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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The metabolic changes which accompany hyperglycemia in a person with diabetes are thought to cause renal hyperperfusion and intraglomerular hypertension, especially in the person with a predisposition to essential hypertension. Intraglomerular hypertension causing deposition of protein in the mesangium leads to glomerulosclerosis and renal failure. Screening for microalbuminuria can predict which type I diabetic patients will develop nephropathy. The decline in renal function in established diabetic nephropathy can be slowed with aggressive treatment of hypertension. The use of ACE inhibitors may also decrease intraglomerular hypertension. Whether similar treatment in the person with preclinical diabetic nephropathy would delay or prevent the onset of diabetic nephropathy is being investigated. Restricted protein intake, anti-platelet and rheolitic drugs may have a role in the treatment of established diabetic nephropathy. In end stage renal failure, renal transplantation is the treatment of choice. When transplantation cannot be performed, chronic ambulatory peritoneal dialysis is preferable to hemodialysis.
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PMID:Diabetic nephropathy: changing concepts of pathogenesis and treatment. 200 Aug 93

Clinical disorders causing hyperkalemia require a basic understanding of normal K homeostasis, which consists of external and internal K balances. The kidney is predominant in maintaining the external balance of K, and a number of mechanisms exist to provide a renal adaptation to defend against K excess. Likewise, several factors are known to modulate internal K balance--i.e., its distribution within the body. Some of these factors may provide defense against hyperkalemia before the kidneys have time to adapt. Potassium retention by the kidney causes hyperkalemia when renal failure is advanced, or earlier in the face of impaired tubular function in a variety of disorders. Hyperkalemia out of proportion to loss of renal function also occurs in the syndrome of hyporeninemic hypoaldosteronism. Drug-induced hyperkalemia is increasingly common and usually is caused by nonsteroidal anti-inflammatory drugs, angiotensin converting enzyme inhibitors, cyclosporine, or K-sparing diuretics. Clinical disorders of internal K imbalance include diabetes mellitus, systemic acidosis, and use of beta-blockers. Hyperkalemia is usually asymptomatic, but the danger of cardiac arrest or arrhythmia in severe hyperkalemia forces prompt clinical attention. Available treatment choices include agents that antagonize the effect of K on membrane potentials, redistribute it internally into cells, and remove it altogether from the body. The diagnostic work-up can then proceed, first by distinguishing renal and extrarenal causes, then by examining the roles of specific factors outlined in the section on normal K homeostasis.
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PMID:Endocrine crises. Hyperkalemia. 200 12

The effect of treatment with enalapril (10 days at 10 mg/d followed by 4 weeks at 20 mg/d) on forearm hemodynamics was assessed in eight normotensive patients and eight patients with hypertension affected by Type II diabetes as well as in eight patients with essential hypertension and normal glucose tolerance. The ACE inhibitor decreased regional vascular resistances and increased the maximum arteriolar-vasodilating capacity and venous distensibility in the three groups of patients. Thus, this study shows that ACE inhibition by enalapril improves regional hemodynamics in patients with Type II diabetes.
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PMID:The effect of ace inhibition on peripheral hemodynamics in normotensive and hypertensive patients with type II diabetes. 201 May 59

It is proposed that the systemic hyperinsulinemia and hepatic portal hypoinsulinemia that occurs with conventional injectable preparations of insulin currently used in the treatment of patients with diabetes mellitus is largely responsible for the morbidity associated with this disease. Epidemiological evidence and animal experimentation strongly support systemic hyperinsulinemia as a major factor in genesis of atherosclerosis in diabetic patients. In addition, in vitro studies demonstrate a direct effect of insulin on endothelial cell and arterial smooth muscle proliferation. On the other hand, inadequate hepatic delivery of insulin is associated with overproduction of renal vasoregulatory factors leading to glomerular hyperfiltration and ultimately to glomerulosclerosis and its clinical endpoint--end-stage renal disease. In the absence of widespread success of pancreatic and islet-cell transplantation as a means to deliver insulin physiologically into the hepatic portal circulation, methods must be devised and perfected to accomplish such delivery using approaches such as orally administering insulin in intestinal-enzyme protected capsules. Until such methods of delivery are available for safe and widespread use, one should abandon the illusory goal of rigid glucose control in favor of methods that reduce insulin requirement. Along these lines, dietary restriction and aerobic exercise should be the major life style changes advised for diabetic patients. Reduction of glomerular hyperfiltration in diabetic patients can be promoted with the use of low protein diets and/or angiotensin converting enzyme inhibitors.
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PMID:Hypothesis: insulin is responsible for the vascular complications of diabetes. 205 21

To assess the effects of ACE-inhibition on insulin action in Type 2 (non-insulin-dependent) diabetes mellitus associated with essential hypertension, 12 patients with Type 2 diabetes (on diet and oral hypoglycaemic agents) and arterial hypertension were examined on two occasions, in a single blind, cross-over study after two days of treatment with either captopril or a placebo. The study consisted of a euglycaemic-hyperinsulinaemic clamp (two sequential steps of insulin infusion at the rates of 0.25 mU.kg-1.min-1 and 1 mU.kg-1.min-1, 2 h each step), combined with an infusion of 3-3H-glucose to measure the rate of hepatic glucose production and that of peripheral glucose utilization. The results show that blood pressure was lower after captopril (sitting, systolic 148 +/- 5 mm Hg, diastolic 89 +/- 2 mm Hg) compared to placebo (155 +/- 6 and 94 +/- 2 mm Hg) (p less than 0.05). Captopril treatment resulted in a more suppressed hepatic glucose production (2.7 +/- 0.4 vs 4.94 +/- 0.55 mumol.kg-1.min-1), and a lower plasma non-esterified fatty acid concentration (0.143 +/- 0.05 vs 0.200 +/- 0.05 mmol/l) (captopril vs placebo, p less than 0.05) at the end of the first step of insulin infusion (estimated portal plasma insulin concentration 305 +/- 28 pmol/l); and in a greater glucose utilization (36.5 +/- 5.1 vs 28 +/- 3.6 mumol.kg-1.min-1, p less than 0.001) at the end of the second step of insulin infusion (arterial plasma insulin concentration of 604 +/- 33 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:ACE-inhibition increases hepatic and extrahepatic sensitivity to insulin in patients with type 2 (non-insulin-dependent) diabetes mellitus and arterial hypertension. 206 46

This paper synthesizes the pathogenic steps of arterial hypertension in diabetes mellitus: hyperosmolarity due to the hyperglycemia and increased sodic tubular reabsorption accounting for the expansion of the extracellular volume with hypervolemia; abnormalities of the ionic membrane pumps leading to abnormal intracellular calcium distribution, thereby inducing an increased vascular tone; atypical vasomotor reactivity to cathecolamines; modifications of the renin-angiotension-aldosterone system. The pathophysiological derangements by which hypertension could induce nephropathy are examined: the vasodilatation which can be detected from the onset of diabetes, may be a determinant in the transmission of systemic hypertension to the glomerular microcirculation with resulting enhancement of the hydrostatic transglomerular pressure gradient (i.c. the major factor producing glomerular injury), glomerular plasmatic flow and filtration rate. The nephron hyperfiltration increases the movement of plasmatic proteins across the glomerular capillary wall with subsequent mesangial hyperactivity and sclerosis. Antihypertensive treatment in diabetes follows general guidelines and it should be instituted even in the case of microhypertension being facilitated in this setting the appearance of microalbuminuria i.e. the starting point of nephropathy. Even if experimental studies are to favor ACE inhibitors as the first-line drugs for abating glomerular hypertension by mitigation of the direct effect of angiotensin II on the efferent arteriolar tone, clinical observations suggest that, regardless of type of treatment, the normalization of systemic arterial pressure, by reversing glomerular hypertension may be effective in preventing diabetic nephropathy.
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PMID:[The pathogenesis of arterial hypertension in diabetes mellitus and its role in nephropathy]. 207 80

The frequent concurrence of other cardiovascular risk factors in hypertensive patients, such as obesity and diabetes mellitus, suggests that overlapping genetic and environmental factors may contribute to the common metabolic and cardiovascular derangements observed in these populations. Hypertension and hyperglycemia accelerate atherosclerosis in diabetics, and play an important role in associated morbidity and mortality. Several abnormalities in blood pressure regulatory systems such as the renin-angiotensin system, the sympathetic nervous system, and sodium/volume control have been described in diabetes mellitus. Sodium retention and cardiovascular hyperreactivity appear to occur early in the course of diabetes mellitus, even at normal blood pressure levels and before onset of renal failure, and could set the stage for the development of hypertension. The relationship between obesity and hypertension is also well-established, and may reflect metabolic and cardiovascular adaptations in obese subjects which predispose to blood pressure elevations. Obese subjects display changes in sympathetic nervous system activity, sodium metabolism, and vascular hemodynamics. Sodium-sensitive blood pressure responses in the obese may be secondary to increased cardiac output or fluid volume, and are directly related to circulating insulin levels. Certain metabolic and vascular characteristics of obesity and diabetes mellitus are found in patients with essential hypertension. It has been suggested that insulin and insulin resistance may be the common link between these risk factors. Improved understanding of metabolic considerations in the treatment of obese and diabetic hypertensives should lead to more careful selection of medications that avoid metabolic complications. Although diuretics and beta-blockers may be useful in some patients, there are several reasons not to recommend their use as initial therapy in obese and diabetic hypertensives. On the other hand, calcium channel blockers and angiotensin converting enzyme inhibitors are highly effective, with minimal effects on metabolic parameters, and are well-suited as first-line therapy in the treatment of obese and diabetic hypertensives.
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PMID:Metabolic considerations in hypertension. 207 23

Endothelin is a 21-residue peptide vasoconstrictor produced by endothelium. Using a radioimmunoassay, endothelin values were measured in four groups of individuals: normal controls (0.54 +/- 0.12 pmol/l, n = 20); undialysed patients with chronic renal failure (CRF) (0.82 +/- 0.13 pmol/l, n = 38); chronic renal failure patients on continuous ambulatory peritoneal dialysis (CAPD) (2.81 +/- 0.63 pmol/l, n = 20); and patients with CRF on haemodialysis (HD) (4.52 +/- 1.21 pmol/l, n = 14). The endothelin values were significantly greater in undialysed patients with CRF when compared with controls (P less than 0.001) and significantly greater in both dialysis groups when compared with controls and the undialysed CRF group (P much less than 0.001). The difference between the two dialysis groups was not significant (P = 0.07). There was no correlation between endothelin and serum creatinine, mean arterial pressure, presence of chronic hypertension and/or diabetes, use of calcium-channel blockers and/or ACE inhibitors, or primary renal diagnostic category. A single haemodialysis session had no significant effect on endothelin values in the ten patients in whom this was assessed. Fast protein liquid chromatography (FPLC) appeared to confirm that the molecular species found in chronic renal failure were the same as those found in diabetic patients.
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PMID:Endothelin in renal failure. 212 16

Elevation of glomerular filtration rate (GFR) is a feature of diabetes mellitus in humans and in animal models. Angiotensin II has been implicated as a mediator of GFR in diabetes. The acute effect of inhibition of angiotensin converting enzyme with captopril on renal haemodynamic and endocrine parameters was therefore studied in 14 normotensive male Type 1 diabetic patients, and the responses compared with those in five normal male control subjects. Following captopril 12.5 mg orally the diabetic patients exhibited an acute fall in GFR from 122 +/- 3.8 to 113 +/- 4.5 ml min-1 1.73-m-2 (p less than 0.02) and a rise in renal plasma flow (RPF) from 670 +/- 57 to 797 +/- 46 ml min-1 1.73-m-2 (p less than 0.01) which resulted in a fall in filtration. This did not occur in normal control subjects. Natriuresis occurred only in normal control subjects. There was no change in urinary excretion of PGE2 or kallikrein in either group but excretion of 6-keto-PGF1 alpha fell in the diabetic patients. There was a significant correlation between glycosylated haemoglobin and baseline RPF (rs = -0.79, p less than 0.001) and filtration fraction (rs = 0.83, p less than 0.001) that persisted when the change in these variables following captopril was analysed. Our results are compatible with the response to ACE inhibition in diabetic patients being secondary to inhibition of angiotensin II and suggest that this response may be related to blood glucose control.
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PMID:Blood glucose control determines the renal haemodynamic response to angiotensin converting enzyme inhibition in type 1 diabetes. 213 98

1. To dissociate the effects on the development of diabetic renal injury of angiotensin converting enzyme (ACE) inhibition per se, and a reduction in systemic blood pressure, we have studied the effects of chronic ramapril treatment in streptozotocin diabetic spontaneously hypertensive rats, with modulation of the hypotensive effect by a high salt diet. 2. Three weeks following uninephrectomy and induction of diabetes with streptozotocin, spontaneously hypertensive rats were allocated to three treatment groups. Groups 1 and 2 received 1% sodium chloride and Group 3 water as drinking solution. Groups 2 and 3 received 0.4 mg/kg per day ramapril in drinking solution over the subsequent 2 month study period. 3. Sodium chloride drinking solution (1%) completely prevented any hypotensive effect of ramapril. Blood pressure was reduced in Group 3 rats over the entire period of study, when compared with Group 2 rats (P less than 0.001). 4. Urinary protein excretion progressively increased in Group 1 and 2 rats, and was significantly reduced (P less than 0.001) in Group 3. After 2 months treatment, urinary protein (expressed as mean and s.e.m.) was 160 +/- 30 mg/day in Group 1, 240 +/- 50 mg/day in Group 2, and 60 +/- 11 mg/day in Group 3. 5. Angiotensin converting enzyme inhibition per se was not associated with a reduced protein excretion in diabetic nephropathy, requiring concomitant control of systemic blood pressure to become renoprotective.
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PMID:High salt diet ameliorates effects of angiotensin converting enzyme inhibition in spontaneously hypertensive streptozotocin diabetic rats. 214 Mar 3


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