to identify individuals at high risk for T1D.

Conclusions:

  • A transition from increasing to decreasing AUC C-peptide approximately 1.5 years before T1D diagnosis was observed and validated.
  • The Index60 value at this transition point can serve as a pathophysiologic-based threshold for identifying individuals at high risk for T1D.