Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiological connections between insulin resistance, hypertension and type 2 diabetes are discussed in this review article. Increased blood pressure levels are often found in type 2 diabetic patients long before the diabetes itself is diagnosed. By contrast, in type 1 diabetes hypertension is predominantly the consequence of diabetic glomerulopathy. Non-pharmacological strategies should be favoured in the treatment of hypertension in type 2 diabetic patients before specific pharmacological intervention is started. Antihypertensive treatment with beta-blocking agents and diuretics is criticized by many experts in the field of metabolic disorders, since these drugs induce a deterioration of glycaemic control and lipid metabolism in diabetic patients. Since calcium channel blockers, ACE inhibitors and alpha 1-specific blocking agents have no influence on metabolism, these drugs are recommended for the antihypertensive treatment of diabetic patients. Further studies should be undertaken to clarify, whether ACE-inhibitors have a specific nephroprotective effect. Since most type 2 diabetic patients do not develop diabetic nephropathy, a possible nephroprotective effect of ACE inhibitors is only relevant to the antihypertensive treatment of type 1 diabetic patients.
 ...
PMID:[Hypertension, insulin resistance and diabetes mellitus: pathophysiological interactions and therapeutic consequences]. 198 Jul 67

Hypertension is known to place the individual with IDDM at high risk for the development of both renal and cardiovascular disease. Recent data suggest that aggressive antihypertensive therapy (angiotensin I converting enzyme inhibitors, prazosin, and calcium channel blockers) have significantly improved overall prognosis and long-term survival for individuals with IDDM. Because in individuals with IDDM the development of both hypertension and renal disease has its roots in childhood, it is important that early and effective antihypertensive treatment begin there.
 ...
PMID:Hypertension in individuals with insulin-dependent diabetes mellitus. 841 12

The author describes the assessment of the effectiveness of antihypertensive drugs according to the T-P (Trough-Peak) ratio, i.e. the effect at the end of the dosage period to the effect during its peak after subtraction of the placebo effect. He draws attention to methodological difficulties which make it so far difficult to compare data from the literature. It is, however, advisable in clinical practice of the treatment of hypertension to assess the blood pressure at the end of the dosage period rather than during the peak of effectiveness, as frequently practiced. Drugs with a long biological half-life are particularly useful. The most important criterion of effectiveness of antihypertensives is, however, their effect on the cardiovascular and cerebrovascular mortality and morbidity. Only on diuretics and beta-blockers extensive data are available indicating that they lead to a decline of the morbidity and mortality. Therefore they should be the drugs of first choice, in particular in elderly hypertonics. Data on calcium channel blockers, in particular nifedipine are controversial. ACE inhibitors are suitable in heart failure, asymptomatic dysfunction after acute myocardial infarction and in type 1 diabetes mellitus. Only at present investigations are under way to assess whether the effect of new and more expensive antihypertensives on mortality and morbidity is greater than the effect of diuretics and beta-blockers and whether they will be suitable drugs of first choice.
 ...
PMID:[Evaluation of the effectiveness of antihypertensive therapy. Is the trough-peak ratio the determining factor?]. 868 81

Lisinopril, like other ACE inhibitors, lowers blood pressure and preserves renal function in hypertensive patients with non-insulin-dependent or insulin-dependent diabetes mellitus (NIDDM or IDDM) and early or overt nephropathy, without adversely affecting glycaemic control or lipid profiles. On available evidence, renoprotective effects appear to be greater with lisinopril than with comparator calcium channel blockers, diuretics and beta-blockers, despite similar antihypertensive efficacy. As shown by the EUCLID (EUrodiab Controlled trial of Lisinopril in Insulin-Dependent Diabetes) trial, lisinopril is also renoprotective in normotensive patients with IDDM and microalbuminuria. The effect in normotensive patients with normoalbuminuria was smaller than in those with microalbuminuria, and no conclusions can yet be made about its use in patients with normoalbuminuria. In complications other than nephropathy, lisinopril has shown some benefit. Progression to retinopathy was slowed during 2 years' lisinopril therapy in the EUCLID study. Although not yet fully published, these results provide the most convincing evidence to date for an effect of an ACE inhibitor in retinopathy. The drug may also improve neurological function, but this finding is preliminary. Lastly, post hoc analysis of the GISSI-3 trial indicates that lisinopril reduces 6-week mortality rates in diabetic patients when begun as early treatment after an acute myocardial infarction. The tolerability profile of lisinopril is typical of ACE inhibitors and appears to be similar in diabetic and nondiabetic individuals. Hypoglycaemia has occurred at a similar frequency with lisinopril and placebo, as shown in the EUCLID trial. In addition, the GISSI-3 study indicates that the incidence of persistent hypotension and renal dysfunction is increased with lisinopril in general, but the presence of diabetes does not appear to confer additional risk of these events in diabetic patients with acute myocardial infarction receiving lisinopril. In summary, lisinopril lowers blood pressure and produces a renoprotective effect in patients with IDDM and NIDDM without detriment to glycaemic control or lipid profiles. Like other ACE inhibitors, lisinopril should thus be viewed as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy in hypertensive diabetic patients with IDDM or NIDDM and microalbuminuria or overt renal disease. The EUCLID study, using lisinopril, provides new data supporting an additional place in managing normotensive patients with microalbuminuria and IDDM. These findings, together with some evidence for an effect of lisinopril in delaying progression of retinopathy and in reducing mortality, suggest a broader role for the drug in managing diabetic vascular complications.
 ...
PMID:Lisinopril. A review of its pharmacology and use in the management of the complications of diabetes mellitus. 917 32

Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) in the United States, and accounts for 35% of all the patients with ESRD entering a dialysis program; 63% of patients with diabetic nephropathy have type II diabetes mellitus. Hypertension is a major risk factor for renal disease and is common in people with diabetes mellitus. Strategies for preventing the progression of renal failure in patients with diabetes mellitus include glycemic control, and control of blood pressure. Blocking the renin-angiotensin system (RAS) slows the progression of established diabetic nephropathy in type I diabetes mellitus, and inhibiting angiotensin II formation retards or impedes the progression from microalbuminuria to established diabetic nephropathy (macroproteinuria) in people with type I diabetes mellitus. The situation could be the same for people with type II diabetes mellitus. The ability of RAS blockade using irbesartan, an AT1 angiotensin II receptor antagonist, to slow the progression in renal failure has been compared with that of the calcium channel blocker amlodipine and placebo in a pilot study. The results suggest that blockade of the RAS, in this case with irbesartan, is at least equivalent to calcium channel blockers with respect to antihypertensive efficacy, but provides better renoprotective benefits.
 ...
PMID:Renoprotection and renin-angiotensin system blockade in diabetes mellitus. 943 77

Cardiovascular complications are frequently present in insulin-dependent (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) patients and confer a very poor prognosis. In this overview we critically analyse the current literature with regard to the benefits and also the possible harms of the available pharmacological treatment strategies in these patients. To date, insulin is the only hypoglycaemic agent which has been proven both effective and safe in NIDDM patients with cardiovascular complications. Also, several trials indicate that treatment with oral hypoglycaemic agents may confer a substantial risk in such patients. Conventional antihypertensive treatment, including betablockers and diuretics, has been convincingly shown to reduce mortality and morbidity in diabetic nephropathy and in NIDDM patients. However, this may not be the case with newer antihypertensive agents, such as angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers. Likewise, convincing evidence is lacking that these newer antihypertensive agents provide meaningful clinical benefit when compared to the conventional treatment regarding slower progression of diabetic nephropathy or their impact on lipid and glucose metabolism. Cholesterol lowering therapy with statins and aspirin treatment have also been repeatedly shown to improve the prognosis of diabetic patients with coronary heart disease.
 ...
PMID:Pharmacological treatment of diabetic patients with cardiovascular complications. 962 54

Diabetic nephropathy has become the single most important cause of endstage renal failure in most countries of the Western world. Against this background, the role of the renin-angiotensin system (RAS) and its blockade command considerable interest. In diabetic patients and in diabetic animals, the circulating components of the RAS are suppressed. Although the evidence is not completely uniform, there are indirect arguments (renal hemodynamic response to RAS blockade, AT1 receptor expression), however, which would be consistent with increased intrarenal action of angiotensin (ANG) II. There is solid evidence that ACE inhibitors effectively interfere with progression of micro-albuminuria both in IDDM and NIDDM. They also prevent progression of advanced renal failure in IDDM, while there is only preliminary evidence in this respect for NIDDM. ACE inhibitors are superior to conventional antihypertensive agents (with the possible exception of some calcium channel blockers), but such superiority is seen only when the levels of blood pressure are relatively high. In diabetic animals, treatment with ANG II receptor blockers interferes with the development of glomerular lesions. In acute and subacute studies on diabetic patients, ANG II receptor blockers reduced albuminuria (or proteinuria) more than beta-blockers. Head-on comparison of equipotent doses ACE inhibitors and ANG II receptor blockers in non-diabetic patients produced equal reductions in proteinuria. The long-term effects of ANG II receptor blockers on progression of advanced diabetic nephropathy is the object of two large international studies. The results will not be available before the year 2000.
 ...
PMID:Diabetes--renal function--what are the special problems? 983 74

The aim of this study is to compare the efficacy of an angiotensin-converting enzyme inhibitor with a dihydropyridine calcium channel blocker in preventing progression to macroalbuminuria and/or a decline in renal function in normotensive patients with type 1 diabetes and microalbuminuria. Forty-two patients were randomized to treatment with either perindopril, slow-release nifedipine, or placebo. In the first 3 months, drug dosage was titrated to achieve a decrease in diastolic blood pressure of at least 5 mm HG: Thirty-three patients had a minimum of 24 months' data, and 25 patients were followed up beyond 36 months (mean, 67 +/- 4 months). Patients were studied every 3 months and at the end of the treatment period; those who remained normotensive discontinued therapy and were followed up for an additional 3 months. Baseline geometric mean albumin excretion rates (AERs) were as follows: perindopril, 66 microg/min; nifedipine, 59 microg/min; and placebo, 66 microg/min. During the first 3 years, 7 of the perindopril-treated but none of the placebo or nifedipine-treated patients reverted to normoalbuminuria (P < 0.01). Median AERs at 3 years of treatment in each group were 23 microg/min for perindopril, 122 microg/min for nifedipine, and 112 microg/min for placebo patients (P < 0.01). In patients with more than 3 years' follow-up, median AERs decreased by 45% in the first year and then stabilized in the perindopril group, but increased by 17.6% in the nifedipine group and 27.6% in the placebo group (P < 0.03) in the first year, then increased progressively. In these same patients, there was a significant decline in glomerular filtration rate in the nifedipine group (-7.8 +/- 1.8 mL/min/1.73 m(2)/y), but not in the other two groups (perindopril, -1.0 +/- 1.2 mL/min/1.73 m(2)/y; placebo, -1.3 +/- 1.1 mL/min/1.73 m(2)/y; P = 0.004). At the end of the study, cessation of treatment for 3 months was associated with a doubling of AERs in the perindopril-treated group, but no change in the other two groups (P < 0.001). In conclusion, long-term perindopril therapy is more effective than nifedipine or placebo in delaying the progression of diabetic nephropathy and reducing AER to the normoalbuminuric range (<20 microg/min) in normotensive patients with type 1 diabetes and microalbuminuria.
 ...
PMID:Long-term comparison between perindopril and nifedipine in normotensive patients with type 1 diabetes and microalbuminuria. 1132 69

In type 1 diabetes, hypertension is closely linked to the development of nephropathy. An association of hypertension and the impact of hypertension on the clinical course of type 2 diabetes, including the development of vascular complications, has been well established. However, the association with nephropathy in type 2 diabetes is less clear. Despite that, antihypertensive treatment has a crucial impact on the course of nephropathy in both types of diabetes. In this article, we discuss recent evidence focusing on the nephroprotective potential of various classes of antihypertensive agents and confront it with current recommendations for the treatment of hypertension in diabetic patients with nephropathy. Unlike type 1 diabetes, where the nephroprotection could be a good sole measure for assessing the efficiency of a particular agent or their combination, defining of the optimal antihypertensive agent or agents in type 2 diabetes requires consideration of both cardiovascular, cerebrovascular, and nephroprotective potentials of such a treatment. In both types of diabetes, recent data support the use of inhibitors of the renin-angiotensin system with or without diuretics as the initial therapy. In type 1 diabetes, additional beneficial effect can be expected from calcium channel blockers (CCBs). In type 2 diabetic patients, combining more agents may be necessary early in the course of nephropathy to affect both micro- and macrovascular targets. beta blockers should be applied early to enhance cardioprotectivity, followed by CCBs to achieve goal blood pressure. Although not supported by all recent data, aggressive blood pressure control (< 130/75 mm Hg) is warranted. Furthermore, multifactorial intervention targeting metabolic derangements and lifestyle, is a necessary complimentary measure that must accompany antihypertensive treatment.
 ...
PMID:Treatment of hypertension in diabetic patients with nephropathy. 1264 7

Diabetic nephropathy is one of the most frequent causes of end-stage renal disease (ESRD), and, in recent years, the number of diabetic patients entering renal replacement therapy has dramatically increased. The magnitude of the problem has led to numerous efforts to identify preventive and therapeutic strategies. In normoalbuminuric patients, optimal glycemic control (HbA(1c) lower than 7.5%) plays a fundamental role in the primary prevention of ESRD [weighted mean relative risk reduction (RRR) approximately 37% for metabolic control versus trivial renoprotection for intensive anti-hypertensive therapy or ACE-inhibitors (ACE-I)]. In the microalbuminuric stage, strict glycemic control probably reduces the incidence of overt nephropathy (weighted mean RRR approximately 50%), while blood pressure levels below 130/80 mmHg are recommended according to the average blood pressure levels obtained in various studies. In normotensive patients, ACE-I markedly reduce the development of overt nephropathy almost regardless of blood pressure levels; in hypertensive patients, ACE-I are less clearly active (weighted mean RRR approximately 23% versus other drugs), whereas angiotensin-receptor blockers (ARB) appear strikingly renoprotective. Once overt proteinuria appears, it is uncertain whether glycemic control affects the progression of nephropathy. In type 1 diabetes, various anti-hypertensive treatments, mainly ACE-I, are effective in slowing down the progression of nephropathy; in type 2 diabetes, two recent studies demonstrate that ARB are superior to conventional therapy or calcium channel blockers (CCB). In clinical practice, pharmacological tools are not always used to the best benefit of the patients. Therefore, clinicians and patients need to be educated regarding the renoprotection of drugs inhibiting the renin-angiotensin system (RAS) and the overwhelming importance of achieving target blood pressure.
 ...
PMID:Treatment of diabetic nephropathy in its early stages. 1267 78


1 2 Next >>