Endocrine pancreas in cystic fibrosis: An immunohistochemical study

Iannucci, Antonio; Mukai, Kiyoshi; Johnson, Dana E.; Burke, Barbara A.

doi:10.1016/s0046-8177(84)80191-4

Cited by 149 publications

(128 citation statements)

References 18 publications

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“…By contrast, CFRD more commonly appears later in life when the number of insulin-producing beta cells falls below that in normoglycaemic CF patients [5,11].…”

mentioning

confidence: 90%

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients

Sequeiros

Hester²,

Callaway³

et al. 2010

BJR

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ABSTRACT. We investigated differences in the volume of the pancreas in cystic fibrosis (CF) patients with and without diabetes using MRI to study the natural history of CFrelated diabetes (CFRD). We investigated 29 pancreas-insufficient adult CF patients, 13 with CFRD and 16 without diabetes. Patients with CFRD were receiving insulin therapy at the time of study. None of the non-diabetic CF patients had evidence of impaired glucose tolerance. Pancreas volume was estimated by MRI scans using T 1 weighted fatsuppression sequences and assessed by an examiner who was unaware of the patients' diabetes status. Pancreas volume of CF patients was measured and subsequently compared with that of non-CF age-matched Type 1 diabetes (T1DM) patients and healthy controls previously investigated. The two CF groups were matched for age and gender. There were no differences in spirometry values, body mass index or pancreatic exocrine function. The pancreas was visible by MRI in only 3 of 13 (23.1%) patients with CFRD and in 5 of 16 (31.3%) patients without diabetes (p-value50.7). In total, the pancreas was not detected by MRI as an anatomical entity in 21 of 29 (72.4%) CF patients, irrespective of their diabetes status. When comparing the four study groups, the pancreas was significantly smaller in CF patients than in T1DM patients and healthy controls.

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“…By contrast, CFRD more commonly appears later in life when the number of insulin-producing beta cells falls below that in normoglycaemic CF patients [5,11].…”

mentioning

confidence: 90%

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients

Sequeiros

Hester²,

Callaway³

et al. 2010

BJR

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“…Autopsy findings of individuals with cystic fibrosis have revealed minimal islet disease before the 2nd decade but extensive replacement of pancreatic acinar tissue with fibrous and fatty tissue. As patients age, autopsy data demonstrate the eventual loss of islet tissue and decreased ␤-cell numbers (12,13). Other findings include deposition of amyloid in the islets, a chronic architectural change, found in cystic fibrosis patients who also have CFRD (6).…”

mentioning

confidence: 99%

Cystic Fibrosis Transmembrane Conductance Regulator Deficiency Exacerbates Islet Cell Dysfunction After β-Cell Injury

et al. 2006

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The cause of cystic fibrosis-related diabetes (CFRD) remains unknown, but cystic fibrosis transmembrane conductance regulator (CFTR) mutations contribute directly to multiple aspects of the cystic fibrosis phenotype. We hypothesized that susceptibility to islet dysfunction in cystic fibrosis is determined by the lack of functional CFTR. To address this, glycemia was assessed in CFTR null (CFTR ؊/؊ ), C57BL/6J, and FVB/NJ mice after streptozotocin (STZ)-induced ␤-cell injury. Fasting blood glucose levels were similar among age-matched non-STZ-administered animals, but they were significantly higher in CFTR ؊/؊ mice 4 weeks after STZ administration (288.4 ؎ 97.4, 168.4 ؎ 35.9, and 188.0 ؎ 42.3 mg/dl for CFTR ؊/؊ , C57BL/ 6J, and FVB/NJ, respectively; P < 0.05). After intraperitoneal glucose administration, elevated blood glucose levels were also observed in STZ-administered CFTR ؊/؊ mice. STZ reduced islets among all strains; however, only CFTR ؊/؊ mice demonstrated a negative correlation between islet number and fasting blood glucose (P ‫؍‬ 0.02). To determine whether a second alteration associated with cystic fibrosis (i.e., airway inflammation) could impact glucose control, animals were challenged with Aspergillus fumigatus. The A. fumigatus-sensitized CFTR ؊/؊ mice demonstrated similar fasting and stimulated glucose responses in comparison to nonsensitized animals. These studies suggest metabolic derangements in CFRD originate from an islet dysfunction inherent to the CFTR ؊/؊ state.

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“…As such, islet function is affected globally and not limited to β-cells. [29][30][31] In support of this hypothesis, CFRD occurs more commonly in the presence of the severe CF mutations associated with pancreatic exocrine insufficiency. 32 However, while autopsy studies of CF pancreas do reveal loss of β-cell mass, the extent of β-cell mass loss does not completely agree with presence or absence of diabetessuggesting additional mechanisms are at play.…”

Section: Pathophysiologymentioning

confidence: 97%

Cystic fibrosis-related diabetes: links, challenges, and future directions

Sheikh¹,

Kelly²

2015

RRED

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Cystic fibrosis-related diabetes (CFRD) is a common comorbidity in cystic fibrosis (CF) and portends worse clinical outcomes including lower lung function and nutritional status, and decreased survival. CFRD is distinct from other forms of diabetes, but relative insulin deficiency is a predominant feature. The catabolic effects of insulin deficiency coupled with the pro-inflammatory effects of hyperglycemia likely affect clinical outcomes. Posited mechanisms of CFRD development include collateral damage from pancreatic exocrine destruction, inherent β-cell defect, CFTR dysfunction, and incretin deficiency or unresponsiveness. Even though CF clinical care teams are increasingly aware of its implications, CFRD screening and management remain a challenge. Promising clinical and basic research in the fields of diabetes and CF and the advent of novel therapeutics targeting the protein defect in CF have potential to change CFRD care. This review presents newer data on insulin defects and glucose derangements and highlights continuing challenges and unanswered questions.

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Endocrine pancreas in cystic fibrosis: An immunohistochemical study

Cited by 149 publications

References 18 publications

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients

MRI appearance of the pancreas in patients with cystic fibrosis: a comparison of pancreas volume in diabetic and non-diabetic patients

Cystic Fibrosis Transmembrane Conductance Regulator Deficiency Exacerbates Islet Cell Dysfunction After β-Cell Injury

Cystic fibrosis-related diabetes: links, challenges, and future directions

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