Pathophysiology of Diabetes Nephropathy and Atherosclerosis
Nathan & Delhanty (2005, p. 42) maintains that these complications may be present at the time of diabetes mellitus diagnosis and refer to diabetes as a ‘silent killer” as diabetes can go unnoticed until a major health event occurs. Diabetes is a major risk factor in the development of diabetes nephropathy and atherosclerosis. The person with diabetes (PWD) is at increased risk of mortality and morbidity than the general population but these are further increased in the presence of complications.
There is a crossover in pathophysiology of both nephropathy and atherosclerosis and the choice of these diabetes complications for this paper is purposeful as they have persistent hyperglycaemia over time as a common denominator (Fowler 2008; Chadban et al. 2009, pp. 32). The severity of hyperglycaemia and presence of hypertension were in evidence in the U. K. Prospective Diabetes Study (UKPDS) (Adler et al. 2003, pp. 225-232). Hypertension from nephropathy also influences cardiovascular risk by exacerbating atherosclerosis.
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Although both type 1 diabetes (T1D) and type 2 diabetes(T2D) are affected by complications, the focus of this paper will be on T2D. Firstly, analysis on the microvascular complication of diabetes nephropathy will be discussed and secondly, the macrovascualr complication of atherosclerosis. Major risk factors associated with these complications will be discussed along with the pathophysiological processes of diabetes nephropathy and atherosclerosis.
Management strategies for treating diabetes nephropathy and atherosclerosis complications will be discussed with one treatment strategy for each condition which may be delivered by a diabetes educator. The role of risk management for diabetes complications is to take a proactive multifactorial approach with better glycaemic and blood pressure control, the most common two strategies utilised. For the PWD making strategies sustainable achieves better outcomes (Thomas et al. 2006, pp. 140-144) Diabetes patient education of diabetic complications has proven to have beneficial positive health outcomes (Colagiuri et al. 009, p. 7). Promoting self-monitoring of blood glucose(SMBG), lifestyle education(diet, exercise, smoking and alcohol cessation) and increase in knowledge are some of the benchmarks. The National Consensus Report was introduced to address desired key outcomes and avoid criticism (Colagiuri et al. 2009, p. 8). In Australia Diabetes Educators work within their scope of practice to deliver patient education; in this paper the delivery of management strategies is within the scope of the diabetes educator(DE) and nursing practice. DIABETES NEPHROPATHY
Diabetes nephropathy is a common microvascular complication of diabetes and is the leading contributor to end-stage kidney disease (ESKD). In Australia, 20-22% of the patients with this condition will require dialysis and possibly a kidney transplant (Ali, 2011; O’Reilly; Bilious & Donnelly 2010). Nephropathy in persons with diabetes is more prevalent in Type 1 Diabetes (T1D) than Type 2 Diabetes (T2D) with a higher incidence in Indigenous Australians. statisics Progression is more clearly cut in T1D but has a significant impact on T2D(Chadban et al. 009, p. 31). Diabetes nephropathy is defined by proteinuria greater than 500 mg in 24 hours. Microalbuminuria is measured by the albumin excretion rate (AER) and levels between 30 to 300 mg/24 hr mark the beginning of renal involvement but without immediate intervention, the PWD will progress to proteinuria and nephropathy (Chadban et al. 2009,p. 33). Approximately 7% of T2D have microalbuminuria at the time of diagnosis, which can progress to ESKD (Fowler, 2008, p. 77-82; Bilious & Donnelly, 2010, p. 120).
UKPDS incidence in T2D of microalbuminuria was 2% per year, with 10-year prevalence from diagnosis of 25%; which increases cardiovascular risk that has a cumulative incidence of 10 to 40% (Adler et al. 2003, p. 225-32; Bilious & Donnelly, 2010, p. 121; Chadban et al. 2009, p. 11). Diabetes nephropathy is the commonest cause of hypertension in patients with diabetes (Fowler, 2008, p. 77-82; Bilious & Donnell, 2010,p. 119). Kaartinen et al(2007, p. 778) indicate strong evidence that insulin resistance is present in even mild to moderate chronic renal insufficiency before any sign of kidney function impairment is manifested.
It is not clearly understood why a PWD progresses to renal failure and others do not, as there does not appear to be a casual correlation between good or poor control. What is relevant is the amount of protein that contributes to progression of this condition. (Chadban et al. 2009; Gaede et al. 1999). Diabetes nephropathy is a chronic condition that takes years to manifest itself and it is approximately an average of 5 to 8 years before an initial diagnosis of diabetes is made, by which time microvascular and macrovascular damage has occurred (Nuovo 2007, p. 40; Pirart 1978, pp. 168-188). The early sign of renal impairment is the leakage of protein into the urine from abnormal GFR. However serious signs and symptoms are persistent hypertension, oedema, anaemia, hyperglycaemia, proteinuria, haematuria, oliguria and anuria(less than 100ml urine per day). The presence of overt proteinuria requires immediate intervention and early referral to nephrologist. Blood pressure and glycaemic control has been shown to decrease protein and stabilise renal function (RACGP Diabetes Management Guidelines 2011/2012, pp. 62-63).
Risk Factors Hypertension and hyperglycaemia are seen as the major contributing factors to the development of nephropathy. The presence of central obesity with the addition of smoking, sedentary lifestyle all adds to the demand on the body that over stresses insulin to meet these demands. Genetic phenotypes, genetic susceptibility, has been indicated as risk factors, but past studies have been inconclusive. Other factors of elevated serum lipids and the amount and origin of dietary protein is crucial and ethnicity with increased incidence in indigenous Australians.
The predictability of diabetes nephropathy can be gauged by the length of long standing diabetes from diagnosis (RACGP Diabetes Management Guidelines 2011/2012, pp. 62-63; Fowler, 2008). Pathophysiology of Diabetes Nephropathy Understanding the anatomy and function of the glomerulus is pivotal in understanding diabetes nephropathy. The glomerulus is a globular shaped capsule with numerous capillaries that actively work at filtering fluid from the blood to form urine. The glomerulus is one of the key structures that make up the filtration section of the nephron, the functional unit of the kidney which supports the mesangial cells and matrix.
Diabetes cycle of care can also contribute to the reduction of diabetes complications if followed diligently (RACGP Diabetes Management Guidelines 2011/2012, p. 34). Thirdly, the DE can deliver relevant information on the correlation between risk factors and possible complications to promote self-management of regular medications and SMBG; making target levels available and recognising the relevance of their own levels. There is no point in self-monitoring without understanding. The target HbA1c is lower or equal to 7 %( Chadban et al. 2009, p. 30-35). Nuovo (2007,p. 45) states a 1% drop in HbA1c will lower mortality in total mortality by 14%, and significantly a 43% decrease in amputations with a 24% decrease in renal failure. ACE/ARBS ACE/ARBs slow the development of CKD and CVD. As a management strategy in T2D introducing angiotensin-converting enzyme (ACE) inhibitors decrease blood pressure. Several studies have demonstrated reno protective effects of treatment with ACE inhibitors and angiotensin receptor blockers (ARBs) and decreases risk of progression to microalbuminuria in patients by 60-70% (Adler 2003, pp. 25-232; RACGP Diabetes Management Guidelines 2011/21012, p. 58; Fowler 2008,pp. 77-82). Intensive intervention in T2D patients can reduce the progression of nephropathy and possibly slows progression of renal impairment(Schrier et al. 2007, p. 431). CARI recommends interventions including, “antihypertensive therapies, ACE inhibitors, and A II receptor antagonists, calcium channel blockers, dietary protein restriction and glucose control, and interventions to control hypercholesterolemia and hyperlipidaemia”(Chadban et al. 2009, p. 30-35).
Diuretics may be considered to maintain urine output (Chadban et al. 2009, p. 30-35). Blood pressure control Hypertension is associated with an increased risk of many complications of DM, including cardiovascular disease, and the findings from the UKPDS indicate that any reduction in a person’s average blood pressure significantly reduces the risk of complications in nephropathy(Thomas 2006, pp2213-2234 ). Hypertension and diabetes should be diagnosed early and treated aggressively to prevent associated complications. The UKPDS showed hat blood pressure control helps to avoid cardiovascular complications in T2D and “…each 10 mmHg decrease in mean systolic blood pressure was associated with 12% reduction in the risk for any complication related to diabetes, 15% reduction in deaths related to diabetes, 11% reduction in myocardial infarction, and 13% reduction in microvascular complications” (Lago et al. 2007, p. 667). ATHEROSCLEROSIS The Australian Institute of Health and Welfare (AIHW) found PWD have an increased risk of developing coronary heart disease (CHD), stroke and peripheral vascular disease (PVD) with 60% reported they also had cardiovascular disease.
Diabetes, kidney disease and CVD account for 25% of the burden of disease in Australia, and just under two-thirds of all deaths (AIHW 2004; AIHW 2009). Atherosclerosis leads to myocardial infarction, congestive cardiac failure (CCF) and cerebral vascular accident (CVA) stroke, PVD and lower extremity amputation (LEA). Atherosclerosis is 2 to 4 times more prevalent in T2D. Principally, the beta cells become insulin resistant, adding strain to the body and making it difficult for insulin to perform effectively(Bilious & Donnelly, 2010, p. ). Risk factors
Risk factors that contribute to the development of and increase the risk for atherosclerosis are abdominal obesity, physical inactivity, hyperinsulinaemia, lipid abnormalities, altered platelet function, hypertension, smoking, microalbuminuria, increased fibrinogen levels and hyperglycaemia. Increased triglycerides and increased high density lipoproteins greatly impacting atherosclerosis(Maiti & Agrawal 2007, pp. 292-306). PWD with impaired kidney function and persons with metabolic syndrome are more prone to atherosclerosis (Kaartinen et al. 2007, p. 782). . Pathophysiology of Atherosclerosis
Diabetes is a pro-inflammatory condition fuelling metabolic factors that contribute to atherosclerosis. Conventional risk factors are dyslipidaemia, hypertension, and coagulopathy as a result of the prolonged hyperglycaemic state of diabetes. Central to diabetes related risk factors for atherosclerosis is hyperglycaemia from insulin deficiency and insulin resistance. Diabetes specific risk factors play a role in the acceleration of atherosclerosis by increased levels of advanced glycation end-products (AGEs), increased oxidative stress, altered matrix production and altered endothelium, smooth muscle cells and macrophages.
Macrophages are converted to foam cells that secrete pro-inflammatory cytokines (Goldberg 2004 , pp. 613-615; Maiti & Agrawal 2007,pp. 292-306). Hyperglycaemia promotes oxidative stress and glycation directing release of free radicals. Subsequently, lipid perioxidation allows foam streaky cells to form on the arterial walls causing endothelial dysfunction. Creager et al. 2003, p. 1527). A precursor to atherosclerosis is impaired nitric oxide which breaks down in response to hypertension, diabetes and dyslipidaemia (Maiti & Agrawal 2007, pp. 292-306).
Release of increased free radicals promotes increased platelet aggregation with elevated levels of plasminogen activator inhibitor type 1 and impaired fibrinolysis, allowing an increased inflammatory response to occur (Morgensen 2003, pp. 45-46; Maiti & Agrawal 2007, pp. 292-306). Growth factors cause a proliferation and migration of smooth muscle cells associated with thrombosis and Angiotensin II promotes endothelial damage. Diabetes is a thrombolytic state leading to an imbalance of atherosclerotic lesions and plaque instability, in turn increases the PWD risk of cardiovascular events.