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

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

Morgan Obura  1 , Joline W J Beulens  1   2 , Roderick Slieker  1   3 , Anitra D M Koopman  1 , Trynke Hoekstra  1   4 , Giel Nijpels  5 , Petra Elders  5 , Robert W Koivula  6   7 , Azra Kurbasic  6 , Markku Laakso  8 , Tue H Hansen  9   10 , Martin Ridderstråle  9 , Torben Hansen  9   11 , Imre Pavo  12 , Ian Forgie  13 , Bernd Jablonka  14 , Hartmut Ruetten  14 , Andrea Mari  15 , Mark I McCarthy  7   16 , Mark Walker  17 , Alison Heggie  17 , Timothy J McDonald  18 , Mandy H Perry  19 , Federico De Masi  20 , Søren Brunak  20   21 , Anubha Mahajan  16 , Giuseppe N Giordano  6 , Tarja Kokkola  8 , Emmanouil Dermitzakis  22   23   24 , Ana Viñuela  22   23   24 , Oluf Pedersen  9 , Jochen M Schwenk  25 , Jurek Adamski  26   27   28 , Harriet J A Teare  29 , Ewan R Pearson  30 , Paul W Franks  6   7   31 , Leen M 't Hart  1   3   32 , Femke Rutters  1 ; IMI-DIRECT Consortium
Affiliations

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

Morgan Obura et al. PLoS One. .

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.

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Conflict of interest statement

The authors have read the journal’s policy and have the following competing interests: IP is employed by Eli Lilly Regional Operations GmbH, Vienna, Austria and BJ and HR are employees of Sanofi-Aventis Deutschland GmbH, R&D, Frankfurt am Main, Germany. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Figures

Fig 1
Fig 1. Flow chart of inclusion (n = 668) and exclusion (n = 221) of participants in the DIRECT study.
Fig 2
Fig 2. Glucose curve subgroups following a MMT depicting estimated mean trajectories with 95% confidence intervals identified by the latent class trajectory analysis in individuals with type 2 diabetes (n = 787).
Fig 3
Fig 3. Glucose curve subgroups following a MMT depicting estimated mean trajectories of the 4 group solution identified by the latent class trajectory analysis in 651 individuals with type 2 diabetes at 18 months of follow-up.
See this image and copyright information in PMC

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