Natural Solution for High Blood Pressure

Blood Pressure Decreaser

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Blood Pressure Decreaser Summary

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Blood Pressure Decreaser Review

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The author presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this book are precise.

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Essential Hypertension

Approximately 50 of patients with essential hypertension are insulin resistant hyperinsulinemic 75 , and it is this subset of patients with essential hypertension that have the atherogenic lipoprotein phenotype characteristic of individuals with the IRS high TG and low HDL-C concentrations, smaller and denser LDL-particles, and an exaggerated degree of postprandial lipemia 69 . Furthermore, there is evidence that it is these patients in whom essential hypertension is present as a component of the IRS that are at the greatest CVD risk 76-79 . The importance of the link between the dyslipidemia present in insulin-resistant hyperinsulinemic patients with essential hypertension and CVD has received considerable support from results of the Copenhagen Male Study. In one publication 78 , Jeppesen and colleagues demonstrated that blood pressure, per se, was less predictive of CVD in individuals with the characteristic dyslipidemia of the IRS - a high TG and a low HDL-C concentration - than in...

The Role Of Genetic Hypertension

As discussed elsewhere in this text, hypertension is one of the most important predictors of the onset and progression of nephropathy in patients with diabetes. While there are many environmental influences on blood pressure, hypertension also comes under significant genetic control. A number of studies have demonstrated that blood-pressure traits appear to segregate with the risk of nephropathy in patients with diabetes.41,42 The concept that genetic hypertension may predispose to accelerated nephropathy is clearly demonstrated in the spontaneously hypertensive rat, a model of polygenetic (essential) hypertension. When compared to normotensive diabetic rats, hypertensive diabetic rats have an earlier and more rapid rise in urinary albumin excretion and increased glomerular basement-membrane thickness.43 However, the evidence for the role of human genetic hypertension in determining the susceptibility to diabetic nephropathy is less clear. Some studies have suggested that parental...

Prevention of Stroke in Diabetic Patients Hypertension

Hypertension is the single most important and potentially reversible risk factor for cerebrovascular disease in both diabetic and non-diabetic individuals (see also Chapter 6). Epidemiological studies confirm that usual systolic and diastolic blood pressure levels are directly and continuously associated with risk of stroke (both cerebral infarction and primary intracerebral haemorrhage) in patients with and without a previous history of hypertension (Prospective Studies Collaboration, 1995 Eastern Stroke and Coronary Heart Disease Collaborative Research Group, 1998). In addition, a similar linear relationship exists between systolic and diastolic blood pressure and risk of recurrent cerebrovascular events in survivors of stroke and TIA (Rodgers etal., 1996). Reducing diastolic blood pressure by 5-6mmHg in people with hypertension and no history of cerebrovascular disease reduces their risk of stroke by approximately one-third, with all major classes of antihypertensive agents...

Nephropathy and Hypertension in Diabetic Patients

Strict and steady near normoglycemia over many years is of paramount importance for the prevention and postponement of renal disease, as well as other complications in most patients with type 1 and type 2 diabetes. Later, several other factors appear to affect progression in renal disease of which blood pressure (BP) elevation seems most important. This seems also to be the case for macrovascular complications along with dyslipidemia, smoking and, as mentioned, hyperglycemia. Incipient renal disease in diabetes, as judged by the occurrence of microalbuminuria, is frequently characterized by hypertension starting with increase in BP from a normal level. The increase, however, is often subtle and may only be detectable by careful and continuous monitoring, e.g. by 24-hour ambulatory recordings. Elevation of BP is found in both types of diabetes, but there appear to be several distinctions between type 1 and type 2 diabetes some of these variations are clearly explained by the different...

Treatment Of Nocturnal Hypertension

Normal subjects have a diurnal variation in BP, with lower nocturnal BP. Patients with neurogenic OH have nocturnal hypertension. To minimize the problems of nocturnal hypertension, pressor medications should not be taken after 6 PM. The head of the bed should be elevated, resulting in lower intracranial BP. A nighttime snack with a glass of fluids (not coffee or tea) results in some postprandial hypotension, and can be used to increase fluid intake and decrease nocturnal hypertension. Patients who enjoy a glass of wine should drink it at this time for its vasodilator effect. Occasionally, it is not possible to control OH without marked nocturnal hypertension. For these patients, hydralazine (Apresoline), 25 mg, can be given at night. Because this drug has sodium-retaining properties, it is especially suitable. Alternatives include the angiotensin-converting enzyme inhibitor nifedipine (Procardia), 10 mg, or a nitroglycerin patch.

Anti Hypertensive Medications Thiazides

Thiazides have been associated with glycemic disturbance for many decades. In 1981, a randomized, controlled trial from the Medical Research Council suggested that patients receiving bendrofluazide developed more impaired glucose tolerance (IGT) than those receiving propranolol (15.4 vs. 4.8 cases patient-years, respectively) (13). This study was criticized for using extremely high dose of bendrofluazide. There are, however, many prospective clinical trials that have demonstrated definite adverse effects of thiazide diuretics on glucose homeostasis (14). In a post hoc analysis of the Systolic Hypertension in the Elderly Program (SHEP) trial, 3 years of low-dose chlorthalidone was associated with a significant elevation in fasting glucose compared to placebo (0.51 mmol L vs. 0.31 mmol L, respectively P 0.01) (15). This trail also demonstrated a clinically significant increase in the incidence of diabetes (13 vs. 8.7 , respectively P 0.001). In anti-hypertensive and lipid-lowering...

The Use Of Antihypertensive Agents In Normotensive Dm With Microalbuminuria

The possibility that early therapy will postpone or retard progression of renal injury in diabetes has led to the use of antihypertensive agents in normotensive subjects. UAE has been shown to be reduced in a group of normotensive DM2 patients with microalbuminuria treated with captopril over a period of 6 months, whereas the untreated group had no change in albuminuria 50 . In the Melbourne study 43 there was no change in albuminuria after 12 months treatment with either nifedipine or perindopril in normotensive microalbuminuric patients, despite a small but significant reduction in blood pressure (4 mmHg). Nonetheless, on stopping therapy at 12 months a dramatic increase in albuminuria was detected in the DM2 but not in the DM1 subjects, which was independent of mode of treatment 51 . The inability of either agent to reduce albuminuria in the normotensive cohort coupled with the rapid rise after stopping therapy needs to be considered in the setting of the natural history of...

The Use Of Antihypertensive Agents In Hypertensive Dm Patients With Normoalbuminuria And Microalbuminuria

Comparison of the use of ACEI versus placebo in DM2 subjects with hypertension and normoalbuminuria or microalbuminuria has not been well studied A double blind study compared captopril with conventional therapy (metoprolol and hydrochlorothiazide) in normoalbuminuric and microalbuminuric hypertensive DM2 subjects over a 3 year period 31 . Both regimens reduced blood pressure without altering UAE in the normoalbuminuric DM2 subjects. However, their findings in hypertensive DM2 patients with microalbuminuria indicated that despite a comparable reduction in blood pressure, only the ACEI induced a persistent decline in albuminuria during the 36 months of therapy. Sano et al found in a small number of normotensive and well controlled hypertensive patients with microalbuminuria, treated with enalapril for a period of four years, that there was a 47 decrease in albuminuria, whereas in the placebo group there was no change 32 . Trevisan et al reported similar findings when comparing ramipril...

Glomerulopathy And Antihypertensive Treatment

Glomerulopathy is observed as early as 2 years after onset of diabetes 34 and is associated with the level of nocturnal diastolic blood pressure after 10 years in children and adolelescents in whom persistent microalbuminuria has not developed 35 . Antihypertensive treatment has been shown to have a beneficial effect on the course of nephropathy. Further, several recent data present evidence that administration of this treatment regimen in the stage of microalbuminuria to normotensive patients has protective effect 36 . (ACEI) or beta-blockers on renal structural changes in Type I diabetes, we studied 13 young normotensive patients with microalbuminuria 37 . Patients were randomised to either an ACE-inhibitor (enalapril 20 mg daily, n 7) or a beta-blocker (metoprolol 100 mg daily, n 6), and renal biopsies were taken before and after 36-48 months' treatment. As a reference group we used 9 patients on conventional insulin treatment and without antihypertensive treatment (AHT) that had...

Longterm Risk Of Esrd In Diabetic Patients Treated With Different Antihypertensive Drugs

The incidence of ESRD in diabetic patients has continued to increase despite the extensive use of ACEi to prevent DN. Recently, Suissa, et al. (75) have assessed the long-term effect of ACEi on the risk of ESRD in a population-based cohort of all diabetic patients treated with antihypertensive drugs between 1982 and 1986. The cohort of 6102 patients, in which 102 cases developed ESRD until 1997, were matched to 4129 controls. Relative to thiazide diuretic use, the adjusted rate ratio of ESRD associated with the use of ACEi was 2.5, whereas it was 0.8 for BB and 0.7 for CCB. The rate ratio of ESRD with the use of ACEi was 0.8 during the first 3 years of follow-up, but increased to 4.2 after 3 years. The authors concluded that ACEi use does not appear to decrease the long-term risk of ERSD in diabetes. The finding of an elevated risk may have at least two possible explanations. First, it could be that ACEi prolong life, thus increasing the opportunity for ESRD incidence. Alternatively,...

Pregnancy Induced Hypertension

In the USA, including 3-5 of pregnancies in previously normotensive women (115). Gestational hypertension is defined as elevated blood pressure on two occasions that develops after the twentieth week of pregnancy, without systemic symptoms, in previously normotensive women (171). Preeclampsia is the development of gestational hypertension plus proteinuria of greater than 300 mg protein in 24 h. Complications of preeclampsia include hepatic dysfunction, hemolysis, disseminated intravascular coagulation and seizures (115). While many factors influence a woman's likelihood of developing PIH, there has been considerable interest in metabolic factors that may contribute. Studies have shown that women with PIH demonstrate exaggerated hyperinsulinemia compared with those with normal pregnancy. In a prospective cohort study, Hamasaki et al. found that the incidence of gestational hypertension was higher among patients with hyperinsulinemia than among controls (24.1 vs. 7.3 , p 0.005) (172)....

Antihypertensive Therapy In Dm More Than Just Reducing Albuminuria

Particular cardiovascular mortality 75, 76, 78 , the effects of these antihypertensive agents must include assessment of cardiovascular endpoints. In the ABCD study it was suggested that ACEI therapy was superior to dihydropyridine CCBs in conferring cardiovascular protection 89 . Similar findings were reported from the FACET study which suggested that fosinopril was associated with less cardiovascular events than amlodipine 90 . However, It was not clear from those small studies whether ACEI confer cardioprotective effects while the dihydropyridine CCB have a deleterious effect. It is likely that the ACEI may confer in certain contexts an additional beneficial effect rather than the CCBs having a deleterious effect on cardiovascular events in the DM2 population. For example, in the Syst-EUR study, a subgroup analysis of the diabetic cohort with systolic hypertension revealed a beneficial effect of nitrendipine on cardiovascular outcomes 91 . In the HOT study which involved...

Clinical Trials Relevant To Treatment Of Hypertension And Prevention Of Cardiovascular Complications In Diabetes

Treatment of hypertension is crucial for the reduction of cardiovascular complications. There have been a considerable number of prospective randomized trials showing the benefits of treating hypertension in diabetes. The SHEP (Systolic Hypertension in the Elderly Program) trial showed that treatment of isolated sys- -o tolic hypertension in elderly type 2 diabetic patients with a diuretic, chlorthali-done, was associated with a significant decrease in the 5-year rates of cardiovas- S cular events and mortality compared to placebo (66). Similarly, in the Systolic Hypertension in Europe (Sys-Eur) Trial, treatment of isolated systolic hypertension in elderly patients with type 2 diabetes with an intermediate-acting calcium channel blocker, nitrendipine, showed a significant decline in cardiovascular J In the United Kingdom Prospective Diabetes Study (UKPDS), 1148 hypertensive patients with type 2 diabetes were randomized either to tight blood pressure control (defined as

Pathogenesis Of Hypertension In Diabetes

Several factors are involved in the pathogenesis of hypertension in patients with diabetes mellitus. These include genetic factors, sodium retention, and hyperin-sulinemia. Genetic predisposition plays an important role in the development of hypertension in both type 1 and type 2 diabetes. The higher prevalence of hypertension in certain ethnic groups, such as African Americans, suggests the role of genetic factors (5). Diabetic patients with hypertension are reported to have high frequencies of family history of hypertension (23). Elevated levels of sodium-lithium countertransport activity (24,25) and sodium-hydrogen countertransport activity (26) have also been found to play a role in the genetic predisposition to hypertension.

Obesity and hypertension

A rise in blood pressure is associated with increased body weight. Epidemi-ological studies indicate that obesity is a strong independent risk factor for hypertension (Modan et al., 1985 Stamler et al., 1993). In the Framingham Study, for example, the prevalence of hypertension among obese individuals was twice that of those individuals with normal weight irrespective of sex and age (Hubert et al, 1983). The INTERSALT Study involving 10000 men and women showed that a 10-kg increase in weight was associated with 3-mmHg rise in systolic and 2.3-mmHg rise in diastolic blood pressure (Dyer and Elliott, 1989). This level of blood pressure elevation is associated with a 12 per cent increase risk for CHD and 24 per cent increase for stroke. In the Nurses' Health Study, the relative risk of hypertension in those women who gained 5.0 to 9.9 kg and greater than 25.0 kg was 1.7 and 5.2, respectively (Huang et al., 1998). The risk of hypertension was even higher with abdominal obesity (WHR 0.9 in...

Hypertension ReninAngiotensin Aldosterone System Blockade

Hypertension frequently coexists with diabetes mellitus in adults. The prevalence is greater than 50 in persons with type 2 diabetes mellitus (54), increasing with age, and approx 25 in those with type 1 diabetes (55). As mentioned previously, the onset of hypertension in type 1 diabetes appears to be primarily a complication of DN, whereas in type 2 the hypertension is frequently present at the time of the diagnosis of diabetes with both being components of the metabolic syndrome. Despite the possible difference in pathophysiology of hypertension in the two types of diabetes, it is clear that uncontrolled hypertension increases the risk for progressive renal damage in patients with either type. Treatment of hypertension in diabetes clearly decreases the risk of microvascular and macrovascular complications, including nephropathy. Large prospective, randomized trials (UKPDS and the Appropriate Blood Pressure Control in Diabetes trial) have shown decreased rates of progression of...

The Use Of Antihypertensive Agents In Dm Subjects With Established Diabetic Nephropathy

The impact of angiotensin converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), calcium channel blockers (CCB) and conventional antihypertensive agents on renal function has been evaluated in both normotensive and hypertensive DM2 subjects with persistent proteinuria and variable degrees of renal impairment. In hypertensive DM2 subjects with persistent proteinuria studied for periods of greater than 6 months, ACEI 1321 , ARB 4, 6 and certain CCB 19, 21-23 reduced albuminuria. In general, the earlier reports showed that ACEI were very effective in reducing blood pressure and urinary albumin excretion 13-15, 17-21 . The decrease in blood pressure and albuminuria was usually associated with a slowing of the progression of renal failure. Parving's group has reported a disparity in effects on albuminuria and renal function 15 . Whereas lisinopril was more effective than atenolol in reducing albuminuria, both agents were similar in efficacy in terms of rate of decline...

Treatment of hypertension

Management of hypertension as part of an aggressive overall treatment strategy to reduce cardiovascular risk in patients with diabetes is clearly important (see also Chapter 6). Data are also available on the impact of hypertension specifically in patients with diabetes associated with PAD. The Framingham epidemiological study provides observational evidence that patients with high blood pressure are at greater risk of developing intermittent claudication (Murabito etal., 1997). Isolated systolic hypertension, in particular, is very common in the elderly and is closely associated pathophysiologically with increased arterial stiffness, pressure-wave reflection and an increased systolic blood pressure load on the heart causing left ventricular hypertrophy. The UKPDS showed that a 10 mmHg increase in systolic blood pressure was associated with a 25 increase in risk whereas a 10 mmHg lowering in systolic blood pressure translated into a non-significant 16 reduction in risk of lower limb...

When should the treatment of hypertension in diabetic patients begin and in what way How long will the treatment last

Since hypertension in the diabetic individual is defined as the presence of BP levels 130 80 mmHg, it is obvious that the therapeutic approach should begin when its values exceed these limits. Initially, for blood pressure levels of 130-139 80-89 mmHg, it is advisable for the first approach to be non-pharmaceutical, and to try to reduce the BP with lifestyle modification measures. These include an effort of body weight reduction in obese patients (with diet and exercise), reduction of salt and alcohol consumption, and smoking cessation. Weight loss is the most efficient of these measures, as regards the success of BP reduction (a loss of 10kg body weight usually produces a BP fall by 5-20mmHg). A reduction of dietary caloric consumption is very important, with fat restriction, mainly saturated animal fat, being the basic factor. Salt should be limited to less than 6g per day. Alcoholic beverages should also not exceed 2-3 glasses of wine (or equivalent alcohol quantity in other...

What is the effect of hypertension in diabetic patients

Both hypertension and DM constitute extremely important risk factors for the development of cardiovascular events (coronary artery disease, strokes, peripheral obstructive arteriopathy). However, the coexistence of these two abnormalities has a multiplicative effect on the risk, rather than a simple additive effect. The effects of hypertension on the risk of coronary heart disease mortality in diabetic individuals are increased two to five times, compared to non-diabetics. The frequency of strokes, the appearance of cardiac failure and the probability of peripheral obstructive arteriopathy are also significantly increased in hypertensive diabetic individuals. Furthermore, the probability of microvascular diabetic complications, mainly nephropathy and retinopathy, are considerably increased by the presence of hypertension. This has also been proven by the beneficial effects that the treatment of hypertension has on the reduction of microvascular complications progress in Type 2...

What is the frequency of hypertension in DM

Hypertension constitutes a frequent problem among diabetic patients. Its frequency differs, however, between Type 1 and Type 2 DM. Specifically, in Type 1 DM the frequency of hypertension increases with the duration of the disease and has a direct relationship to the appearance of nephropathy in these patients. Hypertension is relatively unknown in patients without nephropathy, and the coexistence of nephropathy and hypertension appears to worsen both conditions. Thus, the incidence of hypertension increases from 5 percent for duration of DM of 10 years, to 33 percent for duration of 20 years and 70 percent for duration of 40 years. Blood pressure begins to increase in these patients (even within the considered normal limits) within three years of the appearance of microalbuminuria (which constitutes the first clinical indication of diabetic nephropathy). Finally, the incidence of hypertension as a whole is roughly 15-25 percent for patients with microalbuminuria and 75-85 percent for...

Arterial hypertension

In Type 1 DM, hypertension is usually a result of diabetic nephropathy and manifests at the stage of microalbuminuria. In Type 2 DM, hypertension is present at the time of diagnosis of diabetes in a third of the patients and may coexist with other parameters of the metabolic syndrome X, a common pathogenetic mechanism which is insulin resistant. It may also be due to diabetic nephropathy, coexistent idiopathic arterial hypertension, renal vascular disease or other causes. Systolic and diastolic hypertension promote diabetic nephropathy to a significant degree. Aggressive antihypertensive treatment in Type 1 diabetic patients with already overt diabetic nephropathy, not only decreases albumin excretion rate (AER) but may also essentially delay decline of glomerular filtration rate (GFR) and decelerate progression to end stage renal disease. The UKPDS study also showed that BP control in Type 2 DM may decrease nephropathy risk (by 29 percent) irrespective of the kind of antihypertensive...

What is the pathogenetic mechanism for the development of hypertension in DM

In Type 1 DM, as was already mentioned, hypertension is usually due to the development of nephropathy. For Type 2 DM, things are not that simple. Both Type 2 DM and hypertension are frequent abnormalities in the general population and it could be considered that their coexistence is subject to chance. In certain cases, however, it appears that there is likely to be common cause for their development. Insulin resistance (see Chapter 3) has been incriminated as the common pathogenetic factor for the development of both Type 2 DM and hypertension. This is due to the fact that certain insulin actions are intensified in situations of insulin resistance, when it appears that there is in reality increased insulin sensitivity for certain actions of insulin. Thus, the hyperinsulinaemia that insulin resistance causes (as regards its action in the entry of glucose into the cells), results as a consequence in an intensification of other insulin actions, for which its sensitivity is preserved....

Selection of antihypertensive drug in diabetes mellitus

ACE inhibitors, nondihydropyridine CCBs, TDs, and bBs reduced CV complications in patients who had diabetes and hypertension in several long-term, large, RCTs (Tables 3 and 4). Limited data is available with direct comparisons of various drugs in diabetic, hypertensive patients (Table 5). There was no convincing evidence from several large RCTs (eg, CAPPP 26 , Swedish Trial in Old Patients with Hypertension 2 STOP-2 68 , Nordic Diltiazem NORDIL study 69 , and Intervention as a Goal in Hypertension Treatment INSIGHT 70 ) that newer agents, such as ACE inhibitors and CCBs, are better than diuretics and bBs in reducing CV events in treating hypertension in the general population. Because diabetes is an important and independent risk factor for CV morbidity and mortality and because most diabetics die of CV complications 1 , subgroup analysis of diabetic, hypertensive patients in these trials revealed that most required multiple drugs for adequate control of their BP. In the CAPPP trial,...

Is a pregnant woman allowed to take antihypertensive medicines and which ones Which particular hypertensive problem

All antihypertensive medicines should be discontinued if hypertension is under control ( 130 80 mmHg) with restriction of table-salt and proper nutrition. These levels should be maintained during the whole course of the pregnancy. ACE inhibitors and inhibitors of angiotensin receptors are contraindi-cated in pregnancy due to a nephrotoxic action on the foetus and should be discontinued before a woman becomes pregnant. If during the course of the pregnancy hypertension develops, rest is recommended and frequently prescription of various medicines is required, such as methyldopa, labe-talol, clonidine or hydralazine or even beta-blockers, with the provision that they can mask the early symptoms of hypoglycaemia.

Role Of Glomerular Capillary Hypertension

Of the glomerular hemodynamic determinants of hyperfiltration, the available evidence suggests that glomerular capillary hypertension plays the key role in progression of renal injury. Long-term protection against albuminuria and glomerular sclerosis was obtained in normotensive diabetic rats by angiotensin converting enzyme inhibitor (ACEI) therapy in doses which modestly lowered systemic blood pressure, but selectively normalized PGC, without affecting the supranormal SNGFR and QA 26 . Studies in a variety of experimental models, including diabetes, have consistently shown that interventions which control glomerular capillary hypertension are associated with marked slowing of the development of structural injury 115 . Until recently, little was known of the exact mechanism(s) by which glomerular capillary hypertension eventuates in structural injury. Recently, innovative new techniques using a variety of in vitro systems have been developed to address this question. These studies...

What kind of antihypertensive medicine would you choose

Since the administration of two kinds of antihypertensive agents (ACE inhibitor and calcium channel blocker) are not enough for controlling BP of the patient, the addition of a thiazide diuretic could be a good choice (thiazides have a synergistic action with ACE inhibitors and there are fix combinations in the market). The primary target is to achieve BP levels 130 80 mmHg, necessarily using a medicine blocking the renin-angiotensin axis. Monitoring of the patient's BP and repeat of urine protein measurement will show if this target can be achieved in the next 3-6 months. If not, treatment should be intensified with the addition of a fourth antihypertensive medicine (ARB or other category see Table 22.1 in Chapter 22 for a list of categories of antihypertensive medicines).

Antihypertensive treatment

Although many intervention trials have been conducted using different anti-hypertensive agents in diabetic and non-diabetic subjects, few studies have been conducted exclusively in obese subjects, and some studies have specifically excluded very obese patients. The average body mass index (BMI) in the UKPDS study was approximately 29kg m2, but no sub-group analysis based on BMI has been reported. There is clear evidence from the literature that obese hypertensive patients have higher circulating catecholamine concentrations and greater activity of the renin-angiotensin system than non-obese patients, but it is unknown whether this is also the case in diabetic patients. It is therefore difficult to draw firm conclusions about the optimal antihypertensive strategy for obese patients with type 2 diabetes. Angiotensin-converting enzyme (ACE) inhibitors are certainly effective, and may have other advantages in subjects with cardiovascular disease, nephropathy and retinopathy they have been...

Antihypertensive Treatment And Renal Autoregulation

The interplay between impaired renal autoregulation on one hand, and systemic BP 20,78,113-116 , glomerular mechanical strain 75,76,117-120 , different growth hormones 121-124 , glomerular permselective properties 125,126 , diabetes 69,127,128 , albuminuria 81,82,85 on the other hand, and the development progression of renal histological changes has been studied 84,113,129 . Although the pathogenesis in the different models differs in several aspects, impairment of renal autoregulation might induce the following pathological events Enhanced transmission of systemic BP into the capillary network, induces wide swings and increased glomerular volume 119,130 . These alterations are further magnified by hypertension 119 . The pressure induced wide swings induces capillary distension and mesangial stretch 131 . Capillary distension induces glomerular epithelial cell hypertrophy with epithelial cell protein droplets, increase in lysosomes, vacuolisation 132 , focal and segmental detachment...

How is hypertension defined in DM and what are the targets of therapeutic intervention

Hypertension in the general (non-diabetic) population is defined as the presence of arterial blood pressure (BP) levels above 140 90 mmHg. These limits were set based on large epidemiological studies (e.g. Framingham Study, Multiple Risk Factor Intervention Trial, etc), which revealed that the risk of cardiovascular complications is considerably increased above these levels, while the risk for lower BP levels, although existent, is not significant enough to justify therapeutic interventions, apart from lifestyle advice. For DM, however, the data from large, controlled, randomized, clinical studies showed that the reduction of BP should be more aggressive in order to decrease the risk of cardiovascular complications. Thus, the UKPDS 36 study (Adler, et al. 2000) showed that the reduction of BP levels from 154 87 mmHg (for the control group) to 144 82 mmHg (for the treatment group) decreased considerably the chance of micro- and macro-vascular complications. The HOT (Hypertension...

Antihypertensive Agents

Recently, losartan and olmesartan, antihypertensive drugs known to act through angiotensin receptor inhibition, have been shown to decrease AGE formation (191). Hydralazine, another antihypertensive agent whose effect does not involve the renin-angiotensin system, has AGE-inhibitory effects similar to those of low-dose olmesartan (192). The renoprotective effects shown by these drugs suggest that they derive not only from the drugs effect on lowering blood pressure and blocking angiotensin but also from reduced AGE formation (193).

Pathophysiology Of Hypertension Is Different In Type And Type Diabetes

There are substantial differences in the causes of hypertension in T1DM and T2DM. In patients with T1DM diabetic nephropathy appears to be the most common cause of hypertension (13). A strong family history of essential hypertension and diabetes mellitus appears to identify those people with T1DM who are most likely to develop renal disease and hypertension (14). Probably an equal number of people with T2DM develop renal disease (15) but hypertension often occurs with normal renal function associated with obesity or older age. Various hypotheses have been suggested to account for the increased prevalence of hypertension particularly in T2DM patients (16). Hypertension may be related, in part to central obesity and increased sympathetic nervous system stimulation and catecholamine production observed in diabetics (16). It is now generally believed that essential hypertension is a part of the insulin resistance syndrome (17), and that hypertension precedes the development of T2DM in a...

Impressive Reduction Of Risk For Cvd In Diabetic Patients By Antihypertensive Treatment

There is strong evidence for a beneficial effect of BP reduction on CVD risk in T2DM, and these benefits have been demonstrated with all classes of antihypertensive drugs. In recent years many antihypertensive intervention studies (19-34), which have included a representative number of diabetic patients, have been published. All these intervention studies illustrate that BP lowering is very important for improving the poor prognosis of diabetic patients. Disagreements in the outcome of different clinical trials can easily be explained by heterogeneity of these studies. The included patients showed a wide variation concerning initial BP values and lowering of BP values. Most of the patients had long-standing diabetic disease, however the exact duration of diabetes and or hypertension was not reported in most of the studies. The follow-up of the hypertensive patients ranged from 2 to 8 years and only newly diagnosed patients were only enrolled in the United Kingdom Prospective Diabetes...

Lifestyle Treatments for Hypertension

High blood pressure, or hypertension, goes hand in hand with diabetes and obesity, affecting about 75 percent of people with type 2 diabetes. The combination of the two increases your risk of developing eye, kidney, and heart disease and stroke. If you throw in abnormal cholesterol levels, which will be discussed later in this chapter, you have a potentially lethal combination that increases the risk of heart disease and stroke even more. All three hypertension, obesity, and abnormal cholesterol and other blood fats are connected to the prediabetic and diabetic states, and all three can be improved with lifestyle changes. High blood pressure responds to the lifestyle changes that lead to weight loss and increased activity levels, as we have already discussed. For example, a weight loss of five to fifteen pounds, achieved in studies such as the Diabetes Prevention Program and Trials of Hypertension Prevention Study, can lower blood pressure by two to five points (for example, from 135...

Risk For Development Of New Diabetes In Relation To Antihypertensive Drug Therapy

Because hypertension is often associated in large populations with impaired glucose tolerance, insulin resistance, and obesity, many patients with hypertension develop diabetes even when treated with placebo. Since in most diabetic patients combination therapy with two, or even three antihypertensive agents is likely to be required, the choice of which antihypertensive class should be given seems to be less problematic. When it comes to nondiabetic hypertensive patients, it seems to be more crucial. A meta-analysis of hypertension trials (91) involving about 116,000 patients, two-thirds of whom did not have diabetes at baseline, found an overall 25 reduction by RAS inhibition (27 for ACEi and 23 for ARB) in new-onset diabetes compared with other antihypertensive classes or placebo (91). Table 5 shows the Effect of antihypertensive drug treatment on systolic and diastolic blood pressure in diabetic hypertensive patients of 10 trials

The Use Of Antihypertensive Agents In Dm Patients

The choice of an antihypertensive agent in the management of abnormal albuminuria in DM2 depends not only on its potential renoprotective effect but must also take into consideration other factors, which could be deleterious to the patient. Microalbuminuria in the DM2 patient is more closely linked to subsequent death from cardiovascular disease than from nephropathy 75-78 , although this association has not been substantiated in all populations 77, 79 . It has also been shown that rapid progression of albuminuria is an independent predictor of cardiovascular mortality in DM2 with microalbuminuira 80 . Therefore it is important that any antihypertensive intervention in the DM2 patient, especially those with albuminuria does not exacerbate existing lipid abnormalities such as further reducing HDL-cholesterol 81 . Furthermore, reduced sensitivity to insulin after administration of thiazides and various beta-blockers may be detrimental 82 . However, subsequent studies suggest that low...

Risk of Diabetes Mellitus with Antihypertensive Drugs

Individuals with hypertension, whether treated or untreated, are at increased risk of developing type 2 diabetes. In treated hypertensive subjects, compared with those who received no antihypertensive therapy, the risk of development of diabetes was not significantly altered with ACE inhibitors, calcium channel blockers or thiazide diuretics. Only those treated with beta-blockers were of increased risk of developing diabetes (Gress etal., 2000). Early experience with ACE inhibitors suggested no detrimental effect on fasting blood glucose after long-term administration (Neaton etal., 1993). The Swedish Trial in Old Patients with Hypertension 2 (STOP-2) study failed to show a protective effect of ACE inhibition against type 2 diabetes mellitus (Hansson etal., 1999a). The study population was elderly (average age 76 years) and the criteria for definition of diabetes were not specified. In the CAPPP study there was significant reduction in new-onset diabetes in the captopril group...

Diabetic Patients With Hypertension Have A Significantly Higher Risk For Cvd Than Nondiabetic Patients

Hypertension increases CV risk in type 2 diabetes mellitus (T2DM) enormously, as clearly demonstrated in the Multiple Risk Factors Intervention Trial, in which 350,000 men between 35 and 57 years of age were followed up for twelve years (3). The absolute risk of CV death was three-fold higher in those who were diabetic, even after adjusting for other common risk factors such as age, race, income, serum cholesterol and smoking. Importantly, the risk at any given level of systolic blood pressure (SBP) was 2.5-3 times higher in those with T2DM than in the non-diabetic patients at every level of SBP assessed (3). Hypertension is also thought to play a major etiologic role in the development of diabetic nephropathy (DN) and diabetic retinopathy (4,5). As a result, many experts and authors have argued that blood-pressure (BP) management is the most critical aspect of the care of patients with T2DM. Recently, findings from the Strong Heart Study (6) demonstrated that the high risk for CVD...

What is the Evidence That Microcirculatory Dysfunction Can Contribute to Hypertension

The established phase of human essential hypertension is characterized by a normal cardiac output and an elevation in peripheral vascular resistance. Peripheral vascular resistance is dictated primarily by resistance across vessels between 10 and 300 m in luminal diameter, and the increase in total peripheral vascular resistance in essential hypertension is, therefore, likely to reflect changes in these vessels. Changes in the microcirculation of hypertensive patients include a reduction in the number of capillaries and arterioles, so-called rarefaction, in many tissues (41,50). Microvascular rarefaction, similar in magnitude to the rarefaction observed in patients with established hypertension, can already be demonstrated in subjects with mild hypertension, and in normotensive subjects with a genetic predisposition to high blood pressure. This suggests that rarefaction is not solely secondary to sustained elevation of blood pressure, but may precede and thus be a causal component of...

Hypertensionblood pressure control

Hypertension is a common comorbidity found in the majority of patients with diabetes, particularly those with type 2. Additional risk factors include age, obesity, and ethnicity. Hypertension is a major risk factor for CVD and microvascular complications such as retinopathy and nephropathy. Key recommendations monitoring and preventing hypertension All patients with diabetes and hypertension should be treated with a regimen that includes either an ACE inhibitor or an ARB. In patients with type 1 diabetes, with hypertension and any degree of albuminuria, ACE inhibitors have been shown to delay the progression of nephropathy. Lowering of blood pressure with regimens based on antihypertensive drugs, including ACE inhibitors, ARBs, beta-blockers, diuretics, and calcium-channel blockers, has been shown to be effective in lowering cardiovascular events. Several studies suggest that ACE inhibitors may be superior to dihy-dropyridine calcium channel blockers (DCCBs) in reducing cardiovascular...

No of antihypertensive agents Trial Target BP mm Hg

Multiple antihypertensive agents are needed to achieve target blood pressure. BP, blood pressure DBP, diastolic blood pressure MAP, mean arterial pressure SBP, systolic blood pressure. (Adapted from Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes a consensus approach. Am J Kidney Dis 2000 36(3) 646-61 with permission.) Fig. 4. Multiple antihypertensive agents are needed to achieve target blood pressure. BP, blood pressure DBP, diastolic blood pressure MAP, mean arterial pressure SBP, systolic blood pressure. (Adapted from Bakris GL, Williams M, Dworkin L, et al. Preserving renal function in adults with hypertension and diabetes a consensus approach. Am J Kidney Dis 2000 36(3) 646-61 with permission.) The Losartan Intervention for Endpoint Reduction in Hypertension trial also demonstrated beneficial effects of ARBs in the prevention of stroke events. To conclude, pharmacologic therapy to block the renin-angiotensin...

Can Endothelial Dysfunction Cause Hypertension Insulin Resistance And Type Diabetes

The association between essential hypertension and insulin resistance is well established but presently unexplained. Compensatory hyperinsulinemia has been proposed to be the missing causal link explaining this association. However, this explanation has remained controversial, mostly because acute administration of insulin, despite its presumed prohypertensive effects on the sympathetic nervous system, transmembrane cation transport, and renal sodium reabsorption, leads to vasodilatation (38,39) rather than vasoconstriction, and even exerts a small blood pressure-lowering effect in patients with essential hypertension (40). As an alternative, a connection between the two abnormalities can be envisioned at the level of the microcirculation (Fig. 2). Fig. 2. Microvascular dysfunction as a potential link between common risk factors on the one hand and insulin resistance, type 2 diabetes, hypertension, and renal disease on the other. Fig. 2. Microvascular dysfunction as a potential link...

Nonpharmacological Treatment Of Hypertension In Diabetic Patients

The goal of treating hypertension in patients with diabetes mellitus is to prevent associated morbidity and mortality. Lifestyle modification, including weight management, diet, salt reduction, moderation of alcohol intake, increased physical activity and smoking cessation are the cornerstones of therapy. Weight loss in overweight individuals can improve control of both hypertension and diabetes mellitus. Many studies have shown that even modest reduction of body weight can improve BP and glycemic control. Reduction in weight may be associated with BP reductions because of reduction of insulin levels, sympathetic nervous system activity, and vascular resistance.

Type diabetes and hypertension

The prevalence of hypertension in the diabetic population is 1.5 to 3 times higher than that of the non-diabetic age-matched population (Wingard, 1995). In type 2 diabetes, hypertension may be present at the time of the diagnosis or precedes the development of hyperglycaemia (HDS, 1993) and is implicated in development of both micro- and macrovascular complications. Epidemio-logical studies indicate that diabetic individuals with hypertension have greatly increased risks of cardiovascular disease, renal inefficiency and retinopathy. In UKPDS, every 10-mm rise in systolic blood pressure was associated with a 15 per cent increase in risk of coronary artery disease. Both systolic and dias-tolic hypertension markedly accentuate the progression of diabetic nephropathy and aggressive antihypertensive management will decrease the rate of fall of glomerular filtration rate (UKPDS, 1998). Hypertension is also implicated as a risk factor for diabetic retinopathy resulting in increasing hard...

Management of hypertension

Weight reduction has been shown to be an effective non-pharmacological approach to improve blood pressure in several studies (Schotte and Stunkard, 1990 Krzesin-ski et al., 1993). Loss of 1 kg body weight is associated with a mean decrease in blood pressure of 1 mmHg (Staessen et al., 1989). The reduction in blood pressure is related to the amount of weight loss rather than to the various treatment modalities employed such as different caloric restrictions or behaviour therapy. Weight reduction can also reduce the number of antihypertensive medications prescribed (Fagerberg et al., 1984). The role of sodium restriction is controversial. The INTERSALT Study showed that dietary sodium restriction can independently lower blood pressure and is additive with weight loss (Fagerberg et al., 1984). Studies have shown that moderate sodium restriction to 100 mmol (2300 mg) per day can reduce systolic pressure by 5 mmHg and diastolic pressure by 2-3 mmHg (Cutler et al., 1997). In addition, the...

Familial Hypertension And Renal Disease

The frequent association of renal disease with hypertension has led to the examination of blood pressure in non-diabetic family members of persons with diabetes and in individuals thought to be at high risk of developing diabetes in the future. Viberti et al. found that both systolic and diastolic blood pressures were significantly higher in the parents of diabetic subjects with proteinuria than in the parents of diabetic subjects without proteinuria 29 . The difference between the mean blood pressures averaged 15 mmHg. Similarly, Krolewski et al. 30 reported that the risk of nephropathy among subjects with type 1 diabetes was three times as high in those having a parent with a history of hypertension as in those whose parents had no such history, and Takeda et al. 31 found evidence suggesting that paternal hypertension might be related to the development of nephropathy in patients with type 2 diabetes. Beatty et al. Among diabetic Pima Indians whose parents did not have proteinuria,...

Hypertension

Women with PCOS would appear to be highly predisposed to the development of hypertension by virtue of their characteristic obesity and insulin resistance. However, the presence of systolic and or diastolic elevations in blood pressure are not a uniform feature of PCOS during the reproductive years. In one study (33), women with PCOS and controls were compared using 24-h ambulatory blood pressure monitoring and echocardiography. Despite the fact that the PCOS women were significantly more insulin resistant than their matched controls, there was no difference in systolic or diastolic blood pressure levels or in left ventricular mass between groups. It is possible, however, that measurement of ambulatory blood pressures or left ventricular mass are not sufficiently sensitive to detect subtle effects, direct or indirect, of hyperinsulinemia upon the resistance vessels. -o With age, insulin resistance and secondary hyperinsulinemia may play a central role in the development of hypertension...

High Blood Pressure

High blood pressure is one of the easiest problems to correct without resorting to drugs. The toxicity of cadmium, in fact, the high blood pressure connection, has been known a long time. After finding the cadmium start on the kidney cleanse. You might miss the cadmium problem if you don't attend to it first. Also remove all metal from your mouth. All (100 ) cases of high blood pressure I have seen could be easily cured by eliminating cadmium and other pollutants, followed by cleansing the kidneys. Bala Cuzmin, age 72, had high blood pressure for ten years but the upper (systolic) pressure remained high in spite of various medicines that were tried. She had three kinds of kidney stones and only one functional kidney. She stopped using caffeine, switching to arginine tablets to get over the let-down. Her diet was changed to reduce phosphate and add calcium, and she took magnesium and Vitamin B6 to assist the kidneys. She was very anemic and her mean cell volume (MCV) was high due to...

The Brenner Hypothesis

Glomerular number shows wide biological variation in both humans (400,000 -1,200,000) 27, 28 and rats (20,000 - 35,000) 11, 29 . Brenner et al, proposed that individuals with a mean glomerular number at the lower end of or below the physiological range are at increased risk of developing hypertension 5 , due to a reduction in total filtration surface area. During the growth phase of a human being, hypertension may result in glomerular capillary hypertension and later on in glomerular sclerosis, which will further reduce the total glomerular filtration surface area, thus perpetuating a vicious cycle 30 . Surgical reduction in glomerular number by unilateral nephrectomy in childhood 43 , and unilateral renal agenesis 44 are associated with increased risk of hypertension but the prevalence of hypertension in adults undergoing nephrectomy are small 43 . These findings suggest that the early reduction in glomerular number in the pathogenesis of hypertension but the majority of people with...

Overnight Albumin Excretion Rate And Arterial Blood Pressure

Altered glomerular haemodynamics with increased glomerular plasma flow and transcapillary pressures are considered key factors in the initiation and progression of diabetic nephropathy 73,74,75,76 . Therapy with an angiotensin converting enzyme (ACE) inhibitor has been shown to lower albumin excretion rate and mean arterial blood pressure in normotensive adolescents 77,78 and adults 79 with Type 1 diabetes and microalbuminuria, in the short term at least. Recently, long-term studies have demonstrated that ACE-inhibition delays progression to diabetic nephropathy in normotensive Type 1 diabetic patients with persistent microalbuminuria 80,81,82,83 . Rudberg et al. 84 found less progression of early diabetic glomerulopathy in Type 1 diabetic young microalbuminuric patients who were treated with either ACE-inhibitors or beta blockers (for an average of 3 years) than in patients who did not receive antihypertensive treatment and that this effect possibly was due to maintenance of a normal...

Prevalence Of Impaired Gfr During Microalbuminuria In Type And Type Diabetes

The first population-based study on the prevalence of impaired renal function in the United States was performed in NHANES III 8 (Table 1). Impairment of GFR in the range 15-60 ml min 1.73m2 was observed in 3.9 of non-diabetic and 15.1 of diabetic participants. The prevalence of impaired GFR 60 ml min 1.73m2 in diabetic participants was too low to calculate in the 2040 year age group, but increased from approximately 3 in the 40-59 year age group to approximately 35 in the 70 year age group 8 . NHANES III also showed that impaired GFR is observed with a greater prevalence in older, hypertensive subjects without diabetes 76 .

Effect Of Pregnancy On The Subsequent Progression Of Diabetic Nephropathy

For years, there has been concern that the hyperfiltration, hypertension, or heavy proteinuria of pregnancy might damage glomeruli, tubules, and interstitium and accelerate the postpartum progression of DN to end-stage renal disease. In a pooled series of 195 women experiencing pregnancies with DN and having renal function assessed 1-10 years afterwards, 23 were in renal failure and 5.6 had died (table 4). Not surprisingly, the frequency of progression to renal failure after pregnancy was 49 in the group of women with impaired renal function in early pregnancy, compared to 7 if Cr was 80 ml min in early gestation (table 5) 38,95,96, 98,100,101,148,189-192 . A similar risk of post-pregnancy decline of renal function based on pre- or early pregnancy CrCl was also reported by Biesenbach, and he speculated that inadequate antihypertensive therapy may have contributed to the original and further decline in renal function 104 .

Molecular Cell Biology Of Endothelial Dysfunction In Diabetes

High Glucose Insulin Pathway

The metabolic syndrome insulin resistance, insulin, hypertension, dyslipidaemia, and obesity Hypertension. Hypertension is a major determinant of microangiopathy and atherothrombosis in diabetes. Hypertension causes endothelial activation and impaired nitric oxide availability (see above) whether the latter then contributes to increased blood pressure is not clear. Experimental data indicate that decreased nitric oxide availability in the kidney may contribute to vasoconstriction and decreased glomerular filtration impaired tubuloglomerular feedback decreased medullary blood flow and impaired pressure natriuresis and progressive proteinuria. Salt sensitivity of blood pressure may denote an inability to increase nitric oxide availability in response to increased blood pressure 81 . of atherothrombosis and microangiopathy. These effects may be mediated through the associations of obesity with hypertension, dyslipidaemia and insulin resistance, and also through mediators directly...

Emerging Concepts Regarding Albumin Handling By The Kidney

In experimental and human diabetes, an increase in total albuminuria may reflect both an increase in the intact to fragment ratio of urinary albumin as well as alterations in the activity of a trans-tubular transport pathway 92 . By contrast, in experimental hypertension, increases in total albuminuria appear to be explained purely on the basis of a change in the intact fragment ratio of urinary albumin 89 . The complexity of albumin-derived components in urine has recently been highlighted as intact albumin appears to be excreted in two forms, i.e. immuno-reactive and immuno-unreactive. Preliminary results have demonstrated a high prevalence of immuno-unreactive intact albumin, as measured by HPLC, in the early stages of diabetic renal disease. The exact

Role Of Combination Therapy

It has been proposed that the combination of two or more antihypertensive agents may be beneficial in the treatment of hypertension in the diabetic patient with or without evidence of renal involvement. The various combinations have been reviewed recently 57 . Brown et al postulated in 1993, that the combination of a calcium antagonist with a converting enzyme inhibitor should result in a greater reduction in urinary protein excretion and slow progression of nephropathy, as assessed morphologically 58 . Bakris et al have compared the renal hemodynamic and antiproteinuric effects of a calcium antagonist, verapamil, and an ACEI, lisinopril, alone and in combination in three groups of DM2 subjects with documented nephrotic range proteinuria, hypertension, and renal insufficiency 23 . Patients treated with the combination of a calcium antagonist and an ACEI manifested the greatest reduction in albuminuria. In addition, the decline in GFR was the lowest in that group. Similar findings are...

Disparity Between Declining Gfr And Increasing

Most patients with diabetic renal disease display a decline in GFR that is preceded or accompanied by an increase in AER. However there is a growing body of evidence to suggest that some patients possibly follow an alternate, non-albuminuric pathway to renal impairment. The combination of impaired renal function in association with normoalbuminuria was first highlighted by Lane et al. 3 who identified eight women with type 1 diabetes who had low creatinine clearance but a normal AER. A recent study from this group has examined the clinical characteristics and renal ultrastructure in 105 normoalbuminuric type 1 diabetic patients 10 . A total of 23 (22 ) normoalbuminuric patients had a GFR 90 ml min 1.73 m2 and a median AER of 7.7 (range 2.0-17.6) g min. These patients showed increased mesangial and mesangial matrix fractional volumes and glomerular basement membrane width when compared with age- and gender-matched controls. The glomerular lesions seen in normoalbuminuric patients with...

Glomerular Hyperfunction

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. Early renal changes in experimental diabetes in some degree parallel the characteristic glomerular hyperfunction in early stages of human diabetes. As described elsewhere in this book, besides hyperperfusion, increased intraglomerular hydraulic pressure is an important factor in hyperfiltration in diabetic animals. In humans the larger increase in GFR than RPF (increased filtration fraction) suggests similar intraglomerular hypertension. However, elevation of the ultrafiltration coefficient due to increased filtration surface may also represent a mechanism for the increased filtration fraction 13 .

Evolution Of Diabetic Nephropathy

Diabetic Nephropathy Evolution

The major clinically identifiable initiators are hyperglycaemia and blood pressure control. Increases in AER into the microalbuminuric range may occur transiently with exercise, urinary tract infection, uncontrolled hyperglycaemia and cardiac failure, and on a long-term basis with hypertension, non-diabetic renal disease, and in association with large vessel disease. However, progression to overt diabetic nephropathy does not occur without long-term hyperglycaemia. Following the onset of overt nephropathy there is usually a close coupling of increases in AER with decreases in GFR. The subsequent rate of decline of GFR is influenced by several progression promoters including the level of blood pressure, hyperglycaemia and proteinuria, as well as retinopathy and smoking. Recent evidence suggests that a decline in GFR may occur, less commonly, in subjects with minimal or no increases in AER. This raises the question of whether the sequence of microalbuminuria leading to macroalbuminuria...

The Relevance Of The Problem

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. Yet, the outcome in terms of ESRD, cardiovascular events and death is becoming predictable from the constellation of risk factors. The pivotal role of albuminuria has been further elaborated. In addition, the classical cardiovascular risk factors hypertension, dyslipidemia, obesity and smoking all seem to be involved in progression of renal disease. In contrast, the role of proteinuria in type 2 DM has been less well-studied -until recently. Notably, type 2 diabetic patients usually are resistant to antihypertensive therapy, often requiring several drugs to control blood pressure. This therapy-resistance also applies to the antihypertensive and antiproteinuric effect of ACE inhibitors and ARBs these effects are considerably smaller in type 2 DM than usually observed in non-diabetics or type 1 DM and this has previously...

The Relation To Clinic Bp

We have found a markedly lower day time BP (147 85 mmHg) than clinic BP (163 95 mmHg) in 102 consecutive NIDDM and IDDM patients referred to ambulatory BP measurement because of repeated clinic BP 140 90 mmHg 124 . The frequency of white coat hypertension in normoalbuminuric diabetic patients is about 25 124,125 . If patients are selected for the presence of organ lesions related to hypertension (diabetic nephropathy) the proportion of white coat hypertension may be reduced 125 . One study reported a much higher frequency of white coat hypertension (41 ) probably due to a shorter observation period before labelling patients as hypertensive and because patients was designated as true normotensive on the basis of 24h BP (containing the lower night BP) rather than day time values 126 . Obviously the reported frequency of white coat hypertension also varies with the definition of a normal ambulatory BP 22,23 . An extremely high frequency of white coat hypertension (62 ) was reported in a...

Longitudinal Studies Of Gfr In Microalbuminuric Patients With Type Diabetes Figure

Ml min 1.73m2 year after the age of 40 years 74, 75 . Secondly, there is a higher prevalence of hypertension in type 2 diabetes, which may accelerate renal injury 81 . Thirdly, a proportion of microalbuminuric patients with minimal or no detectable renal structural lesions may never progress to macroalbuminuria and may be expected to have stable GFR. Despite the above considerations, the rate of decline of GFR at the stage of overt nephropathy has been shown to be similar in type 2 and type 1 diabetes 81 . The available GFR data in microalbuminuric patients will be considered in the normotensive and then in the hypertensive setting. Preservation of creatinine clearance was also observed during 5.3 years of antihypertensive therapy in the normotensive Appropriate Blood Pressure Control in Diabetes (ABCD) Study 11 . This study included 109 patients with microalbuminuria who were treated moderately or intensively with nisoldipine or enalapril based therapy. The mean arterial pressure...

Microalbuminuria In The Non Diabetic Population

Essential Hypertension Microalbuminuria is attracting increasing interest in essential hypertension. The quoted prevalence of microalbuminuria varies between 5 and 25 in treated hypertension and up to 40 in untreated hypertension 32-35 although some estimates are even higher 33 . Several observations indicate that those with microalbuminuria represent a distinct subpopulation amongst those with essential hypertension who may be at highest risk. Those with microalbuminuria have more activation of the renin angiotensin system with higher peripheral renin activity 34 which some believe may drive the increased urinary albumin excretion. In addition those with essential hypertension and microalbuminuria have other distinguishing features. Microalbuminuria in essential hypertension is related to higher salt intakes and to salt-sensitive hypertension. In one study of 839 patients either normotensive or with untreated essential hypertension systolic blood pressure and urinary sodium excretion...

Actions Of Angiotensin Ii

Inhibition of Angiotensin II might be the main issue in the diabetes patient with hypertension, nephropathy or both conditions in coexistence. The effects of this active metabolite are potentially damaging to an extent superior to many other peptides and metabolites. This makes inhibition and control of Angiotensin II essential. Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. All these factors are essential to the subsequent pathogenesis of renal and cardiovascular disease in patients with diabetes and hypertension.

Early treatment in type diabetic patients without complications

Type 2 diabetic patients with established nephropathy aggressive treatment In the past, once hypertension and increased serum cholesterol had been identified as risk factors, the effect of treatment specifically aimed to lower these risk factors was tested in randomized trials -and several antihypertensive and cholesterol lowering drugs proved to be effective in reducing end-organ damage. Evidence from the large trials in type 2 diabetic nephropathy is now available showing the importance of proteinuria as a modifiable risk factor. In particular, this is underscored by the finding that the degree of proteinuria reduction predicts the efficacy of end-organ protection. 21. Weidmann P, Boehlen LM, de Courten M Effects of different antihypertensive drugs on human diabetic proteinuria. Nephrol.Dial.Transplant. 8 582-584, 1993 36. Lee TM, Su SF, Tsai CH Effect of pravastatin on proteinuria in patients with well-controlled hypertension. Hypertension 40 67-73, 2002 42. Barton M, Carmona R,...

Intervention Programme For Treatment Of Persistent Microalbuminuria gmin

In children with microalbuminuria ( 20-200 g min) blood glucose control should be improved over a period of 6 months and the status of microal-buminuria should be monitored closely. If microalbuminuria disappears or improves there is no indication for pharmacological intervention. However, if the microalbuminuria deteriorates, whether or not blood glucose control improves and blood pressure is within the normal limits, antihypertensive treatment by an ACE-inhibitor should be instituted. The ACE inhibitors have potential therapeutic advantages over other antihypertensive drugs because they may selectively reduce efferent arteriolar pressures, and thereby glomerular capillary pressures, by lowering angiotensin II levels 88,89 . There has been extensive experience with ACE inhibitor use in children and therapy has been associated with very few side effects at low doses in the presence of normal renal function 78,84,90,91 . However, long-term follow up studies in children are required to...

Human Diabetic Kidney Disease And Tgfb

Another study was designed to determine if diabetic patients have enhanced renal production of TGF-P 88 . Aortic, renal vein, and urinary levels of TGF-P were measured in fourteen type 2 diabetic and eleven non-diabetic control patients undergoing elective coronary artery catheterization. Both groups were roughly matched with regard to the range of renal function and the presence of hypertension and proteinuria. Renal blood flow was measured to calculate the net mass balance across the kidney. The gradient of TGF-P1 concentration across the renal vascular bed was negative in the non-diabetic patients indicating net renal extraction of TGF-P1, whereas the gradient was positive in the diabetic patients indicating net renal production of TGF-P1. When the renal TGF-P1 mass balance was calculated, a similar pattern was observed with the non-diabetic kidney removing approximately 3500 ng min of TGF-P1 from the circulation, and the diabetic kidney adding approximately 1000 ng min of TGF-P1...

When To Intervene In Type Diabetic Patients

Regarding assertion I), the lack of predictive power of microalbuminuria, it is important to recognize methodological problems, such as selection bias In a study by Forsblom et al 23 progression of microalbuminuria to proteinuria ten years later was found in only 25 . However, by selecting patients with over 15 years of duration mean duration 26 years the study was biased towards patients less likely to progress. This was demonstrated by Rossing et al. who reported progression to proteinuria in 45 of microalbuminuric patients with duration 15 years 24 . Also changes in treatment strategies over time must be taken into consideration the reduction in progression to proteinuria in some recent series of patients may reflect the increased use of antihypertensive treatment especially in microalbuminuric patients and the effectiveness of this intervention in postponing overt nephropathy. In the largest double-blind randomized trial of 235 normotensive type 1 diabetic patients with...

Low Birth Weight Glomerular Number And Diabetic Nephropathy

These glomerular changes result in decreased total glomerular filtration surface area, giving rise to reduced total filtration surface area resulting in glomerular hypertension due to reduced renal functional reserve. The diabetic patients with the least and or smallest glomeruli will then be more prone to develop irreversible renal failure when exposed to a renal insult in later life. Such a unification of the Barker and Brenner hypothesis within respect to diabetic nephropathy is disputed. Rats exposed to low protein diet (LPD) in utero have reduced birth weight, smaller kidneys and hypertension compared to those exposed to normal protein diet (NPD) in utero 36, 50 . One study has examined the acute renal response to streptozotocin diabetes in LPD rats 36 . LPD rats demonstrate a greater proportional increase in glomerular volume and renal size in response to diabetes compared to NPD rats and they fail to normalise glomerular volume with insulin. Human studies suggest that...

Peripheral vascular resistance

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. these grounds, it has been argued that insulin-induced vasodilatation is not an important determinant of insulin's metabolic effects. A possible objection is that if tissue perfusion increases in insulin sensitive but decreases in noninsulin sensitive tissues then total blood flow will not be substantially altered. Recent PET studies 16 have indeed shown that leg muscle blood flow is distributed in a heterogeneous pattern, and that glucose uptake tends to co-localise with higher perfusion rates in response to strong insulin stimulation. However, no difference between normal subjects and insulin resistant type 2 diabetic patients has been observed. These findings may simply reflect regional differences in muscle fibre composition, as oxidative type I fibres are both more sensitive to insulin and more richly capillarised...

Diabetic Nephropathy And Perinatal Outcome

In spite of the dramatic improvements in perinatal outcome over the last 25 years in pregnancies of diabetic women 228 , complications remain more frequent when DN is present. Examining the pooled results of 13 clinical series published in 1981-96 (table 6) 36,38, 95,96, 98, 100,101,148, 189192,229 , of 265 infants born to women with DN, nearly 2 3 were preterm deliveries prior to 37 weeks gestation, 72.5 were delivered by cesarean section, and respiratory distress syndrome was diagnosed in 24.5 of liveborn infants. Fetal growth restriction was noted in 14.3 , and the major correlates of small size for dates were the degree of maternal hypertension and impaired renal function 95,96,191 . Major congenital malformations were diagnosed in 7.6 of the 265 infants. The frequencies of these perinatal complication were similar in 90 pregnancies reported in 1981-88 compared to 175 reported in 1992-96 (table 6), and in the subsequent reports of Reece et al 193 and Biesenbach and colleagues 230...

Generalised Endothelial Dysfunction Chronic Lowgrade Inflammation Microalbuminuria And Atherothrombosis

In both type 1 and type 2 diabetes, patients with advanced nephropathy (macroalbuminuria) have a greatly increased risk of severe retinopathy, neuropathy and atherothrombotic disease. This pattern can be observed even in early nephropathy, i.e. microalbuminuria, which has raised the question of what common mechanisms may be at work 1,2,22 . Because (micro-)albuminuria is often associated with classic risk factors for microangiopathy and atherothrombosis, notably poor glycaemic control, hypertension, obesity, dyslipidaemia and smoking, an obvious possibility is that such risk factors cause both (micro-)albuminuria and atherothrombosis and thus explain their

Structural Changes That May Impair Autoregulation Of

The most characteristic glomerular lesion in patients with incipient or overt nephropathy is mesangial expansion. Biopsies from patients with hypertension and or diabetic nephropathy have furthermore revealed arteriolar hyalinosis 71,72 . Arteriolar hyalinosis may impair the afferent arteriole capacity to constrict, and can thereby lead to enhanced transmission of the systemic BP into the glomerular capillary network, and lead to glomerular hypertension 19,73,74 . This haemodynamic alteration is associated with increase wall tension causing distension of the elastic glomerulus. Studies have shown that mechanical stretch of vascular smooth muscle cells, vascular endothelial cells and mesangial cells leads to an overproduction of extracellular matrix 75,76 . Mesangial expansion is closely associated with renal function in diabetic nephropathy 77 . This relationship probably results from the expanding mesangium compromising the structure of contiguous glomerular capillaries and from a...

Microalbuminuria As A Risk Factor Type diabetes

It is important to identify all Type 1 diabetic patients with microalbuminuria because the progression of their disease can be delayed. Antihypertensive treatment reduces the fall rate of GFR by 50 from 10 to less than 5 ml (min*year) as observed in patients with clinical nephropathy 66-69 . The effect may be even more impressive when treatment is started at the first signs of an increasing blood-pressure but before development of overt hypertension 56, 70 . The effect of antihypertensive treatment is further emphasized by the important observation of an increased patient survival following the implementation in the late seventies of early antihypertensive treatment 71 . Also in Type 2 diabetic patients the causal link between microalbuminuria and generalized vascular disease is unknown. It is likely that a link should be found in alterations in the composition of the basal membranes of the capillaries and of the extracellular matrices as also hypothesized in Type 1 diabetic patients....

Predicting Patients With Nondiabetic Renal Disease

The course of diabetic nephropathy, with microalbuminuria preceding heavier proteinuria and nephrotic syndrome, is well documented, particularly in type 1 diabetes 32 . Patients who develop significant, nephrotic range proteinuria without preceding microalbuminuria despite appropriate testing should be considered for biopsy. For patients who develop lesser degrees of proteinuria (for example

Patients with diabetes mellitus

In a prospective controlled trial with concealed randomisation, Hansen et al. 36 demonstrated a reversible decline in GFR (51Cr-EDTA plasma clearance) and albuminuria in 14 type 1 diabetic patients with diabetic nephropathy during short-term (3-5 weeks) treatment with a low protein diet (recommended 0.6 g kg day). Correspondingly with a decrease in dietary protein intake of 0.4 g kg day, there was a reversible decline in GFR and albuminuria of approximately 8 and 29 , respectively. These changes were independent of glycaemic control, energy intake and blood pressure. The initial decline in GFR during dietary protein restriction was greater in patients with elevated GFR, as demonstrated in the MDRD study 39 . Interestingly, the antiproteinuric effect of dietary protein restriction was obtained during antihypertensive treatment mostly with ACE-inhibitors and was associated to the degree of dietary protein restriction, suggesting at least partly independent but additive effects of these...

Course Of Nephropathy During Pregnancy

Reassuring since hyperfiltration and hypertension in the glomerulus is considered a prerequisite for human DN. With DN in pregnancy, the expected rise in CrCl is seen in only about one-third of patients, as summarized in table 2 38,95,96 . In another one-third of DN patients, CrCl actually decreases, probably reflecting the underlying natural progression of nephropathy or accelerating hypertension. In a recent analysis, initial elevated Cr of 109-163 M (1.0-1.5 mg dL) was associated with a decline in CrCl during pregnancy in 12 women with DN, whereas in 9 patients with initial Cr 163 M (1.5 mg dL), CrCl remained stable but low at 41-65 ml min 97 . When inverse serum Cr levels are used as an indicator of GFR, about one third of DN patients show a rise in Cr by the third trimester, related to reduced renal function at baseline and or superimposed PET 98-102 . A rise in Cr was associated with cross-over from a hyperdynamic cardiac output to a vasoconstricted state in a preliminary report...

Transforming Growth Factor And Other Cytokines In Experimental And Human Diabetic Nephropathy

Penn Center for Molecular Studies of Kidney Diseases, Renal-Electrolyte and Hypertension Division, Department of Medicine, University of Pennsylvania Philadelphia, PA, USA Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved.

Dietary Salt Intake And Diabetic Nephropathy

Systemic blood pressure elevation accelerates the progression of diabetic nephropathy in both type 1 and type 2 diabetic patients 93 , and effective antihypertensive treatment reduces albuminuria and the rate of decline in GFR in these patients. Extracellular fluid volume expansion due to impaired renal sodium excretion is the most clinically important mechanism that leads to the development of secondary hypertension in diabetic and non-diabetic patients with chronic renal disease 94 95 . Regardless of which specific antihypertensive agent is used, sodium restriction and treatment with loop diuretics is of major importance for the management of hypertension in these patients 95 . Recent short-term studies have demonstrated that the antiproteinuric effect of blockers of the renin-angiotensin-system RAS and nondihydropyridine calcium channel blockers is enhanced during dietary salt restriction independently of the blood pressure reduction in both diabetic and non-diabetic renal diseases...

Progression of diabetic nephropathy

Protein diet (achieved 0.67 g kg day) of 33 months. The rate of decline in GFR was 7.3 ml min year during a normal protein diet and 1.7 ml min year during a low protein diet (p80 ), predominantly with ACE-inhibitors. In the MDRD study 4G 585 patients with chronic renal diseases were randomly assigned to a low protein diet (pre-scribed G.58 g kg day achieved G.77 g kg day) or an usual protein diet (pre-scribed 1.3 g kg day achieved 1.1 g kg day) for two years. At entry and during follow-up, an equally number of patients in each diet group received antihypertensive treatment (8G ), mainly with ACE-inhibitors. In the intention-to-treat analysis the projected decline in GFR was 1.2 ml min year less (NS) in the low protein diet group compared to the usual protein diet group. However, dietary protein restriction induced a biphasic decline in GFR, with a faster initial and a slower subsequent decline in GFR. The subsequent decline in GFR was 28 less in the low protein diet group compared to...

Evaluation Before Conception

Control hypertension angiotensin inhibition prior to pregnancy other agents during pregnancy Evaluation for diabetic microvascular disease and hypertension are critical. Creatinine clearance (CrCl) as an estimate of glomerular filtration rate (GFR), and the degree of microalbuminuria (incipient DN, urinary albumin excretion UAE 30-299 mg 24 hrs, 20 .g min) or urinary total protein excretion TPE (overt DN, 500 mg 24 hrs total protein or 300 mg 24 hrs albumin, 200 g min albumin,) 12 should be quantified, preferably with a 24-hour specimen 13-20 . If overt DN is diagnosed, the patient should be thoroughly counseled regarding measures used to improve outcomes of pregnancy and the possible vascular complications and life expectancy. Hopefully then the decision on whether to attempt pregnancy will be more informed. Renoprotective or antihypertensive therapy is indicated for patients with microalbuminuria or overt nephropathy 28 and agents used should be effective and safe in early pregnancy...

Endothelial Dysfunction Insulin Resistance And The Metabolic Syndrome

Insulin resistance usually precedes the development of type 2 diabetes and is often accompanied by a cluster of other risk factors (see above). The mechanisms underlying this clustering are still unclear, but all elements of the cluster share two important pathophysiological features, namely insulin resistance and endothelial dysfunction. A widely accepted theory states that insulin resistance is the primary abnormality that gives rise to type 2 diabetes, hypertension and How can endothelial dysfunction impair insulin-induced glucose disposal Firstly, insulin is a vasoactive hormone. Insulin increases muscle blood flow in a time- and concentration-dependent fashion through a mechanism that involves binding to the insulin receptor on the endothelial cell membrane and that can be abolished by inhibiting nitric oxide synthase. Nevertheless, insulin-induced increases in glucose uptake and total blood flow have different concentration-effect curves as well as time kinetics. Therefore, it...

Pregnancy After Renal Transplantation

Ogburn et al. compiled the experience of 9 diabetic women from several centers who had pregnancy after renal transplantation for DN 290 . All were managed with prednisone and azathioprine no transplant rejections occurred during pregnancy. Complications were frequent, including PET in 6, fetal distress in 6, and preterm delivery in all. Armenti and the US National Transplant Pregnancy Registry (NTPR) reported 28 pregnancies in diabetic renal transplant recipients after cyclosporine A (CsA) was added to the immunosuppression regimen to decrease acute rejection 291 . Rejection was observed in 4 and graft dysfunction in 11 . Preeclampsia was diagnosed in 17 although 59 had hypertension - 47 of the infants had neonatal complications. prematurity to low birth weight is unclear 218, 292,293, 299,300 . Perinatal mortality ranges 30-270 1000 in pregnancies after renal allografts across several decades, but the high figures are in earlier pregnancies without recent improvements in perinatal...

Traditional Cardiovascular Risk Factors

Hypertension, dyslipidemia, obesity and smoking, that is, the classic cardiovascular risk factors, each contribute to the risk profile in the patient with type 2 DM. Hypertension develops in about half of the patients with type 2 DM. This is important, not only because increased systemic blood pressure is a cardiovascular risk factor, but also because of the association between hypertension and accerated renal function loss. Moreover, effective blood pressure control is associated with a slower disease progression, possibly because of a concomitant amelioration of intracapillary hypertension and protein ultrafiltration in the kidneys. Thus, patients in the IDNT who had lower systolic blood pressure levels during treatment also had a markedly lower risk to reach a renal endpoint 28 . Although the study was not designed to compare the renal effects of different levels of achieved blood pressure control, the findings do favour an important effect of lowering systolic blood pressure in...

Efficacy of treatment

Beta-blockers are able to reduce post-MI mortality in diabetic patients, with an absolute and relative beneficial effect in most cases larger than that observed in non-diabetics. Current evidence is based on subgroup analysis of several trials performed during the eighties and on non-randomized studies 21 , in which the population of patients with diabetes was scarcely represented. However, the pooled data indicate a 37 mortality reduction during the acute phase (13 in non-diabetics) and a 48 mortality reduction post-discharge (33 in non-diabetics). Since all these studies were performed before the advent of fibrinolytic therapy, the question remains whether this marked beneficial effect is still present in more updated populations. In a recent observational study conducted on 613 MI survivors with diabetes 22 , use of beta-blockers (recorded in 53 of patients with diabetes) was associated with a 27 risk reduction in the incidence of a new coronary event, adjusted for age, sex,...

Cardiovascular Disease And Proteinuria

The Losartan Intervention For Endpoint reduction in hypertension (LIFE) trial provided an opportunity to study the effects of treatment with the angiotensin II receptor antagonist losartan versus the beta-blocker atenolol in hypertensive patients with diabetes. This study investigated the effects of losartan- versus atenolol-based therapy in 9193 patients with hypertension and left ventricular hypertrophy followed for a mean of 4.8 years 127 . Lindholm et al analyzed the LIFE subgroup of 1195 patients with diabetes, hypertension, and left ventricular hypertrophy, and reported that in this subgroup of patients losartan reduced the risk of the primary composite endpoint of cardiovascular morbidity and mortality by 24 P 0.031. The risk of cardiovascular mortality was 37 lower in the losartan group than in the atenolol group (P 0.028). Total mortality was 39 lower in the losartan group (P 0.002) 128 .

Extraglomerular Changes

In quantitative ultrastructural studies the composition of arteriolar walls was estimated in NA and MA IDDM patients and in controls 18 . All of the patients had clinical blood pressure within the normal range. Increased matrix per media was found in afferent and efferent arterioles in the MA patients, showing that matrix abnormalities have developed in this location at the earliest stage of nephropathy. The matrix media volume fraction of the afferent arterioles correlated with glomerular parameters, both BMT and matrix glomerular volume fraction. Quantitative data are now available in one follow-up study, before and after antihypertensive treatment 19 . At baseline highly significant alterations were present in afferent and efferent arterioles. In the follow-up period of 2,5 years a moderate progression was observed in matrix media volume fraction in afferent arterioles, but no significant worsening in the efferent arterioles. After 8 years a large increase in the matrix media...

The Reninangiotensinaldosterone System And Proteinuria

Inhibitor therapy have not been replicated in type 2 diabetes. Studies of the effect of angiotensin converting enzyme inhibitors on proteinuria beyond blood pressure control have been relatively small and inconsistent, with some trials demonstrating a reduction in proteinuria 82-85 , while others, including United Kingdom Prospective Diabetes Study (UKPDS) 80 and Appropriate Blood pressure Control in Diabetes study (ABCD) 86 , failing to demonstrate these benefits beyond blood pressure control. Data in support of prevention of end-stage renal disease with the use of angiotensin converting enzyme inhibitors in patients with type 2 diabetes do not exist 80, 82-86 . When renoprotection is a goal, patients with type 2 diabetes should have an angiotensin receptor antagonist as part of their antihypertension regimen. Angiotensin receptor blockers have been efficacious in overt hypertensive type 2 diabetic nephropathy (RENAAL and IDNT), and diabetic microalbuminuria with 87 and without...

Albuminuria And Renal Structure In Niddm

Although the principal endpoint in evaluating the influence of an antihypertensive agent on renal function in diabetes is its ability to alter the progression of the disease, it is clear that abnormally elevated albuminuria is also associated with progressive renal injury 132 . Nevertheless, many of the short-term trials that have been performed in DM2 subjects only document a reduction in albuminuria in the absence of a change in glomerular filtration rate. Long-term studies in both DM1 and DM2 subjects suggest that the severity of proteinuria also correlates with the rate of progression of renal disease 4, 6, 133 . Nonetheless, studies involving renal structural assessment are warranted to more accurately determine the response to antihypertensive agents. Fioretto et al have investigated the underlying renal pathology which occurs in DM2 patients with various stages of nephropathy 134 . There appears to be a marked variation in the degree of glomerulosclerosis and tubulointerstitial

Studies Investigating The Barker Hypothesis

The Leningrad Siege Study compared two groups of offspring from Leningrad those born during the siege (1941 - 1944) as an intra-uterine malnutrition group, those born before the siege as an infant malnutrition group and a group from outside the city as an unexposed group. In contrast to Barker's studies there was no difference between the intra-uterine and infant groups with respect to the following glucose intolerance, insulin concentration, blood pressure and lipid levels. Despite the problems of the lack of accurate birth weight data and low case ascertainment (only 44 of eligible subjects were screened) this study subjects that intra-uterine malnutrition does not have a major role in the pathogenesis of adulthood glucose intolerance and hypertension 17 . hypertension

The Relationship Between Low Birth Weight Systolic Blood Pressure And Glomerular Number

Hypertension is an independent risk factor for the development of chronic diseases in adulthood such as ischaemic heart disease 45, 46 and its presence prior to the development of diabetes increases the risk of developing diabetic nephropathy 47 - 49 . All of the large epidemiological studies investigating the link between hypertension and LBW have been unable to determine whether this association was due to a reduction in glomerular number. It is likely that other factors such as family history, adulthood obesity and smoking are much more important in the pathogenesis of hypertension. Very few published animal studies have measured systolic blood pressure and estimated glomerular number in LBW rats. In studies using intra-uterine low protein diet, rats exposed to low protein diet have reduced glomerular number, raised systolic blood pressure and lower birth weights compared to controls 36, 50 . This suggests that the relationship between LBW and systolic blood pressure may only hold...

Value Of Early Therapy

The treatment of hypertension has long been recognized as a means for attenuating the course of overt nephropathy 18 (See Chapters 31 and 33). In recent years the particular value of ACEI or ARBs in such treatment has been established 1, 25-28 . When applied at a GFR of approximately 40 ml min, ARBs delays ESRD by about two years compared to other antihypertensives. Probably another two years reprieve would occur for every 30 ml min higher level of initiation 1, 25 . That is, four years would likely be gained if the drugs were started with overt proteinuria but a GFR of 70 ml min. The earlier the treatment of overt nephropathy, the more time free of ESRD is gained. For some observers, the major remaining point of uncertainty is the advantage of applying these drugs during the microalbumiuric phase and particularly in those who remain normotensive at that phase. Most patients with type 2 diabetes and microalbuminuria have hypertension especially if current JNC 7,

The Barker Hypothesis

Changes in hormone levels occur during fetal life 13 . Extensive research has focused upon changes in maternal glucocorticoids 14, 15 to explain the association between LBW and hypertension. It is hypothesised that dysfunction of the placental glucocorticoid barrier results in increased fetal exposure to maternal glucocorticoids which, in turn, effects the development of fetal vessels and thus increases the risk of adulthood hypertension 14 .

Methodological Aspects A Guide To The Critical Reader

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. Patients who are hypertensive by clinic measurements but show a normal ambulatory BP are designated white coat hypertensive 22 . This term is well understood in literature although isolated clinic hypertension may be more precise 23 . The effect of the white coat was originally described as a transient (5 min) elevation of BP 23 . At present the white coat effect is usually calculated as the difference (clinic BP - day time BP) 24 . The proportion of white coat hypertensive subjects in a hypertensive population depends on i The definition of hypertension (usually clinic BP 140 90 mmHg) ii How carefully the hypertensive subjects are identified (if patients are labelled as hypertensive based on only one clinic BP the frequency of white coat hypertension is high, if a several clinic BP measurements -as recommended- are...

Racial Differences In Prevalence Of Renal Disease

Mogensen CE (ed.) THE KIDNEY AND HYPERTENSION IN DIABETES MELLITUS. Copyright 2004 by Martin Dunitz, a member of the Taylor & Francis Group, plc. All rights reserved. The reasons for inter-population differences in rates of renal disease are unclear. Rostand 10 has argued that barriers to medical care for African Americans and Mexican Americans may impede early detection, and therefore, control of microalbuminuria and hypertension with a consequent adverse effect on the prevalence of renal disease. However, the cost, one of the major barriers to medical care, is not a factor for the Pima Indians, who have access to free medical care by providers who are well aware of the high risk of diabetic renal disease in this population. Thus, cost of medical care cannot be the only reason for racial differences. However, other aspects of access to medical care, such as transportation or cultural barriers, could be important.

The Role Of Proteinuria In The Diagnosis And Treatment Of Type Diabetes

Diabetic nephropathy as a sequela to type 2 diabetes has become the leading cause of end-stage renal disease. Diabetic nephropathy is approximately twice as common a cause of end-stage renal disease than is nephropathy caused by hypertension or primary glomerular diseases. Mortality among patients receiving chronic hemodialysis is estimated to be 21-25 per year, with the majority of deaths secondary to cardiovascular causes. Even though current recommendations for diabetics include the need for early screening for microalbuminuria, these patients who are at high risk for the development of nephropathy often go unidentified. At the time of diagnosis of type 2 diabetes, approximately 30 of the patients will already have albumin or protein in the urine 75 will have microalbuminuria (30-300 mg 24 hr), and 25 will have overt proteinuria ( 300 mg 24 hr). Persistent albuminuria indicates underlying structural changes in the kidney consistent with diabetic nephropathy 4-8 . Microalbuminuria...

Cardiovascular Risk Factors In Microalbuminuria Familial Predisposition

Positive family histories of hypertension or CVD in the non-diabetic parents are related to the development of albuminuria in the diabetic proband emphasising the shared predisposition to these two conditions. These associations hold true for both Type 1 and Type 2 diabetes after adjustment for age, sex and duration of diabetes 56, 57 . There is also some evidence for a familial predisposition to develop microalbuminuria in association with essential hypertension. Children with one hypertensive parent have a higher AER than children of a normotensive parent while normotensive adults with at least one hypertensive parent have elevated AER compared to normotensive adults with a negative family history for arterial hypertension 58 .

Placebocontrolled trials of diureticbased and betablockerbased therapy

By 1990, the benefits of blood pressure lowering on the risk of initial stroke among hypertensives had been clearly established from an overview of 14 randomised controlled trials that principally used regimens based on diuretics and beta-blockers 15 . The findings of these trials, which were mainly conducted among middle-aged subjects with mild-moderate essential hypertension, were subsequently extended by results of trials in older subjects with both essential hypertension and systolic hypertension. In combination, these trials demonstrated that net reductions of 10-12mmHg in usual systolic blood pressure and of 5-6 mm Hg in usual diastolic blood pressure were associated with a 38 reduction in the risk of stroke within just a few years of starting treatment 16 , matching the benefit predicted from epidemiological studies 6,7 . Table 1. Characteristics of placebo-controlled trials of antihypertensive therapy that included participants with diabetes Table 1. Characteristics of...

Summary And Conclusions

Despite intensified metabolic control and antihypertensive treatment of diabetic patients, the development of diabetic nephropathy remains a serious problem. There is increasing evidence for a multifactorial pathogenesis of diabetic kidney disease, including various growth factors and cytokines as active players. This article has reviewed recent evidence for the significance of GH and VEGF in the development of experimental diabetic kidney disease. In addition, experimental data strongly suggest that GH and VEGF blockade may present new concepts in the treatment of diabetic renal complications. Future studies are warranted to fully characterize the clinical potential of GH and VEGF inhibitors as drugs for treatment of diabetic complications in general. Recent observations have suggested that there most likely in an important interaction or cross-talk among various growth factors that may promote the development of diabetic kidney disease. This would imply that strategies which involve...

Mechanisms Of Albuminuria

Altogether, the present data indicate that the increased loss of albumin across the glomerular filtration barrier is a sign associated with early structural lesions of diabetic glomerulopathy and that the further development can be arrested or at least slowed by intensive insulin and or antihypertensive treatment. 19. Gulmann C, Rudberg S, 0sterby R. Renal arterioles in patients with type I diabetes and microalbuminuria before and after treatment with antihypertensive drugs. Virchows Arch 1999 434 523-528. 38. No author listed Effect of 3 years of antihypertensive therapy on renal structure in type 1 diabetic patients with albuminuria the European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT). Diabetes 2001 50 843-850. 61. Bonnet F, Cooper ME, Kawachi H, Allen TJ, Boner G, Cao Z. Irbesartan normalises the deficiency in glomerular nephrin expression in a model of diabetes and hypertension. Diabetologia 2001 44 874-877

Guidelines And Recommendations

Current national and international guidelines on the management of hypertension emphasise the need for effective lowering of blood pressure in diabetic subjects to reduce the high risk of cardiovascular complications such as stroke and myocardial infarction. Both JNC-VI and WHO-ISH 1999 specifically recommend a lower threshold for institution of blood pressure lowering treatment, and a lower target blood pressure for such treatment, in diabetics than in hypertensive patients without diabetes 52,53 both While there has been extensive debate about the merits of different classes of blood pressure lowering drug, there is now substantial evidence that any of five major classes of drug (diuretics, beta-blockers, ACE inhibitors, calcium antagonists and angiotensin receptor blockers) is effective in the primary prevention of stroke (i.e. the prevention of initial stroke) in hypertensive subjects. While there is less direct evidence in individuals with diabetes, with or without hypertension,...

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