MON-660 Hypoglycemia Following OGTT Is More Frequent and Pronounced in CF Compared with Controls

Glucose homeostasis is often abnormal in people with pancreatic insufficient cystic fibrosis (PI-CF). This dysfunction is viewed on a continuum from “normal” glucose tolerance to cystic fibrosis-related diabetes (CFRD), and may also include postprandial and oral glucose tolerance test (OGTT)-related hypoglycemia. This study aimed to delineate the mechanism(s) underlying OGTT-related hypoglycemia. We compared extended OGTT with frequent blood sampling of glucose and insulin in adolescents and young adults with PI-CF [CF(+)] to historical data from a healthy cohort [CF(-)]. We hypothesized that the subset of CF(+) with hypoglycemia would demonstrate 1-hour glucose ≥ 155 mg/dL and impaired early phase insulin secretion (insulin secretion within first 30 min of OGTT). Hypoglycemia [hypo(+)] was defined as plasma glucose <65 mg/dL and was used to assign subjects to exposure groups. We restricted analyses to 180 minutes given available control data. Glucose and insulin incremental areas under the curve (Glc-AUC; Ins-AUC) for 30-minute intervals were calculated. One-hour glucose, nadir glucose, Glc-AUC0-30, and Ins-AUC0-30 and were compared between CF(+) and CF(-) subjects using Student’s t-test or Wilcoxon Rank Sum depending upon normality. Participants were 60.5% male, age: 25.4±4.8 years, with BMI-Z: 0.06±0.96kg/m2 [no differences for CF(+) vs CF(-)]. FEV1%-predicted for CF(+) was 83±21. 69.6% of CF(+) participants self-reported prior episodes of hypoglycemia, 68.7% of whom reported confirmation via glucometer. Hypoglycemia occurred by 180 minutes [hypo(+)] in 15/23 (65%) CF(+) and 5/15 (33.3%) CF(-) subjects (p=0.028). For hypo(+), nadir glucose occurred on average at 180 minutes for both CF(+) and (-). Hypo(+) CF(+) had higher mean 1-hour glucose (197±49mg/dL vs 134±66mg/dL, p=0.035), lower mean glucose nadir (48±7mg/dL vs 61±4mg/dL, p<0.01), and lower early-phase insulin secretion (Ins-AUC0-30: 263±168 versus 650±275 µU/mL, p<0.01) than hypo(+) CF(-). There was no difference in Glc-AUC0-30 for hypo(+) CF(+) vs CF(-). Hypoglycemia is frequent in CF, and is associated with early glucose dysregulation (elevated 1-hour glucose) and compromised early-phase insulin secretion compared to controls with presumed non-pathologic reactive hypoglycemia. The mechanism of hypoglycemia in CF appears to be different than that seen in healthy individuals, and its association with progression to CFRD warrants further evaluation.