Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study

PLoS One. 2020 Nov 30;15(11):e0242360. doi: 10.1371/journal.pone.0242360. eCollection 2020.

Abstract

Aim: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.

Methods: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.

Results: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.

Conclusions: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / metabolism*
  • Fasting / blood
  • Fasting / metabolism
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Glycated Hemoglobin / metabolism
  • Humans
  • Male
  • Middle Aged
  • Triglycerides / blood
  • Triglycerides / metabolism

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Triglycerides
  • hemoglobin A1c protein, human

Grants and funding

The work leading to this publication was supported by the Innovative Medicines Initiative Joint Undertaking under grant agreement n°115317 (IMI-DIRECT ), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007- 2013) and EFPIA companies’ in kind contribution. The IMI-DIRECT grant was awarded to ML, IM, IF, BJ, HR, AM, MW, TJM, SB, GNG, ED, OP, JMS, JA, ERP, PWF, LMT and FR. The Amsterdam Public Health research institute provided support in the form of a PhD fellowship for MO. Eli Lilly Regional Operations GmbH, Vienna, Austria provided support in the form of a salary for IP, and Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt am Main, Germany provided support in the form of salaries for BJ and HR. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders played a role in data collection, but did not have any additional role in the study design, analysis, decision to publish, or preparation of the manuscript.