Effect of short-term rHuEPO treatment on insulin resistance in haemodialysis patients.
OBJECTIVE
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.
Spaia
S
S
Renal Department, Second Hospital of IKA, Thessaloniki, Greece.
Pangalos
M
M
Askepidis
N
N
Pazarloglou
M
M
Mavropoulou
E
E
Theodoridis
S
S
Dimitrakopoulos
K
K
Milionis
A
A
Vayonas
G
G
D000368:Aged; D000369:Aged, 80 and over; D004921:Erythropoietin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013997:Time Factors
D011994:Recombinant Proteins; D004921:Erythropoietin