Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia

Kilberg, Marissa J; Sheikh, Saba; Stefanovski, Darko; Kubrak, Christina; León, Diva D. De; Hadjiliadis, Denis; Rubenstein, Ronald C.; Rickels, Michael R.; Kelly, Andrea

doi:10.1016/j.jcf.2019.07.006

Cited by 12 publications

(16 citation statements)

References 29 publications

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“…When glucose levels during the OGTT were below the normal range, insulin secretion in the hypoglycaemia group did not appear to decrease appropriately, possibly driving glucose concentrations to a lower level. An inappropriate insulin response in the presence of low glucose has also been suggested in a recent study of patients with CF experiencing hypoglycaemia [27]. The mechanism for this apparent dysfunction cannot be discerned from the current data, but it is credible this may result from insufficient local noradrenaline release so that insulin secretion is not suppressed normally [28].…”

Section: Discussionsupporting

confidence: 54%

Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis

et al. 2020

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Aims/hypothesis The aim of this study was to determine the mechanism(s) for hypoglycaemia occurring late following oral glucose loading in patients with cystic fibrosis (CF). Methods A 3 h 75 g OGTT was performed in 27 non-diabetic adults with CF who were classified based on this test as experiencing hypoglycaemia (glucose <3.3 mmol/l with or without symptoms or glucose <3.9 mmol/l with symptoms, n = 14) or not (n = 13). Beta cell function, incretin (glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic peptide [GIP]) and counterregulatory hormone responses (glucagon, catecholamines, growth hormone and cortisol) were assessed. Results The two groups did not differ in age, weight or BMI. There were more male participants and individuals with pancreatic exocrine insufficiency in the hypoglycaemia group. Fasting plasma glucose did not differ between the two groups (5.3 ± 0.16 vs 5.3 ± 0.10 mmol/l). Both fasting insulin (20.7 ± 2.9 vs 36.5 ± 4.8 pmol/l; p = 0.009) and C-peptide (0.38 ± 0.03 vs 0.56 ± 0.05 nmol/l; p = 0.002) were lower in those who experienced hypoglycaemia. Following glucose ingestion, glucose concentrations were significantly lower in the hypoglycaemia group from 135 min onwards, with a nadir of 3.2 ± 0.2 vs 4.8 ± 0.3 mmol/l at 180 min (p < 0.001). The test was terminated early in three participants because of a glucose level <2.5 mmol/l. Insulin and Cpeptide concentrations were also lower in the hypoglycaemia group, while incretin hormone responses were not different. Modelling demonstrated that those experiencing hypoglycaemia were more insulin sensitive (439 ± 17.3 vs 398 ± 13.1 ml min −1 m −2 , p = 0.074 based on values until 120 min [n = 14]; 512 ± 18.9 vs 438 ± 15.5 ml min −1 m −2 , p = 0.006 based on values until 180 min [n = 11]). In line with their better insulin sensitivity, those experiencing hypoglycaemia had lower insulin secretion rates (ISR fasting : 50.8 ± 3.2 vs 74.0 ± 5.9 pmol min −1 m −2 , p = 0.002; ISR OGTT : 44.9 ± 5.0 vs 63.4 ± 5.2 nmol/m 2 , p = 0.018) and beta cell glucose sensitivity (47.4 ± 4.5 vs 79.2 ± 7.5 pmol min −1 m −2 [mmol/l] −1 , p = 0.001). Despite the difference in glucose concentrations, there were no significant increases in glucagon, noradrenaline, cortisol or growth hormone levels. Adrenaline increased by only 66% and 61% above baseline at 165 and 180 min when glucose concentrations were 3.8 ± 0.2 and 3.2 ± 0.2 mmol/l, respectively. Conclusions/interpretation Hypoglycaemia occurring late during an OGTT in people with CF was not associated with the expected counterregulatory hormone response, which may be a consequence of more advanced pancreatic dysfunction/ destruction.

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Section: Discussionsupporting

confidence: 54%

Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis

et al. 2020

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“…None of the patients with CFRD had hypoglycemia, while 79% (15/19) of the remaining subjects showed hypoglycemia at the 3-hour time point, with 5 being symptomatic (sweaty, clammy hands and dizzy). Similar to the study by Kilberg et al 24 , those with hypoglycemia had a higher peak glucose and delayed and higher insulin release 25 . Incretins, hormones produced by the intestines that signal insulin secretion after eating, were not different between groups, and there was no change in the counter regulatory glucagon response.…”

Section: Cystic Fibrosis Related Diabetessupporting

confidence: 81%

“…Another outcome of screening for CFRD, can be the appearance of post-prandial or OGTT-related hypoglycemia. While the mechanism remains unclear, it is speculated to be related to derangement in glucose homeostasis involving both insulin and glucagon 24,25 . Kilberg et al 24 used a mixed meal tolerance test (MMTT) in 34 nondiabetic adolescents and young adults with pancreatic insufficiency, finding 26% (9/34) with hypoglycemia.…”

Section: Cystic Fibrosis Related Diabetesmentioning

confidence: 99%

“…While the mechanism remains unclear, it is speculated to be related to derangement in glucose homeostasis involving both insulin and glucagon 24,25 . Kilberg et al 24 used a mixed meal tolerance test (MMTT) in 34 nondiabetic adolescents and young adults with pancreatic insufficiency, finding 26% (9/34) with hypoglycemia. Those with hypoglycemia, had a higher peak glucose (215 +-21 versus 168 +-33 mg/dL, p<0.01) and had a later peak phase of insulin, defined by peak after 60 minutes, (89% versus 48%, p=0.03).…”

Section: Cystic Fibrosis Related Diabetesmentioning

confidence: 99%

See 1 more Smart Citation

Year in Review 2020: Multisystemic Impact of Cystic Fibrosis

Sharma

Sathe

Savant

2021

Preprint

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Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Awareness of the multisystem concerns that face persons with CF (PwCF) has also continued to be recognized as an important aspect of the burden of the disease. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, an understanding of worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served, ranging from the advances in care in the United States (US) to the challenges of disease recognition and diagnosis in low-and-middle-income countries (LMIC). This review is the third in a three-part CF Year in Review 2020 series, focusing on the multi-system effects of CF. Part one focused on the literature related to CFTR (cystic fibrosis transmembrane conductance regulator protein) modulators, while part two focused on pulmonary outcomes, radiographic and physiologic assessments, as well as infection and inflammation. Part three has been split into two individual parts, Part 3A presented here, and Part 3B related to CF specific nutrition and gastrointestinal publications will also be published this year. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.

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“…None of the patients with CFRD had hypoglycemia, while 79% (15 of 19) of the remaining subjects showed hypoglycemia at the 3‐h time point, with 5 being symptomatic (sweaty, clammy hands, and dizzy). Similar to the study by Kilberg et al, 24 those with hypoglycemia had a higher peak glucose and delayed and higher insulin release 25 . Incretins, hormones produced by the intestines that signal insulin secretion after eating, and the counter‐regulatory glucagon response did not differ between OGTT classification groups.…”

Section: Diagnosissupporting

confidence: 80%

Year in Review 2020: Multisystemic impact of cystic fibrosis

Sharma

Sathe

Savant

2021

Pediatric Pulmonology

View full text Add to dashboard Cite

Clinical care in cystic fibrosis (CF) has continued to advance over the last several years, particularly with the widespread eligibility and use of highly effective modulator therapy. Improved outcomes and longevity of persons with CF (PwCF) have increased recognition of the multisystem impact of the disease on the daily lives of PwCF. This review will cover a broad array of topics, from diagnosis to multisystem effects related to mental health, endocrine, palliative care, reproductive health, otolaryngology, and cardiac issues. Additionally, worldwide care delivery will be reviewed, demonstrating variation in outcomes based on resources and populations served. This review is part of the CF Year in Review 2020 series, focusing on the multi‐system effects of CF. This review focuses on articles from Pediatric Pulmonology but also includes articles published in 2020 from other journals that are of particular interest to clinicians.

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Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia

Cited by 12 publications

References 29 publications

Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis

Impaired counterregulatory responses to hypoglycaemia following oral glucose in adults with cystic fibrosis

Year in Review 2020: Multisystemic Impact of Cystic Fibrosis

Year in Review 2020: Multisystemic impact of cystic fibrosis

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