Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oral angiotensin converting enzyme inhibition was introduced eight years ago and is becoming increasingly popular for the treatment of hypertension and congestive heart failure. This treatment causes blood pressure lowering associated with suppression of angiotensin and aldosterone, lack of orthostatic hypotension or metabolic disturbances, redistribution of regional blood flows in favor of vital organs and, in the long term, decreased sympathetic drive and regression of left ventricular hypertrophy. It is effective as monotherapy in more than 50 percent of unselected patients; addition of a diuretic increases the percentage of responders to more than 80 percent. It is the treatment of choice for patients with concurrent diabetes, asthma, gout, depression, or very active life-style. Side effects, observed originally in patients with severe hypertension and renal failure treated with very high doses of captopril, are rare in otherwise healthy hypertensive patients receiving smaller doses of this drug and virtually absent with second-generation angiotensin converting enzyme inhibitors like enalapril.
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PMID:Clinical utility of angiotensin converting enzyme inhibitors in hypertension. 302 82

This study was designed to clarify the cause of hyporeninemic hypoaldosteronism (HH) associated with diabetes mellitus. Fourty diabetic patients (DP) were divided into 3 groups; 12 patients without neuropathy or nephropathy, 13 with neuropathy and without nephropathy, and 15 with neuropathy and nephropathy; in the third group 3 HH patients were included. Fourteen normal subjects served as controls. In all DP and the normal subjects, plasma concentration of aldosterone (PAld), 18-hydroxycorticosterone (P18-OH-B), corticosterone (PB), 11-deoxycorticosterone (PDOC) and cortisol (PF) were measured before and after intravenous administration of angiotensin II (AII, 10 ng/kg/min, for 30 min) or ACTH (1-24 ACTH, 0.25 mg). In 27 DP, plasma renin activity (PRA) increased from 0.8 +/- 0.6 SD to 2.4 +/- 2.2 ng/ml/h (normal: 1.2 +/- 0.7 to 3.2 +/- 1.7 ng/ml/h) 2 hours after intravenous administration of furosemide (1 mg/kg) and assumption of the upright posture. No significant difference in PRA was found between DP and controls, whereas the response to these stimuli decreased significantly in 9 DP with neuropathy and nephropathy (from 0.4 +/- 0.2 to 0.7 +/- 0.4 ng/ml/h). The major results were as follows: 1) The mean of PAld (5.9 +/- 2.4 ng/100 ml) in DP was significantly lower than that in controls (7.7 +/- 2.2 ng/100 ml). There was no significant difference of PAld between DP without complications and controls. PAld in DP with neuropathy alone (5.0 +/- 1.5 ng/100 ml, p less than 0.05) and that in DP with neuropathy and nephropathy (4.7 +/- 2.4 ng/100 ml, p less than 0.05) were lower than that in controls. The mean of P18-OH-B (12.3 +/- 4.3 ng/100 ml) in DP was similar to that (14.2 +/- 3.2 ng/100 ml) in controls. P18-OH-B in DP without complications and that in DP with neuropathy alone were similar to that in controls. However, P18-OH-B (8.8 +/- 3.2 ng/100 ml) in DP with neuropathy and nephropathy was significantly lower than that in controls (p less than 0.001). No difference in PB, PDOC or PF was observed between DP and controls. 2) PAld increased from 6.0 +/- 2.5 ng/100 ml in DP (p less than 0.001) and from 7.6 +/- 2.2 to 15.7 +/- 5.3 ng/100 ml in controls (p less than 0.001) 30 min after A II infusion.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on hypoaldosteronism associated with diabetes mellitus: response of plasma steroids to angiotensin II or ACTH administration]. 302 51

Diabetes mellitus is frequently accompanied by specific abnormalities of the renin-angiotensin system, but it is not known whether these alterations modify the response to converting enzyme inhibition. To evaluate this possibility, 129 patients with severe chronic heart failure were treated with captopril or enalapril for one to three months, while doses of digoxin and diuretics were kept constant; 35 patients had diabetes mellitus. Prior to therapy, diabetic patients had lower plasma renin activity (3.4 +/- 0.5 versus 7.0 +/- 1.1 ng/ml/hour) than did nondiabetic control subjects (p less than 0.05); yet the initial hemodynamic response to captopril was similar in both groups. Plasma renin activity predicted the hypotensive response to the first dose of captopril in nondiabetic control subjects (r = 0.70, p less than 0.001) but not in diabetic patients (r = 0.29). During long-term treatment with captopril or enalapril, both diabetic and nondiabetic patients had similar increases in cardiac index and decreases in mean arterial pressure and systemic vascular resistance. Diabetic patients, however, showed larger reductions in left ventricular filling pressure (-13.8 versus -9.1 mm Hg, p less than 0.02) and mean right atrial pressure (-6.2 versus -3.9 mm Hg, p less than 0.05) than did nondiabetic subjects; this was accompanied by a notable decline in body weight in diabetic patients only. Renal function remained unaltered during converting enzyme inhibition in nondiabetic patients, but deteriorated significantly in diabetic patients, as reflected by a marked increase in serum creatinine concentration (1.7 +/- 0.1 to 2.1 +/- 0.1 mg/dl, p less than 0.001). In conclusion, despite lower pretreatment plasma renin activity, diabetic patients with severe chronic heart failure demonstrated improvement during long-term converting enzyme inhibition to a degree similar to (if not greater than) that seen in nondiabetic control subjects, but were more susceptible to the development of functional renal insufficiency than their nondiabetic counterparts. These differences are explicable by abnormalities of renin/aldosterone synthesis and angiotensin-mediated vasoregulation that are known to be present in the diabetic state.
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PMID:Influence of diabetes mellitus on changes in left ventricular performance and renal function produced by converting enzyme inhibition in patients with severe chronic heart failure. 303 96

Effect of metoclopramide (MCP), a dopaminergic antagonist, on orthostatic hypotension associated with diabetes mellitus, was investigated to prove its plausible role of renin-angiotensin-aldosterone and catecholamine activation by comparative study in 6 diabetics with orthostatic hypotension (OH) and 9 diabetics without OH. With MCP treatment, drop of systolic blood pressure (SBP) on standing was significantly improved. However, the postural responses of plasma renin activity (PRA), plasma aldosterone and norepinephrine were not enhanced by MCP treatment. Moreover, MCP treatment did not modify the vascular reactivity to the exogenously infused angiotensin II and norepinephrine. Thus, it would be interesting to speculate that MCP can improve SBP through its suppressive effect on some depressor substance(s) such as bradykinin which liberates exaggeratively in diabetic OH.
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PMID:Effect of metoclopramide on orthostatic hypotension in diabetes mellitus: failure to demonstrate the role of vasoconstrictive hormones. 304 7

Hypertension in patients with diabetes mellitus increases the risk of both macrovascular and microvascular complications. Such microvascular complications as diabetic nephropathy and retinopathy are accelerated in the presence of arterial hypertension. Evidence suggests that the complications of diabetes mellitus begin early in the course of the disorder as manifested by microalbuminuria and increased vascular reactivity. These findings are accompanied by changes in the renin-angiotensin-aldosterone system including reductions in plasma renin activity. These changes could be secondary to volume expansion that may be a direct consequence of elevated blood glucose, suggesting that the metabolic disorder in diabetes contributes to the etiology of hypertension in these patients. Adequate treatment of hypertension is crucial to the prevention of complications; however, many antihypertensive agents have limited usefulness in diabetes mainly because of their unfavorable side effects. Diuretics lower blood pressure in hypertensive diabetics, but their metabolic effects are especially undesirable in this population. beta-Blockers alter glucose and lipid metabolism in diabetic patients and reduce regional blood flow. Central acting agents and alpha-blockers are often associated with orthostatic hypotension, sexual dysfunction, and central nervous system side effects. Angiotensin-converting enzyme inhibitors (ACEIs) such as captopril effectively lower blood pressure in diabetic patients and have few unwanted effects. They may improve metabolic control and have favorable effects on glucose metabolism. The ACEIs also produce improved regional hemodynamics which may lead to the improvement in or prevention of the progression of diabetic nephropathy.
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PMID:Management of hypertension in the patient with diabetes mellitus. Focus on the use of angiotensin-converting enzyme inhibitors. 305 49

This study was designed to evaluate the effects of domperidone, a peripheral dopaminergic antagonist, in diabetic patients with symptomatic orthostatic hypotension. Nine patients were admitted to the hospital, placed on a diet containing 150 mEq sodium, and studied for periods of 4 hours, on different days, in the following conditions: (1) supine position, (2) upright posture (UP), (3) UP after 10 mg domperidone, intravenously in bolus, and (4) UP after 3 days of domperidone, 30 mg orally. Before domperidone the mean blood pressure observed in supine position of 132 +/- 37/75 +/- 6 mm Hg fell to 75 +/- 22/57 +/- 13 mm Hg after 2 hours in UP. Acute domperidone did not change the blood pressure response to UP. After 3 days of oral domperidone and in UP for 2 hours, the mean blood pressure value of 89 +/- 21/61 +/- 8 mm Hg was higher than that before domperidone (p less than 0.05), with relief of symptoms in all patients. This blood pressure response to UP has been maintained in six patients who completed 6 months of therapy. No differences were observed in plasma renin activity, aldosterone, sodium, and potassium and in 4-hour urinary excretion of aldosterone, epinephrine, norepinephrine, and dopamine, determined during the UP tests. Administration of domperidone for 3 days reduced the falls in creatinine clearance and the urinary excretion of sodium and potassium induced by UP but did not alter the blood pressure and aldosterone dose-response curves to angiotensin II. Although the mechanism of action is not defined, it is concluded that domperidone is effective for the treatment of orthostatic hypotension in patients with diabetes.
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PMID:Peripheral dopaminergic blockade for the treatment of diabetic orthostatic hypotension. 305 73

Data from several epidemiologic studies have suggested that the prevalence of hypertension in patients with diabetes mellitus is approximately 1.5-2.0 times greater than in an appropriately matched nondiabetic population. In patients with insulin-dependent diabetes mellitus (IDDM), hypertension is generally not present at the time of diagnosis. As renal insufficiency develops, blood pressure rises and may exacerbate the progression to end-stage renal failure. In non-insulin-dependent diabetes mellitus (NIDDM), many patients are hypertensive at the time of diagnosis. The incidence of hypertension in NIDDM is related to the degree of obesity, advanced age, and extensive atherosclerosis that is typically present, and it probably includes many patients with essential hypertension. Several other pathophysiologic mechanisms also contribute to the genesis and maintenance of hypertension in the patient with diabetes. Hyperglycemia and increases in total-body exchangeable sodium may lead to extracellular fluid accumulation and expansion of the plasma volume. In some patients, alterations in the function of the renin-angiotensin-aldosterone system and vascular sensitivity to vasoactive hormones may also play a role. It has recently been suggested that hyperinsulinemia and insulin resistance may also contribute to the maintenance of an elevated blood pressure because insulin is known to promote sodium retention and enhance sympathetic nervous system activity. The evidence for these hypotheses and their respective contributions to the etiology of hypertension in IDDM and NIDDM are discussed.
Diabetes Care
PMID:Etiology and prevalence of hypertension in diabetic patients. 307 72

The aim of this work was to investigate, in an experimental model of diabetes mellitus, the levels of renin activity in vascular and adrenal tissues and their relationship to several circulating renin-angiotensin system components. Rats with chronic (12 weeks) streptozocin-induced diabetes showed a significant decrease in plasma renin activity (PRA), plasma renin concentration, and plasma aldosterone. However, plasma trypsin activatable inactive renin concentration was increased (11.65 +/- 1.40 vs 6.73 +/- 0.57 ng angiotensin I/ml/hr; p less than 0.001), as were aortic reninlike activity (p less than 0.001) and adrenal renin, both in the zona glomerulosa (p less than 0.01) and the fascicular-reticular-medullary portion (p less than 0.001) with respect to an age-matched control group. After bilateral nephrectomy, plasma renin-angiotensin system components (PRA and plasma active and inactive renin concentrations) as well as aortic and fascicular-reticular-medullary renin activity significantly decreased in both control and diabetic rats. However, glomerular renin activity increased in control nephrectomized rats to the levels observed in diabetic animals but did not change in diabetic nephrectomized rats. The parallel changes of aortic and fascicular-reticular-medullary renin activity and plasma inactive renin concentration in diabetes and nephrectomy suggest an interdependent relationship, whereas the increase of glomerular renin activity in diabetic and nephrectomized animals, both with low levels of PRA, suggests the existence of a local autonomic renin-angiotensin system regulated by plasma feedback. Tissue renin-angiotensin system alterations in diabetes could mean that a pathogenic factor is involved in long-term diabetic complications or that only a compensatory physiological process is at work.
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PMID:Vascular and adrenal reninlike activity in chronically diabetic rats. 328 97

Autonomic neuropathy is one of the complications of diabetes. Recently, several authors reported that measuring R-R interval variation of ECG is a noninvasive and useful method for testing parasympathetic function. However, there were few reports about sympathetic function in diabetics. In order to evaluate sympathetic function in diabetics quantitatively, we studied the responses of plasma norepinephrine (NE), epinephrine (E) and related factors after 60 min bed rest and sequentially during 10 min of upright posture and 5 min handgrip while still upright. We also studied the responses of NE and E during 5 min smoking in supine position. Subjects were divided into four age-matched groups. These were 15 normal subjects (Group I), 20 diabetics without complications (Group II), 20 diabetics with peripheral neuropathy but no autonomic symptoms (Group III) and 15 diabetics with autonomic symptoms (Group IV). We also studied R-R interval variation (CV: Coefficient of Variation) as a parameter of parasympathetic function and compared this with sympathetic function. Upon standing, blood pressure (BP) dropped precipitously in Group IV, whereas no significant changes were observed in the other three groups. Heart rate (HR) increased in Groups I and II, but not in Groups III and IV. During handgrip, BP and HR did not change significantly in all groups. Basal NE levels in Group IV were significantly smaller than those in Group I. NE responses to both standing and handgrip stimuli were markedly reduced in Group IV and, even in Group III, increments were significantly smaller than those in Groups I and II. Basal E levels did not differ, and significant changes were not observed after standing and handgrip in all groups. Both plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) in Groups III and IV were lower than those in Groups I and II at rest and standing. After smoking, both BP and HR increased significantly in Groups I, II and III, whereas no changes were observed in Group IV. Both NE and E responses were markedly reduced in Group IV and, even in Group III, responses were significantly smaller than those in Groups I and II. CV in Groups III and IV were significantly smaller than those in Groups I and II. In diabetics, CV was strongly correlated with NE increments after standing (r = 0.78, p less than 0.01). Also, CV was correlated with both NE and E increments after smoking (r = 0.71 (NE), r = 0.82 (E), p less than 0.01).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Autonomic neuropathy in diabetics--autonomic function and plasma catecholamines]. 328 1

The aldosterone response to increments in plasma potassium concentration in disease states associated with abnormal potassium tolerance remains undefined. We evaluated the plasma aldosterone response to an acute oral potassium load (0.25-0.50 mmol/kg body weight) in 30 patients (19 with chronic renal failure (CRF) and 11 with diabetes mellitus) with normal or decreased baseline plasma aldosterone levels and in 12 control subjects. In control subjects, plasma aldosterone levels increased initially and then declined below baseline, whereas in the patients the late decrease was not observed. In patients with CRF with and without hypoaldosteronism (5 undialyzed and all 9 dialyzed patients), plasma aldosterone increased significantly. Eight of the diabetic subjects had normal and 3 had low baseline aldosterone levels. In the former, plasma aldosterone levels did not increase above baseline following the KCI load. We conclude that diabetic patients and those with CRF manifest several abnormalities in aldosterone-potassium responsiveness that may contribute to the disturbed potassium homeostasis observed in these conditions.
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PMID:Aldosterone responsiveness to an acute potassium load in diabetes mellitus and chronic renal insufficiency. 330 79


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