Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function

Piona, Claudia; Volpi, Sonia; Zusi, Chiara; Mozzillo, Enza; Tosco, Antonella; Franzese, Adriana; Raia, Valeria; Boselli, Maria Linda; Trombetta, Maddalena; Cipolli, Marco; Bonadonna, Riccardo C.; Maffeis, Claudio

doi:10.1210/clinem/dgaa932

Cited by 21 publications

(24 citation statements)

References 27 publications

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“…The utilization of a lower glycemic threshold for intermediate OGTT glucose values has been proposed as associations with CFRD progression have been shown at thresholds as low as 155 mg/dL (8.6 mmol/L), which is below the current definition for INDET [39] , [40] . These data are further supported by demonstration of beta cell decline at these thresholds [23] . CGM data also provide supporting evidence of this [36] , [41] , [42] , [43] .…”

Section: Indeterminate Glycemia (Indet)supporting

confidence: 57%

“…In addition to the known defects in insulin secretion described in CF, they determined that the loss of first phase insulin secretion is more pronounced in INDET relative to other non-diabetes glucose tolerance categories. They also described mild abnormalities of all three determinants of glucose regulation in individuals with mid-OGTT glucoses of 140–200 mg/dL (7.8 mmol/L) [23] , a group not currently included in traditional OGTT classifications.…”

Section: The Relationship Between Glucose Tolerance and Beta Cell Dysfunctionmentioning

confidence: 99%

“…In the mid 2000′s, larger studies in CF showed that elevated 30 min and 1 h glucose values were predictive of lung function along with other metrics such as glucose AUC [27] , [29] . This was further augmented by insulin clamp studies showing beta cell dysfunction in individuals with INDET, studies characterizing beta cell dysfunction with glucose tolerance categories, and continuous glucose monitoring studies correlating CGM data to indeterminate glucose tolerance on OGTT [21] , [23] , [25] , [35] , [36] .…”

Section: Indeterminate Glycemia (Indet)mentioning

confidence: 99%

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Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis

Kasim

Khare

Sandouk

et al. 2021

Journal of Clinical & Translational Endocrinology

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Highlights Oral glucose tolerance testing is used for screening, diagnosis, and risk stratification of cystic fibrosis related diabetes. Abnormal glucose tolerance in cystic fibrosis has prognostic utility with regards to progression towards overt diabetes, pulmonary function, weight loss, and mortality. Further research is needed to delineate the significance of impaired glucose tolerance and indeterminate glycemia within the CF population. Lower thresholds for indeterminate glycemia may be needed within the cystic fibrosis population.

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Section: Indeterminate Glycemia (Indet)supporting

confidence: 57%

Section: The Relationship Between Glucose Tolerance and Beta Cell Dysfunctionmentioning

confidence: 99%

Section: Indeterminate Glycemia (Indet)mentioning

confidence: 99%

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Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis

Kasim

Khare

Sandouk

et al. 2021

Journal of Clinical & Translational Endocrinology

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“…OGTT identifies patients with CFRD and with pre-diabetes using the following diagnostic categories: normal glucose tolerance (NGT); INDET; IGT (Table 11). Two more categories named AGT (4,37) and impaired fasting glucose (IFG) can also to be considered (46) (Table 11).…”

Section: Resultsmentioning

confidence: 99%

“…The main cause of CFRD is insulin insufficiency with insulin secretion being increasingly impaired in correlation with exacerbation of pre-diabetes (4). According to this pathophysiological evidence, current guidelines of the International Society for Pediatric and Adolescent Diabetes (5) recommend insulin therapy initiation for the treatment of CFRD.…”

Section: Introductionmentioning

confidence: 99%

Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED)

Mozzillo¹,

Franceschi

Piona

et al. 2021

Front. Endocrinol.

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Cystic fibrosis related diabetes (CFRD) is a comorbidity of cystic fibrosis (CF) that negatively impacts on its clinical course. Prediabetes is an important predictor of either CFRD development and unfavorable prognosis of CF in both pediatric and adult patients. International guidelines recommend insulin only in case of CFRD diagnosis. Whether early detection and treatment of prediabetes may contribute to improve the clinical course of CF is still debated. A subgroup of pediatric diabetologists of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED) performed a systematic review of the literature based on predefined outcomes: impact of pre-diabetes on clinical outcomes and on the risk of developing CFRD; diagnosis of diabetes and pre-diabetes under 10 years of age; effectiveness of therapy on glycemic control, impact of therapy on pulmonary function and nutritional status. Thirty-one papers were selected for the analysis data presented in these papers were reported in tables sorted by outcomes, including comprehensive evidence grading according to the GRADE approach. Following the grading of the quality of the evidence, the entire ISPED diabetes study group achieved consensus for the Italian recommendations based on both evidence and clinical experience. We concluded that in patients with CF, prediabetes should be carefully considered as it can evolve into CFRD. In patients with CF and prediabetic conditions, after complete evaluation of the OGTT trend, glucometrics, glycemic values measured during pulmonary exacerbations and/or steroid therapy, early initiation of insulin therapy could have beneficial effects on clinical outcomes of patients with CF and prediabetes.

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Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study

Nielsen,

Mathiesen,

Krogh-Madsen

et al. 2024

Diabetologia

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Aims/hypothesis The aim of this study was to investigate insulin secretion, insulin sensitivity, disposition index and insulin clearance by glucose tolerance status in individuals with cystic fibrosis (CF) and exocrine pancreatic insufficiency. Methods In a cross-sectional study, we conducted an extended (ten samples) OGTT in individuals with pancreatic-insufficient CF (PI-CF). Participants were divided into normal glucose tolerance (NGT), early glucose intolerance (EGI), impaired glucose tolerance (IGT) and CF-related diabetes (CFRD) groups. We used three different oral minimal models to assess insulin secretion, insulin sensitivity and insulin clearance during the OGTT. We evaluated insulin secretion using total secretion (Φ total), first-phase secretion (Φ dynamic) and second-phase secretion (Φ static) from the model, and we estimated the disposition index by multiplying Φ total and insulin sensitivity. Results Among 61 participants (NGT 21%, EGI 33%, IGT 16%, CFRD 30%), insulin secretion indices (Φ total, dynamic and static) were significantly lower in the CFRD group compared with the other groups. Insulin sensitivity declined with worsening in glucose tolerance (p value for trend <0.001) and the disposition index declined between NGT and EGI and between IGT and CFRD. Those with CFRD had elevated insulin clearance compared with NGT (p=0.019) and low insulin secretion (Φ total) was also associated with high insulin clearance (p<0.001). Conclusions/interpretation In individuals with PI-CF, disposition index declined with incremental impairment in glucose tolerance due to a reduction in both insulin secretion and insulin sensitivity. Moreover in CF, reduced insulin secretion was associated with higher insulin clearance. Graphical Abstract

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Glucose Tolerance Stages in Cystic Fibrosis Are Identified by a Unique Pattern of Defects of Beta-Cell Function

Cited by 21 publications

References 27 publications

Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis

Impaired glucose tolerance and indeterminate glycemia in cystic fibrosis

Diabetes and Prediabetes in Children With Cystic Fibrosis: A Systematic Review of the Literature and Recommendations of the Italian Society for Pediatric Endocrinology and Diabetes (ISPED)

Insulin sensitivity, disposition index and insulin clearance in cystic fibrosis: a cross-sectional study

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