Diabetic microvascular complications
Diabetic microvascular disease
The 3 main manifestations of diabetic microvascular disease, retinopathy, nephropathy, and neuropathy are reviewed.
Retinopathy: Diabetic microvascular disease is strongly associated with hyperglycemia. In the range of chronic hyperglycemia commonly seen in practice, there is an 11-fold increase in retinopathy compared to a 2-fold increase in coronary artery disease. Despite the importance of hyperglycemia, some patients may develop early evidence of retinopathy up to 7 years before the development of Frank’s type 2 diabetes mellitus, indicating the contribution of insulin resistance.
In addition to the severity of hyperglycemia and the duration of diabetes mellitus, other factors associated with retinopathy include hypertension, smoking, and dyslipidemia. These and other pathophysiological mechanisms, including insulin resistance and inflammation, contribute to the diabetic microvascular disease process.
The early histopathological sign of retinopathy related to diabetes mellitus is the loss of pericytes. Pericytes surround arterial and capillary endothelial cells and participate in the maintenance of capillary tone, growth, and resistance to damage from oxidative stress. Then the disease is characterized by hardening of the basement membrane, permeability of endothelial cells, and the formation of microaneurysms.
Broadly speaking, there are 2 types of retinopathy, non-proliferative (background), and diffuse. In nonproliferative retinopathy, patients may develop point bleeds, which are small hemorrhages in the middle of the retina surrounded by tight lipid exudates. Retinal edema can also be seen. Proliferative retinopathy is the development of neovascularization in the retina, which is complicated by vitreous hemorrhage. These later changes, without treatment, can lead to vision problems.
According to an analysis of the National Health and Nutrition Survey, the prevalence of retinopathy in the diabetic population is 28.5% and the general risk of vision loss is 4.4%. Male gender, high levels of glycated hemoglobin, long duration of diabetes mellitus, high blood pressure, and insulin use are associated with the development of retinopathy. In a group of 35 studies of people with diabetes from around the world from 1980 to 2008, retinopathy was 35% prevalent in people aged 20 to 79 years, 7% for proliferative retinopathy, and 10% for vision threat.
Rates of retinopathy are higher for patients of African or Caribbean descent compared to Caucasians or South Asians. The presence of the diabetic microvascular disease is also a sign of contagious vascular disease. Diabetic patients with retinopathy have a higher rate of atherosclerosis than diabetic patients without retinopathy.
Diabetic retinopathy is the leading cause of blindness in the United States. It is responsible for 8% of the cases of legal blindness and 12% of the cases of blindness in the United States each year during the last decade of the 20th century. However, newer therapies have improved outcomes with a significantly reduced rate of acute visual impairment. Although the number of patients with diabetes mellitus and diabetic retinopathy has increased from 4 million to మి 5 million in the United States over the past few decades, the number of visually impaired diabetes mellitus patients decreased from 26% in 1997 to ≈19% in 2011, while the general visual disability in the civilian population was 9.3%. It is constant.
Systemic medical treatment plays an important role in diabetic microvascular disease and will be discussed later. 2 specific eye treatments slow the progression to blindness. Two clinical trials, the Diabetic Retinopathy Early Treatment Study and the Diabetic Retinopathy Study established macular and pan-retinal photocoagulation as the main treatment for these two eye problems. Recently, the use of injected vascular endothelial growth factor antagonists has been shown to improve outcomes in proliferative retinopathy and has become fashionable. The timing, use, and role of this treatment about photocoagulation have not been established and depend on the results of clinical studies.
Nephropathy: The pathophysiology of nephropathy in diabetes mellitus has many similarities to retinopathy, including hardening of the basement membrane and the formation of microaneurysms. Furthermore, glomerular hyperfiltration is associated with the proliferation of the extracellular matrix and the progression of tubular and glomerular sclerosis. These changes can cause albuminuria. Nephropathy is defined as a protein loss> 500 mg/day. Previously, microalbuminuria was defined as a loss of 299 mg / d28.
Neuropathy: The development of diabetic neuropathy is associated with vascular and non-vascular abnormalities. In addition to basement membrane hardening and percussion damage, there is evidence that capillary blood flow to C fibers is reduced, resulting in nerve perfusion and consequent endocrine hypoxia. Neuropathy is characterized by axonal hardening and eventual loss of neurons. Although there are 2 main types, the clinical manifestations of diabetic neuropathy can vary widely.
The most common is length-dependent, symmetric, chronic sensorimotor polyneuropathy, which is associated with the severity and duration of hyperglycemia. The pathophysiology of this subtype is similar to other microvascular manifestations of diabetes mellitus. Polyneuropathies that develop at more unpredictable times during diabetes mellitus are less likely to be symmetrical. Polyneuropathy is often accompanied by pain or spontaneous symptoms and can have a fluctuating course.
Medical therapy and diabetic microvascular disease
Clinical trials have shown that diabetic microvascular disease can be prevented or progressed by aggressive treatment of hyperglycemia and cardiovascular risk factors. Seminal trial Diabetes Control and Complications Trial (DCCT) in glycemic control. In DCCT, 1,441 type 1 diabetic patients, 726 without retinopathy, and 715 with mild retinopathy were randomly assigned to routine or intensive glycemic monitoring and followed for more than 6.5 years.
Median hemoglobin A1c as a result of intensive monitoring was ~ 7%, compared with 9% in the general care group. Intensive treatment is associated with a 76% reduction in the development of retinopathy and a 56% reduction in the need for laser therapy in patients with mild retinopathy at baseline. Similarly, intensive therapy reduced the rate of microalbuminuria by 43% and neuropathy by 69%.
The benefits of lowering glucose in patients with type 2 diabetes mellitus have also been demonstrated in the UK Prospective Diabetes Study (UKPDS). Diabetes and Vascular Disease in More Aggressive Glucose Control Action: Action to Control Cardiovascular Risk in Pretrox and Diamicron Modified Release (Advance) and Diabetes (ACCORD) Controlled Evaluation Trials. In both attempts, the intensive glycohemoglobin target gly6.5% arm was treated, some with modest benefits but not all signs of diabetic microvascular disease, which were not sufficient to change glycemic treatment goals.
Controlling blood pressure also reduces the likelihood of diabetic microvascular disease. A recent meta-analysis examined the effect of blood pressure control on diabetic retinopathy. The improved control of blood pressure resulted in an 18% reduction in the incidence of retinopathy in patients with type 1 diabetes mellitus and a 22% reduction in patients with type 2 diabetes mellitus. In contrast, no one has been identified. benefit in preventing the progression of retinopathy.
For nephropathy, some blood pressure agents are more effective. Angiotensin-converting enzyme (ACE) inhibitors reduce the incidence of nephropathy by 30% as determined by albuminuria42. Although there is no significant difference in blood pressure reduction, ACEIs are superior to calcium channel blockers. In contrast, the data supporting the efficacy of angiotensin receptor blockers are conflicting, with recent data being less positive than the initial studies.