Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with diabetes mellitus may have any one of several forms of hypertension. These include essential hypertension, systolic hypertension of three varieties, the hypertension associated with diabetic nephropathy ("diabetic hypertension"), and the hypertension associated with neuropathy (supine hypertension with orthostatic hypotension). Because there are differences in the hypertensive mechanisms in each of these hypertensions, the use of antihypertensive medications should be tailored to the type of hypertension present. In this review, the rationale for treating hypertension in the diabetic will be discussed, the mechanisms of action and potential side effects of antihypertensive drugs peculiar to the diabetic will be outlined, and specific antihypertensive therapy programs based on the mechanisms involved in producing each of the hypertensions will be detailed.
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PMID:The hypertensions of diabetes. 714 May

In both essential hypertension and diabetic nephropathy (DN), the ubiquitous cellular Na+/H+ exchanger (NHE) exhibits altered kinetics with increased transport activity. The mechanism for this phenotype and its dependence on the presence of serum are unknown, but increased lymphoblast NHE activity in DN has been attributed to a defect in post-translational processing of NHE-1 rather than an increased cellular exchanger number. Phosphorylation of NHE-1 has been proposed to play a role in its activation in a variety of cell models. We have examined, therefore, the role of NHE-1 phosphorylation and the effect of serum in determining the increased NHE-1 activity in lymphoblasts from patients with DN. Cells from these patients exhibited increased NHE activity in the presence and absence of fetal calf serum (range 42-59%, P < 0.005, analysis of variance) and an increased proliferation rate (P < 0.01) when compared with cells from both normoalbuminuric diabetic patients and non-diabetic control subjects. However, NHE-1 abundance was very similar among all groups in the presence and absence of serum, indicating that increased NHE activity in cells of nephropathy patients was due to an increased turnover number. This nephropathy phenotype was not accompanied by an increased net phosphorylation of NHE-1 in the presence or absence of serum. Our findings suggest that increased NHE-1 activity in cells of DN patients is independent of the presence of serum and is not attributable to altered NHE-1 phosphorylation. Additional post-translational mechanisms for activation of NHE-1, therefore, may be involved.
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PMID:Phosphorylation and activity of Na+/H+ exchanger isoform 1 of immortalized lymphoblasts in diabetic nephropathy. 755 55

Microalbuminuria is defined as urinary excretion of albumin that is persistently above normal, although below the sensitivity of conventional semiquantative test strips. Several studies have reported that Type 1 diabetic patients with microalbuminuria are apparently more likely to develop diabetic nephropathy eventually progressing to renal failure. Microalbuminuria is also a strong predictor of mortality in Type 2 diabetes, and is correlated with increased blood pressure in patients with benign essential hypertension. Radioimmunoassay revealed a significantly higher urinary albumin excretion rate in normal pregnant women in the third trimester of pregnancy, compared to the second and first, and compared to non-pregnant women. Microalbuminuria was found in 30% of women who had a record of gestational diabetes mellitus. Published results are controversial regarding the assumption that microalbuminuria is an early predictor of pregnancy-induced hypertensive complications.
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PMID:Microalbuminuria: prognostic and therapeutic implications in diabetic and hypertensive pregnancy. 758 1

Antihypertensive treatment can slow down the decline in glomerular filtration rate (GFR) with time. In patients with diabetic nephropathy, angiotensin converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. Whether this applies to the much larger population of patients with essential hypertension is not yet known. In the present study, the effects of two different antihypertensive therapies on the loss of GFR with time, determined with Cr51-EDTA clearance after 6, 12 and 24 months of treatment, were assessed in a prospective, randomised, double-blind trial in 257 patients with essential hypertension. All had normal renal function and none had diabetes mellitus or glucosuria. Proteinuria (dipstick positive or trace) was detected in 7 patients initially. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering systolic blood pressure (e.g. from 168 mmHg to 152 mmHg with cilazapril and from 170 mmHg to 155 mmHg with atenolol after 6 months, p < 0.001 for both). However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure at 6, 12 and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months the reduction in GFR was 1.0 vs. 4.0 ml/min x 1.73 m2, p = 0.008 (cilazapril vs. atenolol) and after 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2, p = 0.04 and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2, respectively (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACE inhibition preserves renal function better than beta-blockade in the treatment of essential hypertension. 759 59

Captopril renography was utilized to assess the presence of angiotensin II dependent renovascular dysfunction in (1) 28 patients with mild to moderate essential hypertension (EH) with unimpaired renal function, and (2) 25 hypertensive patients with diabetic nephropathy (HDN). These studies were classified according to the diagnostic criteria outlined by the Working Party on Diagnostic Criteria of Renovascular Hypertension with Captopril Renography and the mean parenchymal transit time (MPTT) was used as an index for detecting the presence of angiotensin II dependent renal haemodynamic change. Patients with EH showed non-significant or non-specific alterations in the MPTT. Four patients in the HDN group showed a significant prolongation of MPTT in the presence of renin-angiotensin-aldosterone activation due to renal artery stenosis, and the other patients in this group showed a significant decrease in MPTT after captopril, consistent with increased blood flow and improved tubular transport function in the presence of microangiopathy only. We conclude that addition of MPTT to the standard diagnostic criteria of captopril renography may be helpful in predicting the beneficial or detrimental impact of angiotensin II inhibition treatment in HDN and in limiting the test protocol in EH to one post-captopril study.
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PMID:Predictive value of captopril transit renography in essential hypertension and diabetic nephropathy. 760 34

Antihypertensive treatment has been shown to slow down the decline in glomerular filtration rate (GFR) with time. This has been most extensively studied in patients with diabetic nephropathy and, to some extent, with other forms of renal disease. Angiotensin-converting enzyme (ACE) inhibition has been shown to be more effective in this regard than conventional antihypertensive therapy. This important aspect of antihypertensive treatment has not been studied previously in patients with essential hypertension. Preliminary results regarding the effects of two different antihypertensive therapies on the loss of GFR with time, determined with 51Cr-EDTA clearance after 6, 12, and 24 months of treatment, are presented here. The GFR was assessed in a prospective, randomized, double-blind trial in 257 patients with essential hypertension. All had a normal renal function, and none had diabetes mellitus or glucosuria. The two therapeutic modalities were the ACE inhibitor cilazapril and the beta-adrenoceptor blocking agent atenolol. Both therapies were equally effective in lowering the systolic blood pressure. However, atenolol was slightly but significantly more effective in lowering the diastolic blood pressure after 6, 12, and 24 months. The decline in GFR with time was significantly smaller with cilazapril than with atenolol. After 6 months, the reduction in GFR was 1.0 (cilazapril) vs. 4.0 (atenolol) ml/min x 1.73 m2 (p < 0.01). After 12 months the corresponding changes were 2.0 vs. 4.5 ml/min x 1.73 m2 (p < 0.05) and after 24 months 3.0 vs. 4.0 ml/min x 1.73 m2 (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of angiotensin-converting enzyme inhibition versus conventional antihypertensive therapy on the glomerular filtration rate. 761 4

Mortality and morbidity from coronary heart disease (CHD), diabetes mellitus (DM) and essential hypertension (HTN) are higher in people of South Asian descent than in other groups. There is evidence to believe that essential fatty acids (EFAs) and their metabolites may have a role in the pathobiology of CHD, DM and HTN. Fatty acid analysis of the plasma phospholipid fraction revealed that in CHD the levels of gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are low, in patients with HTN linoleic acid (LA) and AA are low, and in patients with non-insulin dependent diabetes mellitus (NIDDM) and diabetic nephropathy the levels of dihomo-gamma-linolenic acid (DGLA), AA, alpha-linolenic acid (ALA) and DHA are low, all compared to normal controls. These results are interesting since DGLA, AA and EPA form precursors to prostaglandin E1, (PGE1), prostacyclin (PGI2), and PGI3, which are potent platelet anti-aggregators and vasodilators and can prevent thrombosis and atherosclerosis. Further, the levels of lipid peroxides were found to be high in patients with CHD, HTN, NIDDM and diabetic nephropathy. These results suggest that increased formation of lipid peroxides and an alteration in the metabolism of EFAs are closely associated with CHD, HTN and NIDDM in Indians.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Essential fatty acid metabolism in patients with essential hypertension, diabetes mellitus and coronary heart disease. 764 60

The primary aim of the management of hypertension should be to prevent coronary heart disease. Antihypertensive treatment should have a beneficial effect on the risk factors associated with coronary heart disease, particularly hypertension, dyslipidemia, hyperinsulinemia, and/or glucose intolerance. Other important risk factors include central obesity, left ventricular hypertrophy, hypokalemia, and smoking. In patients genetically predisposed to essential hypertension, metabolic alterations characterized by insulin resistance, hyperinsulinemia, and dyslipidemia tend to occur already before the development of hypertension, obesity, or redistribution of body fat. In the treatment of normotensive or borderline hypertensive diabetic patients, angiotensin-converting enzyme (ACE) inhibitors have shown superiority to other agents due to their antiproteinuric effect and their beneficial influence on the glomerular filtration rate. ACE inhibitor treatment of patients with overt diabetic nephropathy has been reported to reduce the risk of mortality and the need for dialysis or transplantation. Beta blockers and thiazide diuretics are still the 'gold standard' of antihypertensive therapy in non-diabetic patients, as they offer at least some prognostic benefit, while the influence of the newer antihypertensive drugs on morbidity and mortality in these patients is not yet known. Nevertheless, since practicing physicians have to treat patients rather than statistical numbers, the current trend towards a more individualized selection, including the newer antihypertensive drugs with consideration of their metabolic, cardiac, and renal action profile, is also difficult to rebut. ACE inhibitors and most calcium antagonists have already evolved as the preferred drugs for the treatment of hypertension in diabetics due to their favorable effects on some of the cardiovascular and renal risk factors.
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PMID:Differential effects of antihypertensive drugs on hypertension: associated risk factors. 774 40

In diabetic nephropathy and essential hypertension, the cellular Na+/H+ exchanger (NHE) exhibits increased activity. Whether this reflects increased numbers of NHE isoform-1 (NHE-1) transporters or increased turnover per molecule has not been established. We have used a specific polyclonal antibody directed toward the C-terminal of NHE-1 to measure NHE-1 content in cultured skin fibroblasts from diabetic patients with (DN) and without (DCON) nephropathy and normal controls (CON). NHE-1 content in fibroblasts from DN subjects was significantly less than that in the other two groups. This suggests that increased NHE activity in diabetic nephropathy is attributed to increased NHE-1 turnover per site rather than increased NHE-1 expression.
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PMID:Na+/H+ exchanger isoform-1 abundance in skin fibroblasts of type I diabetic patients with nephropathy. 778 65

Patients with diabetes mellitus are more frequently hypertensive than age-matched non-diabetic subjects. They are confronted with a markedly increased risk of coronary vascular disease, of progressive nephropathy and renal end-stage diseases. The most common type of hypertension in type I and type II diabetics is essential hypertension, probably as a consequence of insulin resistance and hyperinsulinemia. Hyperglycemia and hypertension are both significantly involved in the progression of diabetic nephropathy. Hence, the modern therapeutic concept consists of optimal blood glucose control and strict blood pressure control. Progression of the nephropathy may be halted in most of the cases by adhering to set limits in mean arterial blood pressure, glycated hemoglobin and urinary albumin excretion rate. Furthermore, a significant decrease in cardiovascular mortality may be achieved. In case the blood pressure targets cannot be met by non-drug therapies and life-style modifications, antihypertensive drug therapy has to be initiated. The selection of antihypertensives should be based on the concomitant diabetes mellitus with its additional cardiovascular risk factors hyperlipidemia and hyperinsulinemia. In general, preference should be given to so-called metabolic neutral substances such as ACE inhibitors or calcium antagonists or to alpha-blockers which may have positive metabolic effects. Meanwhile, data from several prospective studies claim that ACE inhibitors and calcium antagonists exert nephroprotective effects beyond their beneficial blood pressure lowering effects, thereby preventing the progression of diabetic nephropathy. However, these drugs should not be uncritically used and we should be aware of their potential adverse effects. The differential therapy of hypertension in diabetes mellitus requires mature consideration before initiation of therapy, an individualized concept of therapy, and careful monitoring during treatment.
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PMID:[Hypertension, microalbuminuria and insulin resistance in diabetes mellitus]. 784 97


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