A high-fat and fructose diet in dogs mirrors insulin resistance and β-cell dysfunction characteristic of impaired glucose tolerance in humans

PLoS One. 2023 Dec 22;18(12):e0296400. doi: 10.1371/journal.pone.0296400. eCollection 2023.

Abstract

This study examined the impact of a hypercaloric high-fat high-fructose diet (HFFD) in dogs as a potential model for human impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM). The HFFD not only led to weight gain but also triggered metabolic alterations akin to the precursors of human T2DM, notably insulin resistance and β-cell dysfunction. Following the HFFD intervention, the dogs exhibited a 50% decrease in insulin sensitivity within the first four weeks, paralleling observations in the progression from normal to IGT in humans. Calculations of the insulinogenic index using both insulin and C-peptide measurements during oral glucose tolerance tests revealed a significant and sustained decrease in early-phase insulin release, with partial compensation in the later phase, predominantly stemming from reduced hepatic insulin clearance. In addition, the Disposition Index, representing the β-cell's capacity to compensate for diminished insulin sensitivity, fell dramatically. These results confirm that a HFFD can instigate metabolic changes in dogs akin to the early stages of progression to T2DM in humans. The study underscores the potential of using dogs subjected to a HFFD as a model organism for studying human IGT and T2DM.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2*
  • Diet, High-Fat / adverse effects
  • Dogs
  • Fructose
  • Glucose Intolerance*
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*

Substances

  • Fructose
  • Insulin
  • Blood Glucose