To explain the variation of OGTT dynamics by biological mechanisms: a novel approach based on principal components analysis in women with history of GDM

Am J Physiol Regul Integr Comp Physiol. 2015 Jul 1;309(1):R13-21. doi: 10.1152/ajpregu.00059.2015. Epub 2015 Apr 29.

Abstract

Early reexamination of carbohydrate metabolism via an oral glucose tolerance test (OGTT) is recommended after pregnancy with gestational diabetes (GDM). In this report, we aimed to assess the dominant patterns of dynamic OGTT measurements and subsequently explain them by meanings of the underlying pathophysiological processes. Principal components analysis (PCA), a statistical procedure that aims to reduce the dimensionality of multiple interrelated measures to a set of linearly uncorrelated variables (the principal components) was performed on OGTT data of glucose, insulin and C-peptide in addition to age and body mass index (BMI) of 151 women (n = 110 females after GDM and n = 41 controls) at 3-6 mo after delivery. These components were explained by frequently sampled intravenous glucose tolerance test (FSIGT) parameters. Moreover, their relation with the later development of overt diabetes was studied. Three principal components (PC) were identified, which explained 71.5% of the variation of the original 17 variables. PC1 (explained 47.1%) was closely related to postprandial OGTT levels and FSIGT-derived insulin sensitivity (r = 0.68), indicating that it mirrors insulin sensitivity in the skeletal muscle. PC2 (explained 17.3%) and PC3 (explained 7.1%) were shown to be associated with β-cell failure and fasting (i.e., hepatic) insulin resistance, respectively. All three components were related with diabetes progression (occurred in n = 25 females after GDM) and showed significant changes in long-term trajectories. A high amount of the postpartum OGTT data is explained by principal components, representing pathophysiological mechanisms on the pathway of impaired carbohydrate metabolism. Our results improve our understanding of the underlying biological processes to provide an accurate postgestational risk stratification.

Keywords: gestational diabetes mellitus; insulin resistance; insulin secretion; oral glucose tolerance test; principal components analysis.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Austria / epidemiology
  • Biomarkers / blood
  • Blood Glucose / metabolism*
  • Body Mass Index
  • C-Peptide / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes, Gestational / blood
  • Diabetes, Gestational / diagnosis*
  • Diabetes, Gestational / epidemiology
  • Disease Progression
  • Female
  • Glucose Tolerance Test*
  • Humans
  • Incidence
  • Insulin / blood
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism
  • Linear Models
  • Muscle, Skeletal / metabolism
  • Predictive Value of Tests
  • Pregnancy
  • Principal Component Analysis
  • Prognosis
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors

Substances

  • Biomarkers
  • Blood Glucose
  • C-Peptide
  • Insulin