Search

Context Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established. Objective To delineate the mechanism(s) underlying OGTT-related hypoglycemia. Design and Setting We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose Main Outcome Measure OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas under the curve (AUC) between 0 and 30 minutes (early) and between 120 and 180 minutes (late), and Δglucagon120-180min and Δfree fatty acids (FFAs)120-180min were compared between individuals with CF and control participants with Hypo[+]. Results Hypoglycemia occurred in 15/23 (65%) patients with CF (43% female, aged 24.8 [14.6-30.6] years) and 8/15 (55%) control participants (33% female, aged 26 [21-38] years). The CF-Hypo[+] group versus the control-Hypo[+] group had higher 1-hour glucose (197 ± 49 vs 139 ± 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 ± 7 vs 59 ± 4 mg/dL; P < 0.01), while insulin, C-peptide, and ISR-AUC0-30 min results were lower and insulin and C-peptide, and AUC120-180min results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared with the control-Hypo[+] group (P < 0.01). Conclusions OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFAs. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.

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

Post-prandial and oral glucose tolerance test (OGTT)-related hypoglycemia is common in cystic fibrosis (CF). The mechanisms underlying this “reactive” hypoglycemia are unclear. We hypothesized that late hypoglycemia would be associated with higher peak plasma glucose, impaired early-phase insulin secretion compared to PI-NGT, and augmentation of late insulin secretion. To understand these relationships, we performed standardized mixed-meal tolerance tests (MMTT) with timed blood sampling for determination of plasma glucose, insulin and C-peptide in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). Glucose tolerance was defined by OGTT as: normal (NGT; 1-hour glucose