Proinsulin associates with poor ß-cell function, glucose-dependent insulinotropic peptide, and insulin resistance in persistent type 2 diabetes after Roux-en-Y gastric bypass in humans.

BACKGROUND: The determinants of type 2 diabetes (T2D) remission and/or relapse after gastric bypass (RYGB) remain fully unknown. This study characterized ß- 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 underwent-either 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 ß-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 non-remitters were minimal. CONCLUSIONS: Individual without diabetes remission after gastric bypass have poorer ß-cell response and lesser suppression of glucagon to an oral challenge; body weight and incretins differ minimally according to remission status.

Longitudinal changes of microbiome composition and microbial metabolomics after surgical weight loss in individuals with obesity.

BACKGROUND: Some of the metabolic effects of bariatric surgery may be mediated by the gut microbiome. OBJECTIVES: To study the effect of bariatric surgery on changes to gut microbiota composition and bacterial pathways, and their relation to metabolic parameters after bariatric surgery. SETTINGS: University hospitals in the United States and Spain. METHODS: Microbial diversity and composition by 16 S rRNA sequencing, putative bacterial pathways, and targeted circulating metabolites were studied in 26 individuals with severe obesity, with and without type 2 diabetes, before and at 3, 6, and 12 months after either gastric bypass or sleeve gastrectomy. RESULTS: Bariatric surgery tended to increase alpha diversity, and significantly altered beta diversity, microbiota composition, and function up to 6 months after surgery, but these changes tend to regress to presurgery levels by 12 months. Twelve of 15 bacterial pathways enriched after surgery also regressed to presurgery levels at 12 months. Network analysis identified groups of bacteria significantly correlated with levels of circulating metabolites over time. There were no differences between study sites, surgery type, or diabetes status in terms of microbial diversity and composition at baseline and after surgery. CONCLUSIONS: The association among changes in microbiome with decreased circulating biomarkers of inflammation, increased bile acids, and products of choline metabolism and other bacterial pathways suggest that the microbiome partially mediates improvement of metabolism during the first year after bariatric surgery.

Role of Ethnicity on Weight Loss and Attrition After Bariatric Surgery.

Ethnicity has been shown to affect weight loss outcome and attrition after bariatric surgery. We analyze data from a multiethnic urban cohort of patients (n = 570) followed up to 12 months after either gastric bypass (RYGB) or gastric banding (AGB) surgery. Percent total weight loss was greater at 1 year after RYGB (35%) compared with that of AGB (13%), regardless of ethnicity. Hispanics were more likely to undergo RYGB (77.3% vs. 61.2% of African-Americans and 50.4% of Caucasians). Ethnicity had no effect on attrition after RYGB, but Hispanics had better follow-up rate after AGB. Our data do not support an effect of ethnicity on surgical weight loss at 1 year.