Cystic Fibrosis Related Diabetes

O’Shea, Donal; O’Connell, Jean

doi:10.1007/s11892-014-0511-3

Cited by 35 publications

(39 citation statements)

References 89 publications

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“…Even in our young T2D study group hsCRP levels were high, consistent with moderate CVD risk. hsCRP levels in CFRD were not far below those in T2D, and were even higher when adjusted for covariates reflecting very high CVD risk, hence the inflammation‐related CVD risk in CFRD should not be underrated . Although levels of all inflammatory markers were numerically lower in the healthy reference group compared to all the other study groups, the results were not statistically significant, which may relate to study size.…”

Section: Discussionmentioning

confidence: 77%

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Associations between circulating inflammatory markers, diabetes type and complications in youth

et al. 2019

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Background Inflammation is implicated in the pathogenesis of diabetes and its complications in adults. Little is known about the relative contribution of inflammation in common types of diabetes in youth: type 1 diabetes (T1D), type 2 diabetes (T2D), and cystic fibrosis‐related diabetes (CFRD). This study investigates inflammatory markers by diabetes type and complication status, and assesses indicators of inflammation and complications. Methods A cross‐sectional study of 134 T1D, 32 T2D, 32 CFRD and 48 subjects without diabetes (including 11 with CF and normal glucose tolerance) was undertaken. Inflammation was assessed by sE‐selectin by ELISA, hsCRP by turbidimetry, WCC and ESR. Nephropathy was defined by albuminuria, autonomic neuropathy by heart rate variability, and peripheral neuropathy by vibration and thermal threshold testing and retinopathy by seven‐field stereoscopic fundus photography. Descriptive statistics, parametric and non‐parametric ANOVA and regression analyses were performed, with significance at P < .05. Results Of 198 diabetic participants; 49% female, mean (SD) age, median diabetes duration and median HbA1c were 16 (2.5) and 6 (3–9) years, and 8.1 (6.9‐9.3)%, respectively. All inflammatory markers were lower in T1D than in other diabetes groups (P < .05) but higher than in non‐diabetic controls. T2D (n = 32) and CFRD (n = 32) subjects had comparable elevated levels of inflammation. Body mass index (BMI) was a strong independent explanatory variable of inflammation. In multivariate analysis, hsCRP and ESR were associated with complications in addition to HbA1c, BMI, and diastolic BP. Conclusions Circulating inflammatory markers are elevated in adolescents with diabetes, being higher and comparable in T2D and CFRD than in T1D. Inflammation is independently associated with diabetes complications, consistent with inflammation driving vascular pathology in diabetes.

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Section: Discussionmentioning

confidence: 77%

“…hsCRP levels in CFRD were not far below those in T2D, and were even higher when adjusted for covariates reflecting very high CVD risk, hence the inflammationrelated CVD risk in CFRD should not be underrated. 44 Although levels of all inflammatory markers were numerically lower in the healthy ref-…”

Section: Discussionmentioning

confidence: 95%

Associations between circulating inflammatory markers, diabetes type and complications in youth

et al. 2019

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“…CFTR mutations cause the common recessive disorder cystic fibrosis. 85% of cystic fibrosis patients develop diabetes, possibly arising from blockage of the pancreatic duct, an accumulation of digestive enzymes and generalized destruction of pancreatic tissues (O’Shea and O’Connell, 2014). …”

Section: Centroacinar Cells Are Specialized Ductal Cellsmentioning

confidence: 99%

Centroacinar cells: At the center of pancreas regeneration

Beer

Parsons

Rovira

2016

Developmental Biology

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The process of regeneration serves to heal injury by replacing missing cells. Understanding regeneration can help us replace cell populations lost during disease, such as the insulin-producing β cells lost in diabetic patients. Centroacinar cells (CACs) are a specialized ductal pancreatic cell type that act as progenitors to replace β cells in the zebrafish. However, whether CACs contribute to β-cell regeneration in adult mammals remains controversial. Here we review the current understanding of the role of CACs as endocrine progenitors during regeneration in zebrafish and mammals.

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“…T2DM is a risk factor for Barrett's esophagus and is hence a possible indirect association with esophageal cancer (Iyer et al, 2013). Cystic fibrosis is not specifically T2DM related, but cystic fibrosis related diabetes shares similarity with both T2DM and type 1 diabetes (O'Shea & O'Connell, 2014). Many of these traits are closely linked, but not necessarily directly.…”

Section: Type 2 Diabetes Mellitusmentioning

confidence: 99%

Evolutionarily derived networks to inform disease pathways

Graham

Darabos

Huang

et al. 2017

Genetic Epidemiology

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Methods to identify genes or pathways associated with complex diseases are often inadequate to elucidate most risk because they make implicit and oversimplified assumptions about underlying models of disease etiology. These can lead to incomplete or inadequate conclusions. To address this, we previously developed human phenotype networks (HPN), linking phenotypes based on shared biology. However, such visualization alone is often uninterpretable, and requires additional filtering. Here, we expand the HPN to include another method, Evolutionary Triangulation (ET). ET utilizes the hypothesis that alleles affecting disease risk in multiple populations are distributed consistently with differences in disease prevalence and compares allele frequencies among populations and their relationship to phenotype prevalence. We hypothesized that combining these methods will increase our ability to detect genetic patterns of association in complex diseases. We combined HPN and ET to identify network patterns associated with Type 2 Diabetes Mellitus (T2DM), a leading causes of death worldwide. Fasting glucose, a continuous trait, was used as a proxy for T2DM and differs significantly among continental populations. The combined method identified several diabetes related traits and several phenotypes related to cardiovascular diseases, for which diabetes is a major risk factor. ET-HPN found more phenotypes related to our target and related phenotypes than the application of either method alone. Not only could we detect phenotype connections related to T2DM, but we also identified phenotypes that are distributed in parallel to it, e.g. Amyotrophic Lateral Sclerosis. Our analyses showed that ET filtered HPN provides information that neither technique can individually.

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Cystic Fibrosis Related Diabetes

Cited by 35 publications

References 89 publications

Associations between circulating inflammatory markers, diabetes type and complications in youth

Associations between circulating inflammatory markers, diabetes type and complications in youth

Centroacinar cells: At the center of pancreas regeneration

Evolutionarily derived networks to inform disease pathways

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