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)

The effect of an acute reduction in arterial blood pressure upon kidney function was studied in 12 patients with Type 1 (insulin-dependent) diabetes and incipient nephropathy (persistent microalbuminuria). Renal function was assessed by measurement of the glomerular filtration rate (single bolus 51Cr-EDTA technique) and by the urinary albumin excretion rate (radioimmunoassay). The study was performed twice within 2 weeks, with the patients receiving a slow intravenous injection of either clonidine (225 micrograms) or saline (154 mmol/l) in random order. Clonidine reduced arterial blood pressure from 125/79 +/- 13/8 to 104/68 +/- 9/7 mmHg (p less than 0.01), urinary albumin excretion rate from 68 (31-369) to 46 (6-200) micrograms/min (median and range) (p less than 0.01), and fractional clearance of albumin in all patients (median 29%) (p less than 0.01). Glomerular filtration rate was 110 +/- 11 before and 106 +/- 13 ml/min/1.73 m2 after clonidine injection. The blood glucose concentration was 15 +/- 4 mmol/l before and 14 +/- 5 mmol/l after clonidine injection. In agreement with findings in animal studies, our results suggest that microalbuminuria is to a large extent pressure-dependent, probably because of glomerular hypertension, and that autoregulation of glomerular filtration rate is normal in most patients with incipient diabetic nephropathy.
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PMID:Acute reduction of arterial blood pressure reduces urinary albumin excretion in type 1 (insulin-dependent) diabetic patients with incipient nephropathy. 371 12

The effectiveness and safety of transdermally administered clonidine hydrochloride was assessed in 16 patients with type-II diabetes mellitus. This group of patients was chosen because of the frequent occurrence of hypertension in diabetic patients and potential problems with transdermal absorption of medication because of small vessel disease. A skin patch containing clonidine hydrochloride (Catapres TTS) was applied at weekly intervals after an appropriate placebo lead-in period. Satisfactory response to therapy was seen in 15 of the 16 patients. One patient developed a generalized skin rash and was withdrawn from the study. Correlation between change in diastolic blood pressure and plasma clonidine levels was noted. Of note was the absence of the usual side effects (drowsiness, dry mouth, etc.) seen with oral clonidine administration. This study thus highlights the success of transdermal clonidine therapy in controlling blood pressure in the mild hypertensive patient with diabetes mellitus.
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PMID:The use of transcutaneous clonidine hydrochloride in the patient with diabetes mellitus and mild hypertension. 383

Clonidine has been reported to adversely affect glucose tolerance in experimental animals and normal man. We assessed its short- and long-term effects in 10 patients with both mild hypertension and diabetes mellitus. Patients were studied before and 10 wk after treatment with 0.1 mg clonidine twice daily, which induced reductions in blood pressure (from 148 +/- 5/93 +/- 2 mm Hg sitting, to 125 +/- 4/80 +/- 2) and control of hypertension in all patients. Clonidine increased the glycemic response to intravenous glucose (incremental glucose AUC from 161 +/- 13 to 184 +/- 14) but did not significantly change long-term diabetic control as assessed by weekly fasting serum glucose, glycosylated hemoglobin, and 24-hr urinary glucose excretions before and after treatment. We conclude that low-dose clonidine controlled blood pressure and impaired the response to an acute glucose challenge in midly hypertensive, type II diabetic patients but did not adversely affect diabetic control over 10 wk.
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PMID:Clonidine in patients with diabetes and mild hypertension. 664 Oct 84

The concentrations of norepinephrine in amniotic fluid and maternal plasma were measured in 71 third trimester pregnancies, 31 of which were uncomplicated and 40 complicated. The amniotic fluid norepinephrine concentration (mean +/- SD) in cases of hypertension treated with clonidine (0.4 +/- 0.1 ng/ml, n = 12) and in insulin-dependent diabetes (0.5 +/- 0.2 ng/ml, n = 7) was lower, and in renal insufficiency (1.7 +/- 0.8 ng/ml, n = 8) higher than in control subjects (0.7 +/- 0.4 ng/ml, n = 31). In fetal-growth retardation (0.6 +/- 0.2 ng/ml, n = 8) and in latent diabetes (0.7 +/- 0.2 ng/ml, n = 5) the values were similar to those in the control subjects. There was a significant positive correlation between mature lecithin-sphingomyelin (L/S) ratio and norepinephrine concentration. Clonidine-treated hypertension was associated with decreased (0.2 +/- 0.1 ng/ml) and renal insufficiency with increased (0.9 +/- 0.7 ng/ml) maternal plasma norepinephrine concentrations (control group, 0.3 +/- 0.1 ng/ml). The present results indicate that measurement of catecholamines in amniotic fluid can be useful in the evaluation of fetal sympathoadrenal function.
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PMID:Amniotic fluid norepinephrine concentration as an indicator of fetal sympathetic nervous activity. Effect of pregnancy complications. 673 72

Clonidine (0.08 to 80.0 ng/ml) caused a dose-related inhibition of glucose-stimulated insulin release, but failed to affect glucose oxidation, glucose-stimulated 45Ca net uptake, and adenylate cyclase activity in isolated rat islets. Phentolamine antagonized the effect of clonidine upon insulin release. Despite profound inhibition of insulin secretion, the drug failed to affect the time course for the changes evoked by glucose in either 45Ca fractional outflow rate from perfused islets or insulin release from the isolated perfused pancreas. The latter changes were multiphasic, revealing an initial secretory peak, a period of low secretory activity, and a second secretory elevation before establishing a period characterized by a steadily and slowly increasing insulin output. In the clonidine-treated islets, the secretory rate was not significantly different from the basal value during the period after the initial secretory response. Thus, despite continuous stimulation with glucose, insulin release appears as a discontinuous phenomenon, even when little insulin is secreted during the initial phase of stimulation.
Diabetes 1980 Mar
PMID:Mode of action of clonidine upon islet function: dissociated effects upon the time course and magnitude of insulin release. 699 21

Clonidine hydrochloride (Catapres), a potent antihypertensive agent, has been in clinical use since 1974 in the United States. Clonidine, an alpha-adrenergic receptor agonist, stimulates central alpha receptors in the depressor site of the vasomotor center of the medulla oblongata and hypothalamus, which diminishes efferent sympathetic tone to the heart, kidneys, and peripheral vasculature with a concomitant increase in vagal activity. Hemodynamic and renal effects include reduction in supine and erect blood pressure, heart rate, total peripheral resistance, plasma renin activity, and urinary aldosterone and catecholamine excretion, with little effect on resting cardiac output, response to exercise, and preservation of renal function. Clonidine alone produces a significant reduction in mean arterial pressure in all degrees of hypertension during acute and chronic administration, with little or no tendency toward tolerance or postural hypotension. Its antihypertensive potency is enhanced with the concomitant use of a diuretic or vasodilator, and it may be used in place of a beta blocker with equal efficacy in the diuretic plus vasodilator combination. Serious adverse effects are uncommon, with more than 93% of patients tolerating the drug well. Sedation and dry mouth, the most common adverse effects, are usually related to dose and duration and are minimized by gradually increasing the dose and by taking the major portion of the twice-daily schedule at bedtime. Clonidine may be safely given to patients with congestive heart failure, ischemic heart disease, obstructive lung disease, chronic renal insufficiency, and diabetes mellitus. Clonidine is one of the most versatile and effective agents presently available for the treatment of hypertension.
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PMID:Clonidine hydrochloride. 704 65

The pathogenesis, clinical manifestations, and management of orthostatic hypotension (OH) are reviewed. OH is a decline in blood pressure that occurs when one moves from a lying to a standing position that results in symptoms of cerebral hypoperfusion, most commonly lightheadedness and syncope. The disorder may result from primary autonomic disorders, such as Shy-Drager syndrome; reversible nonautonomic causes, such as reduced blood volume; underlying diseases, such as diabetes mellitus; and drugs. Elderly people are predisposed to OH. The diagnosis of OH is based on the documentation of postural hypotension accompanied by symptoms of cerebral ischemia. The goal of therapy is to relieve symptoms. Nonpharmacologic approaches are preferred and include increasing sodium intake, avoiding rapid postural changes, and wearing elastic garments. OH is difficult to treat pharmacologically because of varying responses and adverse effects. The drug of choice for all types of OH is fludrocortisone acetate, although caution must be used in patients with congestive heart failure. Prostaglandin synthetase inhibitors can also be used for all types of OH but have had more limited success. Sympathomimetics with or without monoamine oxidase inhibitors, beta-adrenergic antagonists, and ergot alkaloids should be administered only to patients with certain types of OH, and patients must be monitored closely. Clonidine, midodrine, yohimbine, octreotide, dopamine antagonists, desmopressin, and epoetin alfa have not been well studied and should be limited to patients with severe, refractory disease. Although no uniformly effective treatment regimen exists, OH can often be adequately managed with a combination of nondrug and drug therapies.
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PMID:Management of orthostatic hypotension. 820 84

Insulin resistance may contribute to non-insulin-dependent diabetes mellitus, hypertension, and dyslipidemia; increased free fatty acid concentrations could both promote and maintain this state of insulin resistance. Therefore, agents that inhibit lipolysis and decrease plasma concentrations of free fatty acids could be of therapeutic interest. We have measured metabolic effects of clonidine, an alpha 2 adrenergic agonist, and adenosine in healthy human subjects since human fat cells have alpha 2 and adenosine A1 receptors, which inhibit lipolysis in vitro. Clonidine, as expected, significantly lowered systolic and diastolic blood pressure; clonidine also decreased the plasma concentration of free fatty acids. Although clonidine caused a transient mild increase in plasma glucose, insulin and triglyceride concentrations were unchanged. The metabolic effects of adenosine were examined with two protocols. In the first study, volunteers received a graded infusion of adenosine (at 0, 10, 20, 50 and 100 micrograms/kg.min for 30 min/dose), and glucose, insulin, free fatty acids, as well as respiratory rate, systolic and diastolic blood pressures, and heart rate were measured. There was no change in glucose, insulin, or free fatty acid concentrations. In the second study a graded infusion was used and was maintained at 100 micrograms/kg/min for 120 minutes. Heart rate and respiratory rate significantly increased. Glucose and free fatty acid concentrations were unchanged, while insulin concentrations were significantly increased. All subjects had significant symptomatic complaints (dyspnea, chest pressure) during the adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute metabolic effects of clonidine and adenosine in man. 845 15

We reported previously that genetic polymorphisms of the alpha 2-adrenergic receptor are associated with hyperinsulinemia, diabetes mellitus, and hypertension in blacks. The evolutionary driving force for maintaining such deleterious mutations in the black population is unknown. Recognizing that vascular alpha 2-adrenergic receptors mediate cold-induced vasoconstriction and that temperature maintenance is a primary thrust of cellular metabolism, we postulated that vascular alpha 2-adrenergic receptors contribute significantly to metabolic heat generation in homeotherms such as humans. Using aerobic lactate production as an indicator of thermogenesis, we measured metabolic heat production in HT29 cells that expressed the gene encoding human vascular alpha 2-adrenergic receptors. Epinephrine, an alpha 2-adrenergic receptor agonist, increased net lactate efflux from 226 +/- 20 to 280 +/- 20 nmol/min (mean +/- SE) (P = .06). Clonidine, a more specific alpha 2-adrenergic agonist, increased lactate efflux from 110 +/- 6 to 156 +/- 8 nmol/min (P < .01). Similarly, in the presence of physiological concentrations of glucose (5.5 mmol/L), insulin increased lactate production from 123 +/- 6 to 175 +/- 10 nmol/min (P < .01). Because differences in aerobic glycolysis may also explain the heat intolerance and abnormal fuel homeostasis found in genetically hypertensive rats, we also measured lactate production in cultured vascular smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive control Wistar-Kyoto rats (WKY). Vascular smooth muscle cells from SHRSP had significantly greater lactate efflux compared with cells from normotensive WKY (296 +/- 4 versus 172 +/- 2 nmol/min, P < .001). These differences were not due to abnormalities in glucose uptake, as lactate efflux was greater in SHRSP cells compared with WKY cells when dextrose was replaced with equimolar concentrations of fructose (230 +/- 6 versus 138 +/- 2 nmol/min, P < .001). alpha 2-Adrenergic agonists increase lactate efflux in HT29 cells, and abnormalities in vascular smooth muscle lactate metabolism in genetically hypertensive rats is independent of altered glucose uptake. These data provide support for our hypothesis that balanced polymorphisms of the alpha 2-adrenergic receptor could offer protection against cold stress by increasing the thermogenic response associated with aerobic lactate production.
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PMID:Alpha 2-adrenergic agonists increase cellular lactate efflux. 862 Dec 3

We investigated the effect of acute lowering of blood pressure (BP) upon glomerular filtration rate (GFR) in hypertensive non-insulin-dependent diabetes mellitus (NIDDM) patients, 14 with diabetic nephropathy and 12 with normoalbuminuria. The study was performed twice with the subjects receiving an intravenous injection of either clonidine (150 to 225 micrograms) or saline (0.154 mmol/liter). We assessed GFR, albuminuria, and BP. The two groups were well matched with respect to demographic data, baseline GFR and BP. Clonidine induced similar reductions in mean arterial blood pressure 19 (SE +/- 4) and 21 (SE +/- 3) mm Hg in patients with and without nephropathy, respectively. In the nephropathy group GFR diminished in average from 90 (SE +/- 6) to 81 (SE +/- 7) ml/min/1.73 m2 (P = 0.006), fractional clearance of albumin (x 10(-6)) declined from a geometric mean of 219 (antilog SE /divided by 1.3) to 186 (antilog SE /divided by 1.3) (P = 0.04), and four patients had a complete pressure-passive vasculature, defined as delta GFR% = delta MABP%. A significant correlation between relative reductions in MABP and GFR (r = 0.78, P < 0.001) was demonstrated in albuminuric patients. None of the normoalbuminuric patients had a complete pressure-passive vasculature and there were no significant differences in GFR between the two examinations, but five had abnormal autoregulation of GFR. Mean difference between changes in GFR (95% confidence interval) between the nephropathic and normoalbuminuric group was 5.5 (divided by 2.7 to 13.7) ml/min/1.73 m2 (P = 0.18). Our study suggests that hypertensive NIDDM patients, particularly patients with nephropathy, frequently suffer from impaired or abolished autoregulation of GFR.
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PMID:Impaired autoregulation of GFR in hypertensive non-insulin dependent diabetic patients. 935 Jun 61


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