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We report a case of diabetic nephropathy with impaired glucose tolerance. A 52 year obese woman with nephrotic syndrome and hypertension showed severe and remarkable edema, as her legs were elephantiasis. To be clear the etiology of nephrotic syndrome, we performed renal biopsy. The histological findings of the specimen showed glomerulosclerosis. Additionally the examination of ocular fundus revealed microaneurysm and avascular area. We concluded that diagnosis of this case must be non-insulin-dependent diabetes mellitus.
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PMID:[A case of the diabetic nephropathy without hyperglycemia]. 159 32

Renal pathological changes of diabetes include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is related to proteinuria, hypertension, and declining GFR. Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. Parallel findings were documented for type I membranoproliferative glomerulonephritis in which the increased mesangial volume fraction was related to decreased GFR, increased glomerular permeability to protein, and hypertension. As in diabetes, the cortical interstitial volume fraction is correlated with functional abnormalities in type I membranoproliferative glomerulonephritis. Thus, in both of these chronic glomerular disorders, mesangial expansion and interstitial expansion are associated with disordered renal function. Thus, it is not true that glomerular structural changes correlate poorly with glomerular function. Whether it is the glomerular or interstitial pathology or both that is causally responsible for the dysfunction requires further study.
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PMID:Renal structure and function in insulin-dependent diabetes mellitus and type I membranoproliferative glomerulonephritis in humans. 160 Jan 34

Hypertension should be detected and treated early in diabetic patients. It markedly affects the morbidity and mortality of diabetic individuals as a result of both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. No prospective studies have addressed the effects of antihypertensive regimens on the incidence of congestive heart failure, stroke, and coronary artery disease in large groups of diabetic patients. Such studies are urgently needed. Special consideration should be given to the effects of antihypertensive drugs on glycemic control and the lipid profile of the diabetic patient. Because hyperinsulinemia (and insulin resistance) have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may become an important element in the selection an antihypertensive agent. More information, however, is needed in these areas. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer a more favorable metabolic profile as compared with diuretics and beta-blockers. The former agents should be used as initial drugs in most clinical settings.
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PMID:Management of hypertension in diabetes. 161 71

Diabetic nephropathy is the most important complication of diabetes, because it is a major cause of morbidity and mortality for diabetic subjects. Since not all subjects with diabetes are at risk of developing this complication, we conducted a study to determine if heredity might be a possible risk factor for diabetic nephropathy in non-insulin dependent diabetes. Twenty-one factors including inheritance of nephropathy and hypertension were investigated in 109 individuals with NIDDM: 50 patients without proteinuria (Group I), 20 patients with intermittent proteinuria (Group II), and 39 patients with continuous proteinuria (Group III) matched for age and duration of diabetes. Of those patients, 55 patients with inheritance of diabetes were also divided into three groups: 29 patients without proteinuria (Group I), 9 patients with intermittent proteinuria (Group II), and 17 patients with continuous proteinuria (Group III). Individuals in Groups II and III has significantly higher frequency of inheritance of diabetic nephropathy than those in Group I, and also individuals with inheritance of diabetic nephropathy had significantly higher frequency of diabetic nephropathy than those without it. Frequency of hypertension, retinopathy and body mass index in the past were significantly higher in subjects in Groups II or Group III than in those in Group I. There were no significant differences between subjects in Groups II and III. These findings suggest that susceptibility to diabetic nephropathy in NIDDM may be hereditary, although hypertension and obesity may also be important risk factors for diabetic nephropathy.
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PMID:[The possibility of hereditary factors in the susceptibility to diabetic nephropathy in NIDDM]. 163 29

Early screening for hypertension in diabetic patients and for glycoregulation abnormalities in hypertensives is justified by the additive cardiovascular risks when hypertension and diabetes co-exist and by the accelerated development of diabetic nephropathy and retinopathy if hypertension co-exists. In insulin-dependent diabetes, hypertension is generally preceded by microalbuminuria, known to be reduced by angiotensin converting enzyme inhibitors. The requirement for nephropathy prevention and the hemodynamic and/or tissular effects of this therapeutic class could justify their use at a blood pressure level less than that conventionally considered hypertensive. This strategy must be confirmed by prospective trials, already underway, evaluating the nephroprotective efficacy of this therapy. In non-insulin-dependent diabetes, hypertension is often present before the diabetes is diagnosed and antihypertensive therapy, especially thiazide diuretics, could play a demasking or favorizing role. The optimal blood pressure level to which these patients at high renal and coronary risk should be lowered still has to be determined. A prospective study, comparing the effects of strict (treated diastolic blood pressure less than 80 mmHg) and less strict (treated diastolic blood pressure between 90 and 100 mmHg) hypertensive control on coronary event prevention in essential hypertension, is in progress and will have important implications for hypertension treatment in diabetics. Appropriate treatment of other risk factors, such as hyperlipidaemia and smoking, contributes to coronary and renal prevention in all diabetic hypertensives.
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PMID:[Treatment of hypertension in diabetes: threshold of intervention and therapeutic options]. 163 6

The role of a community-based screening programme for microvascular complications of diabetes and hypertension was evaluated in the semi-rural town of Trowbridge (population 31,000). Of 405 diabetic patients identified (prevalence 1.31%), 358 (88%) attended for screening, 94 (26%) of whom were under hospital review for diabetes. In only 136 patients (38%) were all aspects of diabetes care found to be satisfactory. The remaining 222 patients included 162 patients with poor metabolic control (HbA1 greater than or equal to 12%), 118 who were hypertensive at screening, 13 with previously undiagnosed diabetic nephropathy, and 29 with undiagnosed potentially sight-threatening retinopathy. Overall standards of diabetes care in this community population appear inadequate, and might be improved by introduction of a simple screening programme for diabetic complications.
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PMID:Screening programme for microvascular complications and hypertension in a community diabetic population. 164 4

Endogenous digital-like substance (DLS) is increased in patients with essential hypertension and is hypothesized to play a role in the pathogenesis of high blood pressure. Whether an increase in DLS in diabetic patients with hypertension is associated with a family history of hypertension or diabetic nephropathy was investigated. Plasma DLS was measured as Na(+)-K(+)-ATPase inhibitory activity (ATPI) in 100 Type 2 diabetic patients. Ouabain was used as a standard of Na-K-ATPase inhibition. Diabetic patients with hypertension demonstrated a greater ATPI level than normotensive diabetic patients (p less than 0.05). In patients with hypertension groups, the positive family history group had a higher ATPI level than the negative family history group (p less than 0.01). Microalbuminuria was not correlated with the ATPI level in diabetic patients. These results suggest that ATPI might play a role in the pathogenesis of hereditary hypertension associated with diabetes mellitus, but not have etiologic significance in diabetic nephropathy.
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PMID:Elevated endogenous digitalis-like substance in hypertensive diabetic patients with a family history of hypertension. 165 64

Diabetic patients who develop proteinuria show a marked increase in cardiovascular morbidity and mortality. The precise pathogenesis of human diabetic kidney disease and the factors responsible for the susceptibility to it remain, in part, obscure. However, there is now evidence that renal disease clusters in families and that genetic factors may be of central importance in determining susceptibility. Predisposition to arterial hypertension has been suggested as playing a contributory role in the development of kidney disease. Hypertrophic processes may be implicated in the susceptibility to arterial wall damage and glomerular injury in diabetes. Interestingly, fibroblasts of patients with diabetic nephropathy show a higher Na+/H+ antiport activity and a greater 3H-thymidine incorporation into DNA than fibroblasts of diabetic patients without nephropathy. The first clinical signs of renal involvement are the appearance of microalbuminuria and a small elevation in arterial pressure. Mesangial expansion accompanies these changes. Microalbuminuria is associated with abnormalities of lipoprotein profiles and higher Na+/Li+ countertransport rates. The environmental changes brought about by diabetes could lead in susceptible individuals to increased systemic and intraglomerular pressures on the one hand and to mesangial expansion on the other. These two processes would cause proteinuria and glomerulosclerosis. Lipid abnormalities may further aggravate the renal histological damage and, in combination with hypertension, contribute to the accelerated atherosclerosis typical of patients with diabetic kidney disease. A vicious circle would thus be triggered, involving reduction in renal function, further hypertension, proteinuria, glomerular obsolence and hyperlipidaemia, and eventually end-stage renal failure or premature cardiovascular death.
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PMID:Risk factors for renal and cardiovascular disease in diabetic patients. 165 64

Digitalis-like substance (DLS) was measured by Na-K-ATPase inhibitor (ATPI) activity and digitalis-like immunoreactivity (DLI) in 100 patients with type II diabetes. Hypertensive diabetic patients with a positive family history for hypertension had high ATPI levels compared with those patients with a negative family history for the disease. DLI level did not differ between groups. There was no significant difference in ATPI and DLI levels among three groups based on level of urinary albumin excretion. These data suggest that a circulating factor (or circulating factors) determined by ATPI may be linked with genetic factors in the development of hypertension, but not to the development of diabetic nephropathy.
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PMID:Elevated endogenous Na-K-ATPase inhibitor activity in hypertensive diabetic patients with a family history of hypertension. 166 15

Patients with diabetes mellitus have an increased prevalence of hypertension and its vascular consequences, including coronary and cerebrovascular disease. Drug treatment of hypertension in diabetic subjects is fraught with potential difficulties, including the altered efficacy of medications, the increased risk of side effects, and the possibility of worsening glycemic control and increasing serum lipid levels. Despite these difficulties, treatment is an important part of reducing morbidity and mortality from vascular events. Antihypertensive therapy may also have the potential to prevent or retard the development of diabetic nephropathy. In this article, we discuss the efficacy and metabolic and nonmetabolic side effects of the various classes of antihypertensive agents in patients with diabetes mellitus and suggest a stepped-care approach to the drug treatment of patients with hypertension and diabetes.
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PMID:Drug treatment of hypertension in patients with diabetes mellitus. 167 86


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