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)

Endothelin-1 (ET-1) causes dramatic vasoconstriction and reduction of renal blood flow, with a decreased glomerular filtration rate (GFR). Early diabetic nephropathy is characterized by elevation of GFR and the formation of intrarenal microaneurysms. However, the mechanisms are unclear. To elucidate the pathophysiologic significance of urinary ET-1 in early diabetic nephropathy, the 24-h urinary excretion of ET-1 in 12 normal subjects and 20 patients with newly diagnosed type 2 diabetes mellitus were determined by a highly sensitive radioimmunoassay. The 24-h urinary ET-1 excretion in patients with diabetes mellitus (14.2 +/- 3.1 pmol, mean +/- SEM) was significantly lower (p < 0.05) than that of normal subjects (25.0 +/- 3.7 pmol). This decrease in urinary excretion of ET-1 in patients with recent-onset diabetes mellitus suggests a possible role of ET-1 in the pathogenesis of early diabetic nephropathy.
J Cardiovasc Pharmacol 1995
PMID:Does endothelin play a role in the pathogenesis of early diabetic nephropathy? 858 52

The aim of this study was to assess the chronic effects of a highly selective dihydropiridine calcium channel blocker, israpidine, in its sustained release form (I-SRO), on platelet functions and fibrinolytic parameters in subjects with essential hypertension (EH) combined or not with other well-known cardiovascular risk factors, such as cigarette smoking (EH+S) and type II diabetes mellitus (EH+DM). Thirty-six patients with essential hypertension with sitting diastolic blood pressures of 96-104 mmHg without (EH, n = 12) or with other risk factors (EH+S, n = 12, EH+DM, n = 12) were enrolled. After a 4-week, single-blind, placebo run-in period, the subjects received I-SRO 5 mg once daily for 18 weeks. After both placebo and 6 and 18 weeks of I-SRO treatment, the following parameters were measured: sitting blood pressure by mercury sphygmomanometer; platelet aggregation, plasma beta-thromboglobulin (BTG), platelet factor-4 (PF4), and plasminogen activator inhibitor 1 (PAI-1) by means of ELISA methods; and euglobulin lysis time before (ELT) and after standardized (10 min) venous occlusion (ELT-VO). In the group of patients as a whole compared with placebo, I-SRO significantly reduced SBP/DBP platelet aggregation, BTG, PF4, ELT, and ELT-VO. Significant reductions in these parameters were also observed in each group. In addition to the antihypertensive effect, I-SRO chronic treatment may favorably affect the platelet function and fibrinolytic system in essential hypertension with or without other cardiovascular risk factors.
Cardiovasc Drugs Ther 1996 May
PMID:Effects of isradipine sustained release on platelet function and fibrinolysis in essential hypertensives with or without other risk factors. 884 3

Endothelin (ET) plays an important role in the pathogenesis of various cardiovascular lesions. To elucidate the pathophysiologic significance of ET in the development of diabetic retinopathy, we determined immunoreactive ET levels in the vitreous fluid collected during vitrectomy in seven patients with non-insulin dependent diabetes mellitus with proliferative diabetic retinopathy and in 10 nondiabetic subjects as controls. Immunoreactive vitreous ET levels in diabetic patients with proliferative retinopathy (7.5 +/- 3.4 pg/ml, mean +/- SD) were significantly lower than those in the nondiabetic subjects (55.0 +/- 38.1 pg/ml; p < 0.005). The decreased rather than increased immunoreactive ET levels may simply reflect severe endothelial injury to the retinal vessels caused by diabetic microangiopathy rather than an important role in diabetic retinopathy.
J Cardiovasc Pharmacol 1998
PMID:Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy. 959 88

In this prospective study, the 24-h blood-pressure profile of 12 patients with type 2 diabetes was monitored before, at 6, and at 12 weeks after initiation of insulin therapy, to determine whether commencement of insulin therapy increases blood pressure in these patients. Insulin dosage adjustment was carried out by using a predetermined algorithm according to body weight and degree of hyperglycemia. The mean insulin dosage at 12 weeks was 72.9 +/- 3.9 units/day. This was associated with an increase in systolic blood pressure from 134.6 +/- 4.3 mm Hg to 144.8 +/- 4.5 mm Hg (p = 0.0001), diastolic blood pressure from 71.9 +/- 2.6 mm Hg to 74.9 +/- 2.2 mm Hg (p = 0.0001), and body mass index (BMI) from 27.2 +/- 0.8 kg/m2 to 29.6 +/- 0.8 kg/m2 (p = 0.0001). Multiple regression analysis showed insulin dosage to be a significant independent factor (p = 0.0003) accounting for 63% of the variance in blood pressure change after adjusting for age, diastolic blood pressure, and base HbA1c. We conclude that insulin therapy may have a deleterious effect on blood pressure in patients with type 2 diabetes. However, in the clinical setting, it is difficult to isolate this from the confounding effect of weight gain.
J Cardiovasc Pharmacol 1998 Jul
PMID:Does insulin therapy have a hypertensive effect in type 2 diabetes? 967 18

Recent trials in hypertensive patients with type 2 diabetes reveal important differences in the risk for major cardiovascular events when individual agents are compared. In the Fosinopril Amlodipine Cardiovascular Events Trial (FACET), 380 patients with hypertension and type 2 diabetes were randomized to fosinopril or amlodipine and followed for up to 3.5 years to assess effects on serum lipids. Although both agents effectively controlled blood pressure, amlodipine caused a significantly greater decrease in systolic pressure. At the end of the trial, serum cholesterol, high-density lipoprotein cholesterol, triglycerides, HbA1c, serum glucose, plasma insulin, serum creatinine, and microalbuminuria were similar in both groups. The patients randomized to fosinopril were significantly less likely to experience the prospectively defined combined outcome of acute myocardial infarction (MI), hospitalized angina, or stroke compared to those randomized to amlodipine (RR 0.49; 95% CI 0.26-0.95). In the Appropriate Blood pressure Control in Diabetes (ABCD) trial, 470 patients with hypertension and type 2 diabetes who were randomized to long-acting nisoldipine had an adjusted sevenfold increased risk for acute MI compared to those randomized to enalapril (RR 7.0; 95% CI 2.3-21.4). In the Multicenter Isradipine Diuretic Atherosclerosis Study (MIDAS) trial, the patients with hypertension and above the median of HbA1c (> or =6.7%) randomized to isradipine had a threefold increased risk for major cardiovascular events compared to those randomized to hydrochlorothiazide (RR 2.81; 95% CI 1.09-7.26). These findings are supported by several observational studies. Therefore, evidence is emerging that angiotensin-converting enzyme inhibitors and low-dose diuretics may be more effective than calcium antagonists for prevention of cardiovascular events in hypertensive patients with diabetes or impaired glucose control.
J Cardiovasc Pharmacol 1998
PMID:New evidence on the prevention of cardiovascular events in hypertensive patients with type 2 diabetes. 973 37

Although several reports have suggested that calcium channel blockers may inhibit progression of atherosclerosis in animals, it is still controversial whether they have any clinically significant antiatherogenic action in humans. The measurement of intimal-medial thickness (IMT) of the common carotid artery by B-mode ultrasound technique has been recognized as a powerful and noninvasive method to evaluate early atherosclerotic lesions. We investigated the effect of treatment with amlodipine, a powerful calcium channel blocker, on IMT. Twenty-two hypertensive patients with type 2 diabetes were enrolled in a prospective open study. An amlodipine group (amlodipine, 5 mg; n = 11) and a control group receiving angiotensin-converting enzyme inhibitors (n = 11) were studied before and 6 months after treatment. Amlodipine treatment caused a significant decrease in IMT compared with control (-0.052 +/- 0.017 vs. 0.011 +/- 0.021 mm; p < 0.05). Although the exact mechanisms remain to be elucidated, our preliminary result suggests that amlodipine has an antiatherogenic action in type 2 diabetes.
J Cardiovasc Pharmacol 1999 Jun
PMID:Effect of calcium channel blocker amlodipine on the intimal-medial thickness of carotid arterial wall in type 2 diabetes. 1036 92

It has become evident that cardiovascular disease is the major cause of morbidity and mortality in type 2 diabetes mellitus. This raises the possibility that glucose lowering agents with other nonglucose-lowering effects, might have added benefits. In this review, we focus on the metabolic and cardiovascular effects of oral antidiabetic agents that go beyond glucose-level lowering. Such effects include lipid modifying actions, antithrombotic and profibrinolytic activities, and direct action at the level of the vessel wall to improve endothelial function or prevent smooth muscle hyperplasia. These additional activities, particularly those seen with the newer oral antidiabetic agents, hold the promise of reducing cardiovascular complications beyond that achievable by glucose lowering alone.
J Cardiovasc Risk 1999 Oct
PMID:A review of metabolic and cardiovascular effects of oral antidiabetic agents: beyond glucose-level lowering. 1053 39

Among the antihypertensive drugs, fast-acting Ca2+ antagonists have been reported to worsen insulin sensitivity. This effect may be attributable to reflex increases in sympathetic activity. On the other hand, however, it has been reported that long-acting, dihydropiridine Ca2+ antagonists improve insulin-resistance. The purpose of this study was to investigate whether cilnidipine, another long-acting dihydropidine Ca2+ antagonist, improves insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. 25 weeks OLETF rats were divided into the following groups; normal-diet group, cilnidipine-supplemented group (cilnidipine 3 mg/kg/day) and angiotensin II receptor antagonist CS-866-supplemented group (CS-866 1 mg/kg/day). As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Glucose infusion rate (GIR), an index of insulin resistance, as measured by the hyperinsulinemic euglycemic clamp technique was significantly decreased in OLETF rats. Cilnidipine-treatment partially but significantly improved insulin sensitivity in addition to systolic blood pressure in OLETF rats at 30 weeks of age, although it did not decrease accumulation of abdominal fat or serum levels of glucose or insulin. CS-866, an angiotensin II receptor antagonist, which lowers blood pressure through a different mechanism, did not improve insulin resistant states in OLETF rats. These results suggest that cilnidipine has a beneficial effect on insulin-resistance together with the antihypertensive effect.
Cardiovasc Drugs Ther 1999 Nov
PMID:Cilnidipine improves insulin sensitivity in the Otsuka Long-Evans Tokushima fatty rat, a model of spontaneous NIDDM. 1068 61

Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.
J Cardiovasc Pharmacol 2000 Jun
PMID:Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients. 1083 28

The haemodynamic hypothesis for the pathogenesis of diabetic microangiopathy argues that an initial increase in microvascular blood flow leads to microvascular sclerosis and disturbed autoregulation. Endothelin-1 (ET-1) is an endothelium-derived vasoconstrictor peptide that contributes to basal vascular tone. Impairment of the vasoconstrictor response to ET-1 could result in hyperperfusion and subsequent microvascular damage. The purpose of this study was to determine whether vascular responses to ET-1 are impaired in patients with non-insulin-dependent diabetes mellitus (type 2 diabetes). Ten patients with type 2 diabetes and nine control subjects underwent brachial artery cannulation. Forearm blood flow was measured using strain-gauge venous occlusion plethysmography. ET-1 in three doses of 5, 10, and 20 pmol/min and 0.9% saline placebo was infused in a balanced double-blind randomised manner. Vascular smooth muscle function also was assessed using sodium nitroprusside. Control subjects showed vasoconstriction to ET-1 of 5 (p < 0.05), 10 (p < 0.05), and 20 pmol/min (p < 0.01). In the diabetic group, there was no significant response to ET-1 at 5 pmol/min (p > 0.05); however, significant vasoconstriction developed at 10 and 20 pmol/min (p < 0.01). There was a significant difference in response to ET-1 at 5 pmol/min between the diabetic and control groups (p < 0.05). Responses to sodium nitroprusside were similar in both groups (p > 0.05). Patients with type 2 diabetes have a blunted vasoconstrictor response to ET-1 despite preserved vascular smooth muscle function.
J Cardiovasc Pharmacol 2000 Aug
PMID:Vasoconstriction to endothelin-1 is blunted in non-insulin-dependent diabetes: a dose-response study. 1094 62


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>