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Diabetic neuropathy is a common complication of diabetes mellitus. Effective blood glucose control retards changes in nerve conduction velocity in type 1 diabetes. This study examined the relationship between glycemic control and electrophysiologic changes in diabetic neuropathy in 57 type 2 diabetic patients. Nerve conduction in the peroneal motor nerve, tibial motor nerve, and sural nerve were measured at study entry and at follow-up 24+/-3.12 months later. Changes in individual nerves are expressed as a percentage change (PC) and overall electrophysiologic changes are expressed as the sum of individual PCs. The PCs for peroneal motor nerve velocity, tibial motor nerve velocity, and sural nerve velocity were all lower in patients with a mean HbA1c of 8.5% or less compared with those in patients with a mean HbA1c of more than 8.5%, and SPCV (sum of PC in velocity) was significantly inversely correlated with mean HbA1c. However, there was no significant difference in SPCV in subjects with or without hypertension, hypertriglyceridemia, or low high-density lipoprotein cholesterol concentration. In conclusion, hyperglycemia is the most important etiology for electrophysiologic progression in type 2 diabetic patients. Furthermore, a mean HbA1c of more than 8.5% will result in significant deterioration in electrophysiology.
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PMID:Effect of glycemic control on electrophysiologic changes of diabetic neuropathy in type 2 diabetic patients. 1575 84

We aimed to investigate the angiotensin-converting enzyme (ACE) gene polymorphism, ACE activity and their associations with diabetic complications in Turkish patients with type 2 diabetes mellitus. A total of 143 patients and 133 controls were screened for ACE gene I/D polymorphism by using polymerase chain reaction. Serum ACE activities were determined spectrophotometrically. There was no significant difference in the distribution of ACE I/D genotypes between patients and controls. The patients with DD genotype had a higher ACE activity than those with ID and II. Hypertensive diabetic patients with DD genotype had higher ACE activities than those with ID and II. There was no significant difference in the distribution of ACE I/D genotypes between patients with and without nephropathy, retinopathy and hypertension except for patients with and without neuropathy. In patients with DD genotype, creatinine clearance correlated with duration of diabetes. The grade of retinopathy was correlated with duration of diabetes in DD and ID genotypes. The highest ACE activity was measured in hypertensive diabetics with DD genotype. ID genotype was suggested to be a risk factor and II was suggested to be protective for diabetic neuropathy. The DD and ID genotypes might be a predictor for the development of retinopathy in relation to duration of diabetes.
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PMID:Frequency of angiotensin-converting enzyme gene polymorphism in Turkish type 2 diabetic patients. 1617 79

Lipoic acid (LA) and its reduced form dihydrolipoic acid (DHLA, are present in all prokaryotic and eukaryotic cells. Lipoic acid was once considered a vitamin, but now it is commonly accepted that it can be synthesized de novo in human cells. LA has long been known as a coenzyme of multienzymatic complexes catalyzing the decarboxylation of alpha-ketoacids, but the present investigations are focused on its antioxidative properties. Both LA and DHLA have proved to be potent free radicals scavengers and metal chelators. They are also responsible for the regeneration of active forms of other cellular antioxidants, including vitamins C and E. Moreover, lipoic acid is involved in the regulation of carbohydrate and lipid metabolism. LA is easily absorbed from the gastrointestinal tract, is able to cross the blood-brain barrier, and does not exhibit any serious side effects. All these features make lipoic acid a very promising drug. Nowadays, this compound is used in the treatment of diabetic neuropathy, fungi, and metal poisoning, as well as in liver disorders. The application of lipoic acid in treating other diseases, including hypertension and autoimmunological disorders, needs careful evaluation.
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PMID:[Lipoic acid: characteristics and therapeutic application]. 1640 92

Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients ("idiopathic neuropathy"). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a multicenter study of diet and exercise in prediabetes (the Impaired Glucose Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based on the Diabetes Prevention Program results in improved metabolic measures and small fiber function. Prediabetes is part of the Metabolic Syndrome, which also includes hypertension, hyperlipidemia and obesity. Individual aspects of the Metabolic Syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy both for those with prediabetes, and those with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach to individual components of Metabolic Syndrome may slow prediabetic neuropathy progression or result in improvement.
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PMID:Idiopathic neuropathy, prediabetes and the metabolic syndrome. 1644 68

As a result of epidemiologic transition, diabetes mellitus became a major public health problem in Tunisia. We tried to determine the epidemiological and clinical features of patients with type 2 diabetes mellitus in primary health care units in Sousse (Tunisia). It was a cross sectional study about a stratified sample of 404 type 2 diabetes mellitus patients followed in primary care offices in Sousse in 2003. Average age was 60 + 10.9 years and sex-ratio was 0.5. Hypertension and obesity were found in respectively 71.3% and 37.6%. Diabetic neuropathy was the most frequent degenerative complication (41.1%) followed by diabetic retinopathy (18.3%). Thus, type 2 diabetes mellitus patients, followed in primary care units show a high cardiovascular risk with serious and frequent complications. That's why, the national care program of type diabetes mellitus, in primary health care should take in consideration, in its guidelines, the clinical and epidemiological characteristics of these patients.
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PMID:[Epidemiologic and clinical features of patients with type 2 diabetes mellitus in primary care facilities (Sousse, Tunisie)]. 1703 32

Poor glycaemic control and the duration of diabetes mellitus are known to accelerate development and progression of neuropathy. Diabetic co-morbidities: hypertension and hyperlipidaemia, have been postulated to associate with development of neuropathy. A diabetic foot with low temperature and frequent exposure to low temperature environment has recently been hypothesized to be at higher risk to develop early neuropathy. This cross-sectional study is undertaken to identify risk factors for diabetic neuropathy and the association between foot temperature and development of diabetic neuropathy by using simple clinical examination in the outpatient setting. From April 18, to April 30, 2005, universal sampling method was used to select 134 diabetic patients (type 1 or type 2 for >1 year) with peripheral neuropathy. Excluded are those with chronic alcoholism, drug-induced neuropathy, dietary history of vitamin B deficiency and family history of porphyria and hereditary sensorimotor neuropathy. The patient's duration of diabetes, glycaemic control status and the presence of co-morbids: hypertension and hyperlipidemia, were recorded. The temperature of the foot was measured by using thermo buddy. Of 134 patients representing Malaysian ethnic distribution with an equal number of males and females, 20.1% were in the age group of 61 to 65 years and, 85.1% and 67.9% belonged to lower socioeconomic and educational groups respectively. Associations between diabetic neuropathy and glycaemic control (p = 0.018) and duration of diabetes (p < 0.05) were significant. However, hypertension, hyperlipidaemia and low foot temperature were not significantly associated with development of diabetic neuropathy. Poor glycaemic control is significantly associated with diabetic neuropathy. Foot temperature alteration is merely an effect of autonomic neuropathy with a cold foot is attributed to co-existing peripheral arterial disease.
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PMID:Alteration of foot temperature in diabetic neuropathy: is it another piece of puzzle? 1704 21

People with diabetes have an increased risk of developing microvascular complications, diabetic retinopathy, diabetic nephropathy and diabetic neuropathy, which, if undetected or left untreated, can have a devastating impact on quality of life and place a significant burden on health care costs. In addition, diabetic microvascular complications can reduce life expectancy. The strongest risk factors are glycaemic control and diabetes duration; however, other modifiable risk factors such as hypertension, hyperlipidaemia and smoking, and unmodifiable risk factors including age at onset of diabetes and genetic factors may all play a part. Along with the presence of external risk factors, some associations have also been noted between diabetic microvascular complications themselves. There is evidence that diabetic retinopathy in association with increased blood pressure is an important risk factor for diabetic nephropathy progression. Significant correlations have also been shown between the presence of diabetic peripheral neuropathy and the presence of background or proliferative diabetic retinopathy. Clinical trials are currently in progress looking at a number of approaches to designing treatments to prevent the adverse effects of hyperglycaemia. It is essential however, that risk factors associated with the progression and development of diabetic microvascular complications are detected and treated at an early stage in order to further reduce morbidity and mortality. Considering all three complications as interrelated may well facilitate early detection of microvascular disease. Despite good long-term glycaemic and blood pressure control, diabetes remains a major cause of blindness, renal failure and amputations. As the incidence of diabetes continues to rise, the burden of diabetic microvascular complications will increase in future, hence the need for early detection. Considering the microvascular complications of diabetes as related, and enquiring proactively about complications, may well facilitate early detection of microvascular disease.
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PMID:Diabetic microvascular complications: can patients at risk be identified? A review. 1707 42

At least one of four diabetic patients is affected by distal symmetric polyneuropathy (DSP), which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality, and impaired quality of life. Treatment is based on four cornerstones: (a) causal treatment aimed at (near)-normoglycemia, (b) treatment based on pathogenetic mechanisms, (c) symptomatic treatment, and (d) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view it is important to note that, on the basis of these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Among these agents only alpha-lipoic acid is available for treatment in several countries and epalrestat in Japan. Although several novel analgesic drugs, such as duloxetine and pregabalin, have recently been introduced into clinical practice, the pharmacological treatment of chronic painful diabetic neuropathy remains a challenge for the physician. Individual tolerability remains a major aspect in any treatment decision. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors, such as hypertension, smoking, and visceral obesity, play a role in development and progression of diabetic neuropathy and, hence, need to be prevented or treated.
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PMID:Treatment of diabetic polyneuropathy: Update 2006. 1715 6

In most Western countries, diabetic nephropathy (DN) has become the single most common condition found in patients with end-stage renal disease (ESRD). This is to some extent due to better survival of diabetic patients with renal failure, but mostly due to the dramatic increase in the prevalence of type 2 diabetes. The majority of type 2 diabetic patients with renal failure suffer from nodular glomerulosclerosis (Kimmelstiel-Wilson); but ischemic nephropathy, irreversible acute renal failure (mostly acute on chronic) and diabetes co-existing with primary renal diseases are common as well. Classical DN evolves in a sequence of stages. After a period of glomerular hyperfiltration, increased urinary albumin excretion [microalbuminuria (MA)] i.e. 30-300 mg/day or 20 - 200 microg/minute indicates the onset of overt DN. Risk factors for development of DN are positive family history, hyperglycemia in the mother during pregnancy, high blood pressure, obesity and insulin resistance. Poor glycemic control (HbAlc) and elevated systolic blood pressure (> 135 mm Hg) interact in enhancing the risk of DN. Proteinuria and smoking are major promoters of progression. The risk of onset of microalbuminuria can be reduced by lowering of blood pressure and specifically by blockade of the renin angiotensin system (RAS). In patients with established DN, the target systolic blood pressure should be <130 mm Hg and RAS blockade is obligatory. Treating all cardiovascular risk factors is a high priority. Antihypertensive management is rendered difficult by extreme volume sensitivity, pronounced activation of the RAS and autonomic neuropathy. Cardiac events are excessively frequent, glycemic control becomes difficult and autonomic diabetic neuropathy with gastroparesis and diabetic foot are additional problems. Hemodialysis or continuous ambulatory peritoneal dialysis should be started relatively early. In the absence of contraindications, transplantation (renal transplantation, combined kidney/pancreas transplantation or pancreas after kidney transplantation) is the treatment of choice.
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PMID:Diabetic nephropathy. 1718 81

New evidence about diabetic microangiopathy has enabled us to identify an integrated pathogenesis of diabetic complications, including classic metabolic pathways induced by hyperglycaemia, insulin-resistance, hyperinsulinaemia, hormonal alterations and growth factors. Oxidative stress is the most important cause of endothelial damage inducing leukocyte adhesion, altered coagulation and inflammation. Adhesion molecules are a marker of endothelial damage and a potential therapeutic target. Changes in the extracellular matrix induced by TGFbeta1 and lower levels of eparan-sulfate, increased thickness of basement membranes and loss of pericytes are early events of diabetic retinopathy and diabetic nephropathy. Capillary rarefaction produced by genetic factors or by fetal undernourishment contributes to the beginning of insulin-resistance and hypertension. Psychophysical tests, electroretinogram and evoked potentials show retinal functional alterations; fundoscopy and retinal fluorescein angiography show retinal anatomic alterations. The diagnosis of diabetic neuropathy is based not only on traditional neurological examination and electroneurograms, but also on neurothesiometry for sensory testing. Medical treatment of diabetic microangiopathy is based on control of glycaemia, lipemia and blood pressure using glytazones, ACE-inhibitors, angiotensin II receptor antagonists and statins. New knowledgeabout microangiopathy pathogenesis suggests potential drugs for its therapy (ruboxistaurin, AGE-inhibitors, angiopoietin-1 and anti-VEGF, etc.), not yet on sale.
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PMID:Diabetic microangiopathy: physiopathological, clinical and therapeutic aspects. 1791 58


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