Macroangiopathy in Adults and Children with Diabetes: From Molecular Mechanisms to Vascular Damage (Part 1)

Abstract

Type 2 diabetes mellitus (T2DM) is an increasing problem in childhood; however type 1 diabetes mellitus (T1DM) remains by far the most common type of diabetes in this age group. In this review we will focus on T1DM, because this will have the greatest implication for patients diagnosed in childhood. During the atherosclerotic process, several molecular, receptorial and cellular factors provide a continous mechanism of vascular damage. In diabetic children this state seems to be enhanced and facilitated so that accelerated atherosclerosis is associated with an increased risk of cardiovascular events in respect to the non diabetic population. Hyperglycemia PER SE and associated with diabetes is an important risk factor for atherosclerosis. At present a substantial part of children with diabetes do not reach satisfactory glycemic control. Other risk factors for the development and progression of atherosclerosis may be inherited or develop in the course of the disease: hypertension, dyslipidemia, insulin resistance, obesity, cigarette smoking, physical inactivity, disturbance of platelet function, coagulation and fibrinolysis. The development and progression of atherosclerosis should be blocked at an early age, if possible. Primary prevention to all risk factors for cardiovascular disease is important and intervention is indicated if necessary. At the moment the best therapeutic strategy is to maintain metabolic control at a physiologic level and perform screening and early intervention for vascular complications.

Interleukin-18 contributes more closely to the progression of diabetic nephropathy than other diabetic complications

“…The development of macroangiopathy is independent of that of microangiopathy. As previously known [1,3], the expression of macroangiopathy is related to hyperglycemia and hyperlipidemia in this study. The alteration pattern of cytokines suggests the participation of proinflammatory signaling and oxidative stress in the progression of microangiopathy.…”

“…Glycemic control is critical for managing clinical complications in this disease [1,26]. Dyslipidemia is also popularly known as a risk factor of diabetic complications [3,27].…”

“…Each of these complications differs in their incidence and the stage of their occurrence during the disease. Atherosclerosis is known to contribute to the establishment of macroangiopathy [1], and arteriolosclerosis has been suggested to play a role in the etiology of microangiopathy [2]. Hyperlipidemia, hypertension, smoking, and social stress are reported as risk factors worsening vascular complications [3][4][5][6].…”

Association of serum osteoprotegerin with vascular calcification in patients with type 2 diabetes

“…Vascular endothelial impairment is the initial pathological change and is profoundly involved in development of atherosclerosis [1-4]. Progression of diabetic nephropathy, including microalbuminuria, is a risk factor for atherosclerosis in type 2 diabetes mellitus [5,6] and diabetic patients with advanced nephropathy (particularly those on dialysis with end-stage kidney disease) often have vascular calcification [7-10].…”

Prospectively Determined Impact of Type 1 Diabetes on Brain Volume During Development

“…It has been hypothesized that prolonged exposure to hyperglycemia causes mitochondrial dysfunction and increased oxidative stress, leading to cell death in the dependent brain regions (7–12). It is not clear how these proposed mechanisms may differ in the developing brain.…”