Dataset Information

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

ABSTRACT:

Aims

The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment.

Methods

Adults with CF (≥18 years) were included in a cross-sectional study using an extended (-10, -1, 10, 20, 30, 45, 60, 90, 120, 150, and 180 min) or a standard (-1, 30, 60, and 120 min) oral glucose tolerance test (OGTT). Participants were classified according to glucose tolerance status and hypoglycaemia was defined as 3-hour glucose <3.9 mmol/L in those with normal glucose tolerance (NGT) and early glucose intolerance (EGI).

Results

Among 93 participants, 67 underwent an extended OGTT. In addition to worsening in insulin secretion, the progression to CFRD was associated with signs of beta cell stress, as the fasting proinsulin-to-insulin ratio incrementally increased (p-value for trend=0.013). The maximum proinsulin level (pmol/L) was positively associated with the nadir glucagon, as nadir glucagon increased 6.2% (95% confidence interval: 1.4-11.3%) for each unit increase in proinsulin. Those with hypoglycaemia had higher 60-min glucose, 120-min C-peptide, and 180-min glucagon levels (27.8% [11.3-46.7%], 42.9% [5.9-92.85%], and 80.3% [14.9-182.9%], respectively) and unaltered proinsulin-to-insulin ratio compared to those without hypoglycaemia.

Conclusions

The maximum proinsulin concentration was positively associated with nadir glucagon during the OGTT, suggesting that beta cell stress is associated with abnormal alpha cell function in adults with CF. In addition, hypoglycaemia seemed to be explained by a temporal mismatch between glucose and insulin levels rather than by an impaired glucagon response.

SUBMITTER: Nielsen BU

PROVIDER: S-EPMC10501799 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Nielsen Bibi Uhre BU Mathiesen Inger Hee Mabuza IHM Møller Rikke R Krogh-Madsen Rikke R Katzenstein Terese Lea TL Pressler Tacjana T Shaw James A M JAM Ritz Christian C Rickels Michael R MR Stefanovski Darko D Almdal Thomas Peter TP Faurholt-Jepsen Daniel D

Frontiers in endocrinology 20230831

<h4>Aims</h4>The purpose of the study was to further elucidate the pathophysiology of cystic fibrosis (CF)-related diabetes (CFRD) and potential drivers of hypoglycaemia. Hence, we aimed to describe and compare beta cell function (insulin and proinsulin) and alpha cell function (glucagon) in relation to glucose tolerance in adults with CF and to study whether hypoglycaemia following oral glucose challenge may represent an early sign of islet cell impairment.<h4>Methods</h4>Adults with CF (≥18 ye ...[more]

PMID: 37720541

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Project description:Aims/hypothesisThe aim of this study was to determine the mechanism(s) for hypoglycaemia occurring late following oral glucose loading in patients with cystic fibrosis (CF).MethodsA 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.ResultsThe 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 C-peptide 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 (ISRfasting: 50.8 ± 3.2 vs 74.0 ± 5.9 pmol min-1 m-2, p = 0.002; ISROGTT: 44.9 ± 5.0 vs 63.4 ± 5.2 nmol/m2, 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/interpretationHypoglycaemia 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.

Project description:ObjectiveTo explore the relationship between the TyG index and the insulin secretion function of pancreatic β-cells, and to determine the possibility of the TyG index in predicting β-cell dysfunction and the development of diabetes.MethodsA cross-sectional study was performed among 914 participants who took their annual health checkups at the Third Xiangya Hospital. The early- and late-phase pancreatic β-cell secretion was assessed based on the results of the oral glucose tolerance test (OGTT). In addition to anthropometric parameters and laboratory parameters, information about health-related habits and disease histories was obtained from the National Physical Examination Questionnaire. Partial correlation analysis was used to study the relationship between the TyG index and pancreatic β-cell function. The receiver operating characteristic (ROC) curve was used to calculate the cut-off points of the TyG index in predicting β-cell dysfunction. According to the OGTT results and medical history, the participants were categorized into three groups: the normal glucose tolerance group (NGT, n=276), the impaired glucose regulation group (IGT, n=323), and the diabetes group (DM, n=315). The correlation between the TyG index and β-cell function among the three groups and the association between the TyG index and glucose metabolic conditions were further explored.ResultsThe TyG index was negatively correlated with the indexes that reflect the early and late secretory function of β-cells, not only in the NGT group but also in the IGT and DM group. The minimum cut-off values for the TyG index to identify the risk of early- and late-phase β-cell dysfunction are 9.08 and 9.2 respectively. The TyG indexes of the IGT and DM group were higher than that of the NGT group, and with the growth of the TyG index, the risk of prediabetes and diabetes increased significantly.ConclusionIncreased TyG index is associated with impaired β-cell function regardless of the glucose metabolic conditions. The TyG index is an alternative indicator for predicting β-cell dysfunction.

Dataset Information

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Aims

Methods

Results

Conclusions

Publications

Characterization of impaired beta and alpha cell function in response to an oral glucose challenge in cystic fibrosis: a cross-sectional study.

Similar Datasets

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