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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both type 1 and type 2 diabetic patients have an increased incidence of ischemic heart disease and congestive heart failure. Cardiovascular disease accounts for up to 80% of the excess mortality in patients with type 2 diabetes. The burden of cardiovascular disease is especially pronounced in diabetic women. Factors that underlie diabetic heart disease include multiple vessel coronary artery disease, long-standing hypertension, metabolic derangements such as hyperglycemia and dyslipidemia, microvascular disease, and autonomic neuropathy. There is also increased sudden death associated with diabetes, which is due, in part, to the underlying autonomic neuropathy. This article reviews diabetic cardiac disease, with an emphasis on type 2 diabetes.
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PMID:Heart disease in diabetic patients. 1276 70

Dysfunction of the autonomic nervous system is a recognized complication of diabetes. Neuroaxonal dystrophy (NAD), a distinctive axonopathy involving distal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in human and several insulinopenic experimental rodent models. Recent studies have suggested that loss of the neurotrophic effects of insulin and/or IGF-I on sympathetic neurons and not hyperglycemia per se, may underlie the development of sympathetic NAD. The streptozotocin (STZ)-diabetic and BB/W rat, the most commonly used experimental rodent models, develop marked hyperglycemia and concomitant deficiency in both circulating insulin and IGF-I. These animals reproducibly develop NAD in nerve terminals in the prevertebral sympathetic ganglia and the distal portions of noradrenergic ileal mesenteric nerves. The Zucker Diabetic Fatty (ZDF) rat, an animal model of type 2 diabetes, also develops severe hyperglycemia comparable to that in the STZ- and BB/W-diabetic rat models, although in the presence of hyperinsulinemia. In our study, ZDF rats maintained for 6 to 7 months in a severely diabetic state, as assessed by plasma glucose and glycated hemoglobin levels, maintained significant hyperinsulinemia and normal levels of plasma IGF-I at sacrifice. NAD did not develop in diabetic ZDF rat sympathetic ganglia and ileal mesenteric nerves as assessed by quantitative ultrastructural techniques, which is in dramatic contrast to neuropathologic findings in comparably hyperglycemic 6-month STZ-diabetic insulinopenic rats. These data combined with our previous results argue very strongly that hyperglycemia is not the critical and sufficient element in the pathogenesis of diabetes-induced NAD, rather that it is the loss of trophic support, most likely of IGF-I or insulin, that causes NAD.
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PMID:Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy. 1281 7

Diabetic cardiomyopathy is an ill-defined entity. This study was designed to explore the possible association between left ventricular diastolic dysfunction (LVDD) and cardiac autonomic neuropathy (CAN) independently from metabolic control. Three groups of 10 age-matched men each with well-controlled type 2 diabetes were studied: (1) subjects with normal diastolic function, (2) subjects with LVDD characterized by impaired LV relaxation, and (3) subjects with a more severe form of LVDD characterized by a pseudonormalized pattern of LV filling. No subject had evidence of clinical diabetic complications, coronary artery disease (CAD), hypertension, congestive heart failure, or thyroid or overt renal disease, and all had a negative maximal exercise test. LVDD was evaluated by Doppler echocardiographic and CAN was evaluated using spectral analysis of heart rate variability (HRV; time and frequency domains) from 24-hour Holter recordings. Findings showed that the high frequency power (HF: 0.15 to 0.4 Hz) tends to decrease with worsening diastolic function; 5.0 +/- 0.2 ms(2) (mean +/- SE) in group 1, 4.2 +/- 0.3 ms(2) in group 2, and 3.9 +/- 0.4 ms(2) (P =.03) in group 3, respectively, whereas the low frequency power (LF: 0.04 to 0.15 Hz) was similar between groups. In the time domain, the mean squared differences of the successive RR intervals (rMSDD) also showed the same pattern, ie, 31.0 +/- 2.8 ms, 23.8 +/- 1.6 ms, and 21.5 +/- 2.9 ms in groups 1, 2, and 3, respectively (P =.03). The E/A ratio correlated significantly with indices of parasympathetic modulation (HF; r = 0.448, P =.013; rMSDD: r = 0.457, P =.011; pNN50: r = 0.425, P =.019). LVDD and CAN are associated in patients with otherwise uncomplicated well-controlled type 2 diabetes. The parameters defining these 2 abnormalities may serve to better define diabetic cardiomyopathy as a distinct entity and could eventually become useful prognostic indicators as it has been shown in nondiabetic populations.
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PMID:Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes. 1289 73

We recently published the results of the Steno-2 study, which evaluated the benefits of intensified integrated behavior modification and targeted polypharmacy. The results provide abundant evidence that an ambitious treatment strategy is superior to a conventional one. The study involved 160 high-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific significant group differences in the degree of change in key clinical and biochemical variables at the end of the study were (in the intensive group): lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy. There was no difference in weight gain between groups during follow-up and no other major side effects were reported. The primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The differences between groups in surrogate end points translated into the following significant group differences in final clinical end points: 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%. Also, the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half. The challenge is to ensure that this experience is widely adopted in daily practice.
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PMID:Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2 study. 1293 35

To address the pathogenesis of diabetic autonomic neuropathy, we have examined the sympathetic nervous system in non-obese diabetic (NOD) and streptozotocin (STZ)-induced diabetic mice, two models of type 1 diabetes, and the db/db mouse, a model of type 2 diabetes. After only 3 to 5 weeks of diabetes, NOD mice developed markedly swollen axons and dendrites ("neuritic dystrophy") in the prevertebral superior mesenteric and celiac ganglia (SMG-CG), similar to the pathology described in diabetic STZ- and BBW-rat and man. Comparable changes failed to develop in the superior cervical ganglia of the NOD mouse or in the SMG-CG of non-diabetic NOD siblings. STZ-induced diabetic mice develop identical changes, although at a much slower pace and to a lesser degree than NOD mice. NOD-SCID mice, which are genetically identical to NOD mice except for the absence of T and B cells, do not develop diabetes or neuropathology comparable to diabetic NOD mice. However, STZ-treated NOD-SCID mice develop severe neuritic dystrophy, evidence against an exclusively autoimmune pathogenesis for autonomic neuropathy in this model. Chronically diabetic type 2 db/db mice fail to develop neuritic dystrophy, suggesting that hyperglycemia alone may not be the critical and sufficient element. The NOD mouse appears to be a valuable model of diabetic sympathetic autonomic neuropathy with unambiguous, rapidly developing neuropathology which corresponds closely to the characteristic pathology of other rodent models and man.
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PMID:Non-obese diabetic mice rapidly develop dramatic sympathetic neuritic dystrophy: a new experimental model of diabetic autonomic neuropathy. 1457 68

Neuropathy is one of the most debilitating complications of both type 1 and type 2 diabetes, with estimates of prevalence between 50-90% depending on the means of detection. Diabetic neuropathies are heterogeneous and there is variable involvement of large myelinated fibers and small, thinly myelinated fibers. Many of the neuronal abnormalities in diabetes can be duplicated by experimental depletion of specific neurotrophic factors, their receptors or their binding proteins. In experimental models of diabetes there is a reduction in the availability of these growth factors, which may be a consequence of metabolic abnormalities, or may be independent of glycemic control. These neurotrophic factors are required for the maintenance of the neurons, the ability to resist apoptosis and regenerative capacity. The best studied of the neurotrophic factors is nerve growth factor (NGF) and the related members of the neurotrophin family of peptides. There is increasing evidence that there is a deficiency of NGF in diabetes, as well as the dependent neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) that may also contribute to the clinical symptoms resulting from small fiber dysfunction. Similarly, NT3 appears to be important for large fiber and IGFs for autonomic neuropathy. Whether the observed growth factor deficiencies are due to decreased synthesis, or functional, e.g. an inability to bind to their receptor, and/or abnormalities in nerve transport and processing, remains to be established. Although early studies in humans on the role of neurotrophic factors as a therapy for diabetic neuropathy have been unsuccessful, newer agents and the possibilities uncovered by further studies should fuel clinical trials for several generations. It seems reasonable to anticipate that neurotrophic factor therapy, specifically targeted at different nerve fiber populations, might enter the therapeutic armamentarium.
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PMID:Nerve growth factor and diabetic neuropathy. 1466 49

The present study has been conducted to quantify and compare the capacity of gas exchange in patients with type 2 diabetes mellitus (DM) and healthy controls and also to investigate the effects of various factors on alveolar capillary permeability. A total of 37 subjects, 25 patients with DM and 12 healthy controls were recruited for the study. All the participants were evaluated with simple spirometric tests and simple breath carbonmonoxide (CO) diffusion test (DLCO). The ratio of DLCO value to the alveolar ventilation (VA) was used to assess alveolar membrane permeability. Diabetic patients were also evaluated in detail with respect to degenerative diabetic complications including the presence of microalbuminuria, advanced nephropathy, sensorial and autonomic neuropathy, retinopathy, hypertension and macrovascular disease. The results of simple spirometric tests which determined lung capacity were similar in the diabetic patients and the healthy controls. Ratio of DLCO/VA, which determines alveolar membrane permeability, revealed statistically significant decline in pulmonary gas exchange in the diabetic group (p: 0.037). Pearson correlation analysis revealed statistically significant correlation between duration of diabetes mellitus, age and urinary albumin excretion with DLCO/VA values (Pearson: -0.726, p: 0.001; Pearson: -0.438, p: 0.036; Pearson: -0.472, p: 0.023 respectively). This study demonstrated the decreased alveolar gas exchange capacity in diabetic patients compared with healthy controls. Detrimental effects of DM on alveolar capillaries were found to be correlated with age, duration of DM and urinary albumin excretion. Microalbuminuria was the only significant predictor of DLCO/VA.
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PMID:Alveolar gas exchange in patients with type 2 diabetes mellitus. 1470 35

Anaemia is a common complication of chronic kidney disease (CKD). It is often more severe and occurs at an earlier stage in patients with diabetic nephropathy than in patients with CKD of other causes. This anaemia results from erythropoietin deficiency, which seems to develop in patients with type 1 diabetes even at relatively "normal" levels of serum creatinine. Early erythropoietin- deficiency anaemia occurs in both type 1 and type 2 diabetes, although the prevalence may be higher in type 1 diabetes. However, numerically most patients with erythropoietin-deficiency anaemia have type 2 diabetes as it is a much more common disease. There is also a greater prevalence in women than men but this is not related to iron stores. In addition, erythropoietin-deficiency anaemia is associated with the presence of autonomic neuropathy in patients with diabetes. Small studies have suggested that recombinant human erythropoietin (rhEPO; epoetin) treatment is effective in correcting erythropoietin-deficiency anaemia in patients with diabetes. Additionally, rhEPO therapy improves quality of life and well-being in these patients. Studies also suggest that treatment with rhEPO to restore a normal haematocrit ameliorates orthostatic hypotension. Given the high cardiovascular risk in patients with diabetic nephropathy, it is important to determine in prospective clinical trials whether early anaemia correction can also improve cardiovascular outcomes.
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PMID:Anaemia in diabetes. 1510 43

Dysfunction of the autonomic nervous system is a recognized complication of diabetes, ranging in severity from relatively minor sweating and pupillomotor abnormality to debilitating interference with cardiovascular, genitourinary, and alimentary dysfunction. Neuroaxonal dystrophy (NAD), a distinctive distal axonopathy involving terminal axons and synapses, represents the neuropathologic hallmark of diabetic sympathetic autonomic neuropathy in man and several insulinopenic experimental rodent models. Although the pathogenesis of diabetic sympathetic NAD is unknown, recent studies have suggested that loss of the neurotrophic effects of insulin and/or insulin-like growth factor-I (IGF-I) on sympathetic neurons rather than hyperglycemia per se, may be critical to its development. Therefore, in our current investigation we have compared the sympathetic neuropathology developing after 8 months of diabetes in the streptozotocin (STZ)-induced diabetic rat and BB/ Wor rat, both models of hypoinsulinemic type 1 diabetes, with the BBZDR/Wor rat, a hyperglycemic and hyperinsulinemic type 2 diabetes model. Both STZ- and BB/Wor-diabetic rats reproducibly developed NAD in nerve terminals in the prevertebral superior mesenteric sympathetic ganglia (SMG) and ileal mesenteric nerves. The BBZDR/Wor-diabetic rat, in comparison, failed to develop superior mesenteric ganglionic NAD in excess of that of age-matched controls. Similarly, NAD which developed in axons of ileal mesenteric nerves of BBZDR/Wor rats was substantially less frequent than in BB/Wor- and STZ-rats. These data, considered in the light of the results of previous experiments, argue that hyperglycemia alone is not sufficient to produce sympathetic ganglionic NAD, but rather that it may be the diabetes-induced superimposed loss of trophic support, likely of IGF-I, insulin, or C-peptide, that ultimately causes NAD.
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PMID:Experimental rat models of types 1 and 2 diabetes differ in sympathetic neuroaxonal dystrophy. 1519 24

We measured sympathetic skin response (SSR), a measure of sympathetic sudomotor function, and compared SSR with other quantitative neurological tests including power spectral analysis (PSA) of heart rate variations in 60 type 2 diabetic subjects. SSR was detected in all 20 age-matched healthy subjects but was absent in 17 patients with type 2 diabetes (28%) (P<.01). Even after exclusion of diabetic patients with absent SSR, the SSR amplitude in diabetic patients was significantly lower than in healthy subjects (P<.05). Both the low frequency power of R-R intervals, which reflects both cardiac sympathetic and parasympathetic function, and the postural fall in systolic blood pressure were significantly lower in the diabetic patients with absent SSR than in those with present SSR (P<.05 and.001, respectively). However, we found no significant difference in the high frequency power of R-R intervals, which reflects accurately cardiac parasympathetic function, between the diabetic patients with absent SSR and those with present SSR. In the diabetic patients with present SSR, SSR amplitude was also positively correlated with the postural fall in systolic blood pressure, low-frequency (LF) power, and high-frequency (HF) power. These results suggest that SSR is a useful and sensitive method for evaluating diabetic autonomic neuropathy, and that sympathetic sudomotor neuropathy may be preceded by cardiac parasympathetic neuropathy in patients with type 2 diabetes.
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PMID:Relationship between sympathetic skin response and power spectral analysis of heart rate variation in patients with type 2 diabetes. 1520 41


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