Limited Bariatric Surgery-induced Weight Loss in Subjects With Type 2 Diabetes: Predictor Variables in Adipose Tissue

CONTEXT: The impact of type 2 diabetes mellitus (T2D) at baseline on limited weight loss (WL) after bariatric surgery (BS) remains controversial, and the potential underlying mechanisms incompletely understood. OBJECTIVE: We aimed at gaining further insight on this relationship and identifying novel associations between adipose tissue (AT) parameters and short-term WL outcomes in subjects with or without T2D undergoing BS. METHODS: Mid-term WL trajectories after BS have been evaluated in a cohort of 1659 subjects (cohort 1) with (n = 543) and without T2D (n = 1116). Paired subcutaneous and visceral AT samples were obtained from a cohort of 48 pairs of subjects with and without T2D matched for age, sex, BMI, and type of BS (cohort 2). Differences in AT parameters between groups were evaluated and potential associations with WL response explored. RESULTS: T2D was independently associated with a 5% lesser mid-term WL in cohort 1, while HbA1c, insulin treatment, and number of T2D medications prior to BS were only related to short-term WL outcomes. In cohort 2, a number of differentially expressed genes in AT were identified between groups, while fat cell size and fibrosis were comparable. Subcutaneous ATG7 expression was found as an independent predictor of limited WL 1 year after surgery (β: -12.21 ± 4.41, P = .008) and its addition to a clinical model significantly improved the amount of WL variability explained (R2 = 0.131 vs R2 = 0.248, F change P = .009). CONCLUSION: Our results highlight the importance of T2D as determinant of limited WL following BS and suggest that dysregulated macroautophagy in subcutaneous AT may contribute to this association.