Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Kidney disease is a primary cause of morbidity and mortality in diabetic patients. Factors that predetermine development of nephropathy remain unknown. Poor glycemic control, insulin requirement, duration of diabetes and family history of hypertension appear to be associated with an increased risk. Arterial hypertension, which is twice as common in diabetic patients as in the normal population, accelerates the progression of diabetic nephropathy. The pathophysiologic mechanisms responsible for hypertension appear to be different in IDDM and NIDDM. In IDDM, hypertension occurs usually as a consequence of diabetic renal disease. Conversely, the pathogenesis in NIDDM appears to be multifactorial. In either condition, aggressive blood pressure control is the single most important intervention proven to retard the progression of nephropathy. A stepped-care approach similar to that for essential hypertension with slight modifications is indicated in the treatment of the hypertensive diabetic patient with nephropathy. Nonpharmacological therapy, including dietary protein restriction, should be used as first step. Selection of the ideal antihypertensive must be based not only on efficacy but also on its side effect profile. Angiotensin converting enzyme inhibitors and calcium antagonists have a low incidence of side effects and do not induce metabolic disturbances. Therefore, they are the agents of choice for patients who do not respond to nonpharmacological therapy alone. Thiazide diuretics and beta-blockers should be used as first line therapy only for specific indications. Antihypertensive therapy combined with good glycemic control and dietary protein restriction constitute the standard of care for diabetic patients with hypertension and renal disease.
 ...
PMID:Hypertension and kidney disease of diabetes mellitus. 176 55

At present we are able to disclose diabetic nephropathy in the very early stages, i.e. when urinary albumin excretion is only slightly increased (20-200 micrograms/min = microalbuminuria). Good blood glucose control and active antihypertensive treatment may stop or retard the further development towards renal failure. Angiotensin-converting-enzyme (ACE)-inhibitors seem to have a renoprotective effect. In this article we suggest guidelines for the use of ACE-inhibitors in patients with type 1 diabetes and early diabetic nephropathy. Special concerns are included in respect of adolescents, pregnant women and persons with type 2 diabetes.
 ...
PMID:[ACE inhibitors and early diabetic nephropathy]. 757 May 36

Angiotensin 1 converting enzyme (ACE) catalyses the step which generates angiotensin II, and also inactivates bradykinin, peptides which play a key role in modulating vascular tone. Plasma ACE levels are under genetic control and up to 50% of the variation is due to an insertion/deletion (I/D) polymorphism of ACE gene with highest levels found in DD homozygotes. Studies have shown an association of diabetic nephropathy and ischaemic heart disease with angiotensin converting enzyme gene polymorphism in subjects with diabetes. We examined the association between diabetic retinopathy and ACE gene insertion/deletion polymorphism in 363 subjects with NIDDM (aged 68.3 +/- 10.7 years; 201 male, 162 female), 186 subjects with IDDM (aged 42.4 +/- 15.0 years; 100 male, 86 female) and 98 controls. These subjects were characterized for ACE I/D polymorphism employing standard primers. Diabetic retinopathy was diagnosed by ophthalmoscopy through dilated pupils by an ophthalmologist and classified as non-proliferative or proliferative retinopathy. As expected, diabetic retinopathy was strongly associated with duration of diabetes (p < 0.001) in both IDDM and NIDDM. Any retinopathy was present in 51% subjects with IDDM and 49% of subjects with NIDDM, while 22% of IDDM subjects and 5% of subjects with NIDDM had proliferative retinopathy. The frequency of I allele was 0.477 vs 0.482 vs 0.510 and D allele was 0.523 vs 0.518 vs 0.490, among subjects with IDDM, NIDDM and controls, respectively. The frequency of ACE I/D genotype was similar in subjects with IDDM, NIDDM, and controls (chi 2 = 0.46, df = 4, p = ns). Presence or absence of retinopathy was not significantly associated with ACE genotype in subjects with IDDM (chi 2 = 3.42, df = 2, p = ns) or NIDDM (chi 2 = 0.51, df = 2, p = ns). Among subjects with retinopathy, there was no significant association between ACE genotype and type of retinopathy. Controlled for duration of diabetes, the frequency of I/D genotype was not significantly different in 271 subjects with retinopathy (IDDM and NIDDM combined) when compared with 86 subjects without retinopathy at 15 years or more after diagnosis of diabetes (chi 2 = 1.29, df = 2, p = ns). These findings indicate that I/D polymorphism of ACE gene is not a useful marker and is unlikely to play a major role in determining genetic susceptibility to diabetic retinopathy or the severity of diabetic retinopathy.
 ...
PMID:Angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism, and diabetic retinopathy in subjects with IDDM and NIDDM. 858 33

The presence of persistent microalbuminuria in IDDM is strongly predictive of the future development of end stage renal failure and of cardiovascular disease to a lesser extent. Screening for microalbuminuria is an essential component of modern diabetes practice, as effective antihypertensive therapy, and particularly, the use of angiotensin converting enzyme inhibitors is of proven benefit in retarding progression of renal disease. Cost benefit analysis justifies the expense of microalbuminuria screening programmes and early intervention. It has been estimated that the use of angiotensin converting enzyme inhibitors in microalbuminuric IDDM will save 5200 Pounds-11,000 Pounds per year of life saved. Angiotensin converting enzyme inhibitors are not free of side-effects, and it is therefore essential, given the intrinsic variability of the albumin excretion rate, and the regression to normoalbuminuria of a significant proportion of patients, to confirm the diagnosis of microalbuminuria by repeated measurements prior to the commencement of treatment. The value of intensive glycaemic control is unproven, and further prospective studies are required. There are no proven therapies for the prevention of macrovascular disease in IDDM, although the value of cessation of smoking and aggressive blood pressure control are undoubted in the non-diabetic population. Controversy persists about the value of lipid lowering therapy, especially in young patients, although even in this group there is an increased risk of cardiovascular disease. Microalbuminuria is the strongest known predictor of cardiovascular disease in NIDDM; in contrast to the situation in the non-diabetic population, active lipid lowering therapy is not of proven cardiac benefit, but intervention seems justifiable when taken in the context of the very high prevalence of cardiovascular disease. Microalbuminuria is also predictive of end stage renal disease in NIDDM. Although intervention with angiotensin converting enzyme inhibitors has not been proven to prevent end stage renal disease, stabilisation of albumin excretion rate and creatinine clearance have been demonstrated in normotensive NIDDM, and it seems likely that longer term follow-up studies will confirm the benefit of angiotensin converting enzyme inhibitors in the prevention of end-stage renal disease. The observed predictive power of microalbuminuria as regards both cardiac and renal risk in NIDDM when considered in conjunction with the preliminary results of the benefits of angiotensin converting enzyme inhibition lend further support to the employment of microalbuminuria screening in NIDDM.
 ...
PMID:Microalbuminuria: a marker to increased renal and cardiovascular risk in diabetes mellitus. 950 84

The aim of this study is the assessment of the association of human angiotensin-converting enzyme gene I/D polymorphism with type 2 diabetes in 155 diabetic patients and 139 healthy individuals. These polymorphism were studied using polymerase chain reaction. Angiotensin converting enzyme gene DD genotype associated with type 2 diabetes in overweight and obese patients and patients with normal total plasma cholesterol. There is also association of DD genotype with arterial hypertension and with myocardial infarction in type 2 diabetic patients.
 ...
PMID:[Angiotensin converting enzyme gene polymorphism in type 2 diabetes mellitus]. 1094 1

Both diabetic and prediabetic patients have abnormal vascular reactivity and should be considered to have occult cardiovascular disease. Angiotensin-converting-enzyme (ACE) inhibitors are particularly beneficial in diabetes because they reduce the incidence of both cardiovascular events and diabetes-related complications. In prediabetic patients, ACE inhibitors also reduce the risk of a new diagnosis of type 2 diabetes. Managing hypertension is even more beneficial for diabetic patients than for nondiabetic patients. To further reduce the risk of heart disease in patients with diabetes or prediabetes, dyslipidemia should also be treated aggressively.
 ...
PMID:In diabetes, treat hidden heart disease. 1110 30

Uncontrolled hypertension leads to an increased risk of cardiovascular disease and stroke. Hypertensive patients with concomitant type 2 diabetes are at even greater risk of cardiovascular complications; also, this high-risk patient population is at increased risk of renal disease and, ultimately, renal failure. Prospective morbidity and mortality trials have demonstrated that tight blood pressure control improves the cardiovascular prognosis and provides target organ protection. Current treatment guidelines recommend a target blood pressure of < 130/85 mm Hg for patients with hypertension and diabetes. Angiotensin II (A-II), a major component of the renin-angiotensin system, plays an essential role in the pathophysiology of hypertension and diabetes-related renal disease. Currently, the treatment of choice for hypertensive patients with diabetes is angiotensin-converting enzyme (ACE) inhibition, but most of the data are limited to patients with type 1 diabetes. Although ACE inhibition is clearly a mechanism for blocking A-II formation, inhibition at this site may not be complete, as alternate pathways exist for A-II formation. Thus, for interrupting the renin-angiotensin system, A-II receptor antagonists theoretically provide advantages over ACE inhibitors in that they directly inhibit A-II by binding to the AT(1) receptor subtype. The objectives of this review are to: 1) provide an overview of the associated risk of cardiovascular complications with concomitant hypertension and diabetes; 2) demonstrate the cardiovascular benefits of effective blood pressure control in this patient population; 3) review the current treatment guidelines for managing high-risk hypertensive patients; and 4) discuss major, ongoing clinical studies with A-II receptor antagonists in patients with concomitant hypertension, type 2 diabetes, and renal disease. (c)2001 Le Jacq Communications, Inc.
 ...
PMID:Management of high-risk hypertensive patients with diabetes: potential role of angiotensin II receptor antagonists. 1149 50

Proteinuria is the hallmark of renal disease and proteinuria exceeding 1 gm a day in patients with renal disease augers a poorer prognosis. Proteinuria has been shown to be tubulotoxic and directly contributes to renal deterioration. Patients with non-selective proteinuria are more likely to have progressive renal disease. Diabetic patients with persistent microhaematuria have about 20 times the risk of developing diabetic nephropathy. In essential hypertension, the onset of de novo proteinuria after years of adequate BP control is a marker of subsequent decline in renal function. In glomerulonephritis, more severe proteinuria is associated with faster rate of progression. Even though the initial phase of proteinuria in patients with glomerulonephritis is usually of immunological origin, in the vast majority of patients with established disease, the latter progressive phase of proteinuric glomerulopathy is the result of glomerular hyperfiltration which shifts glomerular non-selective pores to larger dimensions resulting in excessive leakage of protein in the urine. Endothelial injury resulting from glomerular hyperfiltration causes increase in local generation of Angiotensin II in the kidney as part of the hemodynamic response. ACE inhibitors and angiotensin II receptor antagonists (ATRA) can improve glomerular pore-selectivity by remodelling the glomerular basement membrane. In addition, these agents also have beneficial effects by decreasing TGF-beta production therapy decreasing mesangial cell proliferation, hence ameliorating disease progression in patients with diabetic nephropathy and IgA nephropathy. A number of recent clinical trials have shown that ACEI and ATRA therapy can retard the progression of renal deterioration in patients with NIDDM and those with IgA nephropathy and even restore normal renal function in those with mild renal impairment. Treatment and control of proteinuria in patients with renal disease should be regarded as important as treatment of hypertension as it can prevent renal failure.
 ...
PMID:Proteinuria: clinical signficance and basis for therapy. 1176 58

Nephropathy associated with type 2 diabetes mellitus is a rising cause of end-stage renal disease and is a major public health problem. If blocking of the renin angiotensin system has a well established nephroprotective effect in type 1 diabetic nephropathy, this remained to be shown for type 2 diabetes. Two large outcome trials using angiotensin II receptor antagonists (ARA's) in proteinuric chronic renal impairment and hypertensive type 2 diabetic patients have now closed this gap: the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with Angiotensin II Antagonist Losartan (RENAAL) trial. Both trials showed a significant reduction in the primary pre-specified end-point of death, or worsening of renal function (doubling of serum creatinine) or the development of end-stage renal disease. This effect goes beyond the reduction in blood pressure and makes of ARA's one of the important tools in the treatment of type 2 diabetic nephropathy.
 ...
PMID:[Clinical study of the month. Nephroprotective role of angiotensin II receptor antagonists in type 2 diabetes: results of the IDNT and RENAAL trials]. 1176 85

The Reduction in End Points in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and the Irbesartan Diabetic Nephropathy Trial (IDNT) are two recently reported trials with hard end points, conducted in patients in advanced stages of diabetic nephropathy. Two other studies--the Irbesartan Microalbuminuria Study (IRMA)-2 and the Microalbuminuria Reduction with Valsartan study (MARVAL)--were trials conducted in patients with type 2 diabetes with microalbuminuria, a cardiovascular risk factor associated with early-stage diabetic nephropathy. These trials all had a common theme--that is, does an angiotensin receptor blocker (ARB) interfere with the natural history of diabetic nephropathy in a blood pressure-independent fashion? Without question, the results of these trials legitimatize the use of the ARB class in forestalling the deterioration in renal function, which is almost inevitable in the patient with untreated diabetic nephropathy. These data can now be added to the vast array of evidence supporting angiotensin-converting enzyme (ACE) inhibitor use in patients with nephropathy associated with type 1 diabetes. It now appears a safe conclusion that the patient with diabetic nephropathy should receive therapy with an agent that interrupts the renin-angiotensin system. These studies have not resolved the question as to whether an ACE inhibitor or an ARB is the preferred agent in people with nephropathy from type 1 diabetes, though the optimal doses of these drugs remain to be determined. Head-to-head studies comparing ACE inhibitors to ARBs in diabetic nephropathy are not likely to occur, so it is unlikely that comparable information will be forthcoming with ACE inhibitors. An evidence-based therapeutic approach derived from these trials would argue for ARBs to be the foundation of therapy in the patient with type 2 diabetes and nephropathy.
 ...
PMID:Type 2 diabetes: RENAAL and IDNT--the emergence of new treatment options. 1182 41


1 2 3 4 5 6 7 8 9 10 Next >>