Unraveling, contributing factors to the severity of postprandial hypoglycemia after gastric bypass surgery.

BACKGROUND: Despite the increasing prevalence of postbariatric hypoglycemia (PBH), a late metabolic complication of bariatric surgery, our understanding of its diverse manifestations remains incomplete. OBJECTIVES: To contrast parameters of glucose-insulin homeostasis in 2 distinct phenotypes of PBH (mild versus moderate hypoglycemia) based on nadir plasma glucose. SETTING: University Hospital (Bern, Switzerland). METHODS: Twenty-five subjects with PBH following gastric bypass surgery (age, 41 ± 12 years; body mass index, 28.1 ± 6.1kg/m2) received 75g of glucose with frequent blood sampling for glucose, insulin, C-peptide, and glucagon-like peptide 1 (GLP)-1. Based on nadir plasma glucose (

Multiplexed Assay to Quantify the PP-Fold Family of Peptides in Human Plasma Using Microflow Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Peptide Tyr-Tyr (PYY1-36), pancreatic polypeptide (PP1-36) and neuropeptide Y (NPY1-36) constitute the PP-fold family of peptides that is involved in metabolic regulation. Very low plasma concentrations and cleavage into active 3-36 fragments challenge bioanalytical assays used for the quantification of these peptides. METHODS: We developed a multiplexed isotopic dilution assay to quantify PYY1-36, PP1-36, and NPY1-36 and their dipeptidyl peptidase-4 (DPP4)-derived metabolites PYY3-36, PP3-36 and NPY3-36. All peptides were immunocaptured from plasma using a monoclonal antibody and quantified by micro-ultra-HPLC-MS/MS. Blood samples from healthy volunteers were collected fasting and 30 min after nutrient stimulation. Method comparison was performed with commercial immunoassays. RESULTS: Linearity was shown in the measured intervals (r2 > 0.99). The lower limit of quantification (LLOQ) with a CV at 20% was 1.5 pM for PYY1-36 and PYY3-36, 3.0 pM for PP1-36 and PP3-36, 0.8 pM for NPY1-36 and 0.5 pM for NPY3-36. In all cases, intra- and inter-assay bias and imprecision were <21%. Pre-analytical stability required addition of a protease inhibitor cocktail. Physiological concentrations of PYY3-36, NPY3-36, PP1-36 and PP3-36 were above the LLOQ in 43% to 100% of the samples. PYY1-36 and NPY1-36 were above the LLOQ in 9% and 0% of the samples, respectively. Immunoassays showed higher concentrations of measurands and poor agreement when compared with micro-UHPLC-MS/MS. CONCLUSIONS: The assay allowed for specific multiplexed analysis of the PP-fold family of peptides and their DPP4-cleaved fragments in a single sample, thereby offering new perspectives to study the role and therapeutic potential of these essential peptide hormones in health and metabolic disease.

Effect of fully automated closed-loop insulin delivery using faster aspart versus standard aspart on gluco-regulatory hormones in type 2 diabetes.

We retrospectively assessed gluco-regulatory hormones over 10 h (including two meals) of fully automated closed-loop insulin delivery using faster (FA) versus standard insulin aspart (IAsp) in adults with type 2 diabetes [n = 15, age 59 ± 10 years, body mass index 34.5 ± 9.1 kg/m2 , glycated haemoglobin 7.7 ± 1.2% (60 ± 13 mmol/mol)]. Plasma concentration of human insulin, IAsp, C-peptide, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine were measured every 15-30 min. Endogenous insulin secretion was calculated using C-peptide deconvolution and exposures to hormones were compared using their mean plasma concentrations. Ten-hour exposure of IAsp was higher with FA versus IAsp (P = .037) in line with the 10% higher insulin requirements to achieve similar glucose control. No significant difference was found for total insulin exposure and endogenous insulin secretion. Similarly, other gluco-regulatory hormones did not significantly differ. In conclusion, the faster pharmacokinetic profile and slightly higher aspart exposure of FA versus IAsp remained without significant effects on endogenous insulin secretion or other gluco-regulatory hormones. Further studies are warranted to explore the metabolic and endocrine effects of novel insulins with accelerated pharmacokinetic properties.