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Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

ABSTRACT: Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity.This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 12 subjects.At the end of each phase, body composition (anthropometric measurements, dual energy X-ray absorptometry (DEXA), abdominal CT), hepatic and muscle insulin sensitivity (2-step hyperinsulinemic euglycemic clamp with 2H2-glucose) were measured and fasting blood adipokines and cardiometabolic risk markers were monitored.Four months treatment with pioglitazone had no effect on total body weight or total fat but decreased the visceral/sub-cutaneous adipose tissue ratio by 16% and decreased the leptin/adiponectin (L/A) ratio from 3.63 × 10(-3) to 0.76 × 10(-3). This was associated with a 20% increase in hepatic insulin sensitivity without changes in muscle insulin sensitivity, a 12% increase in HDL cholesterol and a 50% decrease in CRP.Pioglitazone significantly changes the visceral-subcutaneous fat distribution and plasma L/A ratio in non diabetic subjects on maintenance dialysis. This was associated with improved hepatic insulin sensitivity and a reduction of cardio-metabolic risk markers. Whether these effects may improve the outcome of non diabetic end-stage renal disease subjects on maintenance dialysis still needs further evaluation.ClinicalTrial.gov NCT01253928.

SUBMITTER: Zanchi A

PROVIDER: S-EPMC4199598 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

Zanchi Anne A Tappy Luc L Lê Kim-Anne KA Bortolotti Murielle M Theumann Nicolas N Halabi Georges G Gauthier Thierry T Mathieu Claudine C Tremblay Sylvie S Bertrand Pauline Coti PC Burnier Michel M Teta Daniel D

PloS one 20141016 10

<h4>Background</h4>Fat redistribution, increased inflammation and insulin resistance are prevalent in non-diabetic subjects treated with maintenance dialysis. The aim of this study was to test whether pioglitazone, a powerful insulin sensitizer, alters body fat distribution and adipokine secretion in these subjects and whether it is associated with improved insulin sensitivity.<h4>Trial design</h4>This was a double blind cross-over study with 16 weeks of pioglitazone 45 mg vs placebo involving 1 ...[more]

PMID: 25330088

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Project description:Hospital admissions over weekends have been associated with worse outcomes in different patient populations. The cause of this difference in outcomes remains unclear; however, different staffing patterns over weekends have been speculated to contribute. We evaluated outcomes in patients on maintenance dialysis therapy admitted over weekends using a national database.Retrospective cohort study.We included nonelective admissions of adult patients (?18 years) on maintenance dialysis therapy (n = 3,278,572) identified using appropriate International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for 2005-2009 using the Nationwide Inpatient Sample database.Weekend versus weekday admission.The primary outcome measure was all-cause in-hospital mortality. Secondary outcomes included mortality by day 3 of admission, length of hospital stay, time to death, and discharge disposition.We adjusted for patient and hospital characteristics, payer, year, comorbid conditions, and primary discharge diagnosis common to maintenance dialysis patients.There were an estimated 704,491 admissions over weekends versus 2,574,081 over weekdays. Unadjusted all-cause in-hospital mortality was 40,666 (5.8%) for weekend admissions in comparison to 138,517 (5.4%) for weekday admissions (P < 0.001). In a multivariable model, patients admitted over weekends had higher all-cause in-hospital mortality (OR, 1.06; 95% CI, 1.01-1.10) in comparison to those admitted over weekdays and higher mortality during the first 3 days of admission (OR, 1.18; 95% CI, 1.10-1.26). Patients admitted over weekends were less likely to be discharged to home, had longer hospital stays, and had shorter times to death compared with those admitted over weekdays on adjusted analysis.Use of ICD-9-CM codes to identify patients, defining weekend as midnight Friday to midnight Sunday.Maintenance dialysis patients admitted over weekends have increased mortality rates and longer lengths of stay compared with those admitted over weekdays. Further studies are needed to identify the reasons for worse outcomes for weekend admissions in this patient population.

Project description:BackgroundMany dialysis patients receive intensive procedures intended to prolong life at the very end of life. However, little is known about trends over time in the use of these procedures. We describe temporal trends in receipt of inpatient intensive procedures during the last 6 months of life among patients treated with maintenance dialysis.Study designMortality follow-back study.Setting & participants649,607 adult Medicare beneficiaries on maintenance dialysis therapy who died in 2000 to 2012.PredictorsPeriod of death (2000-2003, 2004-2008, or 2009-2012), age at time of death (18-59, 60-64, 65-69, 70-74, 75-79, 80-84, and ≥85 years), and race/ethnicity (Hispanic, non-Hispanic black, or non-Hispanic white).OutcomeReceipt of an inpatient intensive procedure (defined as invasive mechanical ventilation/intubation, tracheostomy, gastrostomy/jejunostomy tube insertion, enteral or parenteral nutrition, or cardiopulmonary resuscitation) during the last 6 months of life.ResultsOverall, 34% of cohort patients received an intensive procedure in the last 6 months of life, increasing from 29% in 2000 to 36% in 2012 (with 2000-2003 as the referent category; adjusted risk ratios [RRs] were 1.06 [95% CI, 1.05-1.07] and 1.10 [95% CI, 1.09-1.12] for 2004-2008 and 2009-2012, respectively). Use of intensive procedures increased more markedly over time in younger versus older patients (comparing 2009-2012 to 2000-2003, adjusted RR was 1.18 [95% CI, 1.15-1.20] for the youngest age group as opposed to 1.00 [95% CI, 0.96-1.04] for the oldest group). Comparing 2009 to 2012 to 2000 to 2003, the use of intensive procedures increased more dramatically for Hispanic patients than for non-Hispanic black or non-Hispanic white patients (adjusted RRs of 1.18 [95% CI, 1.14-1.22], 1.09 [95% CI, 1.07-1.11], and 1.10 [95% CI, 1.08-1.12], respectively).LimitationsData sources do not provide insight into reasons for observed trends in the use of intensive procedures.ConclusionsAmong patients treated with maintenance dialysis, there is a trend toward more frequent use of intensive procedures at the end of life, especially in younger patients and those of Hispanic ethnicity.

Dataset Information

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

Publications

Pioglitazone improves fat distribution, the adipokine profile and hepatic insulin sensitivity in non-diabetic end-stage renal disease subjects on maintenance dialysis: a randomized cross-over pilot study.

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