Compensated But Failing: Early β-Cell Dysfunction Under Normoglycemia in Children and Adolescents With Overweight and Obesity

Diabetes Metab Res Rev. 2026 May;42(4):e70172. doi: 10.1002/dmrr.70172.

Abstract

Background: The global rise of obesity has accelerated the onset of type-2 diabetes mellitus (T2DM) also among youth. Early detection of impaired β-cell function in at-risk populations is crucial for prevention; however, reference standards for children and adolescents remain scarce. We aimed to establish population-based percentile distributions specific to developmental stage and weight status for multiple markers of β-cell function in Chilean youth, thereby addressing this critical gap.

Methods: Cross-sectional study in 988 children and adolescents aged 6-17 years. Anthropometric measurements included weight, height, and waist circumference; weight status was classified using WHO 2007 standards. Participants were stratified into three developmental groups: Tanner 1-2 (G1), Tanner 3-5 (G2), and adolescents ≥ 16 years (G3). Fasting glucose and insulin were measured; insulin sensitivity and β-cell function were estimated using HOMA. Disposition index (DI) was calculated.

Results: G2 participants exhibited higher insulin, HOMA-IR, and HOMA-β levels, alongside lower HOMA-S levels compared to G1 and G3. Across all developmental groups, β-cell function varied by weight status: normal-weight individuals displayed more favourable insulin profiles than those with overweight or obesity. DI declined significantly with excess weight in G3, although values remained below 1.0 across groups. Fasting glucose was consistently within the normal range, independent of weight status.

Conclusion: Our findings suggest that differences in β-cell function may be present even in the context of normal fasting glucose, indicating that glycaemia alone may not fully capture early variations in glucose-insulin dynamics. Since pubertal stage and adiposity significantly influenced these results, incorporating development- and weight-specific considerations may improve the interpretation of metabolic markers during growth. These findings support the need for more nuanced approaches to characterise metabolic variability in youth.

Keywords: childhood obesity; insulin resistance; normoglycemia; β‐cell function.

MeSH terms

  • Adolescent
  • Biomarkers* / analysis
  • Blood Glucose* / analysis
  • Body Mass Index
  • Child
  • Chile / epidemiology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / etiology
  • Female
  • Follow-Up Studies
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Insulin-Secreting Cells* / metabolism
  • Insulin-Secreting Cells* / pathology
  • Male
  • Obesity*
  • Overweight* / complications
  • Overweight* / physiopathology
  • Pediatric Obesity* / complications
  • Pediatric Obesity* / physiopathology
  • Prognosis

Substances

  • Blood Glucose
  • Biomarkers
  • Insulin