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Query: UMLS:C0011860 (type 2 diabetes)
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In type 1 diabetic patients, ACE inhibitors exert a renoprotective effect which appears to be additional to, but not entirely independent of, changes in systemic blood pressure. This effect includes attenuation of albumin excretion rate (AER) as well as prevention or slowing of the rate of decline of the glomerular filtration rate (GFR). In type 2 diabetic patients, the results of ACE inhibition are more varied with some studies showing similar renoprotection to that observed in type 1 diabetes and others showing no additional effect to lowering of systemic blood pressure. This may be due to the diverse manifestations of the disease itself or to renal factors which may modify the response to ACE inhibitors. The major systemic causes of diversity are variations in age, race and blood pressure. The major renal causes of diversity include changes in the relationship or 'coupling' of AER to onset of decline in GFR and a heterogeneity of renal ultrastructural changes in the glomeruli, tubules, interstitium and the renal vasculature. Factors that may be responsible for different renal responses to ACE inhibitors in type 2 diabetes include coexistence of coronary heart disease which may introduce survival bias in long-term studies, a lower specificity of microalbuminuria for diabetic nephropathy, early onset of a decline in GFR in hypertensive or normotensive patients at or prior to the onset of microalbuminuria, a greater contribution of arteriosclerotic changes in renal arteries to decline in renal function, a higher prevalence of nondiabetic renal disease, a higher prevalence of hypertension in the elderly and yet to be characterized genetic factors. These variants of type 2 diabetes may be expected to influence the response to ACE inhibitors either by altering the initial proteinuric response or by altering the hypotensive response. Future studies taking into account the above variables may help to determine the relative importance of the above factors in modifying the renal responses to ACE inhibitors and thereby leading to different renal outcomes in type 1 and type 2 diabetic patients. Such studies may also help to assess the relative importance of changes in systemic blood pressure and intrarenal effects as well as the role of hemodynamic versus structural factors in contributing to differences in renal outcome with ACE inhibitors in type 1 and type 2 diabetes.
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PMID:Differences in renal outcomes with ACE inhibitors in type 1 and type 2 diabetic patients: possible explanations. 993 Mar 82

Nephropathy may develop in patients with type 1 diabetes because poor glycemic control produces effects that eventually lead to glomerular scarring and renal failure. The worse and more prolonged the hyperglycemia, the greater the risk of diabetic nephropathy. In patients with type 2 diabetes, hyperglycemia, as well as insulin resistance and generalized vascular disease, is involved in the pathogenesis of nephropathy. The glomerular changes of early diabetic nephropathy can be identified only by renal biopsy or by testing for microalbuminuria. Once macroalbuminuria occurs (albumin excretion rate, > 300 mg/day), usually after type 1 diabetes has been present for 10 to 15 postpubertal years, end-stage renal disease is almost inevitable. However, aggressive control of hypertension in diabetic patients without microalbuminuria helps avoid nephropathy, and tight glycemic control in those with microalbuminuria can avoid or delay its onset. Even when macroalbuminuria is present, treatment can prolong renal function. Aggressive antihypertensive therapy, especially with ACE inhibitors, can reduce renal decline by half. Avoiding circumstances that may damage the kidneys (e.g., use of radiocontrast materials or nephrotoxic drugs, dehydration, hyperlipidemia, urinary tract infection, buildup of AGEs) is critical. Some treatment methods are controversial (dietary protein restriction) or still under investigation (use of injected or oral heparin) but may help delay renal transplantation or dialysis.
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PMID:Dealing with diabetic nephropathy. 1002 5

Diabetes is a chronic condition which poses a risk for three major complications. They are diabetic retinopathy, nephropathy and neuropathy. Almost one third of diabetic patients (IDDM or NIDDM) develop diabetic nephropathy in their life time. Because of increased vascular permeability in chronic conditions increased urinary albumin excretion in the range of 30-200 mg/L (microalbuminuria) gives an early signal of incipient diabetic nephropathy. The prevalence of microalbuminuria was found to be 41% in diabetic patients with duration of more than 5 years. Seventy percent of diabetic patients with microalbuminuria were hypertensive. ACE inhibitors are shown to have significant effects on microalbuminuria and hypertension. We conclude that microalbuminuria is an early feature of excessive capillary leakage and its assessment in diabetic patients with duration of more than 5 years provides a simple non-invasive method of early diagnosis of incipient diabetic nephropathy. An early intervention may retard the progression to end-stage renal disease (ESRD).
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PMID:Diabetes, microalbuminuria and hypertension. 1005 42

Present study analyses nephroprotective effect of various therapeutic interventions at different stages of kidney involvement in diabetes mellitus. A MEDLINE search of past 10 years data on various experimental studies, controlled clinical trials, meta-analysis and editorials pertaining to nephroprotection in diabetes mellitus was made. Effect of various therapeutic interventions such as metabolic glycaemic control, restricted protein diet and antihypertensive drugs (especially ACE inhibitors) has been analysed on the progression of different stages of kidney involvement in diabetes mellitus such as normoalbuminuria, microalbuminuria, diabetic nephropathy and end stage renal disease (ESRD). An attempt has been made to analyse differential long-term impact of various therapeutic interventions in relation to type of diabetes mellitus (i.e., IDDM and NIDDM) and associated hypertension. Progression of IDDM patients having microalbuminuria or diabetic nephropathy with or without hypertension has improved during the past decade largely because of adequate glycaemic control and effective antihypertensive treatment with conventional drugs e.g. beta-blockers and calcium antagonists, and more so due to the use of ACE inhibitors e.g. captopril, enalapril etc. Superiority of ACE inhibitor tends to decline from normotensive stage to the degree of rise in systemic blood pressure. However, data in NIDDM patients suffering from diabetic nephropathy is incomplete and inconclusive.
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PMID:Nephroprotection in diabetes mellitus. 1005 45

End-stage renal failure (ESRF) in diabetic patients, mostly type 2, has become the most frequent cause of renal replacement therapy in western Europe. The majority of patients with type 2 diabetes and renal failure suffer from diabetic glomerulosclerosis, but nondiabetic renal disease and atypical presentations, e.g. as irreversible acute renal failure or ischaemic nephropathy, play an increasingly important role. Known risk factors for the onset of diabetic nephropathy include (1) genetic predisposition (indicated by a history of hypertension and cardiovascular events in first-degree relatives), (2) quality of glycaemic control, (3) level of blood pressure, and (4) smoking. At the time when type 2 diabetes is diagnosed, an abnormal blood pressure profile is found in approximately 80%. In patients with established diabetic nephropathy, hypertension is the most important factor which promotes progression, and this is susceptible to intervention. Although less data are available for type 2 diabetes (compared with type 1 diabetes), ACE inhibitors appear to be the antihypertensive agent of first choice, but monotherapy is rarely sufficient to achieve the blood pressure goal. Although, at least in principle, diabetic nephropathy is a preventable condition, currently only a minority of type 2 diabetic patients in western Europe receives adequate medical treatment to prevent onset or progression of diabetic nephropathy. Consequently, novel approaches to patient management and interdisciplinary interaction are necessary to fulfil the postulate of the St Vincent declaration concerning prevention of diabetic complications.
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PMID:Nephropathy in type 2 diabetes. 1008 14

The renal protective effect of antihypertensive drugs is linked to 2 mechanisms. First, reduction in blood pressure (BP) is a fundamental prerequisite common to all antihypertensive drugs. The exact definition of the level to which BP should be reduced remains to be established, although there is some evidence that BP should be reduced below 130/85 mm Hg in patients with diabetic and nondiabetic nephropathies and below 125/75 mm Hg in patients with nondiabetic nephropathies and proteinuria >1 g/day. However, available data suggest that tight BP control (BP<140/80 mm Hg) can reduce the risk of cardiovascular complications in hypertensive patients with type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus; NIDDM). Secondly, intrarenal actions on mechanisms such as glomerular hypertension and hypertrophy, proteinuria, mesangial cell proliferation, mesangial matrix production and probably endothelial dysfunction, which can cause and/or worsen renal failure, are relevant for the renal protective action of some drug classes. ACE inhibitors possess such properties and also seem to lower proteinuria more than other antihypertensive drugs, despite a similar BP lowering effect. Calcium antagonists likewise exert beneficial intrarenal effects, but with some differences among subclasses. It remains to be evaluated whether angiotensin II-receptor antagonists can exert intrarenal effects and antiproteinuric actions similar to those of ACE inhibitors. While primary prevention of diabetic nephropathy is still an unsolved problem. there is convincing evidence that in patients with type 1 (insulin-dependent diabetes mellitus; IDDM) or 2 diabetes mellitus and incipient nephropathy ACE inhibitors reduce urinary albumin excretion and slow the progression to overt nephropathy. Similar effects have been reported with some long-acting dihydropyridine calcium antagonists, although less consistently than with ACE inhibitors. In patients with diabetic overt nephropathy, ACE inhibitors and nondihydropyridine calcium antagonists are particularly effective in reducing proteinuria and both drugs can slow the decline in glomerular filtration rate more successfully than other antihypertensive treatment. Available data in patients with nondiabetic nephropathies indicate that ACE inhibitors can be beneficial, principally in patients with significant proteinuria, in slowing the progression of renal failure. However, it is still unclear whether this beneficial effect of ACE inhibitors is particularly evident in patients with mild and/or more advanced renal failure and whether calcium antagonists possess a similar nephroprotective effect. Overall, data from clinical trials thus seem to indicate that ACE inhibitors and possibly calcium antagonists should be preferred in the treatment of patients with diabetic and nondiabetic nephropathies. However, further information is needed to understand renal protection.
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PMID:Renal protection and antihypertensive drugs: current status. 1035 94

We investigated the independent change in pulmonary diffusing capacity (DLCO) as one manifestation of pulmonary microangiopathy and to analyze the correlation between DLCO and serum ACE. We also examined the association between DLCO and the ACE genes. We examined pulmonary functions, especially %DLCO/VA (DLCO corrected by alveolar volume, percent predicted) in 54 NIDDM patients and 34 age-matched normal control subjects. Subjects were subdivided according to the degree of retinopathy. Serum ACE level was assayed by a colorimetric method in 54 patients and an insertion/deletion polymorphism in the ACE gene was amplified using the polymerase chain reaction in 52 of the 54 patients. There was a significant reduction of %DLCO/VA (percent predicted P < 0.05) in diabetic patients. In the proliferative retinopathy (PDR) group. %DLCO/VA was significantly (P < 0.05) lower than in the no diabetic retinopathy (NDR) and simple diabetic retinopathy (SDR) groups. Although the levels of serum ACE were within normal ranges in all diabetic groups, %DLCO/VA was negatively correlated with serum ACE values (r = 0.49, P < 0.0002, y = -1.4x + 109.3). Differences among DD, ID and II type of the ACE gene, with respect to the incidence of abnormal values of each clinical parameter, were not significant. DLCO was significantly reduced in patients with PDR and the serum ACE was significantly related to impaired DLCO. Our study suggests the existence of microangiopathic involvement of pulmonary vessels in NIDDM patients.
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PMID:Pulmonary diffusing capacity, serum angiotensin-converting enzyme activity and the angiotensin-converting enzyme gene in Japanese non-insulin-dependent diabetes mellitus patients. 1036 26

Patients with type 2 diabetes mellitus often develop micro- and macrovascular complications. In 25% of them, complications are already present at the time of diagnosis. The principal objective of the United Kingdom prospective diabetes study was to determine if good blood glucose control and adequate treatment of hypertension in patients with type 2 diabetes mellitus can prevent development of diabetes-related complications. The question was also studied if they way in which this blood glucose control was achieved and the way of treating the blood pressure affected the prognosis. Blood glucose control was found to reduce the incidence of--especially--microvascular complications. Oral hypoglycaemic agents and insulin both play an important part in achieving good control. Treatment with metformin reduced mortality due to cardiovascular disease in obese patients. Strict control of the blood pressure reduced development of micro- and macrovascular complications; the mortality from diabetes-related disorders and the numbers of patients suffering a stroke or heart failure. Non of the antihypertensive drugs used (an ACE inhibitor and a beta-blocking agent) offered any advantages over the other.
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PMID:[Glycemic regulation and management of essential hypertension in diabetics with type 2 diabetes mellitus; the 'United Kingdom prospective diabetes study' of diabetic complications]. 1038 31

Coronary artery disease is the most common cause of morbidity and mortality in subjects with type 2 diabetes mellitus. The risk of coronary artery disease, myocardial infarction and mortality from myocardial infarction is markedly increased in type 2 diabetic patients compared with non-diabetics. Diabetic patients with acute myocardial infarction should receive thrombolytic therapy as rapidly as possible and for the same indications as non-diabetics. Diabetic retinopathy is not a contraindication to treatment. The management of diabetic patients should also include medication with aspirin, beta-blockers and ACE-inhibitors. An insulin-glucose infusion during acute myocardial infarction, followed by insulin injections subcutaneously, reduces mortality by about 30% after 12 months and improves long-term prognosis. Thus, insulin-glucose infusion in diabetic patients with acute myocardial infarction, especially in those with a high blood glucose level (> 11 mmol/l), seems advisable. Diabetic patients benefit from secondary prevention by drug therapy (aspirin, lipid lowering with statins, beta-blockers and ACE-inhibitors) to the same extent as, or more than, non-diabetic patients.
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PMID:[Type 2 diabetes mellitus and coronary heart disease]. 1040 43

Diabetes mellitus and hypertension is often associated, but with a different type of development in type 1 and type 2 diabetes. Type 1 diabetes, renal disease, starting with microalbuminuria, is associated with increasing blood pressure or hypertension, whereas the patient without renal disease is most often normotensive. Poor metabolic control is a predictor of microalbuminuria or incipient nephropathy, but with microalbuminuria hypertension is an important risk factor for progression along with poor glycemic control. The same is the case for overt renal disease, and metabolic control is important in all stages of renal disease in type 1 diabetes. It has also been shown that good metabolic control as well as antihypertensive treatment, especially with ACE-inhibitors, often combined with other agents is quite effective in preventing progression in renal disease in all its stages. In type 2 diabetes, blood pressure elevation is often found as early as at the actual diagnosis, and blood pressure significantly increases according to the degree of albuminuria, normo-microalbuminuria and clinical proteinuria (macroalbuminuria). Elevated blood pressure is an important risk for renal disease but more importantly so also for cardiovascular disease. Several studies document that antihypertensive treatment in particular with ACE-inhibitors is important in preventing microalbuminuria, in treating microalbuminuria and thus preventing progression, also in overt renal disease. Near-normalization of blood pressure is vital. Regarding cardiovascular disease, a series of studies now document that antihypertensive treatment with various antihypertensive agents is able to significantly reduce a number of major cardiovascular complications in diabetes, such as cardiac disease, stroke, and also microvacular disease, including retinopathy. Several studies show that antihypertensive treatment should be started at a level higher than 140-150/90. The blood pressure to be achieved during treatment is probably around 140/85 mmHg or even 130/80 mmHg as a pragmatic goal. However, there is no sign of a J-shaped curve in any of the studies, and therefore even lower blood pressure could be advantageous. Even mortality, at least from diabetes-related causes can be effected by antihypertensive treatment. With more advanced renal disease, normalization of blood pressure is increasingly difficult, especially systolic blood pressure, and therefore it is recommendable to screen patients much earlier on with focus on blood pressure recordings and measurements of albuminuria, including microalbuminuria, and to treat early.
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PMID:Drug treatment for hypertensive patients in special situations: diabetes and hypertension. 1042 11


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