SUN-580 - Preoperative Metabolic Testing to Identify Risk for Postsurgical Hypoglycemia in the Longitudinal Assessment of Bariatric Surgery Cohort

Introduction: Post-bariatric hypoglycemia (PBH) is a serious consequence of bariatric surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). Hypoglycemia occurs after meals; rapid intestinal delivery and absorption of meal nutrients contribute to postprandial glucose spikes, excessive incretin and insulin secretion, and subsequent hypoglycemia. Since as many as one-third of patients who undergo RYGB or SG report symptoms of hypoglycemia, identifying preoperative risk factors is critical for improving patient selection and preventing PBH. We aim to identify whether metabolic phenotypes identified during pre-surgical testing differ in individuals who develop hypoglycemia after surgery (HYPO) vs. those who do not (NO-HYPO), using data from the Longitudinal Assessment of Bariatric Surgery Sub-Study 3 cohort (LABS-3), a prospective multicenter observational study of participants undergoing RYGB or SG.

Methods: Of 61 participants enrolled in LABS-3, 59 individuals met inclusion criteria for this analysis, including completion of a 4-hour mixed meal tolerance test (MMTT) and intravenous glucose tolerance test (IVGTT) preoperatively and at 6 and/or 24 months postoperatively, with no glucose levels < 70 mg/dL during the preoperative MMTT. Participants included those with and without type 2 diabetes (T2D) at baseline, defined as fasting plasma glucose ≥ 7.0 mM and/or HbA1C ≥ 48 mmol/mol (6.5%). Diabetes medications were stopped 1 week prior to metabolic testing. Analyses were conducted in Python. Continuous variables from preoperative studies were compared using two-sided Welch’s t-tests for small unequal group sizes unless otherwise specified.
Findings: Participants without T2D (n=21) exhibited higher odds of developing hypoglycemia—defined as a postsurgical MMTT glucose nadir < 70 mg/dL—than those with T2D (n=38) (OR 2.55). Presurgical age and BMI did not differ between HYPO and NO-HYPO within either stratum. Presurgical glucose incremental area under the curve (iAUC) did not differ in participants without T2D but was lower in HYPO vs. NO-HYPO in those with T2D (2083 vs 5983 mg/dL·min, p=0.0015). In participants without T2D, insulin levels did not differ, but C-peptide was elevated at 60 min in HYPO vs. NO-HYPO (10.02 vs 6.75 ng/mL, p=0.02). GLP-1 AUC was higher in HYPO without T2D (5884 vs 3461 pg/mL·min, p=0.047) but not in those with T2D. Glucagon response (ANOVA p=0.0005) and peak (30 minutes) were lower in HYPO (81.8 vs 103.7 pg/mL, p=0.028) but only in those with T2D.

Conclusion: Presurgical MMTT identified higher post-meal C-peptide and GLP-1 in individuals without T2D who subsequently developed postsurgical hypoglycemia, suggesting higher prandial hormonal responses may confer increased risk and. offering a foundation for exploratory predictive models leveraging presurgical metabolic features to stratify PBH risk.

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