Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of doxazosin, an alpha 1-adrenoceptor blocking drug, on blood pressure, sensitivity to insulin and serum lipids has been evaluated in 14 hypertensive, non-insulin dependent diabetic patients. The dose was titrated individually upwards from 1 mg until the diastolic blood pressure was below 90 mm Hg, side-effects precluded further dosage increase or the maximum daily dose of 16 mg was achieved. After 12 weeks of treatment (mean doxazosin dose 5.6 +/- 5.1 mg daily), the supine and standing diastolic blood pressure of the patients had declined by about 7 mm Hg, whereas their systolic blood pressure and heart rate were not significantly changed. The metabolic clearance rate of glucose increased from 2.35 to 3.37 ml.min-1.kg-1 during treatment, suggesting improved sensitivity to insulin. Fasting plasma glucose was 11.9 mmol.l-1 before and 10.9 mmol.l-1 after doxazosin therapy (NS). Serum electrolytes and lipids did not change significantly but serum uric acid decreased from 305 to 281 mumol.l-1. Doxazosin may be a useful alternative for the treatment of hypertension in NIDDM patients.
 ...
PMID:Effect of doxazosin on insulin sensitivity in hypertensive non-insulin dependent diabetic patients. 145 14

Hyperglycaemia, a raised fibrinogen, an increased serum triglyceride and a reduced HDL-cholesterol are common metabolic features of non-insulin dependent diabetes mellitus (NIDDM). Hypertension is frequently associated with NIDDM, however the influence of antihypertensive therapy on these combined factors in the diabetic is at present unclear. In a double-blind placebo-controlled crossover study in 20 stable NIDDM subjects with hypertension, the metabolic effects of 6 weeks' treatment with the alpha-blocker, doxazosin, was compared with treatment with the beta-blocker, atenolol. Similar and significant reductions in BP were produced by both drugs. Significant increases in weight, HbA1, apoprotein B, serum triglyceride and cholesterol/HDL ratio were observed with atenolol therapy. Doxazosin therapy was associated with opposite patterns of changes in fasting glucose, lipids and lipoproteins but only for serum triglyceride was difference between treatments significant. Fibrinogen was not altered by either treatment. Conclusions from this study indicate; 1) adrenergic mechanisms may be an important influence on glucose homeostasis and lipid metabolism in NIDDM and 2) the beta-blocker, atenolol, has a small adverse effect on weight, glycaemic control and the atherogenic lipid profile, whereas the alpha-blocker, doxazosin, has no such effect and may, in part, correct the disturbances of lipoprotein metabolism characteristic of NIDDM.
 ...
PMID:Alpha-blocker therapy; a possible advance in the treatment of diabetic hypertension--results of a cross-over study of doxazosin and atenolol monotherapy in hypertensive non-insulin dependent diabetic subjects. 198 Sep 30

Doxazosin is a long-acting alpha 1-adrenoceptor antagonist structurally related to prazosin and terazosin. Its antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate. In benign prostatic hyperplasia, doxazosin's effect of relieving bladder outflow obstruction is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade. In most comparative trials doxazosin has proven to be equally effective as the comparator drug in the treatment of mild to moderate hypertension. It has been used in a variety of patient populations including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM) and respiratory disease. Doxazosin has also been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy. Doxazosin has a beneficial effect on some of the risk factors associated with coronary heart disease including elevated serum lipid levels, impaired glucose metabolism, insulin resistance and left ventricular hypertrophy. Modest decreases in total cholesterol, low density lipoprotein cholesterol and triglycerides are seen with doxazosin therapy while small increases in high density lipoprotein cholesterol and the high density lipoprotein cholesterol/total cholesterol ratio are consistently reported. Some studies have reported an improvement in glucose tolerance although this effect has been more consistently seen in nondiabetic patients than in patients with NIDDM. Additionally, doxazosin produces a similar reduction in left ventricular hypertrophy to other antihypertensive agents. Modelling-based calculations suggest that doxazosin significantly reduces the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long term prospective studies. Doxazosin appears to be a promising agent in the treatment of urinary symptoms associated with benign prostatic hyperplasia. Similar to other alpha 1-adrenoceptor antagonists, doxazosin treatment produces increases in peak and mean urinary flow rates and improves other objective and symptomatic measures.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Doxazosin. An update of its clinical pharmacology and therapeutic applications in hypertension and benign prostatic hyperplasia. 753 94

Hypertension is common in patients with type 2 diabetes mellitus (DM), and contributes to the progression of its complications in patients with diabetes. Doxazosin is a selective alpha1-adrenoceptor-blocking anti-hypertensive agent and has a favorable impact upon lipid metabolism. We investigated the effect of doxazosin on the lipid metabolism in hypertensive patients with type 2 diabetes, especially low-density lipoprotein (LDL) particle size that is associated with many elements of the insulin resistance syndrome. Cross-sectional study (n=19) was designed to determine whether doxazosin, administered with an angiotensin II-converting enzyme inhibitor (ACEI) and a Ca antagonist, affects LDL particle size. As a follow-up study (n=6), lipid and glucose metabolism and LDL particle size were followed for 12 weeks before and after the initiation of doxazosin administration (1-4 mg/day). The average size of LDL particle was significantly larger in the patients treated with doxazosin (LDL-migration index (LDL-MI): 0.348+/-0.027) than those in the patient treated without doxazosin (0.378+/-0.035), although LDL cholesterol levels did not differ between the two groups. The plasma glucose and HbA1c levels remained unchanged. Lipid profile showed normolipemia throughout the period of the study. However, LDL particle size was demonstrated to become larger during the following period. Small LDL fraction (LDL3-7) diminished remarkably and large LDL (LDL1-2) increased on the polyacrylamide gel electrophoresis (PAGE) LDL system (LipoPrint). From this pilot study, it was concluded that doxazosin is a useful anti-hypertensive agent for hypertensive type 2 diabetic patients in improving the size of LDL particle.
 ...
PMID:Effect of doxazosin on the size of LDL particle in the type 2 diabetic patients with hypertension. 1098 21

Small dense low density lipoprotein (LDL) and remnant lipoproteins are potent atherogenic lipoproteins, often elevated in the plasma of patients with type 2 diabetes. The alpha1-blocker doxazosin has been reported to favorably affect the plasma lipid profile. We examined whether doxazosin could reduce these atherogenic lipoproteins in hypertensive subjects with and those without type 2 diabetes. Seventeen nondiabetic hypertensive patients and 33 hypertensive patients with type 2 diabetes were studied. Doxazosin (2 to 4 mg) was administered alone or with other previously received antihypertensive drugs for 6 months. Mean LDL size was measured by 2% approximately 16% gradient gel electrophoresis. Remnant-like particle (RLP)-cholesterol was measured with the use of an affinity column containing anti-apoA1 and B100 monoclonal antibodies. Doxazosin effectively decreased blood pressure (BP) without significantly affecting glucose, glycosylated hemoglobin (HbA1c), or C-peptide levels in both nondiabetic and diabetic patients. Doxazosin significantly reduced triglyceride, apo CIII, and apo B, but did not alter total-, LDL- or HDL-cholesterol. Mean LDL particle diameter was significantly increased from 25.6+/-0.6 nm to 25.9+/-0.4 nm (P < .001) by doxazosin treatment, regardless of the presence of diabetes. Consequently, the prevalence of small dense LDL (<25.5 nm) was halved in both groups. The increase in LDL size significantly correlated with decrease in triglyceride level (r=-0.798, P < .0001). Doxazosin significantly reduced RLP-cholesterol in both groups. These results suggest that doxazosin may help to prevent coronary artery disease by reducing atherogenic lipoproteins, including small dense LDL and remnant lipoproteins, in hypertensive patients, regardless of the presence of diabetes.
 ...
PMID:Doxazosin reduces prevalence of small dense low density lipoprotein and remnant-like particle cholesterol levels in nondiabetic and diabetic hypertensive patients. 1158 57

The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P </= 0.05) reductions observed at study end compared with baseline in glycosylated hemoglobin, fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and Homeostasis Model Assessment Index. In conclusion, both doxazosin and irbesartan reduced BP during long-term treatment, but not to recommended levels, and doxazosin had the more beneficial effect on glucose metabolism and lipid profile.
 ...
PMID:Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension. 1589 88

Metabolic syndrome, a cluster of metabolic abnormalities with visceral obesity and insulin resistance as its central component, is highly prevalent among hypertensive patients. Hypertension complicated by metabolic syndrome is associated with an increased risk of cardiovascular disease and new-onset Type II diabetes mellitus that further aggravates the prognostic outlook. Such a complex condition requires a multifactorial intervention including blood pressure lowering, improvement of the adverse metabolic profile and delayed onset of new diabetes. In this respect, doxazosin and other alpha-1 adrenoceptor blocking agents are of interest given their effect on the lipid profile in dyslipidemic, obese hypertensive patients, either diabetic or not. Doxazosin improves insulin sensitivity, apparently by accelerating insulin and glucose disposal through vasodilatation of skeletal muscle vascular beds. Whether long-term treatment with the drug might delay, or possibly prevent, incident Type II diabetes in hypertension complicated by metabolic syndrome is an intriguing possibility to be tested in appropriately designed clinical trials.
 ...
PMID:Doxazosin in metabolically complicated hypertension. 1803 18

Doxazosin, an alpha(1)-adrenergic receptor inhibitor, is commonly administered to patients with type 2 diabetes, hypertension and nephropathy. The impact of 3 months' doxazosin therapy on the prevalence of activated and regulatory T lymphocytes was analysed in this pilot study of men with type 2 diabetes (n = 10) who received doxazosin 4 mg/day in addition to their ongoing therapy. The prevalence of CD4(+), CD8(+), CD25(+) and CD69(+) cells at baseline and after 3 months of add-on therapy was determined. The prevalence of regulatory T-cells was detected by two different approaches: forkhead box P3 (FoxP3) positivity; and the number of CD4(+)CD25(+high) cells. During 3 months of doxazosin therapy, patients' blood pressure, blood glucose control and lipid profiles all significantly improved. Simultaneously, the prevalence of activated T-cells (CD4(+)CD69(+) and CD8(+)CD69(+) cells) decreased, whereas that of regulatory T-cells increased. These results indicate an immunomodulatory action of doxazosin in type 2 diabetic patients.
 ...
PMID:Effect of 3 months of doxazosin therapy on T-cell subsets in type 2 diabetic patients. 2014 98