Insulin Resistance in Patients with Chronic Kidney Disease

Liao, Min; Sung, Chih Chien; Hung, Kuo-Chin; Wu, Chia Chao; Lo, Lan; Lu, Kuo Cheng

doi:10.1155/2012/691369

Cited by 119 publications

(124 citation statements)

References 138 publications

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“…This indicates that the uremic condition might reduce the RBC-NOS response to these stimuli possibly due to biochemical or metabolic alterations such as increased insulin resistance [44]. As mentioned above, in our study, we found that basal RBC-NOS was significantly more activated in uremic erythrocytes than in controls.…”

Section: Discussionsupporting

confidence: 77%

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

et al. 2016

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Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRDRBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/ Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD-than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMPmembrane transporter) was significantly lower in ESRDRBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRDRBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRDRBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin.Keywords End-stage renal disease Á Red blood cells Á Nitric oxide Á cGMP Á Nitric oxide synthase Mario Bonomini, and Assunta Pandolfi have contributed equally to the study.Electronic supplementary material The online version of this article

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Section: Discussionsupporting

confidence: 77%

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

et al. 2016

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“…This discrepancy between our results and previous studies (29) may be due to treatment of type 2 DM. Renal dysfunction promotes insulin resistance in patients with mild to moderate stage of CKD, even when eGFR is maintained within the normal range (30). In addition, insulin resistance is associated with increased risk for CKD and is an independent predictor of cardiovascular diseases (30).…”

Section: Discussionmentioning

confidence: 99%

“…Renal dysfunction promotes insulin resistance in patients with mild to moderate stage of CKD, even when eGFR is maintained within the normal range (30). In addition, insulin resistance is associated with increased risk for CKD and is an independent predictor of cardiovascular diseases (30). Therefore, annual screening for type 2 DM is recommended for all CKD subjects (31).…”

Section: Discussionmentioning

confidence: 99%

Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study

et al. 2016

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Abstract. The aim of the present study was to examine the association of renal function with clinical parameters and conditions in the general population. Study subjects comprised 6,027 community-dwelling individuals who were recruited to the Inabe Health and Longevity Study: A longitudinal genetic epidemiological study of atherosclerotic, cardiovascular and metabolic diseases. The cutoff value, which was used to divide the subjects into those with normal and those with low estimated glomerular filtration rate (eGFR), was 60 ml/min/1.73 m 2 . Bonferroni's correction was applied to establish the statistical significance of the association. Longitudinal analysis using the generalized linear mixed-effect model, following adjustments for age and gender, revealed that the eGFR was significantly associated (P<0.0017) with serum levels of triglycerides, low-density lipoprotein cholesterol, uric acid, blood glycosylated hemoglobin content, fasting plasma glucose and body mass index. These parameters decreased curvilinearly with increases in eGFR. Furthermore, eGFR correlated positively with serum levels of high-density lipoprotein (HDL) cholesterol. Longitudinal analysis using the generalized estimating equation following adjustment for age and gender indicated a significant association (P<0.0024) between eGFR and prevalence of hypertension, type 2 diabetes mellitus, hypo-HDL cholesterolemia, hyperuricemia and obesity. Thus, low eGFR results in detrimental effects on various clinical parameters and conditions, resulting in increased risk of hypertension, dyslipidemia, type 2 diabetes mellitus, hyperuricemia and obesity.

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“…In patients with end-stage renal disease, IR is an independent predictor of CV disease and is linked to protein energy wasting and malnutrition. 23 Nutritional, metabolic, and CV complications of renal disease may be a consequence of abnormal insulin action. Systemic inflammation, oxidative stress, elevated serum adipokine and fetuin-A, metabolic acidosis, vit D deficiency, depressed serum erythropoietin, endoplasmic reticulum stress, and suppressors of cytokine signaling all cause IR by suppressing insulin receptor-PI3K-Akt pathways in CKD.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D deficiency, insulin resistance, and ventricular hypertrophy in the early stages of chronic kidney disease

et al. 2013

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Materials and methods:The study comprised 67 patients with CKD (eGFR ! 30 mL/min) and 15 healthy controls matched for age and sex. The phlogosis indexes, vit D levels, IR, carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured. Results: In our study, the mean value of LVMI and cIMT was significantly higher in patients with eGFR ! 30 mL/min compared with controls (p ¼ 0.037 and p50.001). The IR and intact parathyroid hormone (iPTH) levels were increased in CKD patients, whereas the serum levels of vit D were significantly reduced (p ¼ 0.044, p ¼ 0.012, p ¼ 0.038). A positive correlation was found between LVMI and IR (r ¼ 0.704, p ¼ 0.041) and a negative correlation was found between IR and vit D levels (r ¼ À0.238, p ¼ 0.031). Conclusions: In our study, IR and vit D deficiency were found to be independent predictors of left ventricular hypertrophy and atherosclerotic disease. Vitamin D deficiency and IR are thus associated with increased CV risk. More novel approaches to improving IR and vit D supplementation in the CKD population might lead to potential strategies for preventing excess CV mortality.

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Insulin Resistance in Patients with Chronic Kidney Disease

Cited by 119 publications

References 138 publications

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients

Association of renal function with clinical parameters and conditions in a longitudinal population-based epidemiological study

Vitamin D deficiency, insulin resistance, and ventricular hypertrophy in the early stages of chronic kidney disease

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