학술논문
Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis
CLINICAL RESEARCH ARTICLE
CLINICAL RESEARCH ARTICLE
Document Type
Report
Author
Source
Journal of Clinical Endocrinology & Metabolism. October 2020, Vol. 105 Issue 10, p1v, 11 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Glucose homeostasis is often abnormal in individuals with pancreatic-insufficient cystic fibrosis (PI-CF), existing on a continuum from early glucose intolerance to impaired glucose tolerance to cystic fibrosis-related diabetes (CFRD) based [...]
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 [DELTA][glucagon.sub.120-180min] and [DELTA]free fatty acids [(FFAs).sub.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 [+ or -] 49 vs 139 [+ or -] 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 [+ or -] 7 vs 59 [+ or -] 4 mg/dL; P< 0.01), while insulin, C-peptide, and ISR-AU[C.sub.0-30 min] results were lower and insulin and C-peptide, and AU[C.sub.120-180min] results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower [DELTA][glucagon.sub.120-180min] and [DELTA]FF[A.sub.120-180min] 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. (J Clin Endocrinol Metab 105: 1-11,2020) Key Words: cystic fibrosis; hypoglycemia; glucose tolerance; pancreatic insufficiency; insulin secretion; glucose counterregulation
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 [DELTA][glucagon.sub.120-180min] and [DELTA]free fatty acids [(FFAs).sub.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 [+ or -] 49 vs 139 [+ or -] 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 [+ or -] 7 vs 59 [+ or -] 4 mg/dL; P< 0.01), while insulin, C-peptide, and ISR-AU[C.sub.0-30 min] results were lower and insulin and C-peptide, and AU[C.sub.120-180min] results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower [DELTA][glucagon.sub.120-180min] and [DELTA]FF[A.sub.120-180min] 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. (J Clin Endocrinol Metab 105: 1-11,2020) Key Words: cystic fibrosis; hypoglycemia; glucose tolerance; pancreatic insufficiency; insulin secretion; glucose counterregulation