International Journal of Obesity (2000) 24, Suppl 2, S134±S135 ß 2000 Macmillan Publishers Ltd All rights reserved 0307±0565/00 $15.00 www.nature.com/ijo
The relationship between obesity, vascular reactivity and endothelial dysfunction in subjects with non-insulin dependent diabetes mellitus ]>
SE Baldeweg1*, AM Pink1, JS Yudkin1 and SW Coppack1 1
Centre for Diabetes and Cardiovascular Risk, Department of Medicine, University College London, London, UK
International Journal of Obesity (2000) 24, Suppl 2, S134±S135 Keywords: obesity; type 2 diabetes; insulin; vascular reactivity; endothelial dysfunction
Introduction The control of forearm blood ¯ow and vascular tone involves the coordinated integration of many systems. Insulin resistance and obesity both appear to affect vascular reactivity. It has been demonstrated that the vasodilation induced by systemic insulin infusion is mediated through endothelially generated nitric oxide (NO) synthesised from L-arginine.1 Acetylcholine (ACh) also causes vasodilation by the same mechanism.2 Previously the integrity of this pathway has been assessed by intra-arterial infusion of acetylcholine into a local vascular bed and comparison of the changes in blood ¯ow with those achieved through infusion of an endothelium-independent NO-donor, such as sodium nitroprusside (SNP).3 An impaired vascular response to ACh, compared to SNP, has been assumed to be due to a defect in endothelial function, through the L-arginine=NO pathway. This could re¯ect either endothelial dysfunction or be the result of impaired responsiveness to endogenous NO. Defects in the L-arginine= NO pathway have been demonstrated in humans with non-insulin-dependent diabetes, obesity and other insulin resistant states.3 Our study examines the relationship between vascular reactivity to insulin, to ACh and to SNP with insulin sensitivity, as well as obesity in a group of patients with type 2 diabetes.
Methods We studied 10 subjects with uncomplicated NIDDM (7M : 3F, age 58.5 19.5 y, BMI 27.6 6.9 kg=m2). Approval of the protocol by the local Ethics Com*Correspondence: SE Baldeweg, Centre for Diabetes and Cardiovascular Risk, UCLMS, G-Block, Archway Wing, Archway Road, London N19 3UA, UK. E-mail:
[email protected]
mittee and informed consent from all subjects was obtained prior to the studies. All subjects had oral hypoglycaemic medication withdrawn for at least three weeks prior to study. Body mass index was calculated. Insulin sensitivity was evaluated using the glucose uptake during a euglycaemic hyperinsulinaemic clamp (insulin at 40 mU=m2=min). Venous occlusion plethysmography was used to measure vascular responses to increasing doses of ACh and SNP infused into the brachial artery and to a systemic insulin infusion.
Results As expected, there was a signi®cant relationship between BMI and insulin sensitivity (r 7 0.68, P 0.032). There was no relation between vascular response to either ACh (r 7 0.23, NS at 15 mg= dl=min) or insulin (r 0.23, NS at 120 min) and insulin sensitivity. We also found no relation between response to SNP and insulin sensitivity (r 0.26, NS at 4 mg=dl=min). There was no relationship between BMI and response to either ACh (r 7 0.02, NS) or insulin (r 7 0.29, NS). However, we found a strong inverse relation between vascular response to SNP and BMI (r 7 0.69, P 0.006 at 2 mg=dl=min and r 7 0.68, P 0.016 at 4 mg=dl=min) (Figure 1).
Discussion A number of studies have shown impaired endothelium-dependent vasodilation in type 2 diabetes, others have found no association or even an increased response. There is no consensus whether vascular response to NO donors is normal in non-insulin dependent diabetic patients.4 In diabetic subjects vascular reactivity to ACh appears to be in¯uenced by obesity.4 An impaired endothelium-dependent vascular response in non-diabetic obese subjects and
Obesity, vascular reactivity and endothelial dysfunction SE Baldeweg et al
cular response (to SNP). However, we did ®nd a signi®cant negative correlation between obesity and endothelium-independent vasodilation. Our results suggest a direct effect of obesity on the vascular response to exogenous NO in non-insulin-dependent diabetic patients.
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References
Figure 1 Vascular reactivity in response to intra-arterial sodium nitroprusside infusion at a dose of 4 mL=min=dL in relation to body mass index (r 7 0.68, P 0.016).
an independent association between endothelial dysfunction and insulin resistance have been reported.5 This suggests that endothelial dysfunction in obese type 2 diabetic subjects may be more related to obesity than to diabetes. In our group, after correction for BMI, insulin resistance was not correlated with either endotheliumdependent (to ACh) or endothelium-independent vas-
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