Abstract

A growing body of evidence indicates that dietary polyphenols could be used as an early intervention to treat glucose-insulin (G-I) dysregulation. However, studies report heterogeneous information, and the targets of the intervention remain largely elusive. In this work, we provide a general methodology to quantify the effects of any given polyphenol-rich food or formulae over glycemic regulation in a patient-wise manner using an Oral Glucose Tolerance Test (OGTT). We use a mathematical model to represent individual OGTT curves as the coordinated action of subsystems, each one described by a parameter with physiological interpretation. Using the parameter values calculated for a cohort of 1198 individuals, we propose a statistical model to calculate the risk of dysglycemia and the coordination among subsystems for each subject, thus providing a continuous and individual health assessment. This method allows identifying individuals at high risk of dysglycemia—which would have been missed with traditional binary diagnostic methods—enabling early nutritional intervention with a polyphenol-supplemented diet where it is most effective and desirable. Besides, the proposed methodology assesses the effectiveness of interventions over time when applied to the OGTT curves of a treated individual. We illustrate the use of this method in a case study to assess the dose-dependent effects of Delphinol® on reducing dysglycemia risk and improving the coordination between subsystems. Finally, this strategy enables, on the one hand, the use of low-cost, non-invasive methods in population-scale nutritional studies. On the other hand, it will help practitioners assess the effectiveness of an intervention based on individual vulnerabilities and adapt the treatment to manage dysglycemia and avoid its progression into disease.

Highlights

  • Disequilibrium in glucose-insulin (G-I) homeostasis is a widespread condition in modern society and is associated with poor dietary habits and poverty [1,2,3,4]

  • We found that basal glycemia and insulinemia are not correlated to any other parameter/non-dimensional numbers (NDNs), so the clinical status of internal subsystems cannot be inferred from these basal levels alone derived from the current 2-point Oral Glucose Tolerance Test (OGTT) procedure of diagnostic

  • We present evidence supporting the notion that dysglycemia risk can be masked by current threshold-based diagnostic criteria and that vulnerability to dysglycemia depends on individual circumstances and physiology

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Summary

Introduction

Disequilibrium in glucose-insulin (G-I) homeostasis (dysglycemia) is a widespread condition in modern society and is associated with poor dietary habits and poverty [1,2,3,4]. Dysglycemia may progress through insulin resistance and glucose intolerance to type 2 diabetes mellitus (T2DM), and increase the risk for cardiovascular diseases and other comorbidities. There is a need for quantitative methods to address such questions and follow the effects of any given polyphenolic formula over glycemic regulation to advance towards standardisation and comparison, in clinical cohort results. Such methods must be sensitive enough to detect subtle changes to keep track of the nutritional treatment since dietary interventions are often subtle and long term [22]

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