Eutrophic Remodeling of Small Arteries in Type 1 Diabetes Mellitus Is Enabled by Metabolic Control

Abstract

Abstract-Type 2 diabetes mellitus profoundly changes small artery remodeling in response to hypertension. Abnormal increases of both wall thickness and lumen diameter are associated with an increased mortality. Changes to small artery structure in response to blood pressure (BP) in patients with type 1 diabetes mellitus have never been examined. In 1997, 17 patients with type 1 diabetes mellitus and 9 control subjects underwent in vitro assessment of gluteal-fat small arteries using pressure myography. Key Words: diabetes mellitus Ⅲ hypertension Ⅲ microalbuminuria Ⅲ resistance artery Ⅲ remodeling Ⅲ complications H ypertension and diabetes mellitus are 2 main determinants of small artery structure. In patients with essential hypertension, the wall of the small artery undergoes eutrophic inward remodeling, which results in a reduction in lumen diameter by increasing wall thickness. 1,2 In patients with type 2 diabetes mellitus, hypertension causes a very different remodeling response. Outward growth increases wall thickness, and lumen diameter is preserved or increased. 3,4 Recently, this difference in response to blood pressure (BP) has been suggested as an explanation for the propensity of patients to develop target organ damage in diabetes mellitus. 5,6 It has been postulated that the inability of the small artery to reduce the lumen diameter in response to central hypertension may result in the transmission of elevated pressures downstream to susceptible organs, eg, the eye or the kidney. [5][6][7] This appears to be supported by clinical observations, which have shown that the retinal vessel caliber is larger in patients with diabetes mellitus. 8 Also, in patients with type 1 diabetes mellitus, a larger vessel caliber can predict progression to both nephropathy 9 and retinopathy. 10 To date, only 1 study has examined the structure of small arteries in type 1 diabetes mellitus, with no difference found between normoalbuminuric normotensive patients and control participants. 11 In this study, we have had the opportunity to study subcutaneous small artery function and structure in patients with a long duration (23 years) of diabetes mellitus with varying degrees of microalbuminuria and hypertension. In addition, we have performed a 10-year follow-up study in a subgroup that remained normoalbuminuric despite an increase in BP. Subjects and Methods Patient Recruitment and Follow-UpIn 1997, patients with type 1 diabetes mellitus and healthy nondiabetic control subjects gave full written informed consent and took

Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

“…It has been reported that in patients with diabetes mellitus with poor metabolic control, small peripheral resistance arteries presented hypertrophic growth in response to elevated blood pressure, whereas metabolic improvements enabled eutrophic remodeling to occur in response to an increase in blood pressure. 39 In any case, a full regression of eutrophic remodeling is rarely seen in patients with diabetes mellitus, despite treatment with effective drugs, such as ACE inhibitors or angiotensin receptor blockers, is able to induce a reduction of the media-to-lumen ratio of subcutaneous small arteries 15,16 ; therefore, in our study, we did not expect to see major changes in media cross-sectional area values.…”

“…It has been reported that in patients with diabetes mellitus with poor metabolic control, small peripheral resistance arteries presented hypertrophic growth in response to elevated blood pressure, whereas metabolic improvements enabled eutrophic remodeling to occur in response to an increase in blood pressure. 39 In any case, a full regression of eutrophic remodeling is rarely seen in patients with diabetes mellitus, despite treatment with effective drugs, such as ACE inhibitors or angiotensin receptor blockers, is able to induce a reduction of the media-to-lumen ratio of subcutaneous small arteries 15,16 ; therefore, in our study, we did not expect to see major changes in media cross-sectional area values.Mechanisms involved in the observed improvement in microvascular remodeling could be ascribed to the blockade of the deleterious effects of the renin-angiotensin-aldosterone system, including a proinflammatory action, [15][16][17][18]40 or to the restoration of myogenic response whose impairment is possibly involved in the development of hypertrophic remodeling. 41 Recently, it has been shown that aliskiren induced favorable effects similar to that induced by ACE inhibition in improving vascular remodeling in hypertensive rats with high plasma renin levels, independently of blood pressure control.…”

Impaired Myogenic Tone in Isolated Cerebral and Coronary Resistance Arteries from the Goto-Kakizaki Rat Model of Type 2 Diabetes

“…This response plays a central role in the autoregulation of blood flow and control of capillary pressure [7,8,9] and recent studies have shown that both the structure [10] and myogenic response [11] are altered in resistance arteries from patients with diabetes. The myogenic response is the initial response to a given change in transmural pressure across the arterial wall.…”

Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus

“…The microcirculation in diabetes displays a change in phenotype and function of the endothelium and smooth muscle and altered structure and composition of the extracellular matrix. As a result, the diabetic microvasculature exhibits altered wall-tolumen ratios and stiffer vessel walls than vessels from subjects without diabetes (13,23,33,40). Furthermore, in addition to altering wall properties, the complex diabetic milieu influences vascular reactivity that varies with vessel size, region, and function (11,40).…”