Pre-diabetes and arterial stiffness in uraemic patients.
BACKGROUND
In order to address factors of relevance for new onset diabetes mellitus and cardiovascular disease after kidney transplantation, we investigated the presence of pre-diabetes, arterial stiffness and endothelial dysfunction in patients with end-stage renal disease (ESRD) accepted for kidney transplantation.


METHODS
Pre-diabetes and an insulin sensitivity index were estimated by an oral glucose tolerance test in 66 consecutive uraemic patients, without diabetes, being on the waiting list for the first renal transplantation. Mean age was 43 +/- 13 years. Duration of ESRD was 32 +/- 27 months. A control group consisted of 14 healthy subjects. Arterial stiffness was measured by aorta pulse wave velocity (PWV) and aorta augmentation index (AIX). Endothelial function was evaluated by flow-mediated vasodilatation (FMD) and plasma concentrations of von Willebrand factor antigen (vWF). Mean arterial blood pressure (MAP) was measured in supine resting position.


RESULTS
Twenty-seven uraemic patients (41%) had pre-diabetes (IFG+IGT), and 39 had normal glucose tolerance. The uraemic patients were more insulin resistant with lower insulin sensitivity index compared to healthy controls (6.1 +/- 3 vs. 15 +/- 7, P < 0.0001) but with no difference between patients with and without pre-diabetes. HbA1c and fasting plasma glucose was comparable in uraemic patients with and without pre-diabetes. PWV was higher in pre-diabetic compared to normoglycaemic uraemic patients (9.1 +/- 3 vs. 7.3 +/- 2 m/s, P = 0.03) and healthy controls (9.1 +/- 3 vs. 6.7 +/- 1, P = 0.01), while AIX did not differ (24.9 +/- 13 vs. 23.2 +/- 12 vs. 17 +/- 16, P = NS). Presence of pre-diabetes was positively associated to PWV in a univariate analysis. Multivariable analysis revealed age and MAP as independent predictors of PWV in uraemic patients. FMD and vWF were impaired in uraemic patients compared to healthy controls (3 +/- 4 vs. 7 +/- 3, P = 0.007 and 1.8 +/- 0.7 vs. 0.96 +/- 0.3 kIU/L, P = 0.0002, respectively) but with no difference between the two groups of uraemic patients. In conclusion, a high prevalence of pre-diabetes, impaired insulin resistance, increased arterial stiffness of aorta as well as impaired augmentation index and vasodilatation was demonstrated in uraemic patients prior to kidney transplantation. Increased arterial stiffness of aorta and augmentation index were independently associated with age and blood pressure.
Hornum
Mads
M
Department of Nephrology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. mads.hornum@rh.regionh.dk
Clausen
Peter
P
Kjaergaard
Jesper
J
Hansen
Jesper Melchior
JM
Mathiesen
Elisabeth R
ER
Feldt-Rasmussen
Bo
B
D000293:Adolescent; D000328:Adult; D000368:Aged; D001158:Arteries / Q000473:pathology*; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology*; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D018149:Glucose Intolerance; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000503:physiopathology*; D011673:Pulsatile Flow; D014511:Uremia / Q000503:physiopathology*; D014664:Vasodilation; D055815:Young Adult
D001786:Blood Glucose; D007328:Insulin