Early and Late Effects of Erythropoietin on Glucose Metabolism in Maintenance Hemodialysis Patients

Allegra, V.; Mengozzi, Giacomo; Martimbianco, Lucia; Vasile, A.

doi:10.1159/000169014

Cited by 24 publications

(26 citation statements)

References 15 publications

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“…abnormalities and increased insulin sensitivity, with the duration of the treatment positively correlating with insulin sensitivity in these patients (188)(189)(190).…”

Section: Epo In Treatment Of Cardiovascular Diseasesmentioning

confidence: 81%

Epo and Non-hematopoietic Cells: What Do We Know?

Ogunshola

Bogdanova

2013

Methods in Molecular Biology

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“…abnormalities and increased insulin sensitivity, with the duration of the treatment positively correlating with insulin sensitivity in these patients (188)(189)(190).…”

Section: Epo In Treatment Of Cardiovascular Diseasesmentioning

confidence: 81%

Epo and Non-hematopoietic Cells: What Do We Know?

Ogunshola

Bogdanova

2013

Methods in Molecular Biology

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“…Borissova et al [9]have observed an improvement of peripheral insulin sensitivity in 5 diabetic patients on haemodialysis, after rHuEPO treatment, which was attributed to improvement of tissue oxygenation due to increased Hct. Allegra et al [10]noticed an improvement of the glucose metabolism after long-term rHuEPO therapy, not related to a direct effect or correction of anaemia according to their findings, while after short-term administration they did not find any effect. In the present study, no patient had haemosiderosis, and all of them improved their tissue insulin sensitivity before any correction of anaemia, as a response to EPO treatment.…”

Section: Discussionmentioning

confidence: 93%

Effect of Short-Term rHuEPO Treatment on Insulin Resistance in Haemodialysis Patients

Spaia

Pangalos

Askepidis

et al. 2000

Nephron

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Background/Aim: Decreased sensitivity to the hypoglycaemic action of insulin is an almost universal phenomenon in uraemic patients, and it is attributed either to uraemic toxins or to anaemia or even to secondary hyperparathyroidism. Considering the conflicting data of few existing studies, we examined the influence of erythropoietin (EPO) treatment on insulin resistance and tested the probable correlation of this influence with sympathetic nervous system (SNS) activity. Methods: We studied 8 non-obese, non-diabetic, stable dialysis patients using the euglycaemic insulin clamp technique before administration of EPO (phase A), 10 days after (phase B), and after the correction of the haematocrit level, at least 8 weeks later (phase C). We estimated the indices (glucose infusion rate, mg/kg/min), M/G (glucose clearance), and M/I (tissue sensitivity to insulin), and we measured haematocrit, haemoglobin, triglyceride, ferritin, EPO, and fasting insulin levels in each phase. During each phase, we tested the SNS activity using the response of blood pressure to persistent handgrip and the response of blood pressure to the standing position. Results: Our patients appeared to have an increased insulin resistance in phase A (M_A = 6.24 ± 1.01) which was significantly improved 10 days after the beginning of EPO treatment and before the rise of haematocrit (M_B = 7.71 ± 1.54, p < 0.05). There was no further improvement in phase C. Indices M/G and M/I behaved similarly. The serum triglyceride levels decreased in response to the increased insulin sensitivity. The patients studied did not demonstrate fasting hyperinsulinaemia, while the SNS activity was abnormal and remained unchanged throughout the study period in spite of some individual improvement. Conclusions: Our study proves the beneficial effect of EPO treatment on insulin resistance in dialysis patients which could be attributed to the EPO itself and not to the correction of anaemia and is accompanied by improvement in triglyceride levels. Amelioration of insulin resistance did not influence the SNS activity, making the association between EPO treatment and SNS-derived changes in blood pressure quite improbable.

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“…The possible role of the eventual correction of malnutrition was also suggested. 5 In a recent study, insulin resistance improved signi¢cantly 10 days after the beginning of EPO treatment, before the rise of haematocrit. There was no further improvement of insulin resistance after the correction of haematocrit level, at least 8 weeks later.…”

Section: Discussionmentioning

confidence: 95%

“…EPO therapy significantly improves glucose metabolism in maintenance HD patients mainly by reduction of insulin resistance. 5 Since neither anaemia correction nor a direct e¡ect of rHuEPO on some metabolic steps seem to be responsible for these e¡ects, further studies are needed on EPO treatment for improvement of insulin resistance in HD patients. Although both EPO and pulse oral 1-a-D3 treatments corrected anaemia of these patients signi¢-cantly, only EPO produced a marked decrease in lymphocyte PC-1 activity.…”

Section: Discussionmentioning

confidence: 99%

Lymphocyte PC-1 activity in patients on maintenance haemodialysis treated with human erythropoietin and 1-α-D3

Stefanović

Djordjević²,

Ivic³

et al. 2005

Ann Clin Biochem

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Background: Plasma cell differentiation antigen 1 (PC-1) is an inhibitor of insulinreceptor tyrosine-kinase. PC-1 content is elevated in muscle and adipose tissue from insulin-resistant subjects and its elevation correlates with in vivo insulin resistance. It is known that insulin resistance in uraemia may be improved with erythropoietin (EPO) and vitamin D therapy. Therefore, in this study the effects of human recombinant EPO and 1-alpha-D3 treatments on lymphocyte PC-1 expression in patients with end-stage renal failure on haemodialysis (HD) were investigated. Methods: Lymphocyte basal, concanavalin A (Con A), and phorbol-12-myristate13-acetate (PMA)-stimulated PC-1 activity were investigated in HD patients before and after a two-month treatment with subcutaneous EPO (15 patients, 2000-3000 U thrice weekly) or oral 1-α-D3 (14 patients, 2 μg thrice weekly). Twenty-nine patients (16 men and 13 women), aged 22-68 years (49 ± 7 years), on HD from 13 to 112 months, and 30 healthy controls participated in the study. None was obese and all had normal fasting plasma glucose. Results: A two-month EPO treatment produced a 41% haematocrit increase, with a rise in haemoglobin from 6.51 ± 0.18 g/dL to 9.69 ± 0.14 g/dL. Basal lymphocyte PC-1 activity in HD patients was found to be significantly increased ( P < 0.005) over the level in healthy controls. Treatment of patients with EPO decreased unstimulated lymphocyte PC-1 activity to values significantly lower than before the treatment ( P < 0.001). Lymphocyte Con A and PMA-stimulated PC-1 activity in patients on HD was found to be slightly increased over the level in healthy controls, but significantly reduced ( P < 0.005 and 0.05, respectively) after the EPO treatment. A two-month pulse oral 1-α-D3 treatment increased haematocrit by 21% and raised haemoglobin from 7.11 ± 0.32 g/dL to 8.80 ± 0.39 g/dL. This treatment normalized serum alkaline phosphatase activity and slightly reduced serum parathyroid hormone concentration. PC-1 in unstimulated and PMA-stimulated lymphocytes was unchanged, but significantly decreased ( P < 0.05) in Con A-stimulated lymphocytes after 1-α-D3 treatment. Fasting plasma glucose was not changed by the treatment. Conclusion: An increased lymphocyte PC-1 activity over control was found in HD patients. A two-month EPO therapy significantly decreased PC-1 activity to the control values, suggesting that an effect on PC-1 expression could be implicated in the amelioration of insulin resistance in uraemic patients treated with EPO. Treatment with pulse oral 1-α-D3 had an effect only on PC-1 of Con A-transformed lymphocytes of haemodialysed patients and requires further investigation.

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Early and Late Effects of Erythropoietin on Glucose Metabolism in Maintenance Hemodialysis Patients

Cited by 24 publications

References 15 publications

Epo and Non-hematopoietic Cells: What Do We Know?

Epo and Non-hematopoietic Cells: What Do We Know?

Effect of Short-Term rHuEPO Treatment on Insulin Resistance in Haemodialysis Patients

Lymphocyte PC-1 activity in patients on maintenance haemodialysis treated with human erythropoietin and 1-α-D3

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