Baseline β-Cell Secretory Reserve and Its Association with Glycaemic Control and Long-Term Outcomes Across Diabetes...

Area of Science:

• Endocrinology and Metabolism
• Diabetes Pathophysiology
• Clinical Diagnostics

Background:

• Residual beta-cell secretory function is crucial in diabetes, but long-term data on beta-cell decline across phenotypes are limited.
• Understanding these trajectories is essential for accurate diagnosis, prognosis, and personalized treatment strategies.
• Early identification of beta-cell reserve can inform clinical management and research directions.

Purpose of the Study:

• To compare long-term beta-cell secretory function trajectories across different diabetes mellitus phenotypes (T1DM, LADA, T2DM) from diagnosis.
• To evaluate the utility of early C-peptide assessment, including glucagon stimulation testing, in stratifying disease progression and prognosis.
• To investigate the association between baseline beta-cell function and long-term metabolic outcomes.

Main Methods:

• A prospective observational study of 393 adults with newly diagnosed diabetes (T1DM, LADA, T2DM).
• Fasting and glucagon-stimulated C-peptide levels were measured at diagnosis; a subgroup (n=89) was reassessed after ~7 years.
• Longitudinal analyses utilized fasting C-peptide for T1DM/LADA and stimulated C-peptide for T2DM due to safety considerations.

Main Results:

• Significant differences in C-peptide levels at diagnosis across phenotypes (T1DM < LADA < T2DM; p < 0.001).
• T1DM showed a marked decline in fasting C-peptide over 7 years (0.95 to 0.10 ng/mL).
• T2DM demonstrated preserved or increased stimulated C-peptide responses (4.37 to 5.46 ng/mL), while LADA showed intermediate values and a gradual decline (1.41 to 0.31 ng/mL).
• Higher baseline C-peptide correlated with better long-term metabolic profiles (lower insulin resistance, improved glycemic control).

Conclusions:

• Early dynamic assessment of beta-cell reserve using glucagon stimulation testing provides valuable prognostic information beyond fasting C-peptide.
• This approach reveals biologically meaningful heterogeneity in diabetes trajectories, refining phenotypic classification.
• The findings support using early C-peptide dynamics for improved prognostic stratification at diagnosis.