A Mathematical Model-Derived Disposition Index Without Insulin Validated in Youth With Obesity

Area of Science:

• Metabolic Research
• Clinical Diagnostics
• Pediatric Endocrinology

Background:

• Gold-standard clamp measurements for insulin sensitivity, beta-cell function, and disposition index (DI) are impractical for large studies.
• Accurate assessment of glucose-insulin dynamics is crucial for identifying metabolic dysfunction.

Purpose of the Study:

• Validate mathematical model-derived DI from oral glucose tolerance tests (OGTT) against clamp-derived DI.
• Evaluate novel indices for detecting prediabetes and type 2 diabetes (T2D).

Main Methods:

• Secondary analysis of cross-sectional observational studies.
• Applied the Insulin Sensitivity and Secretion mathematical model to 5-point and 3-point OGTTs in 130 obese youth.
• OGTT data synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps.

Main Results:

• Model-derived DI correlated well with clamp DI (R=0.76).
• Indices derived from OGTT without insulin (mDI-woI) showed greater decreases between normal glucose tolerance and impaired glucose tolerance groups (59%) compared to other indices (27%).
• mDI-woI demonstrated superior ability to detect impaired glucose tolerance (AUC 0.87-0.88) compared to other methods.

Conclusions:

• The mathematical model-derived DI without insulin measurements (mDI-woI) is superior to oral DI (oDI) and clamp DI (cDI) for detecting dysglycemia in obese youth.
• This cost-effective approach using OGTT bypasses insulin measurements, making it suitable for large-scale epidemiological studies.
• mDI-woI offers a practical tool for identifying metabolic dysfunction in youth.