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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate whether a combined treatment of ACE inhibitor and exercise training is more effective than either treatment alone in alleviating the insulin resistant states in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type 2 diabetes. OLETF rats (25 weeks old) were randomly divided into 5 groups; sedentary control, exercise-trained, temocapril (ACE inhibitor; 2 mg/kg/day)-treated, with and without exercise, and losartan (AT1 receptor antagonist; 1 mg/kg/day)-treated. Long-Evans Tokushima Otsuka rats were used as a non-diabetic control. Body weight, the amount of abdominal fat and blood pressure were higher for OLETF rats than for control rats. However, glucose infusion rate (GIR), an index of insulin resistance, was decreased greatly in OLETF rats. The fasting levels of blood glucose, insulin and lipids were also increased in the diabetic strain. In OLETF rats, both temocapril and losartan reversed hypertensive states significantly, whereas GIR and hyperlipidemia were improved when rats were treated with ACE inhibitors, but not with the AT1 receptor antagonist. Exercise training decreased body weight and the amount of abdominal fat, and also increased GIR in parallel with improved dislipidemia. The combination of the ACE inhibitor with exercise training also improved obesity, hyperinsulinemia, dislipidemia and fasting level of blood glucose, and this combination resulted in the greatest improvement of insulin resistance. These results suggest that the combination of ACE inhibitor and exercise training may be a beneficial treatment for mixed diabetic and hypertensive conditions.
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PMID:Combined effect of ACE inhibitor and exercise training on insulin resistance in type 2 diabetic rats. 1200 25

In an attempt to examine the role of an ACE gene insertion/deletion (I/D) polymorphism in type 2 diabetes, we conducted a case-control association study among 132 couple-pairs from northern China. The genotype frequencies for II, ID, and DD were 39.8, 39.8, and 20.3%, respectively, in the case group and 44.8, 44.8, and 10.4% in the control group. The DD frequency was significantly higher in the case group than in the control group (chi(2)(1) = 4.77, P = 0.03), suggesting that the DD genotype is associated with an increased susceptibility to type 2 diabetes in our study population.
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PMID:Insertion/deletion polymorphism of the ACE gene is associated with type 2 diabetes. 1203 90

Impaired renal function occurs in about 50% of patients suffering from type 2 diabetes, and diabetic nephropathy has become the leading cause of endstage renal disease. Reduction of blood pressure to levels around 120/80 mmHg is one of the most effective way to slow progression of diabetic nephropathy. Recent meta-analyses, however, have emphasized on the fact that ACE inhibitors (ACEI) and non-dihydropyridine calcium channel blockers (NDHP-CCB) exert nephro-protective effects which go beyond the effect of blood pressure reduction. This has lately been confirmed by a prospective trial in comparison to the betablocker atenolol. Based on these data, demographics of the Swiss population, literature data on mortality rates of type 2 diabetics with impaired renal function and studies on true costs of antihypertensives, we calculated the costs of a longterm intervention (20 years) with antihypertensives in 3536 middle-aged Swiss patients with type 2 diabetes and macro-albuminuria whose antihypertensive regimen was based either on the ACEI lisinopril, or the ND-HP-CCB verapamil, or the betablocker atenolol. Under atenolol, acquisition costs were lowest, whereas faster loss of renal function over time increased mortality rate and thus reduced the number of patients to be treated. Nevertheless, due to the fact that patients reached uremia and had to be dialyzed, 20 years of atenolol-based regimen with costs of 316 millions of Swiss francs turned out to be much more expensive than the lisinopril- or the verapamil-based regimen with 121 and 38 millions of Swiss francs, respectively. Thus, low acquisition cost is not necessarily the only important determinant of overall costs of drug therapy.
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PMID:[Medicamentous kidney protection in type 2 diabetic patients--is cheaper also more economical? A model calculation for Swiss health care]. 1207 Oct 84

Both ACE inhibitors (ACEI) and angiotensin receptor blockers (ARB) are renoprotective beyond their effects on blood pressure (BP), but their widespread use is limited by their tendency to provoke hyperkalemia. The comparative effects of ACEI and ARB on potassium handling have not been investigated. The objective of this study was to determine whether there are differences in dynamic renal potassium handling between ACEI and ARB in response to an oral potassium challenge. This was a randomized crossover study of candesartan versus lisinopril titrated to control BP followed by an inpatient study of renal potassium handling in 24 hypertensive patients with type II diabetes mellitus (DMII) and preserved renal function. Following an oral potassium challenge (0.75 mmol/kg), differences in hourly serum K (mmol/L), rate of urinary potassium excretion (UkV, micromol/min), and fractional excretion of potassium (FEK) were assessed by repeated-measures ANOVA. Hourly UkV(p = .45) and FEK (p = .19) were similar for candesartan and lisinopril, although FEK at 2 hours for candesartan tended to exceed that for lisinopril (.34 [.04] vs. .26 [.03]) and approached significance (p = .096). UkVfor candesartan at hour 2 was 177 (26) and 121 (21) for lisinopril and also approached significance (p = .10). Serial serum potassium did not differ (p = .70). No statistical differences were discovered in renal potassium handling between candesartan and lisinopril in patients with DMII and preserved renal function. Whether there are differences between the drug classes in renal impairment remains to be determined.
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PMID:Comparative effects on dynamic renal potassium excretion of ACE inhibition versus angiotensin receptor blockade in hypertensive patients with type II diabetes mellitus. 1209 42

In the 1970s and 1980s it became evident that progression of renal disease and blood pressure are correlated. Subsequently, it was shown that antihypertensive treatment, especially with agents that block the renin-angiotensin system (RAS), could slow the progression of diabetic renal disease. Several studies, particularly with RAS blockers, have confirmed beneficial effects on urinary albumin excretion in patients with diabetes and microalbuminuria or proteinuria. There are good reasons to explore dual blockade of the RAS with an AT(1)-receptor blocker and an ACE inhibitor. Receptor blockers may block the effects of angiotensin II more effectively than ACE inhibitors; moreover, ACE inhibitors increase bradykinins which may have positive effects on blood pressure and renal function. Such combination treatment has been found to be well tolerated and more effective in reducing blood pressure than either monotherapy. Positive effects on microalbuminuria or proteinuria have also been noted. Studies have shown that treatment with AT(1)-receptor blockers postpones end-stage renal disease and reduces the rate of decline in glomerular filtration rate (GFR) in patients with type 2 diabetes and nephropathy. Moreover, albuminuria was reduced to a greater extent with AT(1)-receptor blockers than with conventional antihypertensive therapy producing the same blood pressure reductions. In summary, AT(1)-receptor blockers are effective in all stages of diabetic renal disease, and have an excellent tolerability profile. Usually the side-effect profile is comparable with placebo. In certain situations, there may be a slight, readily reversible, increase in serum potassium. There may also be a slight reduction in GFR, reflecting a decrease in glomerular filtration pressure.
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PMID:The reno-protective role of AT(1)-receptor blockers. 1214 Jul 29

Diabetic nephropathy is one of the major causes of end-stage renal disease and is often associated with other macrovascular complications such as ischemic heart disease and peripheral vascular disease. Angiotensin converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (AIIR) have both been shown to have a protective effect on the progression of diabetic nephropathy and have thus become the first choice for treatment of hypertension and/or renal involvement in patients with diabetes. However, most of these patients, especially those with type 2 diabetes, require two of more medications in order to reduce their blood pressure to the levels, which have been proposed in recently published consensus papers. These target blood pressure levels are 130/80 mm Hg in diabetic subjects with proteinuria of up to 1 g/day and 125/75 mm Hg in those with proteinuria in excess of 1 g/day. Combinations of different medications may have a synergistic effect. Some of the early studies using a combination of either a nondihydropyridine or a dihydropyridine calcium channel blocker with ACE-I demonstrated a synergistic effect on proteinuria in patients with diabetic nephropathy. However, these studies have not been substantiated, but calcium channel blockers, with their proven ability to reduce blood pressure, play an important role in the treatment of patients with diabetic nephropathy and hypertension. The combination of ACE-I with AIIR may have several theoretical advantages. Many studies using this combination have been performed in animal models of diabetes and in patients with diabetic and nondiabetic renal disease. Some of these studies have demonstrated a synergistic effect of the combination on proteinuria or hypertension, but the results have not been consistent in all studies. It may be concluded that, until additional studies provide more convincing evidence, this combination could be used in patients whose proteinuria or hypertension has not responded to either one of the agents as monotherapy or to a combination of other medications.
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PMID:Combination antihypertensive therapy in the treatment of diabetic nephropathy. 1216 70

Evidence suggests that ACE inhibitors can be advantageous for prevention and halting progression of both micro- and macrovascular complications in patients with diabetes mellitus. ACE inhibitors are useful antihypertensive agents in both type 1 and type 2 diabetes; however, ACE inhibitor therapy often needs to be supplemented with calcium channel antagonists, beta-blockers or diuretics to achieve good blood pressure control. ACE inhibitors are also indicated in non-hypertensive patients with type 1 and type 2 diabetes who have micro- or macroalbuminuria. The effect of ACE inhibitors in halting the development and progression of retinopathy and, potentially, neuropathy needs further proof in large-scale studies. More recently, angiotensin II receptor antagonists are emerging as drugs with the potential to be successfully included in the management of diabetic complications, especially when ACE inhibitors are not suitable because of adverse effects.
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PMID:The role of angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists in the management of diabetic complications. 1226 46

Diabetes has become the most common single cause of end-stage renal disease in many countries. The coexistence of diabetes mellitus and hypertension dramatically increases the risk of developing target organ complications including renal disease. There are good arguments that ESRD in the patient with diabetes is largely preventable with the interventions currently available. For type 2 diabetes the UK Prospective Diabetes Study Group Trial clearly documented that the frequency of microangiopathic sequelae can be diminished by glycaemic control and even more impressively by intensified antihypertensive treatment. An analysis of recent randomized long-term clinical trials that evaluated the rate of decline in renal function demonstrated that the lower the blood pressure within the range of normotensive values, the greater the preservation of renal function. Since the 1994 Working Group Report on Hypertension and Diabetes suggested a goal blood pressure of 130/80 mmHg should be achieved in patients with diabetes and/or renal insufficiency; lower blood pressure levels, i.e. less than 125/75 mmHg are recommended for patients with proteinuria > 1 g/d and renal insufficiency regardless of etiology. Antihypertensive regimens should include an ACE inhibitor or an AT1-receptor blocker in order to provide maximum renal benefits in diabetic and non-diabetic renal diseases. Such low blood pressure are virtually impossible to achieve with monotherapy. In most cases the combination of two and more antihypertensive drugs is necessary. The purpose of this report is to update the previous recommendations with a focus on level of blood pressure control, proteinuria reduction and retarding the progression of renal disease.
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PMID:[Nephrology update. Kidney protection with antihypertensive drugs: I]. 1237 Oct 82

Microalbuminuria (MA) i.e. slightly elevated albumin excretion in the urine, is now considered to be an atherosclerotic risk factor. MA predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. Although microalbuminuria is associated with a certain degree of sub-clinical artherosclerotic damage, it is not known how early in the atherosclerotic process microalbuminuria appears. Epidemiological studies have shown an association between MA and insulin resistance, obesity, salt sensitivity and dyslipidaemia in patients with essential hypertension and diabetes. Patients with microalbuminuria are also characterised by an increased prevalence of left ventricular hypertrophy and retinal microvascular lesions. Microalbuminuria, is associated with an excess of other cardiovascular risk factors. The mechanisms linking microalbuminuria and risk for cardiovascular disease are not fully understood, but in subjects at risk it may be related to increased transvascular leakiness of albumin in systemic as well as renal vessels. A recent concept is that microalbuminuria is a marker of extensive endothelial dysfunction or generalised vasculopathy, which may lead to heightened atherogenic states. One possible explanation is that endothelial dysfunction might promote increased penetration of atherogenic lipoprotein particles in the arterial wall, but glycaemic status, insulin resistance, procoagulant state and adhesion molecules have all been implicated in the pathogenesis. Current evidence suggests that tight blood pressure control may reduce the risk of microalbuminuria in diabetic patients with hypertension and that inhibitors of the rennin-angiotensin system (RAS) can prevent or delay the progression of microalbuminuria to overt nephropathy in normotensive persons. ACE inhibitors are currently recognised as first-line antihypertensive therapy in diabetic patients with proteinuria, and these agents afford unique benefits in modifying the progression and severity of cardiovascular disease (CVD) as well as of diabetic nephropathy. Whether albuminuria is a risk factor or just a marker for CV disease, it identifies the high-risk diabetic patient who should be targeted for early, aggressive intervention against proven risk factors. If persistent microalbuminuria is confirmed, strict blood pressure control with added RAS inhibition should be pursued in an attempt to stabilise or even reduce microalbuminuria, preserve kidney function and possibly improve cardiovascular risk.
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PMID:The link between microalbuminuria, endothelial dysfunction and cardiovascular disease in diabetes. 1238 63

Type 2 diabetes is the leading cause of end-stage renal disease (ESRD) in most industrialized countries in Europe. The RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) Study evaluated the renal protective effects of losartan versus placebo on a background of non-ACE-I/non-AIIA conventional antihypertensive therapy in 1513 patients with type 2 diabetes and nephropathy. Losartan reduced the incidence of doubling of serum creatinine, end-stage renal disease (ESRD), or death by 16% (P=0.022) and reduced the risk of progression to ESRD, defined as the initiation of dialysis or transplantation, by 29% (P=0.002). We set out to estimate the potential effect of losartan on the burden and costs associated with ESRD over 3.5 years in the European Union (EU). The risk reduction in new cases of ESRD was calculated by combining type 2 diabetes population estimates for the EU with the percent absolute risk reduction of ESRD in patients treated with losartan as observed in RENAAL. The number of days each patient experienced ESRD was defined as the length of time from onset of ESRD until the minimum of death or 3.5 years. ESRD-free person-years avoided with losartan treatment were calculated by combining the population estimate with the ESRD days avoided divided by number of days in a year. ESRD costs from Germany were used to approximate the potential cost savings from reduced time with ESRD and fewer ESRD cases on a EU wide basis. There are approximately 700,000 diagnosed type 2 diabetes patients with proteinuria (urine albumin/creatinine >or=300 mg/g) in the EU. The addition of losartan to the treatment regimen of these patients is expected to lead to a reduction of 44,100 cases of ESRD, 64,400 fewer person-years with ESRD, and reduce ESRD-related costs by euro 2.6 billion over 3.5 years based on RENAAL data. Treatment with losartan not only reduced the incidence of ESRD, but also can result in substantial cost savings in the European Union.
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PMID:Losartan reduces the burden and cost of ESRD: public health implications from the RENAAL study for the European Union. 1241 Aug 59


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