Lack of Evidence for a Causal Role of Hyperinsulinemia in the Progression of Obesity in Children and Adolescents: A Longitudinal Study

Abstract

Objective: The carbohydrate-insulin model (CIM) claims that chronic exposure to hyperinsulinemia induced by dietary carbohydrates explains development of obesity via direct effects of insulin and/or low postprandial metabolic fuel levels. We aimed at testing whether indices of hyperinsulinemia and postprandial glucose levels can predict increases in the degree of obesity over time.

Research design and methods: Children and adolescents with obesity attending a pediatric obesity clinic performed oral glucose tolerance tests (OGTTs) and received standard obesity management. Indices of hyperinsulinemia and insulin secretion were derived from the OGTT and evaluated in the face of changes in the degree of obesity over time.

Results: A total of 591 children (217 males and 374 females) participated, and the mean follow-up was 1.86 ± 1.29 years. OGTT-derived area under the curve of insulin, peak insulin, fasting insulin, the insulinogenic index, or insulin at 30 min were not associated with greater changes in the degree of obesity in univariate or multivariate analyses (adjusted for baseline age, BMI z score, sex, and ethnicity). Low postprandial glucose <75 mg/dL was not associated with greater changes in the degree of obesity in univariate or multivariate analyses. In a subsample of 104 participants with a follow-up >4 years, none of these parameters was associated with greater increases in the degree of obesity.

Conclusions: In children and adolescents with obesity, exposure to hyperinsulinemia, greater insulin secretion, or low postprandial glucose is not associated with greater increases in the degree of obesity over 2-4 years. The CIM should be evaluated in children with lower BMI and for longer follow-up periods.

Trial registration: ClinicalTrials.gov NCT00000112 NCT01967849.

Figure 1

Correlations of BMI z-score changes and AUC_insulin (A), peak insulin (B), fasting insulin (C), and Glucose_180min (D) of the OGTT.

Figure 2

BMI z-score changes by AUC_insulin (A and B), fasting insulin (C and D), peak insulin (E and F), and Glucose_180min (G and H) of the OGTT. Simple comparisons are from univariate comparisons. Values presented as means ± SEs. Adjusted values are derived from the linear regression models. The values for AUC_insulin tertiles are: tertile 1 <156; 156 ≤ tertile 2 ≤ 206; tertile 3 >206 (AUC_insulin expressed in microunits per milliliter per minute). The values for fasting insulin tertiles are: tertile 1 <26; 26 ≤ tertile 2 ≤ 39; tertile 3 >39 (fasting insulin expressed in microunits per milliliter). The values for peak insulin tertiles are: tertile 1 <203; 203 ≤ tertile 2 ≤ 358; tertile 3 >358 (peak insulin expressed in microunits per milliliter). Glucose_180min categories compared were <75 or >75 mg/dL.