Complications of Diabetes

Complications of Diabetes

Introduction

Diabetes mellitus is a progressive metabolic condition characterized by hyperglycemia (elevated blood glucose levels). This condition is categorized into type 1 DM, type 2 DM, gestational diabetes, and others. According to statistics released in a report by the International Diabetes Federation, approximately 366 million people were suffering from this condition in 2011(Farrar, 2010). The prevalence keeps increasing by the day. This could be partly blamed on the modern-day sedentary lifestyle and diet. Twigg et al. (2017) state that this condition is progressive; hence, poor control of the blood glucose levels will, in the long run, lead to problems such as nephropathy, diabetic foot, retinopathy and many others.

Part 1

Metabolic memory is a medical term that describes the beneficial effects of prompt intensive control of blood sugar levels. Diabetes, just like any other chronic/lifestyle disease, has no cure. However, with optimal glycaemic control, diabetic patients have been established to lead normal healthy lives. Poor glycaemic control, however, predisposes such patients to a wide array of diabetic complications (Testa et al., 2016). The normal blood glucose levels are 5.6 mmol/l. A fasting blood sugar level higher than 5.6mmol/l is considered abnormal. A person is pronounced to be diabetic after multiple tests have been done, all confirming elevated glucose levels. The earliest definitions and explanations of metabolic memory were derived from an array of studies that conclusively indicated that early and adequate glycaemic control in patients with diabetes had a positive effect in reversing changes in the microcirculation that had resulted due to hyperglycemia.

 According to Testa et al. (2016), research studies done by various researchers have indicated that early optimal glycaemic control in diabetes reduces the risks of complications. Recently, the research literature on a previous survey of Diabetes Complication and Control Trial (DCCT) was released. From the literature, the subjects, who were diabetic patients, were put on either intensive or standard diabetic regimens to manage their blood sugar levels. The findings from this study showed that patients who undertook intensive treatment experienced a decrease in the advancement of diabetic microvascular complications (Testa et al., 2016). This was after an average period of six years and a half, which then resulted in putting all patients on intensive treatment.

A continuation study of the DCCT was done by the Epidemiology of Diabetes Interventions and Complications (EDIC) and revealed that the diabetic patients who were on standard treatment during the DCCT study, despite switching to intensive therapy, had higher incidences of complications compared to those patients who were on intensive treatment throughout. Long-standing diabetic complications are broadly divided into macrovascular and microvascular complications. The macrovascular complications involve damage to large blood vessels due to atherosclerosis. Some of the damages include diseases of the peripheral arteries, coronary arteries, and cerebral vasculature. The microvascular complications are a result of the thickening of the basement membrane, and they include neuropathy, nephropathy, and retinopathy.

From the DCCT study, it is evident that persistent hyperglycemia is a significant catalyst for diabetic-related macro and microvascular complications aforementioned. Therefore, in the fight against reducing such complications, the early diagnosis of diabetes is critical. According to Teodoro et al. (2018), research shows that most diabetic diagnoses are detected by chance, for example, during a routine hospital check-up. Early detection of diabetes and subsequent start on the therapy will enable glycemic control, therefore lowering the chances of a diabetic patient suffering from complications. Diabetic complications can be prevented by various modalities, either pharmacologic or non-pharmacologic interventions. Pharmacologic interventions involve the intake of blood glucose-lowering agents such as sulfonylureas, biguanides, and many other classes of drugs. Also, insulin administration is used in the management of this condition. Non-pharmacologic interventions involve modifications in lifestyle and diet. A sedentary lifestyle predisposes one to complications; hence, the diabetic patient is advised to increase physical activity.

Part 2

The metabolic syndrome is also commonly referred to as Syndrome X. This condition refers to the co-existence of three or more of the following clinical conditions in an individual: systemic hypertension, abdominal and central obesity, diabetes mellitus or insulin resistance and atherogenic dyslipidemia (Reddy, Zhang & Natarajan, 2015). In addition to these conditions, the syndrome has a pro-inflammatory and prothrombic state. This set of symptoms is a risk factor for chronic kidney disease, cardiovascular disease, hyperuricemia, and obstructive sleep apnea. Currently, there is no one specific treatment for metabolic syndrome as a whole. Treatment is limited to the management of individual clinical conditions such as hypertriglyceridemia and hypertension. Also, lifestyle modifications and diet control form part of the intervention for metabolic syndrome.

According to O'neill & O'driscroll (2015), metabolic syndrome affects a large percentage of the current population. This could be attributed to the increase in sedentary lifestyles and changes in diet, from traditional healthy diets to present-day diets full of junk and foods with high-fat content. Metabolic syndrome predisposes one to the development of atherosclerosis. Atherosclerosis refers to the accumulation of cholesterol, proliferation of cells of the smooth muscle, macrophage infiltration, and the accumulation of components of connective tissues in the blood vessels, which eventually cause plaque formation in the vasculature (O'Neill & O' Driscoll, 2015). Metabolic syndrome contributes to atherosclerosis due to the presence of increased levels of cholesterol in plasma. The high levels of cholesterol result in changes in arterial endothelial permeability that allow lipid migration, in particular, the low-density lipoprotein, into the arterial walls. Monocytes in circulation attach to the endothelial cells, leading to the expression of adhesion molecules such as selectins and vascular adhesion molecules. This is followed by the subsequent migration into the sub-endothelial process via a process known as diapedesis. Monocytes then convert into macrophages. Low-density lipoproteins in the subendothelial space undergo oxidation into chemoattractants. This whole process stimulates the accumulation of cholesterol intracellularly via the high expression of scavenger receptors, which have an affinity for binding phospholipids and modified lipoproteins. The process results in the narrowing of blood vessels and either a reduction in oxygen supply to body organs or extremities. Additionally, the process increases the risk of clot formation and, hence, blockage of the blood vessels. Clot formation is as a result of rupturing of the formed plaques.

Atherosclerosis is the leading cause of stroke, cardiovascular disease/heart failure, and periphery artery disease (Reddy, Zhang & Natarajan, 2015). Initially, this condition is asymptomatic because the blood vessels naturally respond by enlarging at all plaque locations. However, with time, severe narrowing of vessels occurs, thus preventing blood flow to different organs in the body. Reduced blood flow results in low or no oxygen supply to vital organs, thus inducing characteristic symptoms. Symptoms vary depending on the organ whose blood supply has been impaired. For instance, marked narrowing of the coronary artery that chiefly supplies the heart will cause symptoms such as shortness of breath, chest pain, dizziness, sweating, and breathlessness. Blockade of carotid arteries that supply the neck and brain will lead to symptoms such as blurred vision, walking difficulties, headache, numbness, and loss of consciousness. If uncontrolled, it can lead to an eventual stroke, which is fatal.

According to Hirsch (2015), the narrowing of peripheral arteries supplying the limbs and pelvis will be characterized by symptoms such as numbness in the lower and upper extremities and pain. Plaque formation in renal arteries can also impair blood supply to the kidneys leading to decreased blood flow to the kidney and chronic kidney disease. Since metabolic syndrome contributes to atherosclerosis, a healthy lifestyle incorporating increased physical activity and diet modification can reduce the chances of getting this condition.

Part 3

Nephropathy is a term used to describe angiopathy of the blood vessels supplying the kidney. It is one of the critical complications of diabetes, both type one and type two diabetes. It has been statistically determined that about forty percent of people with diabetes finally develop diabetic nephropathy. As a complication of diabetes, it is also known as diabetic kidney disease (Lofty et al., 2017). Diabetic nephropathy can be fatal since it can progress to end-stage renal failure, which can lead to death. This clinical syndrome is manifested by chronic angiopathy of capillaries present in the kidney glomeruli, leading to progressive albuminuria, loss of glomerular filtration, and hypertension. These changes develop slowly over many years, and overt signs or symptoms may not develop until very late in the disease course. This means that it is not easy to notice that one has nephropathy in its early stages. It hence manifests in its late stage when much harm to the kidneys has been done. This condition occurs as a result of changes to the basement membrane, in particular, the thickening of this membrane in the glomerular capillaries, referred to as diabetes glomerulosclerosis.

 Studies show that high blood glucose impairs the physiological regulatory mechanism that usually maintains the glomerular capillary pressure at the normal range, thus ensuring the protection of glomerular structures from differences in systemic blood pressure. Impairment of the autoregulatory system will, therefore, result in the transmission of systemic pressure to the glomerular capillaries. This then leads to subsequent increases in trans capillary hydraulic pressure leading to hyper infiltration. Hyperfiltration causes structural changes in the renal system. High blood glucose levels stimulate the renal RAAS (renin-angiotensin-aldosterone system), leading to the production of angiotensin II. This hormone causes constriction of efferent arteriole, resulting in increased capillary pressure. Additionally, angiotensin II activates several signalling pathways, inducing renal cell growth, inflammation, apoptosis, and differentiation. All these changes lead to the loss of glomerular infiltration, albuminuria, and renal hypertension.

Albuminuria is a principal cause of end-stage renal failure. Albuminuria is the presence of albumin in the urine. Albumin is a blood protein and should be present in urine in minute amounts. Its presence in the urine causes a reduction in the glomerular filtration rate to even up to less than 30 ml/min hence lowering the kidney function of excretion.

Signs and symptoms

The signs and symptoms of nephropathy do not occur immediately when one develops nephropathy. They become evident after around five years after the disease has progressed. Chawla & Jaggi (2016) state that the signs and symptoms of nephropathy include frequent nocturia, headaches, fatigue, frequent daytime urination, swelling of lower extremities, itchy skin, nausea and vomiting, proteinuria, and anorexia.

Risk Factors

Some of the common risk factors of this condition include hypertension, poor glycaemic control, blood pressure levels that are high and poorly controlled, high cholesterol level, the onset of type 1 diabetes mellitus before the age of 20, a family history of diabetic nephropathy and tobacco use(cigarette smoking). Poor control of high blood glucose increases the risk of getting high levels of glycated haemoglobin (HbAIc). The high HbAIc levels increase the risk of one developing diabetic nephropathy. Cigarette smoking causes albumin to be present in urine (albuminuria), and this causes a reduction in the glomerular filtration rate of a patient with diabetes. Diabetic patients who are smokers are at a very high risk of developing microalbuminuria (Lofty et al., 2017). This increases the risk of developing nephropathy. High cholesterol levels increase the renal kidney excretion of albumin, hence increasing the glomerular filtration rate in diabetic patients. Patients with family members with diabetes who have developed diabetic nephropathy are at risk of developing diabetic nephropathy. This is because of the predisposing genetic factors. Early onset of diabetes increases the risk of developing diabetic nephropathy. This is because of the long-standing high blood glucose. Hypertensive renal disease refers to a condition where there is kidney damage due to uncontrolled high blood pressure. Management of hypertension, hence, significantly impacts the reduction of nephropathy.

Diagnosis

In the diagnosis of this condition, tests are done to assess albumin levels in urine. These tests are coupled with other tests done to exclude albuminuria caused by other conditions (Asmat, Abad & Ismail, 2016). Urine test to detect the level of the blood protein albumin in the urine. The normal levels of albumin in urine are the excretion of approximately 30mg/day or fewer amounts than an excretion of values > 300mg/day of albumin is indicative of nephropathy.

Additionally, kidney ultrasonography is done as part of medical imaging. The albumin-creatinine ratio (ACR) is also assessed during diagnosis. Detection of an ACR of 2.5 is indicative of microalbuminuria. In individuals with type 2 diabetes, it is advisable to do regular kidney assessments to enable early detection of any kidney problems such as nephropathy. Also, kidney assessment should be done initially after confirmation of the presence of type 2 diabetes mellitus. Glomerular filtration rate should also be measured. This is the best indicator for the overall kidney function.

Prevention

Prevention of diabetes-related complications such as nephropathy is possible since this condition has been established to arise due to lifestyle. Modification of one’s lifestyle and proper caloric intake monitoring are the primary modalities applied in preventing this condition. Patients who are at a high risk of having this condition, for instance, those with metabolic syndrome/syndrome X, can prevent this condition by early incorporation of proper caloric intake and modification of their lifestyle by adopting increased physical activities. Diabetic patients can prevent themselves from acquiring nephropathy by ensuring absolute control of their glucose levels.

Prevention of diabetic nephropathy involves two prevention strategies: primary and secondary prevention. Primary prevention is for patients with normal albuminuria levels, while secondary prevention is for patients with micro and macroalbuminuria levels. The primary level involves control of blood glucose, control of blood pressure, and control of hyperfiltration (Papatheodorou et al., 2016). The blood glucose should be controlled by ensuring that the glycated haemoglobin level is less than seven percent. The blood pressure should be maintained to about 120/80. Hyperfiltration in the glomerulus predicts progression to microalbuminuria. It is best controlled by controlling the body's metabolic rate. Secondary prevention involves control of the blood glucose and blood pressure and cessation of smoking.

Treatment

There is no specific cure for nephropathy. Treatment aims at controlling the underlying hyperglycemia and hypertension. In handling diabetes and its complications, a multidisciplinary team is critical (Bilous &Donnelly, 2010). The multidisciplinary team should include a dietician/nutritionist, a doctor, a nurse, a pharmacist, and an exercise specialist. The inclusion of a dietician in this team is essential so as to advise the patient on healthy feeding. Also, a dietician will serve to train patients on monitoring their caloric intake and what kinds of foods to avoid. The inclusion of an exercise specialist is critical since such a professional will serve to teach patients the importance of increased physical activity and what kind of sports to engage in. A pharmacist will ensure proper pharmacologic therapy is prescribed. Nurses will advise the patient on the importance of monitoring their sugar levels and other care interventions.

The treatment of nephropathy involves optimal glycemic control and blood pressure control. Therefore, diabetic patients are advised to take their glucose-lowering medications well. These agents include insulin, biguanides such as metformin, Thiazolidinediones such as pioglitazone, and α-glucosidase inhibitors such as acarbose(Nentwich & Ulbig, 2015). The choice of the glucose-lowering agent should be determined by the renal function level. Drugs that are eliminated by the kidneys should be avoided since they will further decrease renal function. Sulfonylureas, except glimepiride, are excreted through the kidneys and hence should not be administered to control blood glucose in nephropathy patients. Insulin should be used in patients with type 2 diabetes with nephropathy who have had long-standing diabetes and are not so responsive to oral glucose-lowering agents.

In control of blood pressure, usually angiotensin-converting enzyme inhibitors (ACEIs) such as enalapril, fosinopril, and ramipril can be used. Also, angiotensin receptor blockers (ARBs) such as losartan can be used. ACEIs and ARBs can be given prophylactically to prevent nephropathy or to control hypertension (Hammes, Greffrath &Hillebrands, 2016). Both drugs have been shown to delay the progression of proteinuria in patients with microalbuminuria. ACEIs and ARBs are the preferred antihypertensives because they are nephron-protective. This is because they reduce systemic vascular resistance hence preventing deterioration of the renal function. High blood pressure should be controlled because it is a major contributing risk factor of nephropathy. Calcium channel blockers such as nifedipine are used as adjunctive therapy with ACEIs and ARBs for controlling blood pressure in diabetic patients with nephropathy. Low-dose aspirin has also been used to prevent cardiovascular events in patients with diabetes.

Non-pharmacologic interventions such as lifestyle modifications and strict control of diet are also part of the management strategies for diabetic patients with nephrotic disease. Increased physical activity, such as exercise/sports, increases the amounts of glucose utilized. The glucose is initially obtained from the breakdown of muscle glycogen and, subsequently, from gluconeogenesis and hepatic glycogenolysis. Increased physical activity also reduces the cholesterol level in the body (Hammes, Greffrath &Hillebrands, 2016). With regards to diet, changes should be made such that the patient's diet should contain low fat. Diet and moderate exercise are to ensure that the blood lipid profile is lowered in obese diabetic patients. The other lifestyle modification that should be made should be the cessation of smoking in case one is a smoker. This is because smoking is among the most common risk factors for diabetic nephropathy.

According to Beckman & Creager (2016), if left untreated, diabetic nephropathy can worsen and could lead to many complications. Some of them are fluid retention that manifests as swelling in the legs and arms, hyperkalemia, which is the elevation of blood potassium levels, and cardiovascular diseases such as high blood pressure and stroke. Others include retinopathy, which is damage to the blood vessels present in the retina and irreversible end-stage kidney. When managing nephropathy, the basis of its management is first to manage its root cause, which is the high blood glucose. Its management should hence, be aimed at achieving optimal glucose control. The blood glucose should, therefore, be monitored to determine if the optimal blood glucose is being achieved (Hammes, Greffrath &Hillebrands, 2016).

The target levels for blood glucose should be glycated haemoglobin (HbA1c) levels of less than or equal to seven percent. The normal fasting plasma glucose should be between 3-7 mmol/L. Optimal glycaemic control is the hallmark for the prevention of diabetic complications such as nephropathy.

Glucose control should be coupled with strict maintenance of blood pressure. The target should be a blood pressure value of 120/80 mm HG, which is the normal blood pressure in healthy individuals. It should be ensured that the normal blood lipid profile is less than 200 mg/dl for a total cholesterol level of less than 100 mg/dl for low-density lipoproteins and less than 40 mg/dl for high-density lipoproteins (Beckman & Creager, 2016). Control of the blood lipid profile is crucial because it is implicated in the etiology of nephropathy, especially in obese diabetic patients.

Conclusion

In conclusion, despite being a chronic condition, diabetes can be controlled. Patients with this condition can, therefore, lead a healthy life with proper control involving the use of pharmacologic and non-pharmacologic interventions. On the flip side, poor glycemic control will lead to numerous complications, thus affecting the quality of life of such patients. Therefore, all diabetic patients should be educated on the importance of optimal glycemic control and the advantages of monitoring their blood sugars to avoid complications such as nephropathy, retinopathy and many others.

References

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