Investigating The Aetiology And Pathophysiology Of Renal Microvascular Complications

Diabetes is a disease where the body is unable to produce or use insulin effectively. Insulin is needed for proper storage and use of carbohydrates. Without it, blood sugar levels can become too high or too low, resulting in a diabetic emergency. It affects about 7.8% of the population. The incidence of diabetes is known to increase with age. It’s the leading cause of end-stage renal disease in the US, and is the primary cause of blindness and foot and leg amputation. It is known to cause neuropathy in up to 70% of diabetic patients. Individuals with diabetes are twice as likely to develop cardiovascular disease. There are two types of diabetes: Type 1 and Type 2.

Type 2 Diabetes is a disease that is found in a variety of age groups around the world. This disease is growing at a rapid rate and it is impacting the health of this generation and future generations to come. Diabetes is a disease that impairs the body’s ability to produce or respond to the insulin hormone produced by the pancreas. The insulin allows for the glucose to be effectively used as energy throughout the body. Diabetes causes carbohydrates to be abnormally digested, which can raise blood glucose levels. This means that the glucose is not being taken up by the cells that need it. The cells cannot take up the excess glucose that has accumulated in the blood, so it is excreted through the urine. This can lead to problems with the kidneys, central nervous system, heart, and eyes because high blood glucose can damage the blood vessels of these organs. This diseased is managed by adopting a diet low in fat and high in fiber, increasing physical activity, losing excess weight, and not smoking. If this

Hyperglycemia is a very serious risk for heart disease and strokes. Complications from hyperglycemic diabetes may include coronary heart disease (CHD), heart failure, stroke, arrhythmias, or even death. High blood glucose (sugar) levels over time can lead to excess fatty deposits on the insides of your blood vessel walls. These deposits often affect blood flow, which increases the possibility of blood vessels clogging and/or hardening. As a result, this leads to heart disease. Furthermore, those with diabetic heart disease (DHD) may have less success with heart disease treatments, such as angioplasty or artery bypass grafting. “The common clustering of these risk factors in a single individual has been called the metabolic syndrome.” (Scott 1134) Uncontrolled diabetes, the biggest contributor to heart disease, is almost four times higher for adults than those without diabetes. The best way to prevent diabetic heart disease is to control it by way of reducing the risk factors through diet and lifestyle changes.

Diabetes is one of the most prevalent diseases to this day. With over 171 million cases of diabetes all over the world, this disease is spreading exponentially fast. Lesser known as Diabetes Mellitus, this disease is all about the amounts of sugar in one's body. Glucose, in particular. Glucose is the powerhouse of the body. It helps run your body by transforming into the energy that we use to function on a daily basis. Whether or not one's diabetes is minor or even off the charts it can lead to terrible outcomes. These include stroke, blindness, vascular disease and heart disease. As mentioned before, the major symptom of diabetes is that too much sugar is in one's body. This is similar to a disease previously mentioned, hemochromatosis. However,

Diabetes is associated with an increased risk of developing primarily vascular complications that contribute to morbidity and mortality of diabetic patients. Poor glycaemic control leads to vascular complications that affect large (macrovascular), small (microvascular) vessels or both. Macrovascular complications include coronary heart disease, peripheral vascular disease and stroke. Microvascular complications contribute to diabetic neuropathy (nerve damage), nephropathy (kidney disease) and retinopathy (eye disease).

Patients with type 2 diabetes are at risk of macrovascular and microvascular complications. Evidence has shown that an improvement in blood glucose control, as shown by a reduction in HbA1c levels, is associated with a reduction in microvascular complications (2,3,4).

It is one of the two categories of diabetes: Type 1 is the insulin-reliant while Type 2 is the non-insulin-reliant. The aspects of Type 2 diabetes are insulin-inability where the cells and tissues lack response to insulin. Another aspect is the loss of pancreatic Beta-cell function that damages the creation of insulin and secretion. The Beta-cell function is important because it is balanced by glucagon-like peptide-1 (GLP-1) and oxidative stress that cuts down glucagon secretion, attending to gastric emptying, and weight gain. Type 2 diabetes weakens the activity of GLP-1, causing Hyperglycemia. Hyperglycemia advances to clinical issues such as cardiovascular diseases, kidney deterioration, and neuropathy. There is also the aftermath of lipid metabolism abnormality, leading to lipid toxicity further complicating the individual’s

According to Dugan (2009), “patients with stress hyperglycemia are at higher risk of adverse consequences than are those with pre-existing diabetes” (p. 1798). Acute glucose fluctuations induce more ischemic injury, inflammation, cellular apoptosis, endothelial dysfunction, and oxidative stress responses (Dugan, 2009, p. 1802). One

The management of diabetes mellitus (DM) is to eradicate symptoms and to minimize the development of complications (Khardori, 2014).The minimization of microvascular damages involving kidney and eyes can accomplished through managing glycemia and blood pressure (BP) (Khardori, 2014). The minimization of macrovascular damages, for examples: coronary, cerebrovascular, peripheral vascular, can be achieved by active control of lipids and hypertension (HTN), anticoagulant therapy, and glycemic control. The DM patient should maintain their glucose level close to near-normal levels of 90 to130 mg/dL and hemoglobin A1C (HbA1c) levels below 7% (Khardori, 2014). HbA1c should be evaluated every three to six months (Khardori, 2014).The DM patient’s BP should be maintained below 130/80 mm Hg, and even lower for the patient’s with DM nephropathy (Khardori, 2014). Low-density lipoprotein (LDL) goal of less than 70 mg/dL in patients with preexisting cardiovascular disease (CVD) or patients with the risk factors for coronary vascular disease (CVD) (Domino & Baldor, 2013).

Evidence implicates the role of oxidative stress in different stages of the development of diabetes mellitus, starting from the pre-diabetes state, impaired glucose tolerance, postprandial hyperglycemia, mild diabetes and finally to overt diabetes mellitus. Besides β -cell dysfunction, insulin resistance is a major characteristic feature of type 2 diabetes mellitus in which oxidative stress plays an important role (Erejuwa, 2012).

Background: Diabetic nephropathy is the major micro-vascular complication of type 2 diabetes mellitus (T2DM) and is the main cause for end-stage kidney disease. In view of metabolic derangements of T2DM, we went further to investigate the role played by oxidized low density lipoprotein (ox-LDL), toll like receptor 4 (TLR4), lipocalin-2 (LCN2), and omentin-1 in DN. Patients and methods: 15 normo-albuminuria T2DM, 15 micro-albuminuria T2DM and 15 macro-albuminuria T2DM in addition to 15 healthy volunteer who served as control group were enrolled in this study. Demographic and clinical data were recorded. Plasma Ox-LDL, omentin- 1 and urinary LCN2 levels by immunoassy and TLR4 mRNA level with real time PCR were assessed. Results: TLR4 gene expression, Plasma ox-LDL, urinary LCN2 levels were increased in T2DM cases as compared to their allied control group with the higher values were for macro-albuminuria T2DM cases. Meanwhile Plasma omentin-1 level was decreased in T2DM cases when compared to their allied control group with least values were for macro-albuminuria T2DM cases. Also there were positive correlations between TLR4 mRNA, ox-LDL, urinary LCN2 levels and serum creatinine, fasting blood glucose, urinary albumin/creatinine ratio, meanwhile omentin 1 showed negative correlations with serum creatinine, fasting blood glucose, urinary albumin/creatinine ratio. Conclusions: Ox-LDL, TLR4, LCN2 and omentin 1 may confer a relevant role in diabetic nephropathy development and

One of the diseases is diabetes mellitus which is a major cause of renal failure. This disease can be defined as an increase of fasting blood glucose that is affected by a deficiency in insulin hormone. The normal range for glucose (fasting) in the blood is 2.8-6.0 mmol/L. It is classified into two groups, type 1 (insulin-dependent diabetes mellitus) and type 2 (non insulin-dependent diabetes mellitus). Stein (2008, p.6) points out that kidney failure happens most often when patients have suffered from diabetes mellitus for more than 10 years. According to United States Renal Data System (USRDS) report in 2007, approximately 44% of primary causes of renal failure is diabetes mellitus in the United States in 2005. Also, Stein (2008) indicates that 15% of dialysis patients are influenced by diabetes mellitus in the United Kingdom. Diabetes mellitus has negative affects throughout the kidneys where the increase of the range of blood sugar causes the damages to the cells in the kidneys. This leads to the presence of the glucose in the urine which is known as glycosuric.

Diabetes Mellitus is “a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action or both. It is a disease which is caused by the insufficient insulin secretion or decrease in the peripheral effects of insulin. It is a serious problem in terms of morbidity and mortality. The hyperglycemia is associated with long term damage, dysfunction and failure of various organs especially the eyes, kidneys, nerves, heart and blood vessels. It’s associated with many complications which includes blindness of the eyes and amputations of the extremities. It is also associated with neuropathy, retinopathy, and cardiovascular diseases which lead to mortalities.

Diabetes is a systemic disease caused by a decrease in the secretion of insulin or reduced sensitivity or responsiveness to insulin by target tissue. (Beale, et al., 2011) The incidence of diabetes is growing rapidly in the United States and worldwide. An estimated 347 million people around the world are afflicted with diabetes. (Whalen, et al., 2012) According to World Health Organization (WHO), Diabetes prevalence among adults over 18 years of age has risen from 4.7% in 1980 to 8.5% in 2014. It is the major cause of blindness, kidney failure, heart attack, stroke and limbic amputation. World Health Organization (WHO) projects that diabetes will be the 7th leading cause of death in 2030. It is a complex and costly disease that can affect nearly every organ in the body and result in devastating consequences. The leading cause of non-traumatic lower extremity amputations, renal failure, and blindness in working-age adults, diabetes is also a major cause of premature mortality, stroke, cardiovascular disease, peripheral vascular disease, congenital malformations, perinatal mortality, and disability. (Cefalu, 2000) Insulin therapy and oral hypoglycemic agents have demonstrated improvement in glycaemic control. However, Insulin therapy has some disadvantages such as ineffectiveness following oral administration, short shelf life, of the need for constant refrigeration, and fatal hypoglycaemia, in the event of excess dosage.

Oxidative stress is associated with postprandial hyperglycaemia via destroying the natural antioxidant defense of systems and organs 7. SOD activity indirectly reflects the antioxidant capacity, and the level of MDA indirectly reflects the degree of cells damage by oxygen free radical 36. Largely diminished SOD activity and increased MDA content were measured in BGF model compared with other diabetes model according to a previous study 37. Oxidative stress is produced in the skin of diabetic mice with BGF, which accelerates the skin damage 37. Consistently, the level of SOD was lowest while MDA level was highest in the FHG model rats, which might suggest the most severe oxidative stress injury caused by BGF. Furthermore, NO plays important roles in many processes, including immune, cardiovascular and nervous systems 38, 39. Recent evidence suggests that NO can cause net hemodynamic changes through interacting with other vasodilation mediators, such as adenosine and prostacyclin 40.