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Type I and type II diabetes is associated with increased cardiovascular complications, the most common of which are ischaemic cardiomyopathy and left ventricular dysfunction. The existence of an independent disease, diabetic cardiomyopathy, was suggested by initial anatomic studies, experimental models, and, more recently, by epidemiological studies. The exact cause of this ventricular dysfunction is not known: several mechanisms have been proposed, such as metabolic abnormalities of glucose transport, cellular overload in fatty acid metabolites, alteration of calcium uptake by the sarcoplasmic reticulum leading to cellular calcium overload, coronary microangiopathy, structural collagen abnormalities, interstitial and perivascular fibrosis or the presence of an autonomic neuropathy. The condition is characterised by abnormal left ventricular filling suggesting poor compliance or prolongation of left ventricular relaxation. Left ventricular systolic function is usually normal at rest but abnormally decreased on effort. The value of strict metabolic control and the place of drug therapy, especially calcium antagonists which oppose cellular calcium overload, has yet to be established. The natural history of diabetic cardiomyopathy should be defined by clinical studies taking care to differentiate it from the cardiovascular consequences of hypertension or obesity which aggravate or stimulate this condition.
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PMID:[Diabetic cardiomyopathy]. 764 66

Functional changes of the autonomic nervous system may represent a common pathophysiologic factor in the association between non insulin-dependent diabetes, obesity, and essential hypertension. In all these conditions a number of sympathetic and/or parasympathetic dysfunctions consistent with autonomic neuropathy or simply with functional adaptations to haemodynamic changes have been reported. Autonomic neuropathy is a well known diabetic complication which is responsible for some clinical aspects of different severity. Subtle sympathetic and parasympathetic abnormalities possibly affecting thermogenesis have been shown in obese people. An increased sympathetic activity has been proposed as one of the pathogenetic mechanisms of essential hypertension. Finally, the association between diabetes, obesity, hypertension and sympathetic overactivity could be explained by a common trans-membrane ionic disturbance with an increase of intracellular calcium and a decrease of both intracellular magnesium and pH.
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PMID:[Diabetes, obesity, hypertension and the autonomic nervous system]. 779 91

Little is known about the occurrence and predictive factors of autonomic neuropathy and its relationship to cardiovascular mortality in NIDDM patients, and no long-term follow-up studies including nondiabetic control subjects are available. A total of 133 patients with newly diagnosed NIDDM (70 men) and 144 control subjects (62 men) were examined at baseline and after 5 and 10 years of follow-up. Deep-breathing tests (baseline, 5-year, and 10-year) and active orthostatic tests (5- and 10-year) were performed. Criteria for autonomic neuropathy were parasympathetic (expiration-to-inspiration ratio </- 1.10), sympathetic (systolic blood pressure decrease >/- 30 mmHg in the orthostatic test), and combined autonomic neuropathy (parasympathetic with sympathetic neuropathy). The frequency of parasympathetic neuropathy (NIDDM patients versus control subjects) was 4.9 vs. 2.2% (P = 0.224) at baseline, 19.6 vs. 8.5% (P = 0.017) at 5 years, and 65.0 vs. 28.0% (P < 0.001) at 10 years of follow-up. The frequency of sympathetic neuropathy was 6.8 vs. 5.6% (P = 0.709) at 5 years and 24.4 vs. 9.0% (P = 0.003) at 10 years of follow- up. These figures for combined autonomic neuropathy were 2.1 vs. 1.8% (P = 0.869) at 5 years and 15.2 vs. 4.2% (P = 0.007) at 10 years of follow-up. NIDDM patients with parasympathetic neuropathy at the 10-year examination showed worse glycemic control and higher insulin values than those without parasympathetic neuropathy. Furthermore, in our subjects, women were more prone to have parasympathetic neuropathy than men. Parasympathetic neuropathy at baseline was more frequent in those who died from a cardiovascular cause than those who did not (13 vs. 3%, P = 0.045). Similarly, sympathetic autonomic nervous dysfunction at the 5-year examination predicted the 10-year cardiovascular mortality. In conclusion, the frequency of autonomic neuropathy in NIDDM patients increases sharply with time. The development of autonomic neuropathy is connected with poor glycemic control. Interestingly, a high insulin level seems to have a predictive role in the development of parasympathetic autonomic neuropathy irrespective of obesity and glycemia.
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PMID:Occurrence, predictors, and clinical significance of autonomic neuropathy in NIDDM. Ten-year follow-up from the diagnosis. 859 35

Fifty two diabetic patients and 15 healthy control subjects were prospectively studied for their gall bladder function by ultrasound examination. The fasting gall bladder volume (FGBV) was calculated by using ellipse formula from the dimension of gall bladder shadow seen on ultrasound screen in two different cuts. The contractility of gall bladder was measured by calculating post prandial ejection fraction (EF) of the gall bladder. The mean FGBV and EF in 52 diabetic patients was found to be 20.7 +/- 10.7 cc and 47.5 +/- 20.1%, which was not significantly different from that in normal controls. Age, sex, obesity, diabetic control and presence of dyspeptic symptoms had no impact in FGBV and EF. Diabetic symptoms had no impact in FGBV and EF. However, diabetics with longer duration of disease had poorer gall bladder contractility (p < 0.05). Patients with autonomic neuropathy (AN) had significantly larger FGBV but normal contractility. Our results suggest that (a) long standing diabetics may have poor gall bladder emptying predisposing to gall stone formation (b) patients with autonomic neuropathy have reduced tone of fasting gall bladder but normal contractility.
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PMID:Gall bladder dysmotility in diabetes mellitus--an ultrasound study. 883 37

In 97 IDDM and 64 NIDDM patients aged under 65 years, we evaluated the relationship between autonomic neuropathy (AN) and retinopathy, nephropathy, glycemic control and cardiovascular risk factors. Diabetes duration and HbA1 were significantly higher and body mass index was significantly lower in IDDM patients with AN compared to those without. In NIDDM only age was significantly higher in neuropathic patients. AN was associated with retinopathy in both IDDM (chi2 = 10, P < 0.03) and NIDDM patients (chi2 = 14, P < 0.007), while only in IDDM albumin excretion was significantly higher in patients with AN. Blood pressure (BP) was significantly higher in both IDDM and NIDDM patients with AN compared to those without. There were no differences in smoking and serum lipids between patients with and those without AN. We performed a multiple regression analysis using autonomic score, index of cardiovascular tests impairment, as the dependent variable and age, diabetes duration, body mass index, HbA1, albumin excretion, cholesterolemia, triglyceridemia, systolic BP, and retinopathy as independent variables. With this model in IDDM autonomic score was only related to body mass index (r = -0.29, P < 0.05), to HbA1 (r = 0.46, P < 0.001), and to systolic BP (r = 0.24, P < 0.05), while in NIDDM it was only related to systolic BP (r = 0.54, P < 0.001). In conclusion, AN was related to age in NIDDM, and to diabetes duration and glycemic control in IDDM. AN was associated with retinopathy, with nephropathy (only in IDDM), and with BP levels, but not with dyslipidemia, smoking, or obesity. Excess mortality rate observed in diabetic AN cannot be referred to an association with cardiovascular risk factors.
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PMID:Autonomic neuropathy and cardiovascular risk factors in insulin-dependent and non insulin-dependent diabetes. 906 69

The pertinent literature on the prevalence, clinical manifestations and pathogenic mechanisms of sleep apnoea (SA) in endocrine diseases, namely acromegaly, Cushing syndrome, hypothyroidism and diabetes mellitus was reviewed. An increased prevalence is well documented in patients with active and treated acromegaly. While most authors report peripheral obstruction, due to hypertrophy of tongue and pharyngeal tissues, to be the cause of SA in acromegaly, some findings argue for a role of hormone-induced changes of central respiratory control. SA is also more common in hypothyroidism, especially when myxedema is present. The associated edema and myopathy appear to be of pathogenic importance. Thyroxin substitution is frequently effective for the treatment of SA but nCPAP can be necessary initially and in some patients even after remission of clinical signs of hypothyroidism. In Cushing disease and syndrome, parapharyngeal fat accumulation can cause SA, but no epidemiological information is available. In non insulin dependent diabetes (NIDDM), obesity is the common risk factor for both, nocturnal hypoxia and insulin resistance. In IDDM, the development of autonomic neuropathy may predispose to SA. Where treatment of the underlying endocrine disease is unable cure the associated SA, nCPAP is usually the treatment of first choice. More prospective studies are clearly needed to establish prevalences and resolve the controversies regarding pathogenesis.
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PMID:Sleep apnoea in endocrine diseases. 961 23

Palatable cephalic stimuli induce a simultaneous activation of gastrointestinal motility, gastric acid and pancreatic enzyme secretion, as well as, release of the gastrointestinal hormones gastrin and pancreatic polypeptide. Cholinergic neural input is the dominant mediator of these responses with cholecystokinin and gastrin acting as additional stimulatory modulators. Central cholinergic circuits, neuropeptide Y, and thyrotropin releasing hormone are candidate central stimulators of the cephalic phase. There are good arguments for glucagon-like peptide-1 and peptide YY to be physiological inhibitors of cephalic-phase responses with these peptides being released in the intestinal phase of digestion and putatively contributing to termination of the cephalically stimulated pattern. Cephalic-phase responses are used clinically as diagnostic tests to assess completeness of selective proximal vagotomy and to explore autonomic neuropathy. Pancreatic polypeptide secretion with sham feeding is an appropriate test of abdominal vagal function. Cephalically stimulated motor and secretory activity contribute greater than 50% of overall postprandial responses. Pharmacological inhibition of cephalic-vagal stimulation, resulting in reduced food intake, may be a novel approach to obesity management. Glucagon-like peptide-1 is a particular candidate because it inhibits the cephalic phase of digestion, diminishes food intake, and reduces the glycemic excursion after a meal by retarding gastric emptying, stimulating insulin and lowering glucagon release.
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PMID:Nutritional implications of cephalic phase gastrointestinal responses. 1074 9

As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.
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PMID:Exercise and diabetes. 1157 Jan 19

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type II diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.
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PMID:Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance. 1283 96

The current study sought to examine in a large series of diabetic patients the prevalence of symptoms of autonomic neuropathy and subclinical cardiac autonomic neuropathy (CAN) and their determinants, particularly the influence of diabetes duration, obesity, and microangiopathic complications. Three hundred ninety-six patients, 245 type 1 and 151 type 2, were recruited in 7 French departments of diabetology. CAN was detected by measuring heart rate variability during 3 standardized tests: deep-breathing, Valsalva, and lying-to-standing tests. At least 24.5% of the patients had one or more symptoms suggesting overt autonomic neuropathy. They were older than those free of dysautonomic symptom (P<.001). The deep-breathing test correlated negatively with body mass index (BMI) in type 2 diabetic patients (P<.0001). In the whole population, the deep-breathing and Valsalva tests correlated negatively with diabetes duration (P=.0004 and.019, respectively) and the log urinary albumin/creatinine ratio (P<.002 and.001, respectively). The prevalence of CAN (51%) was higher than the prevalence of other diabetic complications. The rate of moderate and severe CAN (defined by 2 or 3 abnormal CAN function tests) was higher in type 1 than in type 2 diabetic patients (P=.031). It correlated with diabetes duration (P=.026) and was higher in the patients with retinopathy than in those without (P=.035). Among type 2 diabetic patients, the prevalence of CAN was higher in the obese ones (P=.033); in a logistic regression taking age, diabetes duration, and obesity as independent variables, CAN was associated independently with obesity (P=.034). Mild or moderate CAN was found in 33.8% and 13.0% of the 80 patients with diabetes duration less than 18 months. We conclude that CAN is found early in the course of diabetes and should be considered as a prognostic marker of microangiopathic complications. Obesity could be involved in the impairment of CAN function in type 2 diabetics and body weight control could provide an approach to reducing neuropathic complications.
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PMID:Cardiac autonomic neuropathy in diabetic patients: influence of diabetes duration, obesity, and microangiopathic complications--the French multicenter study. 1287 Jan 54


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