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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiomyopathy is a consistent feature of diabetic myocardium as well as in prolonged alcohol consumption. Diabetes-induced myocardial dysfunction has been attributed, in part, to calcium overload within individual myocytes. The present study compares the effectiveness of the calcium channel blocker nifedipine (dihydropyridine-type) with verapamil (phenylalkylamine-type) in reversing myocardial dysfunction and diminishing the negative inotropic effect of ethanol on diabetic rat myocardium. Wistar rats were made diabetic with streptozotocin (55 mg/kg, i.v.) and isolated electrically stimulated papillary muscles were studied under isometric conditions in the absence and presence of clinically relevant concentrations of ethanol (80-240 mg/dl, i e., 17.4-52.1 mM). Subgroups of diabetic and normal animals received daily injections of verapamil or nifedipine 2 weeks after induction of diabetes for 8 weeks. Untreated diabetic animals exhibited hyperglycemia, hyperlipidemia, reduced growth, cardiomegaly, and hepatomegaly. Compared to verapamil chronic nifedipine treatment normalized or reversed the effects of diabetes on myocardial mechanical function. The negative inotropic effect of ethanol was attenuated only in muscles from verapamil-treated diabetic animals. Thus, chronic nifedipine treatment may be more effective than verapamil in reducing hyperglycemia, attenuating both cardiac and liver enlargement, and restoring myocardial mechanical function, in experimental diabetes. However, chronic verapamil therapy is more effective in diminishing the negative inotropic effect of ethanol on diabetic myocardium. These findings may have clinical significance among diabetic patients who consume alcoholic beverages while receiving long-term calcium blocker therapy.
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PMID:Differential effects of chronic calcium channel blocker treatment on the inotropic response of diabetic rat myocardium to acute ethanol exposure. 876 17

The objective of this investigation was to determine whether calcium channel blocker (CCB) treatment effectively restores normal baseline mechanical function in diabetic myocardium and to evaluate its effect on the interval-strength relationship. Wistar rats were made diabetic with streptozotocin (55 mg/kg, IV). Left-ventricular papillary muscles from normal and diabetic (10 weeks) rats were superfused with Tyrode's solution at 30 degrees C. A subgroup of diabetic and normal animals received daily injections of verapamil or nifedipine (10 mg/kg, IP; 8 weeks) to compare the effectiveness of a phenylalkylamine to a dihydropyridine in reversing diabetes-induced contractile dysfunction in vitro. Muscles were electrically stimulated at 0.5 Hz with suprathreshold stimuli, and the following parameters were measured: peak tension developed, time to-peak tension, time-to-90% relaxation, and the maximum velocities of tension development and decay. Experimental diabetes was characterized by: severe hyperglycemia, hepatomegaly, reduced body weight gain, cardiomegaly, and increased plasma phospholipid levels. In addition, baseline values of peak tension developed, time to-peak tension, and time-to-90% relaxation were significantly greater in muscles from diabetic animals. Chronic nifedipine treatment reduced hyperglycemia and plasma phospholipid levels, normalized body weight gain, and reduced both heart and liver sizes in diabetic animals. Nifedipine treatment completely reversed diabetes-induced prolongation in both time-to-peak tension and time-to-90% relaxation. In diabetic myocardium, a slightly positive component was present in the interval-strength relationship between 0.01 and 1 Hz, resulting in a rightward shift in the entire curve across a wide range of stimulation frequencies (0.01-5 Hz). This positive component was absent in muscles from diabetic animals treated with both CCBs, and verapamil produced a leftward shift in the frequency response curve. The results of this study suggest that chronic nifedipine treatment may be more effective than verapamil in restoring normal baseline myocardial mechanical function, reducing hyperglycemia and hyperlipidemia, as well as attenuating both cardiac and liver enlargement in experimental diabetes. In contrast, verapamil treatment tended to normalize more effectively the inotropic response to changes in stimulation frequency in diabetic myocardium.
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PMID:Influence of calcium channel blocker treatment on the mechanical properties of diabetic rat myocardium. 877 89

Isolated diastolic hypertension is not officially recognized as a form of hypertension. It is currently defined as a diastolic pressure greater than 90 mm Hg with systolic pressure < 140 mmHg. It implies an elevation of vascular resistance in the arteriolar sector and small arteries, and persistence of distensibility of the aorta and large vessels. It therefore predominantly affects young patients with relatively recent HT, without any accentuation of aging of the vessel wall by smoking, diabetes, or atheroma. It is responsible for a reduction of pulse pressure, and does not appear to be associated with deterioration of the prognosis. The demonstration of diastolic HT indicates the presence of excess adrenergic tone with predominance of alpha tone, or raised plasma renin, in the absence of any alteration of myocardial function capable of reducing systolic pressure. Monotherapy with angiotensin converting enzyme inhibitors, which reduce stimulation of growth of smooth muscle fibres, and calcium channel blockers, whose effects increase with increasing vasoconstrictor tone, would be preferable to diuretics and non-selective beta-blockers.
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PMID:[What can we think about diastolic hypertension?]. 878 29

Diabetes mellitus and hypertension each confer increased cardiovascular risk. That risk is much greater when the diseases coexist and is further magnified by their frequent association with dyslipidemia and central obesity. Insulin resistance appears to be an important common component to these four entities, whether or not the relationship is truly cause and effect. Increased renal tubule absorption of sodium and increased sympathetic nervous system stimulation from insulin have been said to be the mechanisms by which elevated levels of insulin cause hypertension. However, animal experiments suggest that these are short-term effects only and that long-term insulin may actually increase peripheral blood flow and reduce blood pressure. Experiments in humans suggest that the insulin resistant state in obese patients and type II diabetics is associated with a decrease of the usual vasodilatory effect of insulin. Antihypertensive drugs have differing effects on insulin resistance. Angiotensin converting enzyme inhibitors, alpha-adrenergic blockers, and dihydropyridines appear to improve insulin sensitivity. Other calcium channel blockers appear to be neutral, as is furosemide. Thiazide diuretics, spironolactone, and beta-adrenergic blockers impair insulin sensitivity. The drugs that increase insulin sensitivity also tend to improve dyslipidemia or remain lipid neutral. In contrast, those drugs that tend to impair insulin sensitivity also tend to worsen dyslipidemia.
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PMID:Hypertension in patients with diabetes mellitus. 884 91

Diabetes mellitus is a complex group of diseases that has hyperglycemia as a common metabolic abnormality. Although it is well-known that diabetic patients are susceptible to the effects of large vessel atherosclerosis with specific cardiac and cerebral complications, the association of diabetes mellitus with cardiac dysfunction caused by cardiomyopathy in the absence of significant coronary artery disease has been recognized for many years. However, the pathogenesis of diabetic cardiomyopathy remains unknown and has been somewhat controversial. Specifically, whether diabetes mellitus with its metabolic effects is sufficient to account for cardiomyopathy remains to be proven. This paper reviews the evidence for and against a metabolic etiology. In addition, we review the clinical and experimental evidence that supports the view that diabetes mellitus acts together with hypertension to produce structural damage in the heart that manifests as ventricular dysfunction and ultimately congestive heart failure. The concomitant effects of the metabolic derangements of diabetes and the vascular abnormalities associated with hypertension may lead to microvascular-induced tissue injury. Findings supporting this hypothesis are presented, along with observations suggesting that treatment with vasodilating calcium channel blockers or angiotensin converting enzyme inhibitors may be beneficial in regard to tissue pathology and mortality in experimental models. Recent clinical studies also support a role for the microcirculation in diabetics. Finally, it is suggested that if the microcirculation is pathogenetically involved in diabetic cardiomyopathy, then agents that improve microcirculatory flow along with tight control of hypertension may be as beneficial in the treatment or prevention of diabetic cardiomyopathy as strict metabolic control of hyperglycemia.
Diabetes Res Clin Pract 1996 Jul
PMID:Myocardial alterations in diabetes and hypertension. 886 52

The ABCD (Appropriate Blood Pressure Control in Diabetes) trial is a large, prospective, randomized clinical trial designed to compare the effects of intensive with moderate blood pressure control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in non-insulin-dependent diabetes (NIDDM). The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and of an angiotensin-converting enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations: a hypertensive one (diastolic blood pressure of > or = 90.0 mm Hg at the time of randomization) and a normotensive one (diastolic blood pressure of 80.0-89.0 mm Hg at the time of randomization). A total of 950 men and women aged 40-74 years were randomized and are being followed for 5 years at a single center. There were 470 randomized participants in the hypertensive population and 480 randomized participants in the normotensive population. This report summarizes the demographic, biochemical, and clinical characteristics of the randomized patients at the time of entry into the trial and evaluates the balance between the treatment groups within each population.
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PMID:Baseline characteristics of participants in the Appropriate Blood Pressure Control in Diabetes trial. 887 60

A macroscopic low-voltage-activated (LVA) inward current was found in pancreatic beta-cells isolated from NOD mice. However, this current was not present in nondiabetic prone mouse (e.g., Swiss-Webster) pancreatic beta-cells. We performed pharmacological analyses on this current in NOD insulinoma tumor cells (NIT-1). This cell line was developed from pancreatic beta-cells of a transgenic NOD mouse. The sodium-channel blocker, tetrodotoxin (TTX; 2 micromol/l) had no effect on this LVA current. The amplitudes of currents elicited by a -20 mV test pulse retained similarity when the extracellular sodium concentration was increased from 0 to 115 mmol/l; when the extracellular calcium concentration was decreased from 10 to 2 mmol/l, there was an approximate 50% reduction of this current elicited by a -30 mV test pulse. Neither the L-type calcium-channel blocker, nifedipine (3 micromol/l), nor the N-type calcium-channel blocker, omega-CgTx-GVIA (1 micromol/l), at -30 mV produced an appreciable effect. The T-type calcium-channel blockers, nickel (3 micromol/l) and amiloride (250 micromol/l), effectively reduced the peak of this current. In 2 mmol/l calcium external solution, the threshold of voltage-dependent activation of this calcium current was approximately -65 mV, and the peak current occurred at -20 mV. Half-maximum steady-state inactivation was around -43 mV. The mean time constant of slow deactivating tail currents generated by a preceding 20 mV pulse was 2.53 ms. The intracellular free calcium concentration was two- to threefold higher in NOD mouse pancreatic beta-cells compared with Swiss-Webster pancreatic beta-cells. We concluded that there are LVA calcium channels abnormally expressed in NOD mouse beta-cells. This LVA calcium channel may be factorial to the high cytosolic free calcium concentration observed in these cells, and thereby may contribute to the pathogenesis of NOD mouse beta-cells.
Diabetes 1996 Dec
PMID:Abnormally expressed low-voltage-activated calcium channels in beta-cells from NOD mice and a related clonal cell line. 892 51

Arterial hypertension is the most frequent cardiovascular complication of diabetes mellitus. Diabetes mellitus-type-1 occurs in about 30% of patients and it is connected to development of diabetic nephropathy, while type-2 occurs in as much as 70% of cases, having fast atherosclerosis as a base in its etiopathogenesis. The therapy of arterial hypertension in diabetic patients is specific and in some ways different depending on the type of diabetes mellitus as well as other complications characteristic for diabetes. Apart from drug therapy, it includes: body weight reduction in obese patients, restriction of sodium chloride, proteins and alcohol drinking, as well as other risk factors (smoking, for example). Drug therapy means application of different groups of antihypertensive agents (selective beta-blockers, diuretics, angiotensin-converting enzyme inhibitors, calcium channel antagonists and postsynaptic alpha-1 blockers). Some of them have adverse effects on metabolism of lipids, while some have other adverse effects which must be taken into account when determining therapy. However, angiotensin-converting enzyme inhibitors and calcium channel antagonists are the most preferred today as the most effective and with least adverse effects.
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PMID:[Modern principles of therapy of hypertension in diabetic patients]. 892 53

The effect and mechanism of action of serotonin (5-HT) were studied in the pulmonary circulation of normal and diabetic rabbits. 5-HT (10, 50 and 100 nmol/l) produced a concentration-dependent increase in rabbit pulmonary arterial tension. Pulmonary arterial rings from diabetic rabbits were more responsive to 5-HT compared to those from normal rabbits. The pressor effects of 5-HT in normal and diabetic pulmonary arterial rings were totally abolished by either the 5-HT receptor antagonist, ketanserin (200 nmol/l) or the calcium channel blocker, verapamil (5.5 nmol/l). On the other hand, the cyclo-oxygenase inhibitor, indomethacin (0.4 nmol/l), significantly potentiated the pressor response of 5-HT in normal but not in diabetic pulmonary arterial rings. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA, 20 nmol/l), significantly enhanced the 5-HT-induced pressor response in normal rings while significantly attenuating those responses in diabetic rings. NG-nitro-L-arginine methyl ester (100 nmol/l), an inhibitor of nitric oxide synthase, significantly potentiated the contractile response of 5-HT in normal as well as diabetic pulmonary arterial rings. The results of this study indicate that 5-HT induces pulmonary hypertension in normal as well as in diabetic rabbits. In addition, experimentally induced diabetes exaggerates the pressor response of 5-HT and therefore may increase the risk of pulmonary hypertension. Furthermore, 5-HT alone or in combination with indomethacin, NDGA and a nitric oxide synthase inhibitor may be used to induce experimental pulmonary hypertension and possibly pulmonary edema.
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PMID:Hyperglycemia increased the responsiveness of isolated rabbit's pulmonary arterial rings to serotonin. 893 Nov

Treatment with beta-blockers and diuretics has been associated with an increased risk of developing diabetes mellitus in three prospective cohort studies. Prospective, randomized studies with antihypertensive drugs have demonstrated differences between different classes of drugs regarding effects on insulin sensitivity. Thus, treatment with beta-blockers or diuretics is associated with impairment in insulin sensitivity, whereas most modern calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors are neutral. However, there are exceptions within the different classes. Captopril seems to differ from the other ACE inhibitors and results in improvement of insulin sensitivity. The most pronounced improvements have been obtained with alpha 1-blockers. In populations at high risk for diabetes mellitus, it may be justified to select drugs that improve insulin sensitivity when treating hypertension in insulin resistant individuals.
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PMID:Hyperinsulinemia, insulin resistance, and the treatment of hypertension. 893 47


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