Altered Islet Function and Insulin Clearance Cause Hyperinsulinemia in Gastric Bypass Patients with Symptoms of Postprandial Hypoglycemia
Open accessAbstract
Context Postprandial hypoglycemia, a late complication of gastric bypass (GB) surgery, is associated with an exaggerated insulin response to meal ingestion. Objective The purpose of this study was to characterize insulin secretion and other glucoregulatory hormone responses to meal ingestion after GB based on hypoglycemia and clinical symptoms. Methods We conducted a cross-sectional analysis of insulin secretion rate and islet and gastrointestinal hormone responses to liquid mixed meal ingestion in 65 subjects with GB and 11 body mass index-matched controls without surgery. The GB subjects were stratified by clinical history for analysis of their responses to the test meal. Results The glucose and insulin responses to meal ingestion were shifted upward and to the left after GB, with the largest early insulin response and the lowest nadir glucose levels in patients with a history of hypoglycemia, particularly those with neuroglycopenic symptoms. Hypoglycemic GB subjects had lower postprandial insulin clearance rates and higher insulin secretion rates during the glucose decline after the test meal. Meal-induced glucagon was enhanced in all GB subjects but did not differ between subjects who did and did not develop hypoglycemia. Plasma gastric inhibitory polypeptide and glucagon-like peptide-1 concentrations did not differ between asymptomatic and neuroglycopenic GB subjects. Conclusion Among GB subjects with a clinical history of hypoglycemia, hyperinsulinemia is the result of…
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Decreased insulin clearance, blunted glucagon responses, increased serotonin levels, altered bile acid metabolism, and changes in microbiome composition have been implicated in PBH pathophysiology.
“Decreased insulin clearance, blunted glucagon responses, increased serotonin levels, altered bile acid metabolism, and changes in microbiome composition have also been implicated in the complex pathophysiology of PBH [49,53,54].”
From Non-Diabetic Hypoglycemia: Evaluation and Management in Adults (2025) · cites this paper as [53]
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- Authors
- Salehi, M., Gastaldelli, A., & D'Alessio, D. A.
- Affiliations
- University of Cincinnati (US)
- Istituto di Fisiologia Clinica (IT)
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, University of Cincinnati College of Medicine (M.S., D.A.D.), Cincinnati, Ohio 45219;
- Corresponding author
- Salehi, Marzieh
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2014-06-01
- Volume
- 99
- Issue
- 6
- Pages
- 2008-2017
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC4037736
- OpenAlex
- W1992016036
- Cited by
- 130
- References
- 41
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 6 · 2023: 12 · 2022: 12 · 2021: 6 · 2020: 11 · 2019: 17 · 2018: 13 · 2017: 12 · 2016: 14 · 2015: 14 · 2014: 2
- FWCI
- 13.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (UL1TR001425, UL1TR000077)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK57900, DK083554, R01DK057900, K23DK083554)
- NIH Clinical Center
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- gastric bypass, postprandial hypoglycemia, hyperinsulinemia, insulin secretion, insulin clearance, islet function, glucagon, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, neuroglycopenic symptoms, bariatric surgery complications
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Humans, Hyperinsulinism, Hypoglycemia, Insulin, Islets of Langerhans, Male, Middle Aged, Obesity, Gastric Bypass, Case-Control Studies, Postprandial Period, Young Adult
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