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Amanda Sheehan,1 Mary Elizabeth Patti1,2 1Research Division, Joslin Diabetes Center, Boston, MA, USA; 2Harvard Medical School, Boston, MA, USACorrespondence: Mary Elizabeth PattiResearch Division, Joslin Diabetes Center, 1 Joslin Place, Boston, MA 02215, USATel +1 617-309-1966Fax +1 617-309-2593Email Mary.elizabeth.patti@joslin.harvard.eduContext: Post-bariatric hypoglycemia (PBH) is an increasingly encountered complication of upper gastrointestinal surgery; the prevalence of this condition is anticipated to rise given yearly increases in bariatric surgical procedures. While PBH is incompletely understood, there is a growing body of research describing the associated factors, mechanisms, and treatment approaches for this condition.Evidence Acquisition: Data are integrated and summarized from studies of individuals affected by PBH and hypoglycemia following upper gastrointestinal surgery obtained from PubMed searches (1990– 2020).Evidence Synthesis: Information addressing etiology, incidence/prevalence, clinical characteristics, assessment, and treatment were reviewed and synthesized for the practicing physician. Literature reports were supplemented by clinical experience as indicated, when published data were not available.Conclusion: PBH can be life-altering and severe for a subset of individuals. Given the chronic nature of this condition, and sequelae of both acute and recurrent episodes, increasing provider awareness of both the condition and associated risk factors is critical for assessment, prompt diagnosis, treatment, and preoperative identification of individuals at risk.Keywords: hypoglycemia, post-bariatric hypoglycemia, upper gastrointestinal surgery, bariatric surgery

Low birth weight (LBW) is an important risk factor for type 2 diabetes. We have developed a mouse model of LBW resulting from undernutrition during pregnancy. Restriction of maternal food intake from day 12.5 to 18.5 of pregnancy results in a 23% decrease in birth weight (P < 0.001), with normalization after birth. However, offspring of undernutrition pregnancies develop progressive, severe glucose intolerance by 6 months. To identify early defects that are responsible for this phenotype, we analyzed mice of undernutrition pregnancies at age 2 months, before the onset of glucose intolerance. Fed insulin levels were 1.7-fold higher in mice of undernutrition pregnancies (P = 0.01 vs. controls). However, insulin sensitivity was normal in mice of undernutrition pregnancies, with normal insulin tolerance, insulin-stimulated glucose disposal, and isolated muscle and adipose glucose uptake. Although insulin clearance was mildly impaired in mice of undernutrition pregnancies, the major metabolic phenotype in young mice of undernutrition pregnancies was dysregulation of insulin secretion. Despite normal beta-cell mass, islets from normoglycemic mice of undernutrition pregnancies showed basal hypersecretion of insulin, complete lack of responsiveness to glucose, and a 2.5-fold increase in hexokinase activity. Taken together, these data suggest that, at least in mice, primary beta-cell dysfunction may play a significant role in the pathogenesis of LBW-associated type 2 diabetes.