Inflammation Modifies the Paradoxical Association between Body Mass Index and Mortality in Hemodialysis Patients.
Journal: 2017/May - Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Abstract:
High body mass index (BMI) is paradoxically associated with better outcome in hemodialysis (HD) patients. Persistent inflammation commonly features in clinical conditions where the obesity paradox is described. We examined the relationship between BMI and mortality in HD patients, accounting for inflammation, in a historic cohort study of 5904 incident HD patients enrolled in 2007-2009 (312 facilities; 15 European countries) with ≥3 months of follow-up. Patients were classified by presence (n=3231) or absence (n=2673) of inflammation (C-reactive protein ≥10 mg/l and/or albumin ≤35 g/l). Patients were divided into quintiles by BMI (Q1-Q5: <21.5, 21.5-24.0, >24.0-26.4, >26.4-29.8, and >29.8 kg/m(2), respectively). Noninflamed patients in BMI Q5 formed the reference group. During a median follow-up period of 36.7 months, 1929 deaths occurred (822 cardiovascular), with 655 patients censored for renal transplantation and 1183 for loss to follow-up. Greater mortality was observed in inflamed patients (P<0.001). In fully adjusted time-dependent analyses, the all-cause mortality risk in noninflamed patients was higher only in the lowest BMI quintile (hazard ratio [HR, 1.80; 95% confidence interval [95% CI], 1.26 to 2.56). No protective effect was associated with higher BMI quintiles in noninflamed patients. Conversely, higher BMI associated with lower all-cause mortality risk in inflamed patients (HR [95% CI] for Q1: 5.63 [4.25 to 7.46]; Q2: 3.88 [2.91 to 5.17]; Q3: 2.89 [2.16 to 3.89]; Q4: 2.14 [1.59 to 2.90]; and Q5: 1.77 [1.30 to 2.40]). Thus, whereas a protective effect of high BMI was observed in inflamed patients, this effect was mitigated in noninflamed patients.
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Islets 8(4): e1187352

Ancestral genomic duplication of the insulin gene in tilapia: An analysis of possible implications for clinical islet xenotransplantation using donor islets from transgenic tilapia expressing a humanized insulin gene

+4 authors
Biology Department, Dalhousie University, Halifax, Nova Scotia, Canada
Department of Pathology &amp; Laboratory Medicine/Calgary Laboratory Services, University of Calgary, Calgary, AB, Canada
Department of Pediatrics, University of Calgary, Calgary, AB, Canada
CONTACT James R. Wright, Jr. ac.ba.SLC@thgirw.mij, Departments of Pathology &amp; Laboratory Medicine; University of Calgary and Calgary Laboratory Services; Alberta Children's Hospital;, 2888 Shaganappi Trail NW; Calgary, Alberta, Canada, T3B 6A8
Received 2016 Feb 11; Revised 2016 Apr 21; Accepted 2016 May 2.

ABSTRACT

Tilapia, a teleost fish, have multiple large anatomically discrete islets which are easy to harvest, and when transplanted into diabetic murine recipients, provide normoglycemia and mammalian-like glucose tolerance profiles. Tilapia insulin differs structurally from human insulin which could preclude their use as islet donors for xenotransplantation. Therefore, we produced transgenic tilapia with islets expressing a humanized insulin gene. It is now known that fish genomes may possess an ancestral duplication and so tilapia may have a second insulin gene. Therefore, we cloned, sequenced, and characterized the tilapia insulin 2 transcript and found that its expression is negligible in islets, is not islet-specific, and would not likely need to be silenced in our transgenic fish.

KEYWORDS: Brockmann bodies, diabetes, islets, genomic duplication, insulin gene, tilapia, teleost fish, transgenic fish, xenotransplantation
ABSTRACT

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