The present study was a 4-week randomized trial to assess the efficacy and safety of sitagliptin, a dipeptidyl-peptidase-4 inhibitor, in persistent or recurring type 2 diabetes after Roux-en-Y gastric bypass surgery (RYGB). Participants (n = 32) completed a mixed meal test (MMT) and self-monitoring of plasma glucose (SMPG) before and 4 weeks after randomization to either sitagliptin 100 mg daily or placebo daily. Questionnaires were administered to assess gastrointestinal discomfort. Outcome variables were glucose, active glucagon-like peptide-1 and β-cell function during the MMT, and glucose levels during SMPG. Age (56.3 ± 8.2 years), body mass index (34.4 ± 6.7 kg/m2), glycated haemoglobin (7.21 ± 0.77%), diabetes duration (12.9 ± 10.0 years), years since RYGB (5.6 ± 3.3 years) and β-cell function did not differ between the placebo and sitagliptin groups at pre-intervention. Sitagliptin was well tolerated, decreased postprandial glucose levels during the MMT (from 8.31 ± 1.92 mmol/L to 7.67 ± 1.59 mmol/L, P = 0.03) and mean SMPG levels, but had no effect on β-cell function. In patients with diabetes and mild hyperglycemia after RYGB, a short course of sitagliptin provided a small but significant glucose-lowering effect, with no identified improvement in β-cell function.
Background: The determinants of type 2 diabetes (T2D) remission and/or relapse after gastric bypass (RYGB) remain fully unknown. This study characterized β-and α-cell function, in cretin hormone release and insulin sensitivity in individuals with (remitters) or without (non-remitters) diabetes remission after RYGB. Methods: This is a cross-sectional study of two distinct cohorts of individuals with or without diabetes remission at least 2 years after RYGB. Each individual under-wenteither an oral glucose (remitters) or a mixed meal (non-remitters) test; glucose, proinsulin, insulin, C-peptide, glucagon, incretins and leptin were measured. Results: Compared to remitters (n = 23), non-remitters (n = 31) were older (mean [±SD] age 56.1 ± 8.2 vs. 46.0 ± 8.9 years, P < 0.001), had longer diabetes duration (13.1 ± 10.1 vs. 2.2 ± 2.4 years, P < 0.001), were further out from the surgery (5.6 ± 3.3 vs. 3.5 ± 1.7 years, P < 0.01), were more insulin resistant (HOMA-IR 4.01 ± 3.65 vs. 2.08 ± 1.22, P < 0.001), but did not differ for body weight. As predicted, remitters had higher β-cell glucose sensitivity (1.95 ± 1.23 vs. 0.86 ± 0.55 pmol/kg/min/mmol, P < 0.001) and disposition index (1.55 ± 1.75 vs 0.33 ± 0.27, P = 0.003), compared to non-remitters, who showed non-suppressibility of glucagon during the oral challenge (time × group P = 0.001). Higher proinsulin (16.55 ± 10.45 vs. 6.62 ± 3.50 PM, P < 0.0001), and proinsulin: C-peptide (40.83 ± 29.43 vs. 17.13 ± 7.16, P < 0.001) were strongly associated with non-remission status, while differences in incretins between remitters and nonremitters were minimal. † This study is registered with Clinicaltrials.gov (ID: NCT01512797 and NCT01516320).
β-cell glucose sensitivity (BCGS) improves after gastric bypass (RYGB) in individuals in diabetes (DM2) remission. We sought to assess BCGS (pmol/kg/min/mM) after an oral glucose test (OGT) and an IV graded glucose infusion (GGI) in subjects with and without DM2 remission after RYGB. Twenty five subjects with DM2 were studied with GGI and 75g-OGT before and 3 months after RYGB. Glucose, insulin, C-peptide, insulin secretion rate, GLP-1 and BCGS were assessed during the OGT and the GGI. Data are presented as mean±SD. Within and between group comparisons with paired and unpaired t-test; GLM with repeated measure to assess change during OGT or GGI were (SPSS 24). Of the 25 subjects studied pre-surgery, 10 experienced DM2 remission (REM), 9 remained with DM2 (N-REM) at 3 months; 6 remained glucose intolerant and were not included in the analysis. Pre-surgery BMI (41.5±4.7 kg/m2), weight (108.3±15.9 kg), age (43.8±8.8 years), gender (95% female), HOMA-IR (12.1±6.7) and Matsuda index did not differ between groups; N-REM had longer DM2 duration (14 vs. 2.5 y p<0.001), higher HbA1c (8.2±1.0 vs. 7.0±0.8%, p=0.01) and more likely to be taking insulin (7/9 vs. 0/10 p<0.001). Prior to RYGB, OGT-BCGS was 4x greater (0.83±0.60 vs. 0.22±0.24, p=0.01) and GGI-BCGS was 2.5x greater (0.48±0.30 vs. 0.18±0.15, p=0.04) in REM vs. N-REM. Weight loss did not differ for REM and N-REM (17±5%). HOMA-IR, GLP-1 and GGI-BCGS improved similarly in both groups. OGT-BCGS increased in both groups, but more in REM vs. N-REM (+1.31±1.0 vs. +0.30±0.28, p=0.01). The difference between OGT-BCGS and GGI-BCGS observed pre-RYGB (0.58±0.54 vs. 0.38±.035, p=ns) was exaggerated at 3 months by 4x in REM (2.13±1.vs. 0.58±0.15, p=0.001) and ∼2.5x in N-REM (0.60±.0.43 vs. 0.24±0.17, p=0.07). In conclusion, β-cell function assessed during an IV GGI improves by the same magnitude regardless of DM2 remission status after RYGB. However, β-cell function improved more in REM than N-REM after oral glucose, suggesting a greater incretin effect, or other gut-related mechanisms, in REM after RYGB. Disclosure A. Shah: Employee; Spouse/Partner; Daiichi Sankyo Company, Limited. K. Levesque: None. M. Ahlers: None. M.M. Holter: None. F. Alam: None. E. Pierini: None. B.L. Rojas: None. V. Mark: None. K. Patel: None. R. Dutia: None. E.J. Harvey: None. K. Park: None. N. Koshy: None. S.J. Belsley: None. J.J. Mcginty: None. B. Laferrere: None.
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