Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetics without a prior myocardial infarction have the same risk of a future myocardial infarction as nondiabetics with a prior myocardial infarction; however, epidemiologic studies suggest that lower blood pressure treatment goals may have potential benefit for diabetics with hypertension. Low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and dihydropyridine calcium antagonists have reduced cardiovascular events in patients with diabetes. Angiotensin receptor blockers with diabetic renal disease have reduced the rate of end-stage renal disease, whereas dihydropyridine calcium antagonists show no benefit. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers reduce overall mortality, cardiovascular events, and the development of the overt nephropathy in high-risk patients with diabetes without advanced renal disease. The blood pressure treatment goal for patients with diabetes without macroalbuminuria is less than 130/80 mm Hg and less than 125/75 mm Hg for patients with diabetes and nephrotic syndrome. To achieve these goals, multiple antihypertensive drugs are required.
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PMID:Diabetes mellitus and hypertension: a mandate for intense treatment according to new guidelines. 1297 21

The Maillard reaction involves the non enzymatic combination of carbohydrates such as glucose with protein aminogroups to yield schiff bases and Amadori protein adducts evolving into irreversible advanced glycation end products (AGEs). This phenomenon, part of normal ageing, is accelerated in diabetes, as a result of hyperglycaemia, and in renal failure, as a consequence of the accumulation of reactive carbonyl compounds (RCOs). AGEs and RCOs are implicated in uraemic toxicity both at the biochemical and the clinical level (dialysis amyloidosis, atherosclerosis, alterations of peritoneal membrane permeability). Reduction of plasma AGEs and RCOs is an interesting avenue to reduce uraemic toxicity. Therapeutic strategies involve dialysis technique (haemodialysis membranes, daily haemodialysis, ultrapure dialysate, RCO free peritoneal dialysate) as well as drugs inhibiting AGE formation (aminoguanidine and the less toxic angiotensin converting enzyme inhibitors or angiotensin receptor blockers).
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PMID:Advanced glycation in uraemic toxicity. 1455 90

Type 2 diabetes is an ever-growing problem worldwide. Approximately 40% of the patients with type 2 diabetes will develop diabetic kidney disease. In the United States, diabetes has become the most common single cause of endstage renal disease defined by the need for dialysis or transplantation. Patients with type 2 diabetes and diabetic nephropathy have a dramatically increased cardiovascular risk. The Irbesartan Diabetic Nephropathy Trial was designed to determine whether the use of irbesartan or a calcium channel blocker would provide protection against the progression of nephropathy due to type 2 diabetes beyond that attributable to the lowering of blood pressure. In that study, 1715 hypertensive patients with nephropathy due to type 2 diabetes were randomly assigned to irbesartan 300 mg/day or amlodipine 10 mg/day, or placebo. All patients randomized in this trial had more than 900 mg of protein in their urine and serum creatinines between 1.0 mg/dl and 3.0 mg/dl. The target blood pressure was 135/85 mmHg or less in all groups. The primary outcome was time to a combined endpoint of doubling of their baseline serum creatinine concentration, the development of endstage renal disease, or death from any cause. The mean duration of follow-up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite endpoint that was 20% lower than that in the placebo group ( P = 0.02) and 23% lower than that in the amlodipine group ( P = 0.006). The risk of doubling of the serum creatinine concentration was 33% lower in the irbesartan group than in the placebo group ( P = 0.003) and 37% lower in the irbesartan group than in the amlodipine group ( P < 0.001). Treatment with irbesartan was associated with a relative risk of endstage renal disease that was 23% lower than that in both other groups. These differences were not accounted for by differences in the blood pressures that were achieved. Proteinuria was reduced on average by 33% in the irbesartan group as compared with 6% in the amlodipine group and 10% in the placebo group. The angiotensin II receptor blocker irbesartan was shown to be effective in protecting against the progression of nephropathy due to type 2 diabetes. In a study done in patients with type 2 diabetes and early nephropathy as manifested by microalbuminuria, 590 hypertensive patients with type 2 diabetes and microalbuminuria were randomized to receive either irbesartan 150 mg/day or irbesartan 300 mg/day and followed for 2 years. The primary outcome in that trial was the time to the onset of diabetic nephropathy, defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was more than 200 mg/min or at least 30% higher than the baseline level. The irbesartan 150 mg/day group demonstrated a 39% relative risk reduction versus the control group in the development of overt proteinuria. The irbesartan 300 mg/day group demonstrated a highly significant 70% risk reduction versus the control group ( P < 0.001). The albumin excretion rate was reduced in the two irbesartan groups throughout the study (-11% and -38% at 24 months compared with baseline in the irbesartan 150-mg and 300-mg groups, respectively). The albumin excretion rate remained unchanged in the control group. Irbesartan was demonstrated in the above study to be renoprotective, independent of its blood pressure-lowering effect, in patients with type 2 diabetes and microalbuminuria. Thus, irbesartan, an angiotensin receptor blocker, was demonstrated to be significantly renoprotective in patients with type 2 diabetes with either early nephropathy (microalbuminuria) or late nephropathy (proteinuria). The renoprotective effects of irbesartan were above and beyond the effects irbesartan had on systemic blood pressure. Patients with type 2 diabetes and either early or late diabetic nephropathy should be treated with the angiotensin II receptor blocker irbesartan.
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PMID:Treatment of diabetic nephropathy with angiotensin II receptor antagonist. 1458 37

Authors based on studies fullfiling the principles of evidence based medicine review the efficiency and benefits of angiotensin receptor blocking agents in congestive heart failure and hypertension. Special attention is focused on their application in diabetes mellitus. The data support efficacy, good tolerability, beneficial side effect profile as well as cardio- and renoprotective properties of these drugs. Their safety in diabetic as well as and in non-diabetic persons can be underlined.
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PMID:[Cardiologic and diabetologic aspects of therapy with angiotensin receptor blocking agents]. 1459 24

There is a worldwide epidemic of type 2 diabetes, with numbers predicted to reach over 210 million by the year 2010. Important risk factors for type 2 diabetes are obesity, physical inactivity and dietary factors. Recent evidence shows that type 2 diabetes can certainly be delayed, and possibly prevented, by intensive lifestyle intervention, and therapies including acarbose, metformin, orlistat and the glitazones in selected populations. However, the UK has not had a successful record in trials which aim to prevent diabetes, and therefore implementation of effective and successful intensive lifestyle intervention to prevent diabetes may prove difficult in the UK. Other 'non-glucose lowering' agents, such as statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, may have a role to play in the prevention of diabetes.
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PMID:The prevention of type 2 diabetes mellitus. 1470 48

Some hypertension treatment guidelines published in the late 1990's recommended that diuretics and betha-blockers be used as 1st line drugs for treating uncomplicated hypertension, reserving new antihypertensive drugs for special indications. This recommendation is predicated on the fact that large trials showing cardiovascular protection with antihypertensive drugs used betha-blockers and diuretics. Other guidelines suggested all antihypertensives are equal and that drug selection should be individualized. These disparate guidelines arise from the controversy over "are all antihypertensives created equal?" Since these guidelines, many large hypertension trials have been conducted. This paper will review the recent hypertension trials, the meta-analyses of some of these trials, highlight some of the flaws inherent in the trials that making interpretation difficult, and finally outline a rationale approach to initial treatment of the uncomplicated hypertensive patient. It will provide a rationale for 1) using diuretic and not beth-blocker as the 1st line agent in treating uncomplicated hypertension, 2) switching to an angiotensin converting enzyme inhibitor or angiotensin receptor blocker should side effects occur on diuretic, 3) reserving calcium channel blocker, betha-blocker, and alpha-blocker for 2nd or 3(rd) line therapy, 4) employing a diuretic in combination with any other antihypertensive class, and 5) considering use of lower doses of 2 or more antihypertensives to limit side effects while optimizing blood pressure control. If the incidence of de novo diabetes is indeed higher with diuretics and cost-analysis confirm long-term savings with using a more expensive but less diabetogenic drug to treat hypertension, then the recommendation may shift to using an antihypertensive that acts on the renin-angiotensin axis.
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PMID:Initial therapy for uncomplicated hypertension: insights from the alphabetic maze of recent studies. 1460 87

The development of new-onset diabetes is frequent during the follow-up of treated hypertensive patients. The prevalence of such an event seems to differ depending on the type of antihypertensive therapy used to control blood pressure. Diuretics and b-blockers and their association are particularly harmful in this regard. On the contrary, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, alone or in association with diuretics, are associated with a lower prevalence of this metabolic complication. These statements are confirmed by data from the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study. Long-term studies are required to determine the relevance of development of new-onset diabetes in treated hypertensive patients.
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PMID:New-onset diabetes and antihypertensive therapy: comments on ALLHAT trial. 1460 21

During the past decade, the incidence of end-stage renal disease (ESRD) has risen dramatically, primarily due to an increase in the incidence of diabetes. In patients with diabetes, both hyperglycemia and hypertension are independent risk factors for renal disease. Hypertension is also a risk factor in nondiabetic renal disease and contributes to renal dysfunction by increasing glomerular pressure, glomerular capillary damage, and proteinuria. The resultant nephron damage increases glomerular pressure and damage within remnant functional nephrons, further contributing to deterioration of renal function. In addition to its role in systemic hypertension, angiotensin II has direct effects on the kidney through elevation of glomerular capillary pressure and upregulation of components of the renal injury response. These direct effects of angiotensin II on the kidney support the inclusion of agents that target the renin-angiotensin system (RAS) into treatment regimens for patients at risk for renal disease. Several clinical trials have established the benefits of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with diabetes. The ACE inhibitors have been shown to delay renal decline in patients with type 1 diabetes, whereas the renoprotective effect of these agents in patients with type 2 diabetes is less clear. The ARBs have been shown to provide significant benefits in patients with type 2 diabetes, both at early (microalbuminuria) and late (proteinuria) stages of renal decline. In the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, ARB therapy significantly reduced the progression of overt nephropathy (composite of doubling of serum creatinine, ESRD, and death), a benefit that has not been shown for ACE inhibitors. Moreover, in RENAAL, losartan significantly reduced the incidence of the individual end point of ESRD. The benefits of ARB therapy in IDNT and RENAAL were associated with significant reductions in proteinuria and were independent of blood pressure reductions. In RENAAL, proteinuria was a strong predictor of both renal and cardiovascular events. These findings underscore the importance of RAS blockade as a strategy for improving clinical outcomes in patients with renal disease.
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PMID:Recommendations for the management of special populations: renal disease in diabetes. 1462 61

This study examined whether pulse pressure (PP) could be an independent predictor and associated with severity of peripheral vascular disease (PVD) in 396 type 2 diabetic patients (143 men and 253 women, aged 64.1 +/- 11.2 years). Peripheral vascular disease was diagnosed by an ankle-brachial index (ABI) < 0.90 and as severe PVD if ABI < 0.80. Association was evaluated before and after adjustment for age, sex, diabetes duration, hypertension, smoking, fasting plasma glucose (FPG), total cholesterol (TC), usage of insulin, and usage of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB); and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), respectively. Results showed that PP increased from no (n = 348) to mild (n = 25) and severe (n = 23) PVD (one-way ANOVA, p < 0.001; multiple comparisons, p < 0.05 for any two groups). The PP increase from no to mild PVD was due to SBP increase; while further increase to severe PVD was due to both DBP drop and an even higher SBP. Adjusted odds ratio (AOR) for PVD for every 1-mmHg PP increment was 1.035 (1.012-1.058). When PP was categorized as tertiles (< 50, 50-59 and > or = 60 mmHg), respective AOR for PVD for second and third vs. first tertile was 2.605 (1.008-6.729) and 2.835 (1.123-7.156). Pulse pressure was also predictive for ABI independent of the effects of the confounders and the other parameters of blood pressure. In conclusion, PP was an independent predictor and correlated with severity of PVD in type 2 diabetic patients.
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PMID:Pulse pressure as a risk factor for peripheral vascular disease in type 2 diabetic patients. 1464 5

Hypertension, impaired renal function, and proteinuria are commonly associated to the presence of diabetes. They play a major role in the development of cardiovascular and renal damage. Effective antihypertensive treatment reduces the progression of diabetic nephropathy and improves cardiovascular prognosis. Accordingly, tight BP control (<130/80 mmHg) is currently recommended in diabetic patients. Achieving BP targets represents the most important determinant of cardiovascular and renal protection. However, it has been suggested that specific classes of antihypertensive drugs may exert additional organ protection beyond their BP control. The pharmacologic blockade of the renin-angiotensin-aldosterone system has been shown to convey greater renal and cardiovascular protection compared with other classes of drugs. In particular, studies focusing on renal end point suggest that angiotensin-converting enzyme inhibitors (ACEI) are the first-choice drugs in type 1 diabetes. Both ACEI and angiotensin II receptor blockers prevent the progression from microalbuminuria to clinical proteinuria in type 2 diabetes, but angiotensin blockers provide better renoprotection in patients with overt nephropathy. Regarding cardiovascular protection, several studies (but not all) have shown that ACEI exert a protective effect on diabetic patients. Recently, interesting results in favor of angiotensin receptor blockers have been reported in the IDNT, RENAAL, and LIFE studies. It should be noted that to achieve maximal renal and cardiovascular protection, most diabetic patients require integrated therapeutic intervention, including not only several antihypertensive drugs, but statins and antiplatelet therapy as well.
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PMID:Optimizing therapy in the diabetic patient with renal disease: antihypertensive treatment. 1468 64


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