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Context: Proneurotensin (pNT) is associated with obesity and type 2 diabetes (T2D), but the effects of Roux-en-Y gastric bypass (RYGB) on postprandial pNT levels are not well studied., Objective: This work aimed to assess the effects of RYGB vs a very low-energy diet (VLED) on pNT levels in response to mixed-meal tests (MMTs), and long-term effects of RYGB on fasting pNT., Methods: Cohort 1: Nine normoglycemic (NG) and 10 T2D patients underwent MMT before and after VLED, immediately post RYGB and 6 weeks post RYGB. Cohort 2: Ten controls with normal weight and 10 patients with obesity and T2D, who underwent RYGB or vertical sleeve gastrectomy (VSG), underwent MMTs and glucose-dependent insulinotropic polypeptide (GIP) infusions pre surgery and 3 months post surgery. Glucagon-like peptide-1 (GLP-1) infusions were performed in normal-weight participants. Cohort 3: Fasting pNT was assessed pre RYGB (n = 161), 2 months post RYGB (n = 92), and 1year post RYGB (n = 118) in NG and T2D patients. pNT levels were measured using enzyme-linked immunosorbent assay., Results: Reduced fasting and postprandial pNT were evident after VLED and immediately following RYGB. Reintroduction of solid food post RYGB increased fasting and postprandial pNT. Prior to RYGB, all patients lacked a meal response in pNT, but this was evident post RYGB/VSG. GIP or GLP-1 infusion had no effect on pNT levels. Fasting pNTs were higher 1-year post RYGB regardless of glycemic status., Conclusion: RYGB causes a transient reduction in pNT as a consequence of caloric restriction. The RYGB/VSG-induced rise in postprandial pNT is independent of GIP and GLP-1, and higher fasting pNTs are maintained 1 year post surgically., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Context: Glucose-dependent insulinotropic peptide (GIP) and meal ingestion increase subcutaneous adipose tissue (SAT) perfusion in healthy individuals. The effects of GIP and a meal on visceral adipose tissue (VAT) perfusion are unclear., Objective: Our aim was to investigate the effects of meal and GIP on VAT and SAT perfusion in obese individuals with type 2 diabetes mellitus (T2DM) before and after bariatric surgery., Methods: We recruited 10 obese individuals with T2DM scheduled for bariatric surgery and 10 control individuals. Participants were studied under 2 stimulations: meal ingestion and GIP infusion. SAT and VAT perfusion was measured using 15O-H2O positron emission tomography-magnetic resonance imaging at 3 time points: baseline, 20 minutes, and 50 minutes after the start of stimulation. Obese individuals were studied before and after bariatric surgery., Results: Before bariatric surgery the responses of SAT perfusion to meal (P = .04) and GIP-infusion (P = .002) were blunted in the obese participants compared to controls. VAT perfusion response did not differ between obese and control individuals after a meal or GIP infusion. After bariatric surgery SAT perfusion response to a meal was similar to that of controls. SAT perfusion response to GIP administration remained lower in the operated-on than control participants. There was no change in VAT perfusion response after bariatric surgery., Conclusion: The vasodilating effects of GIP and meal are blunted in SAT but not in VAT in obese individuals with T2DM. Bariatric surgery improves the effects of a meal on SAT perfusion, but not the effects of GIP. Postprandial increase in SAT perfusion after bariatric surgery seems to be regulated in a GIP-independent manner., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose and relief of symptom when glucose is normalized (Whipple triad)., Objective: To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after GB., Setting: The study was conducted at General Clinical Research Unit, Cincinnati Children's Hospital (Cincinnati, OH, USA)., Methods: Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched nonoperated controls using MMT in a control setting and CGMS under free-living conditions., Results: Patients with prior GB had larger glucose variability during both MMT and CGMS when compared with nonsurgical controls regardless of their hypoglycemic status. Sensitivity (71 vs 47%) and specificity (100 vs 88%) of MMT in detecting hypoglycemia was superior to CGMS., Conclusions: Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared with CGMS during free-living state., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Context: Bariatric surgery leads to a rapid and sustained weight loss often accompanied with improvement in glucose homeostasis., Objective: The objective of this study was to investigate the effects of bariatric surgery on pancreatic lipid metabolism, blood flow, and glycemic control., Design: This was a longitudinal study., Setting: The study was conducted in a clinical research center., Participants: This study included 27 morbidly obese and 15 healthy control subjects., Interventions: Measurements were performed using positron emission tomography with the palmitate analog 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid and radiowater ([(15)O]H2O) and computed tomography. In morbidly obese subjects, positron emission tomography/computed tomography imaging studies were performed before and 6 months after bariatric surgery (either Roux-en-Y gastric bypass or sleeve gastrectomy)., Main Outcome Measures: Pancreatic fat and fat-free volume, fatty acid uptake and blood flow were measured as well as parameters of β-cell function, glucose tolerance, and insulin sensitivity., Results: Six months after bariatric surgery, 23% excess weight loss was observed (P < .0001), and diabetes remission was seen in 7 of 10 patients. When compared with preoperative values, after surgery, notable decreases in pancreatic fat volume (P < .01), fatty acid uptake, and blood flow (both P < .05) were seen, whereas no change was seen in pancreatic fat-free volume. The decrease in pancreatic fat volume and the preservation of blood flow were associated with favorable glucose homeostasis and β-cell function., Conclusions: Bariatric surgery elicits marked alterations in pancreatic lipid metabolism and blood flow, which may contribute to the observed improvement in glucose homeostasis and remission of type 2 diabetes.

Context: Glucolipotoxicity is believed to induce pancreatic β-cell dysfunction in obesity. Previously, it has not been possible to study pancreatic metabolism and blood flow in humans., Objective: The objective of the study was to investigate whether pancreatic metabolism and blood flow are altered in obesity using positron emission tomography (PET). In the preclinical part, the method was validated in animals., Design: This was a cross-sectional study., Setting: The study was conducted in a clinical research center., Participants: Human studies consisted of 52 morbidly obese and 25 healthy age-matched control subjects. Validation experiments were done with rodents and pigs., Interventions: PET and magnetic resonance imaging studies using a glucose analog ([(18)F]fluoro-2-deoxy-d-glucose), a palmitate analog [14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid], and radiowater ([(15)O]H2O) were performed. In animals, a comparison between ex vivo and in vivo data was performed., Main Outcome Measures: Pancreatic glucose/fatty acid (FA) uptake, fat accumulation, and blood flow parameters of β-cell function were measured., Results: PET proved to be a feasible method to measure pancreatic metabolism. Compared with healthy participants, obese participants had elevated pancreatic FA uptake (P < .0001), more fat accumulation (P = .0001), lowered glucose uptake both during fasting and euglycemic hyperinsulinemia, and blunted blood flow (P < .01) in the pancreas. Blood flow, FA uptake, and fat accumulation were negatively associated with multiple markers of β-cell function., Conclusions: Obesity leads to changes in pancreatic energy metabolism with a substrate shift from glucose to FAs. In morbidly obese humans, impaired pancreatic blood flow may contribute to β-cell dysfunction and in the pathogenesis of type 2 diabetes.