Evaluation of postprandial hypoglycemia in patients with nonalcoholic fatty liver disease by oral glucose tolerance testing and continuous glucose monitoring

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is often associated with insulin resistance and glucose intolerance. Postprandial hypoglycemia frequently occurs in NAFLD patients; however, the details remain unclear. PATIENTS AND METHODS: The 75-g oral glucose tolerance test (75gOGTT) in 502 patients with biopsy-proven NAFLD and continuous glucose monitoring (CGM) in 20 patients were performed, and the characteristics and causes of postprandial hypoglycemia were investigated. RESULTS: The proportion of patients in the Hypo subgroup [plasma glucose (PG) at 180 min<fasting-PG (FPG)] among patients with normal glucose tolerance was significantly higher than that with diabetes mellitus and impaired glucose tolerance or impaired fasting glucose. FPG and hemoglobin A1c (HbA1c) were lower, and area under the curve of total insulin secretion within 120 min (<120 min) was higher in Hypo than Hyper in overall patients. Although FPG and PG at 30 min were higher in Hypo than Hyper, HOMA-IR and the insulinogenic index were not different in normal glucose tolerance and impaired glucose tolerance or impaired fasting glucose. In multivariate logistic regression analysis, low HbA1c, low fasting immunoreactive insulin, and high area under the curve of total insulin secretion (<120 min) were found to be independent factors associated with hypoglycemia. CGM showed postprandial hypoglycemia until lunch in 70% of NAFLD patients. However, no remarkable relationship in terms of hypoglycemia was identified between the 75gOGTT and CGM. CONCLUSION: Postprandial hypoglycemia was identified in many NAFLD patients detected by 75gOGTT and CGM. It was clarified that important causes of postprandial hypoglycemia were related to low HbA1c, an early elevation of PG, low fasting and relatively low early insulin secretion, and delayed hyperinsulinemia.