Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus

Abstract

O bservations of increased stiffness in the elastic aorta in women with diabetes, but not men, emphasise the need for further analysis regarding early abnormalities in arterial wall properties of women with type 1 diabetes mellitus (DM).Ultrasound was used to study the wall properties of the distal brachial artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident complications and in 53 controls (C). Blood samples were drawn for later analysis.Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1+4.3% vs. 10.3+4.9% (p<0.05), and nitrate-mediated dilatation (NMD) was markedly lower, 21.7+6.6% vs. 31.4+5.7% (p<0.001). Lumen diameter, intima-media thickness and distensibility were similar in DM and C. Insulin-like growth factor (IGF-1) was lower in DM than C, 231+65 vs. 349+68 ng/ml (p<0.001). Glycosylated haemoglobin (HbA 1C ) and matrix metalloproteinase (MMP-9) were independent predictors of the reduced NMD in the DM.Brachial artery responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in type 1 diabetic women despite only limited reduction in endotheliumdependent dilatation. The negative association between NMD and HbA 1C suggests that long-term hyperglycaemia impairs vascular smooth muscle cell function in DM.

Association of Endothelial and Vascular Smooth Muscle Dysfunction with Cardiovascular Risk Factors, Vascular Complications, and Subclinical Carotid Atherosclerosis in Type 2 Diabetic Patients

“…In mice, long-term hyperglycemia and hypertension are also reported to induce fibrosis of the resistance artery by the abnormal release of type 1 collagen from functional vascular smooth muscle cells 30) . Furthermore, in type 1 diabetic patients, the levels of HbA1c and matrix metalloproteinase (MMP-9), which are involved in the metabolism of the extracellular matrix, were found to be independent predictors of impaired NMD 24) . Recently, NMD induced by nitroglycerin (300 μg) administration was clearly demonstrated to predict future cardiovascular events better than FMD in a high-risk group comprising patients with mainly peripheral artery disease and aortic aneurysm 31) .…”

“…The accelerating risk factors for atherosclerosis, such as hyperglycemia, dyslipidemia, hypertension, and uremia, may exert long-term cumulative effects on vascular smooth muscle cell and the surrounding matrix in the medial layer rather than on the endothelium. In fact, advanced glycation endproduct (AGE) accumulation has been shown in the intima-media region of human and canine vascular tissues 28,29) and is closely associated with arterial stifftion 24) . Opinions regarding the interrelations between FMD and IMT are discrepant, although both are recognized as surrogate markers for CVDs.…”

Regulation of Large Conductance Ca2+-activated K+ (BK) Channel β1 Subunit Expression by Muscle RING Finger Protein 1 in Diabetic Vessels

“…There is a large body of evidence showing the abnormality of vascular smooth muscle function in diabetes. However, the underlying molecular mechanisms remain unclear (3)(4)(5)(6)(7)(8)(9).…”

“…The large conductance Ca 2ϩ -activated K ϩ (BK) 3 channels, densely populated in vascular smooth muscle cells (SMCs), play a negative feedback role in the regulation of vascular tone. BK channels are activated by the increase of intracellular free Ca 2ϩ concentrations ([Ca 2ϩ ] i ) to generate spontaneous transient outward currents, which hyperpolarizes the membrane potential of vascular SMCs, inactivates voltage-dependent Ca 2ϩ channels, and leads to vascular relaxation (8, 10 -14).…”

Biphasic insulin aspart 30/70 (BIAsp 30) in the treatment of type 1 and type 2 diabetes

“…The burden arises not just from the need to treat symptoms, but also the complications associated with hyperglycemia. [2][3][4] The cost to society is therefore enormous. 5,6 Given the extent of the problem, it is more important than ever that treatment of diabetes is as effective as possible.…”