Markers of endothelial dysfunction in hyperglycaemic Asian Indian subjects.
OBJECTIVE
The aims of this study were the following: (1). to determine the levels of endothelin-1(ET1), soluble adhesion molecules like intracellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in different stages of glucose intolerance and to identify a suitable marker of endothelial dysfunction and (2). to determine the possible association of these biochemical parameters with diabetic complications and with impaired glucose tolerance (IGT).


METHODS
In this cross-sectional study, plasma ET1, sICAM-1, and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 20 nondiabetic subjects, in 15 subjects with IGT, in 21 Type 2 diabetic subjects without any complication, and in 21 Type 2 diabetic patients with nephropathy and retinopathy.


RESULTS
Median ET1 levels were significantly elevated (P=.004) in IGT subjects (0.31 fmol/ml) when compared with the nondiabetic subjects (0.11 fmol/ml). Subjects with nephropathy (0.50 fmol/ml) had significantly higher (P=.002) ET1 values when compared with those without complications (0.40 fmol/ml). The levels of sICAM-1 and sVCAM-1 did not show any significant difference among the groups. ET1 showed correlation with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), 2 h post glucose (2hPG), waist-to-hip ratio (WHR), total white blood corpuscles count, glycosylated haemoglobin (HbA1c), triglycerides (TG), very-low-density lipoprotein cholesterol (VLDLc), and hypertension (HTN). In the multiple linear regression analysis, plasma ET1 was significantly associated with the presence of Type 2 diabetes either with or without complications (P<.0001 and P=.0098, respectively), WHR (P=.0063), and sVCAM-1 (P=.0051). The total variance explained by the above-mentioned parameters was 55%.


CONCLUSIONS
Elevated levels of ET1 were present in subjects with IGT and in Type 2 diabetic subjects. Such associations with sICAM-1 or sVCAM-1 in these subjects were not seen. ET1 could be an early marker of endothelial dysfunction, which appeared to occur even in the subclinical stages of hyperglycaemia.
Viswanathan
Vijay
V
Diabetes Research Centre, WHO Collaborating Centre for Research, Education and Training in Diabetes 4, Main Road, Royapuram, Chennai 600 013, India. dr_vijay@vsnl.com
Snehalatha
C
C
Nair
Mamtha B
MB
Ramachandran
A
A
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D018149:Glucose Intolerance / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology*; D007194:India; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D019332:Endothelin-1; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1