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Abstract
Diabetes leads to restructuring of vascular extracellular matrix components, resulting in increased media-to-lumen (M/L) ratios, decreased vascular compliance, and decreased relaxation in microvessels, thus increasing cardiovascular risk. This study examined individual and combined roles of hyperglycemia in Type 2 diabetes and oftentimes accompanying co-morbid factor, hyperlipidemia, in mediating mesenteric microvascular remodeling, impaired mechanical properties and vascular dysfunction in Type 2 diabetes. Increased vascular M/L ratios were observed in diabetes that were normalized by glycemic control with metformin, and combined hyperglycemia and hyperlipidemia did not cause further worsening of vessel morphology. Glycemic control also decreased vascular stiffness and myogenic tone in diabetes, thus improving compliance. In addition to worsening cardiometabolic factors, combined hyperglycemia and hyperlipidemia had adverse effects in mediating vascular dysfunction. Thus, by understanding the relative roles of diabetes and obesity, it is beneficial in devising effective therapeutic strategies to treat microvascular complications in diabetes.