Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study.
Obura M., Beulens JWJ., Slieker R., Koopman ADM., Hoekstra T., Nijpels G., Elders P., Koivula RW., Kurbasic A., Laakso M., Hansen TH., Ridderstråle M., Hansen T., Pavo I., Forgie I., Jablonka B., Ruetten H., Mari A., McCarthy MI., Walker M., Heggie A., McDonald TJ., Perry MH., De Masi F., Brunak S., Mahajan A., Giordano GN., Kokkola T., Dermitzakis E., Viñuela A., Pedersen O., Schwenk JM., Adamski J., Teare HJA., Pearson ER., Franks PW., 't Hart LM., Rutters F., IMI-DIRECT Consortium None.
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.