(OR24-05-23) Two Phenotypes of Postprandial Reactive Hypoglycemia Following Mixed Meal Tolerance Test

Objectives: Postprandial reactive hypoglycemia (PRH) may be an early harbinger of risk for both obesity and type 2 diabetes. The postprandial glucose and insulin dynamics that produce PRH have not been described. Whether PRH reflects enhanced postprandial insulin concentration and/or relatively high insulin sensitivity or insulin resistance is not clear. The objective was to use the glucose and insulin responses to a mixed meal tolerance test (MMTT) to characterize PRH, postprandial insulin response, and insulin sensitivity/resistance in overweight Black and White men and women.

Methods: A 4-h MMTT (59% C, 17% P, 24% F) was administered to 69 nondiabetic overweight men and women aged 35±8.3 years (BMI 32.3 ± 4.2 kg/m²).  PRH was defined as a drop in glucose below fasting after consuming MMTT followed by immediate increase in glucose. Peak and nadir values, and area-under-the-curve (AUC), of glucose and insulin were identified. Intravenous glucose tolerance test (IVGTT), Matsuda index, and HOMA-IR were used to assess insulin sensitivity/resistance. Visual Basic Application (VBA) code was written to extract seven curve-shape properties of post-prandial trajectories for glucose and insulin.

Results: 18 of the 69 participants were identified as having a reactive hypoglycemic response to the LMT. Glucose nadir was significantly lower in those with PRH compared to nonPRH (73mg/dl, 111 mg/dl, p < .001). Insulin sensitivity was higher, and HOMA-IR was lower, in PRH compared to non-PRH. Glucose and insulin AUC were also significantly lower in PRH. Two subgroups of PRH were identified based on peak first phase insulin secretion during the LMT, low peak insulin peak (LPI) (n=8) and high peak insulin (HPI) (n=9). Fasting insulin, peak insulin, insulin nadir, insulin area under the curve, and HOMA were significantly higher in the HPI group compared to the LPI group. VBA coding of the glucose showed PRH had increased rate of incline, reduced rate of decline, and lower inflection point compared to nonPRH.

Conclusions: Among overweight individuals, PRH is more common in women and Black individuals, and manifests as two phenotypes: HPI, exaggerated insulin response and higher IR, and LPI, lower insulin secretion and lower IR. Ultimately, results will have implications for establishing precision nutrition approaches for prevention or treatment of obesity and T2D.

Funding Sources: NIH T32