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)

Antihypertensive treatment is frequently needed in type 2 diabetes. In this study we measured the rates of total, oxidative, and nonoxidative glucose disposal, glycogen synthesis, glycolysis, endogenous glucose production, and lipid oxidation using a 4-h euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 300 pmol/L) clamp in combination with a dual glucose tracer infusion ([3-(3)H]- and [U-14C] D-glucose) and indirect calorimetry in 40 nonobese subjects with type 2 diabetes. Subjects were studied twice: after a 4-week run-in period and after a 16-week period of double blind, randomized treatment with 4-6 mg/day lacidipine, a calcium channel blocker (n = 19), or 10-20 mg/day lisinopril, an angiotensin-converting enzyme inhibitor (n = 21). Antihypertensive treatment resulted in a significant increase in total glucose disposal during insulin clamp as well as in basal and insulin-stimulated nonoxidative glucose disposal rates. On the contrary, oxidative glucose disposal was significantly decreased by antihypertensive treatment, mainly in the basal state. The changes in glucose disposal rates were not significantly different in subjects treated with lacidipine and in those treated with lisinopril. The suppression of endogenous glucose production during insulin clamp was significantly greater after lacidipine than after lisinopril. These results suggest that treatment of subjects with type 2 diabetes with either lacidipine or lisinopril has no adverse effect on glucose metabolism. Conversely, both drugs seem to improve insulin sensitivity.
...
PMID:Effect of chronic treatment with lacidipine or lisinopril on intracellular partitioning of glucose metabolism in type 2 diabetes mellitus. 1032 77

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.
...
PMID:Effect of calcium channel blocker amlodipine on the intimal-medial thickness of carotid arterial wall in type 2 diabetes. 1036 92

To evaluate the effects of cilnidipine (CNP), L- and N-type calcium channel blocker and nilvadipine (NVP) on 24-h urinary epinephrine (U-EP), norepinephrine (U-NE), dopamine (U-DA) and C-peptide (U-CPR) in patients associated with hypertension and non-insulin-dependent diabetes mellitus (HT-NIDDM), a randomized crossover study was performed with 35 HT-NIDDM patients. The patients were given CNP (10 mg/day) and NVP (8 mg/day), separately, for 4 weeks each. After CNP treatment, U-NE, U-DA and U-CPR levels were significantly reduced compared with pre-treatment levels: 160.4 +/- 12.7 to 111.7 +/- 8.9 microg/day (mean +/- S.E., P < 0.005); 934.8 +/- 163.4 to 590.3 +/- 33.4 microg/day (P < 0.05); 86.7 +/- 9.9 to 57.6 +/- 7.4 microg/day (P < 0.05), respectively. Although no significant differences were observed in U-EP, U-NE, U-DA and U-CPR levels by NVP treatment, U-NE, U-DA and U-CPR levels after CNP treatment were significantly lower than those after NVP treatment: 111.7 +/- 8.9 versus 155.0 +/- 13.7 microg/day (P < 0.02); 590.3 + 33.4 versus 822.2 +/- 104.3 microg/day (P < 0.05); 57.6 +/- 7.4 versus 80.6 +/- 8.1 microg/day (P < 0.05), respectively. In conclusion, it was demonstrated that CNP treatment significantly reduced U-NE, U-DA and U-CPR excretion compared with NVP treatment in HT-NIDDM patients.
...
PMID:Cilnidipine, the N- and L-type calcium channel antagonist, reduced on 24-h urinary catecholamines and C-peptide in hypertensive non-insulin-dependent diabetes mellitus. 1046 43

The aim of the study was to evaluate the current antihyperglycaemic and antihypertensive treatment schemes as well as the quality of metabolic control and blood pressure in a population with type 2 diabetes, in view of the United Kingdom Prospective Diabetes Study (UKPDS) data. 318 patients were included. 44% were treated with metformin and/or sulfonylurea. 44% received insulin in monotherapy or combined with oral drugs. HbA1c was 8.0 (7.9-9.4)% (median; percentiles 25-75). Chronic neurological and vascular (micro- and macroangiopathy) complications were present in 21-43% of patients and were related to glycaemic control. (Un)treated hypertension was found in 59% of patients. Main treatments were ACE-inhibitors (40%), calcium channel antagonists and diuretics (20%) and/or beta-blockers (18%). Systolic and diastolic blood pressure were 147 +/- 22 and 86 +/- 12 mm/Hg (mean +/- 1 SD). In conclusion, overall glycaemic control of a type 2 diabetic population remains slightly unsatisfactory in view of the UKPDS recommendations. In contrast, blood pressure control was adequate.
...
PMID:Glycaemic and blood pressure controls achieved in a cohort of 318 patients with type 2 diabetes. 1068 5

The role of lipoprotein oxidation in promoting atherosclerosis is gaining recognition as its spectrum of effects is being unveiled. Accelerated atherosclerosis is a major cause of morbidity and mortality in diabetic patients. Treatment with ACE inhibitors reduces oxidation of low-density lipoprotein (LDL-ox) in hypertensive subjects, however, their effect on LDL-ox in diabetic patients is yet obscure. To evaluate the effect of the ACE inhibitor enalapril and the calcium channel blocker nifedipine on LDL oxidation in normotensive type 2 diabetic patients. A randomized single blinded cross-over study was conducted on 24 nonobese, metabolically stable, normotensive patients with type 2 diabetes who were randomly allocated to receive either enalapril, 10 mg/day, or nifedipine, 30 mg/day, for 4 weeks followed by a 2-week washout period. They were then crossed over to a 4-week course with the alternate drug. The oxidation of LDL was evaluated by three methods: dialdehyde analysis using the thiobarbituric acid reactive substances assay with and without the addition of CuSO(4) as well as determination of conjugated dienes in the LDL lipid extract. The propensity of the serum to oxidize LDL was reduced by enalapril by 17-28% depending on the laboratory method used (P=0.0001). Treatment with nifedipine resulted in a rise in LDL-ox of 7-11% as compared to baseline (P<0.05). The difference between the effects of enalapril and nifedipine was statistically significant with all three laboratory methods used (P=0.0001). Both drugs were equally effective in reducing systolic and diastolic blood pressure without affecting HbA(1c) levels and lipid profile. The albumin excretion rate was significantly reduced during treatment with enalapril returning to baseline levels during the washout period and the nifedipine treatment course. Our findings suggest that oxidation of LDL is attenuated by ACE inhibition and augmented by some calcium channel blockers. This observation may contribute insight into the underlying mechanism of the therapeutic effects of ACE inhibition in diabetic patients.
...
PMID:Oxidation of low-density lipoprotein in normotensive type 2 diabetic patients. Comparative effects of enalapril versus nifedipine: a randomized cross-over over study. 1080 51

Fixed verapamil SR/trandolapril combinations 180/1 mg and 180/2 mg (Tarka, Knoll AG) have a significantly superior antihypertensive effect compared to equal dosages of either agent alone. Verapamil SR/trandolapril 180/2 mg combination produces the best dose-response ratio of different dose combinations of these two drugs. Combination therapy has the most pronounced effect on blunting the early morning rise in blood pressure. Thus, verapamil SR/trandolapril combination therapy may be an appropriate treatment option in patients with moderate essential hypertension, particularly in those who have a tendency toward the early morning rise in blood pressure. The adverse effect profile of the fixed combination of verapamil SR/trandolapril includes the typical side effects of its monocompounds. The fixed combination of verapamil SR/trandolapril is also effective and safe in the treatment of hypertension in the elderly. The fixed low-dose combination therapy with verapamil SR/trandolapril 180/2 mg is a suitable treatment option for patients with moderate essential hypertension and Type 2 diabetes mellitus, because it improves parameters of carbohydrate metabolism and uricaemia and does not alter the lipid profile. The insulin-sensitising effect of angiotensin converting enzyme (ACE) inhibitor monotherapy with its theoretical risk of hypoglycaemia is completely neutralised in the combination with verapamil SR. Comparative studies have shown that the low-dose combination of verapamil SR/trandolapril may be a suitable alternative to combinations containing a thiazide diuretic or a beta-blocking agent for the long-term management of hypertensive patients for whom combination therapy is indicated. The combination of an ACE inhibitor with a non-dihydropyridine calcium channel blocker reduces proteinuria to a greater extent than either agent alone. A combination of an ACE inhibitor and a calcium channel blocker may provide additional benefit in inducing the regression of left ventricular hypertrophy. Combination therapy leads to a significant increase in left ventricular ejection fraction, improvement of wall motion index and increases exercise duration time in patients with coronary heart disease and left heart failure. It also improves the ratio of exercise to rest rate-pressure product and decreases the number of angina attacks. These findings support the hypothesis that the combination of verapamil and trandolapril might be useful in patients with attenuated left ventricular function and angina pectoris. Thus, Tarka is an effective and well-tolerated antihypertensive agent with a good safety profile and positive metabolic effects.
...
PMID:The fixed combination of verapamil SR/trandolapril. 1124 35

Cardiovascular and renal diseases in diabetes stem from an accelerated form of atherosclerosis in both small and large blood vessels. Diabetic nephropathy is a clinical hallmark of microangiopathy and often leads to end-stage renal failure. Significantly, microalbuminuria is an independent predictor of cardiovascular morbidity and mortality in both the diabetic and non-diabetic population. In diabetic patients, it is also strongly associated with proliferative retinopathy, neuropathy and hypertension. Effective blood pressure reduction in patients with type 2 diabetes and diabetic nephropathy is known to reduce albuminuria, delay the progression of diabetic nephropathy, postpone renal failure and improve survival. These benefits have been demonstrated with a variety of blood pressure-lowering agents, including beta-blockers, calcium channel blockers, diuretics and angiotensin-converting enzyme (ACE) inhibitors. Less is known about the renal effects of the newest class of antihypertensive agents, the angiotensin II receptor antagonists (AIIRAs). Irbesartan is an AIIRA that provides antihypertensive efficacy comparable to ACE inhibitors but with superior tolerability. The PRogram for Irbesartan Mortality and morbidity Evaluations (PRIME) is an important morbidity and mortality program encompassing the Irbesartan Diabetic Nephropathy Trial (IDNT) and the IRbesartan MicroAlbuminuria type 2 diabetes mellitus in hypertensive patients (IRMA II) study. PRIME is evaluating the effects of irbesartan in preventing diabetic nephropathy and end-stage renal failure and in reducing cardiovascular events in high-risk hypertensive patients with type 2 diabetes. The trials were completed at the end of 2000.
...
PMID:Hypertension and diabetes: the scope of the problem. 1146 14

A case of a 59-year-old male patient with advanced microangiopathic complications at the diagnosis of diabetes mellitus is reported. The patient was referred to ophthalmological investigation due to progressive loss of visual acuity. Although diabetes mellitus was not known, proliferative diabetic retinopathy with significant visual loss was found at fundus examination. Not only newly diagnosed diabetes mellitus (initial fasting blood glucose 19.0 mmol/, HbA1c: 11.6%) but the presence of advanced sensory, motor and autonomic diabetic neuropathy (nervus peroneus motor conduction velocity: 32.1 m/s, nervus suralis sensory conduction velocity could not be detected, postural decrease in systolic blood pressure: 20 mmHg, beat-to-beat variation 6 beats/min, 30:15 ratio 1.03) as well as signs of advanced diabetic nephropathy (daily urinary protein excretion: 1.2-5.7 g, serum creatinine value: 101 mumol/l, sitting blood pressure: 150/100-180/100 mmHg) could be documented by further investigations at Medical Department. Avoiding short-term strict metabolic control insulin therapy was initiated and adequate long-term diabetic control was achieved later (HbA1c: 6.5-6.2%). In order to classify the diabetes, repeated measurements of serum C-peptide, ICA, GADA and IA2-antibodies were performed and type 2 diabetes was diagnosed. After a transient deterioration the proliferative retinopathy remained unchanged. Although laser photocoagulation was performed, no improvement in the visual acuity could be achieved. Only a minor improvement of neurological alterations was documented by repeated electrophysiological investigation at follow-up. Although the antihypertensive treatment (ACE-inhibitor drug in combination with calcium channel blocker) resulted in a significant decrease of elevated blood pressure, only a transient improvement of proteinuria could be achieved. Despite regular control, the advanced microangiopathic complications of diabetes mellitus carry poor prognosis.
...
PMID:[Advanced microangiopathic complications at the diagnosis of diabetes mellitus]. 1155 63

Obesity has been shown to be an independent risk factor for coronary heart disease. The insulin resistance associated with obesity contributes to the development of other cardiovascular risk factors, including dyslipidemia, hypertension, and type 2 diabetes. The coexistence of hypertension and diabetes increases the risk for macrovascular and microvascular complications, thus predisposing patients to cardiac death, congestive heart failure, coronary heart disease, cerebral and peripheral vascular diseases, nephropathy, and retinopathy. Body weight reduction increases insulin sensitivity and improves both blood glucose and blood pressure control. Metformin therapy also improves insulin sensitivity and has been associated with decreases in cardiovascular events in obese diabetic patients. Antihypertensive treatment in diabetics decreases cardiovascular mortality and slows the decline in glomerular function. However, pharmacological treatment should take into account the effects of the antihypertensive agents on insulin sensitivity and lipid profile. Diuretics and beta-blockers are reported to reduce insulin sensitivity and increase triglyceride levels, whereas calcium channel blockers are metabolically neutral and ACE inhibitors increase insulin sensitivity. For the high-risk hypertensive diabetic patients, ACE inhibition has proven to confer additional renal and vascular protection. Because hypertension and glycemic control are very important determinants of cardiovascular outcome in obese diabetic hypertensive patients, weight reduction, physical exercise, and a combination of antihypertensive and insulin sensitizers agents are strongly recommended to achieve target blood pressure and glucose levels.
...
PMID:Treatment of obesity hypertension and diabetes syndrome. 1156 61

A prospective, randomized, three-armed, double-blind, placebo-controlled clinical trial has been completed in 210 sites worldwide to determine whether the angiotensin II receptor blocker irbesartan or the calcium channel blocker amlodipine has a renoprotective effect in patients with overt type 2 diabetic nephropathy. A total of 1,715 subjects randomized during a 3-year period were followed a minimum of 2 years. The goal for all treatment groups was to achieve equivalent blood pressure control, with the blinded study drug (irbesartan, amlodipine, or placebo) as primary therapy with additional antihypertensive drugs, excluding angiotensin-converting enzyme inhibitors, calcium antagonists, and angiotensin II receptor antagonists, to achieve seated systolic blood pressure less than 135 mm Hg and diastolic blood pressure less than 85 mm Hg. The primary outcome was the combined endpoint of time to doubling of entry serum creatinine, end-stage renal disease, or death. Secondary outcomes included fatal and nonfatal cardiovascular events. A Clinical Management Committee monitored the conduct of the study. An Outcome Confirmation Committee classified all study outcome events in blinded fashion. An external Data Safety Monitoring Committee monitored unblinded data for interim safety and efficacy analyses of the study. Eligibility criteria included informed consent, age 30 to 70 years, adult-onset diabetes, hypertension, urine protein excretion greater than 900 mg/24 hours, and serum creatinine values of 90 to 265 micromol/L in women and 110 to 265 micromol/L in men. Baseline characteristics were age, 59 +/- 8 years; body mass index, 31 +/- 7 kg/m(2); 67% male; 73% white, 14% black, and 13% other; duration of diabetes, 15 +/- 9 years; retinopathy, 66%; neuropathy, 48%; congestive heart failure, 7.5%; screening seated systolic blood pressure, 156 +/- 18 mm Hg, and diastolic blood pressure, 85 +/- 11 mm Hg; urine protein excretion, 4.0 +/- 3.5 g/24 hours; serum creatinine, 150 +/- 53 micromol/L; serum potassium, 4.6 +/- 0.5 mEq/L; total cholesterol, 229 +/- 58 mg/dL; and hemoglobin A(1c), 8.1 +/- 1.7%. This large-scale international trial should help define the clinical course and standards of care for hypertensive adults with type 2 diabetes mellitus and nephropathy. Results available on May 19, 2001, will help in defining the current controversy of the risks and benefits of blockade of the renin-angiotensin system versus calcium channel blockade versus standard antihypertensive therapy in this large patient population.
...
PMID:A clinical trial in type 2 diabetic nephropathy. 1157 53


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