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

Cardiovascular disease represents the major cause of morbidity and mortality in noninsulin-dependent diabetic patients. While it was once thought that atherosclerotic vascular disease was responsible for all of these adverse effects, recent studies support the notion that one of the major adverse complications of diabetes is the development of a diabetic cardiomyopathy characterized by defects in both diastolic and systolic function. Contributing to the development of the cardiomyopathy is a shift in myosin isozyme content in favor of the least active V3 form. Also defective in the noninsulin-dependent diabetic heart is regulation of calcium homeostasis. While transport of calcium by the sarcolemmal and sarcoplasmic reticular calcium pumps are minimally affected by noninsulin-dependent diabetes, significant impairment occurs in sarcolemmal Na(+)-Ca2+ exchanger activity. This defect limits the ability of of the diabetic heart to extrude calcium, contributing to an elevation in [Ca2+]i. Also promoting the accumulation of calcium by the diabetic cell is a decrease in Na+, K+ ATPase activity, which is known to increase [Ca2+]i secondary to a rise in [Na+]i. In addition, calcium influx via the calcium channel is stimulated. Although the molecular mechanisms underlying these defects are presently unknown, the possibility that they may be related to aberrations in glucose or lipid metabolism are considered. The evidence suggests that classical theories of glucose toxicity, such as excessive polyol production or glycosylation, appear to be insignificant factors in heart. Also insignificant are defects in lipid metabolism leading to accumulation of toxic lipid amphiphiles or triacylglycerol. Rather, the major defects involve membrane changes, such as phosphatidylethanolamine N-methylation and protein phosphorylation, which can be attributed to the state of insulin resistance.
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PMID:Cardiomyopathy associated with noninsulin-dependent diabetes. 166 89

To understand the mechanisms of diabetic cardiomyopathy and the consequences of combined hypertension and diabetes, cardiac tissue responses to various inotropic agents were measured in experimental diabetes. Streptozotocin was injected into Wistar rats, spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats (WKYs). Six weeks after the injection diabetic rats showed a subsensitivity to beta adrenergic stimulation in ventricular tissue and a supersensitivity and hyper-responsiveness to Ca++ and alpha adrenergic stimulation (except in WKYs) in ventricular tissues and left atria. A supersensitivity to BAY K 8644 in SHR left atria and a hyper-responsiveness to verapamil in ventricular strips were also noted. These alterations may be due to a change in receptor number or to postreceptor alterations. Diabetic SHRs exhibited greater changes in several of the drug responses (responses to isoproterenol, phenylephrine and BAK 8644) were more hyperlipidemic and had a high mortality as compared with Wistar rats and WKY diabetics. These findings confirm that the combination of hypertension and diabetes results in greater cardiac pathology than is seen with either disease alone.
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PMID:Altered inotropic responses in diabetic cardiomyopathy and hypertensive-diabetic cardiomyopathy. 170 26

Diabetes mellitus is associated with significant morbidity and mortality caused by the micro- and macro-vascular complications that all too frequently develop during the lifetime of the diabetic patient. In attempts to treat the complications of diabetes, several different treatment strategies have been investigated. The role of tight blood glucose control in the treatment of diabetic vascular complications has recently been challenged, as the existing data in support of this mode of therapy are currently inconclusive. Perhaps more effective in preventing many of the vascular complications is the rigorous treatment of hypertension that frequently accompanies diabetes mellitus. Epidemiological studies have demonstrated that the presence of hypertension significantly contributes to the development and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and possibly neuropathy. Preliminary clinical studies demonstrate that the progression of diabetic renal disease can be slowed by vigorous antihypertensive therapy. Among the various antihypertensive agents used to treat the hypertension associated with diabetes mellitus, calcium channel blockers are emerging as one of the agents of first choice. This is because of their very low side effect profile and their absence of detrimental effects on serum lipid levels and glucose tolerance. Calcium channel blockers may be of additional potential benefit to the diabetic patient by slowing the progression of atherosclerosis, reversing the intracellular calcium defects that may contribute to the pathogenesis of diabetic cardiomyopathy, and protecting against the progression of chronic renal disease.
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PMID:The future of calcium channel blocker therapy in diabetes mellitus. 172 50

Sixty-four diabetic women had their fetuses studied by M-mode echocardiogram between 20-41 weeks of gestation. The mean septal size during both diastole and systole increased in a linear fashion with advancing gestational age in both the normal and diabetic groups. Ventricular septal hypertrophy (ie, more than 2 standard deviations above the normal mean) was present in 48 of 64 (75%) of the fetuses of diabetic women. The ratio of septal size to the anteroposterior cardiac dimension was significantly greater in the diabetic than in the normal group (12 versus 8%; P less than .05). The anteroposterior cardiac dimension indexed to the estimated fetal weight was also greater in the diabetic group. Because both septum and cardiac dimension are larger with maternal diabetes, there may be a specific diabetic cardiomyopathy that originates in utero.
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PMID:Interventricular septal thickness in fetuses of diabetic mothers. 172 86

The mechanism(s) involved in diabetes-induced changes in the heart is still unclear, but one defect appears to occur in the alpha 1-adrenoceptor system. We evaluated the possibility that the changes in the inotropic responsiveness to alpha 1-adrenoceptor stimulation in streptozotocin-diabetic rat hearts may be linked to altered phosphoinositide turnover. Stimulation of alpha 1-adrenoceptor by norepinephrine (in the presence of propranolol) in right ventricles resulted in the formation of D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] [measured with an Ins(1,4,5)P3 protein binding assay kit] in a time- and concentration-dependent manner in both control and diabetic rats. The increase in Ins(1,4,5)P3 preceded the increase in the norepinephrine-mediated positive inotropic effect. Diabetic hearts showed a greater maximum inotropic response to norepinephrine stimulation and also had higher Ins(1,4,5)P3 levels. These observations suggest that the changes in Ins(1,4,5)P3 levels may be implicated in the increased inotropic responsiveness to alpha 1-adrenoceptor stimulation in diabetic hearts. Ca2+ overload, induced by Ins(1,4,5)P3, could further be involved in the development of diabetic cardiomyopathy.
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PMID:Alpha 1-adrenoceptor-mediated phosphoinositide breakdown and inotropic responses in diabetic hearts. 184 99

Patients with diabetes mellitus are particularly vulnerable to cardiovascular disease. Although both the macrovascular and microvascular complications are present in patients with diabetes alone, they are particularly severe in patients with both diabetes and hypertension. While there is no doubt that a primary diabetic cardiomyopathy occurs with functional consequences, considerable evidence--both in humans and in experimental animal models--points to hypertension as of critical importance in the pathogenesis of severe pathological and symptomatic diabetic heart disease. In hypertensive-diabetic cardiomyopathy, the histopathologic myocardial damage has been attributed to hypertension, while the myocellular dysfunction has been attributed to diabetes. Together, the consequences to the myocardium are devastating. Strict control of the hypertension and diabetes mellitus, along with prevention of the microvascular consequences of both conditions, may have an ameliorative effect on the subsequent development of diabetic heart disease.
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PMID:The diabetic heart: clinical, experimental and pathological features. 192 63

Although several reports have described early changes of cardiac structure and function in diabetic patients, controversy persists regarding the existence of a clinically distinct diabetic cardiomyopathy. To this end, sex-specific linear regression analyses were used to examine the contribution of diabetes mellitus and glucose intolerance to age-adjusted echocardiographic parameters in 1,986 men (mean age 48 years) and 2,529 women (mean age 50 years) from the original Framingham Study cohort and the Framingham Offspring Study. Subjects with evidence of cardiovascular disease at the time of echocardiogram were excluded. Diabetics had higher heart rates than nondiabetics (67.9 vs 64.0 beats/min (p = 0.002) in men, and 73.1 vs 68.3 beats/min (p = 0.004) in women). Diabetic women had increased left ventricular (LV) wall thickness (18.7 vs 17.1 mm, p less than 0.001), relative wall thickness (0.403 vs 0.377, p = 0.008), LV end-diastolic dimension (46.9 vs 45.7 mm, p = 0.03) and LV mass corrected for height (100.4 vs 82.2 g/m, p less than 0.001). Women with glucose intolerance showed similar, less significant trends (p = 0.007 for wall thickness, p less than 0.01 for LV mass). In diabetic men, fractional shortening was slightly reduced (0.355 vs 0.360, p less than 0.05). In a multivariate model that included potentially confounding factors, diabetes remained an independent contributor to LV mass (p = 0.004) and wall thickness (p = 0.008) in women. In a separate linear regression model, which assessed the association of age with LV mass, the age-coefficient for diabetic women was much higher than that for nondiabetics (13.6 vs 6.6 g/m per 10-year increment in age).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Echocardiographic evidence for the existence of a distinct diabetic cardiomyopathy (the Framingham Heart Study). 205 64

The influences of hypertension and hypothyroidism on diabetic cardiomyopathy are not clear. We studied this problem further by characterizing the effects of chronic triiodothyronine (T3) treatment on cardiac performance of diabetic renovascular hypertensive (RVH) rats. Hypertension was effected by clipping the left renal artery of Wistar-Kyoto (WKY) rats, and diabetes was induced 2 weeks later by streptozotocin (STZ; 55 mg/kg i.v.). The WKY strain was selected because it is relatively resistant to the cardiodepressant effects of diabetes, so that the influence of superimposed hypertension would be more apparent. Performance of working Krebs-Henseleit buffer perfused hearts was quantified by measuring left ventricular pressure and flow characteristics. The results showed that renovascular clipping caused a marked hypertension and left ventricular hypertrophy (LVH) but had no effect on perfused heart performance after 10 weeks. They also showed that diabetes during the final 8 weeks (i) caused a marked impairment in the performance of perfused hearts ex vivo of hypertensive rats but had no measurable effect in the normotensive WKY, (ii) had no effect on arterial pressure of either the normotensive or the hypertensive rats but reduced heart rate of hypertensive animals in vivo, and (iii) caused equivalent hyperglycemia, hypoinsulinemia, and hypothyroidism (depressed serum T3 and T4 levels) of hypertensive and normotensive rats. Treatment of diabetic RVH rats with T3 (10 micrograms.kg-1.day-1) in vivo was nearly as effective as insulin therapy (10 U.kg-1.day-1) in preventing the cardiac dysfunction ex vivo and was as effective as insulin therapy in preventing the bradycardia in vivo and the decline loss.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac function of the diabetic renovascular hypertensive rat: effects of insulin and thyroid hormone treatment. 205

Ultrastructure of myocardial cells was studied with a morphometric technique in Wistar rats 6 and 12 months after induction of experimental diabetes with streptozotocin (70 mg/kg i.p.). Weight-matched and untreated rats served as controls. Morphometric analysis showed that volume densities of mitochondria, sarcoplasmic reticulum, lipid droplets and lysosomes were markedly increased and volume density of myofibril was significantly decreased in comparison with those of the control animals. Further measurements of mitochondria indicated that the number density and the transverse profile axis of mitochondria were obviously increased, and inner and cristae membrane surface areas of mitochondria were significantly decreased when compared with the controls. These changes became more serious when diabetic course was prolonged from 6 to 12 months. The results suggest that metabolic disturbances of the myocardial cells in diabetic state may be an important cause of the occurrence of diabetic cardiomyopathy.
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PMID:[Morphometric analysis of myocardial cells in experimental diabetic rats]. 208 51

Diabetic cardiomyopathy appears to be due to "premature ageing" of the myocardium which loses some of its compliance and becomes less sensitive to catecholamines. The condition seems to be severe mainly in those frequent cases where it is associated with hypertensive and/or ischaemic cardiomyopathy. Neuropathic denervation of the heart, usually partial and predominantly affecting the parasympathetic system, might play a part in the myocardial dysfunction. It has been held responsible for sudden death, but its real consequences in diabetic patients remain to be assessed. Coronary artery disease is the most common cardiac complication of diabetes mellitus: it accounts for 50 per cent of deaths among noninsulin-dependent, and 25 per cent among insulin-dependent diabetic subjects. Its incidence does not seem to decline and its severity, notably in women, is demonstrated by a mortality rate that is twice as high as that observed in the non-diabetic population; hence the importance of primary prevention and treatment of risk factors. However, the specificity to abnormal lipid metabolism, notably hypertriglyceridaemia, the potentiation by chronic hyperglycaemia of the harmful effects of arterial hypertension, and the possible responsibility of coagulation disorders and hyperinsulinism are points that have not yet been elucidated. We still do not know whether the objectives to be attained in terms of plasma cholesterol, triglycerides and fibrinogen levels, as well as of blood pressure values, should be different in diabetic and non-diabetic subjects. In any case, the treatment of risk factors should be accompanied by a systematic search for silent ischaemia which is 2 to 3 times more frequent among diabetic patients. Detection of silent ischaemia by electrocardiography during exercise and/or Holter recordings, and by echocardiography and/or thallium scintigraphy should be performed not only in diabetic patients with coronary artery disease but also to those with other risk factors or albuminuria.
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PMID:[Heart involvement in diabetic patients]. 213 51


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