Increased serum pigment epithelium-derived factor is associated with microvascular complications, vascular stiffness and inflammation in Type 1 diabetes.
OBJECTIVE
To determine in Type 1 diabetes patients if levels of pigment epithelium-derived factor (PEDF), an anti-angiogenic, anti-inflammatory and antioxidant factor, are increased in individuals with complications and positively related to vascular and renal dysfunction, body mass index, glycated haemoglobin, lipids, inflammation and oxidative stress.


METHODS
Serum PEDF levels were measured by ELISA in a cross-sectional study of 123 Type 1 diabetic patients (71 without and 52 with microvascular complications) and 31 non-diabetic control subjects. PEDF associations with complication status, pulse-wave analysis and biochemical results were explored.


RESULTS
PEDF levels [geometric mean (95% CI)] were increased in patients with complications 8.2 (7.0-9.6) microg/ml, vs. complication-free patients [5.3 (4.7-6.0) microg/ml, P < 0.001] and control subjects [5.3 (4.6-6.1) microg/ml, P < 0.001; anova between three groups, P < 0.001], but did not differ significantly between control subjects and complication-free patients (P > 0.05). In diabetes, PEDF levels correlated (all P < 0.001) with systolic blood pressure (r = 0.317), pulse pressure (r = 0.337), small artery elasticity (r = -0.269), glycated haemoglobin (r = 0.245), body mass index (r = 0.362), renal dysfunction [including serum creatinine (r = 0.491), cystatin C (r = 0.500)], triglycerides (r = 0.367), and inflammation [including log(e)C-reactive protein (CRP; r = 0.329), and soluble vascular cell adhesion molecule-1 (r = 0.363)]. Age, blood urea nitrogen, systolic blood pressure, pulse pressure and log(e)CRP correlated with PEDF levels in control subjects (all P < 0.04). PEDF levels were not significantly correlated with measures of oxidative stress: isoprostanes, oxidized low-density lipoprotein or paraoxonase-1 activity. On stepwise linear regression analysis (all subjects), independent determinants of PEDF levels were renal function, triglycerides, inflammation, small artery elasticity and age (r(2) = 0.427).


CONCLUSIONS
In Type 1 diabetes, serum PEDF levels are associated with microvascular complications, poor vascular health, hyperglycaemia, adiposity and inflammation.
Jenkins
A J
AJ
University of Melbourne, Department of Medicine, St Vincent's Hospital, Melbourne, Australia. jenkinsa@medtv.unimelb.edu.au
Zhang
S X
SX
Rowley
K G
KG
Karschimkus
C S
CS
Nelson
C L
CL
Chung
J S
JS
O'Neal
D N
DN
Januszewski
A S
AS
Croft
K D
KD
Mori
T A
TA
Dragicevic
G
G
Harper
C A
CA
Best
J D
JD
Lyons
T J
TJ
Ma
J-X
JX
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D003928:Diabetic Nephropathies / Q000097:blood*; D003930:Diabetic Retinopathy / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000097:blood*; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D018384:Oxidative Stress / Q000502:physiology; D011480:Protease Inhibitors / Q000097:blood*; D015843:Serpins / Q000097:blood*; D000099174:Pigment Epithelium-Derived Factor
D015415:Biomarkers; D002097:C-Reactive Protein; D005136:Eye Proteins; D006442:Glycated Hemoglobin; D009414:Nerve Growth Factors; D011480:Protease Inhibitors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor