Individuals With Prediabetes Display Different Age-Related Pathophysiological Characteristics

J Clin Endocrinol Metab. 2019 Jul 1;104(7):2911-2924. doi: 10.1210/jc.2018-02610.

Abstract

Context: Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) are highly pathophysiologic heterogeneous prediabetes conditions that can occur in all age groups, from youth to elderly people.

Objective: We evaluated whether distinct age-related phenotypes exist among individuals with IFG or IGT.

Research design: 479 young (aged 18 to 35 years), 699 adult (45 to 55 years) and 240 older (≥65 years) subjects underwent an oral glucose tolerance test (OGTT). From the OGTT results, the participants were grouped as follows: young age and normal glucose tolerance (NGT), adult age and NGT, older age and NGT, IFG young subjects, IFG adult subjects, IFG older subjects, IGT young (Y-IGT) subjects, IGT adult (A-IGT) subjects, and IGT older (O-IGT) subjects.

Main outcome measures: Insulin sensitivity and secretion, insulin clearance, and β-cell function.

Results: Peripheral insulin sensitivity assessed using the Matsuda index, basal and glucose-stimulated insulin secretion, and β-cell function estimated using the disposition index were decreased in IFG adult subjects and IFG older subjects compared with IFG young subjects. A-IGT and Y-IGT subjects exhibited a progressively greater degree of hepatic insulin resistance assessed using the liver insulin resistance index, and reduced insulin clearance compared with O-IGT subjects. In contrast, the Matsuda index did not differ among Y-IGT, A-IGT, and O-IGT subjects. Basal and glucose-stimulated insulin secretion and β-cell function were lower in A-IGT and O-IGT subjects compared with Y-IGT individuals.

Conclusions: Subjects with IFG or IGT exhibited different age-related pathophysiologic characteristics. A more precise phenotyping of subjects with IGT or IFG could help to better design individualized preventive approaches to counteract diabetes progression.

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Blood Glucose / metabolism
  • Body Mass Index
  • C-Peptide / metabolism
  • Cholesterol, HDL / metabolism
  • Female
  • Glucose Intolerance / metabolism*
  • Glucose Tolerance Test
  • Humans
  • Insulin / metabolism
  • Insulin Resistance*
  • Insulin Secretion*
  • Male
  • Middle Aged
  • Prediabetic State / metabolism*
  • Triglycerides / metabolism
  • Young Adult

Substances

  • Blood Glucose
  • C-Peptide
  • Cholesterol, HDL
  • Insulin
  • Triglycerides