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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the detailed pathogenesis of diabetic polyneuropathy is not known, several mechanisms appear to be involved and may occur sequentially. Hence, the early and much researched activation of the polyol-pathway appears to secondarily affect nonenzymatic glycation, perturbation of vasoactive substances, the immune system and neurotrophism. These metabolic abnormalities may be differentially expressed in the neuropathy occurring in insulin dependent diabetes mellitus (IDDM) and non-insulin dependent diabetes mellitus (NIDDM) diabetes. This notion is supported by differences in the structural abnormalities of the neuropathies in the two types of diabetes. Distinct and characteristic nodal changes occur in IDDM but not in NIDDM neuropathy, which also shows a milder axonal atrophy. On the other hand, nerve fiber loss which characterizes diabetic neuropathy tends to be focal in the older NIDDM patients, suggesting a more prominent vascular genesis. A further characteristic feature of diabetic neuropathy is blunted fiber regeneration, which probably is consequent to impairments of the necessary immune response and local synthesis of neurotrophic factors. Nerve biopsies from diabetic patients, although not necessary for diagnosis, provide valuable tissue for biochemical and molecular analysis of underlying mechanisms, the detailed elucidation of which will facilitate the design of targeted therapies.
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PMID:Neuropathology of diabetic neuropathy and its correlations with neurophysiology. 935 80

Thirty patients with juvenile insulin dependent diabetes mellitus (IDDM) were electrophysiologically evaluated. In addition to the conventional motor and sensory nerve conduction studies, intrafascicular microneurography was performed in the median nerve. In this method a tungsten microelectrode was inserted into the median nerve trunk at the elbow, and a compound nerve action potential (CNAP) was recorded with supramaximal electrical stimulation at the wrist. The subjects' age ranged from 8 to 31 years with an average (SD) of 15.4 (6.2) years; the disease duration varied from 1 to 23 years with an average (SD) of 8.3 (5.8) years. Polyneuropathy index (PNI), expressed as a mean percentage of the normal for twelve indices over the four nerves obtained by motor conduction studies, was 93.9% on the average in patients with IDDM. The mean amplitude of CNAP obtained by intrafascicular microneurography was 417 microV. These results indicate that neuropathy in IDDM is milder than that in adult non-insulin dependent diabetes mellitus (NIDDM). The mean value of PNI decreased at a rate of 0.56% per year; the mean glycosylated hemoglobin (A1c) level was as high as 8.2 +/- 0.9%, findings consistent with those of the previous analysis of adult patients with NIDDM. The PNI value had a significant negative correlation with the duration of diabetes mellitus (p < 0.001) and with mean glycosylated hemoglobin (A1c) level (p < 0.01). CNAP amplitude had a tendency to correlate with duration of diabetes mellitus (p < 0.1). In patients with IDDM we can tell exactly when the disease occurred. Progression of neuropathy in juvenile IDDM was identical to that of adult NIDDM. Careful management of diabetes mellitus is of importance to prevent the progression of neuropathy.
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PMID:[Electrophysiological evaluation of polyneuropathy in juvenile insulin dependent diabetics]. 939 28

Anti-cardiolipin antibodies, oxidatively modified low-density lipoproteins (oxLDL) and circulating immune complexes are humoral factors that have been linked to vascular damage. To analyse their possible role in the vascular complications in type 1 diabetes mellitus, we investigated patients with and without vascular complications (retinopathy, nephropathy, polyneuropathy, foot ulcers). The patients were matched for age, sex and duration of diabetes. The patients were also compared with 102 healthy individuals. Anti-cardiolipin antibodies of IgG and IgA type were more common in patients compared with healthy individuals. There was no difference between patients with and without vascular complications. There was no increased prevalence of IgM anti-cardiolipin antibodies, but the levels of these antibodies were higher in patients with vascular complications compared with patients without complications and controls. Eighty-three percent of patients had circulating immune complexes in comparison with 5% of healthy individuals. Such complexes were more common in patients with complications. Both the prevalence and the levels of immune complexes were higher in patients with null alleles of complement factor C4. Patients with vascular complications had higher prevalence of C4A than of C4B null alleles. Anti-cardiolipin antibodies were present in higher relative concentrations in immune complex form than in serum in all six patients analysed. There was no increased prevalence of antibodies against oxidatively modified LDL in the patients. The higher prevalence and levels of anti-cardiolipin antibodies and circulating immune complexes in patients with vascular complications suggests that these humoral factors might be involved in the vascular complications of type 1 diabetes mellitus.
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PMID:Anti-cardiolipin antibodies and circulating immune complexes in type 1 diabetes mellitus: increased prevalence and relation to vascular complications. 993 50

Aberrant neurofilament phosphorylation occurs in many neurodegenerative diseases, and in this study, two animal models of type 1 diabetes--the spontaneously diabetic BB rat and the streptozocin-induced diabetic rat--have been used to determine whether such a phenomenon is involved in the etiology of the symmetrical sensory polyneuropathy commonly associated with diabetes. There was a two- to threefold (P < 0.05) elevation of neurofilament phosphorylation in lumbar dorsal root ganglia (DRG) of diabetic rats that was localized to perikarya of medium to large neurons using immunocytochemistry. Additionally, diabetes enhanced neurofilament M phosphorylation by 2.5-fold (P < 0.001) in sural nerve of BB rats. Neurofilaments are substrates of the mitogen-activated protein kinase (MAPK) family, which includes c-jun NH2-terminal kinase (JNK) or stress-activated protein kinase (SAPK1) and extracellular signal-regulated kinases (ERKs) 1 and 2. Diabetes induced a significant three- to fourfold (P < 0.05) increase in phosphorylation of a 54-kDa isoform of JNK in DRG and sural nerve, and this correlated with elevated c-Jun and neurofilament phosphorylation. In diabetes, ERK phosphorylation was also increased in the DRG, but not in sural nerve. Immunocytochemistry showed that JNK was present in sensory neuron perikarya and axons. Motoneuron perikarya and peroneal nerve of diabetic rats showed no evidence of increased neurofilament phosphorylation and failed to exhibit phosphorylation of JNK. It is hypothesized that in sensory neurons of diabetic rats, aberrant phosphorylation of neurofilament may contribute to the distal sensory axonopathy observed in diabetes.
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PMID:Aberrant neurofilament phosphorylation in sensory neurons of rats with diabetic neuropathy. 1010 7

Patients with diabetic polyneuropathy are known to have an impaired neurovascular reflex arc compared to healthy controls. This is seen in a delayed decrease in microcirculation of the ipsilateral hand after cooling of the contralateral hand. The aim of this pilot study was to investigate whether intravenous alpha-lipoic acid (ALA) (Thioctacid, Asta Medica) therapy might be able to improve this impaired neurovascular reflex arc in patients with diabetic neuropathy. In addition, clinical effects were evaluated with the aid of the neuropathy symptom score (NSS) and the neuropathy disability score (NDS). Ten patients with diabetes mellitus and polyneuropathy (5 females, 5 males, 2 smokers, 5 IDDM, 5 NIDDM, body mass index 26.1 +/- 1.0 kg/m2, age 58.3 +/- 9.5 years, diabetes duration 15.7 +/- 11.2 years, Hb A1c 6.8 +/- 0.3%) were investigated by nail-fold capillaroscopy after contralateral cooling before and after intravenous therapy with 600 mg alpha-lipoic acid per day over 3 weeks. Cardiac autonomic neuropathy was excluded by beat-to-beat variation analysis. Symptoms of diabetic neuropathy were evaluated before and after therapy with the aid of the NSS and NDS. Capillary blood cell velocity (CBV) of the hand was determined before, during, and for the following 30 min after cooling (3 min at 15 degrees C) of the contralateral hand. Blood pressure, heart rate, and local skin temperature were monitored at 2-min intervals. ALA therapy resulted in a significant improvement of the microcirculatory response to cooling, as seen by an immediate decrease in CBV of 12. 3% (P < 0.02 vs before treatment), which was absent before therapy. Blood pressure, heart rate, and local skin temperature were not different between investigations. There was a significant improvement of the NSS after therapy (5.4 +/- 1.1 vs 8.6 +/- 1.1 points, P < 0.01). These results demonstrate that intravenous therapy with ALA has a positive influence on the impaired neurovascular reflex arc in patients with diabetic neuropathy.
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PMID:The effect of alpha-lipoic acid on the neurovascular reflex arc in patients with diabetic neuropathy assessed by capillary microscopy. 1038

In a prospective cohort study, the authors examined risk factors for progression of distal symmetric polyneuropathy (DSP) in type 1 (insulin-dependent) diabetes mellitus. The study population consisted of participants in the Sorbinil Retinopathy Trial, a randomized trial of aldose reductase inhibition among patients aged 18-56 years with type 1 diabetes mellitus of 1-15 years' duration. Diagnosis of DSP was based on standardized clinical neurologic evaluation. A total of 407 participants who did not have definite DSP at randomization and had at least one follow-up visit were included in the analysis. Stepwise Cox proportional hazards models were used to examine the independent contribution of baseline variables to progression of DSP. During follow-up (median, 40 months), 68 participants (17%) showed progression to definite DSP. After adjustment for age and treatment assignment, independent predictors of progression to definite DSP were total glycosylated hemoglobin (relative risk (RR) for increase of one percentage point = 1.25; 95% confidence interval (CI) 1.12, 1.39), height (RR associated with being one inch (2.54 cm) taller = 1.15; 95% CI 1.05, 1.26), cigarette smoking (ever vs. never) (RR = 1.87; 95% CI 1.09, 3.21), and female gender (RR = 2.26; 95% CI 1.09, 4.67). These data indicate that, in addition to the previously established role for total glycosylated hemoglobin, other factors including height, cigarette smoking, and female gender may also be independent risk factors for progression of DSP in type 1 diabetes mellitus.
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PMID:Risk factors for progression of distal symmetric polyneuropathy in type 1 diabetes mellitus. Sorbinil Retinopathy Trial Research Group. 1058 75

Background: Peripheral somatic and autonomic neuropathies are the most common types of diabetic polyneuropathy. Although duration and degree of hyperglycemia are considered to be risk factors for both autonomic and peripheral neuropathy, recent studies have raised the question of a different development and natural history of these neuropathies in diabetes. In addition, a few studies have investigated the relationship between chronic painful and autonomic neuropathy. The aim of this study was to investigate to what extent autonomic and peripheral neuropathy coexist, as well as whether painful neuropathy is more common in diabetic patients with autonomic neuropathy. Methods: Subjects with type 1 (n=52; mean age 31.7 years) and type 2 diabetes (n=53; mean age 54.5 years) were studied. Evaluation of peripheral neuropathy was based on clinical symptoms (neuropathic symptom score), signs (neuropathy disability score), and quantitative sensory testing (vibration perception threshold). Assessment of autonomic neuropathy was based on the battery of standardized cardiovascular autonomic function tests. Results: Prevalence rates of pure autonomic and of pure peripheral neuropathy in patients with type 1diabetes were 28.8 and 13.5%, respectively. The respective rates in patients with type 2 diabetes were 20.7% (P=0.33 vs. type 1 diabetes) and 20.7% (P=0.32). Peripheral and autonomic neuropathy coexisted in 28.8% of type 1 and in 45.3% of type 2 diabetic subjects (P=0.08). Prevalence rates of chronic painful neuropathy in subjects with type 1 diabetes, with and without autonomic neuropathy, were 16.6 and 22.7%, respectively (P=0.85) and in type 2 diabetic subjects 20 and 22.2%, respectively (P=0.58). Multivariate analysis after adjustment for age, sex, blood pressure, duration of diabetes, HBA(1c), and presence of retinopathy or microalbuminuria showed that neither the indices of peripheral nerve function (neuropathic symptom score, neuropathy disability score, vibration perception threshold) nor the presence of peripheral neuropathy or chronic painful neuropathy are associated with the presence of autonomic neuropathy in individuals with either type 1 or type 2 diabetes. Conclusions: Peripheral and autonomic neuropathies do not invariably coexist in diabetes. In addition, chronic painful neuropathy may be present irrespective of the presence of autonomic neuropathy.
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PMID:Peripheral neuropathy does not invariably coexist with autonomic neuropathy in diabetes mellitus. 1117 7

alpha-Lipoic acid is a very efficient antioxidants for the treatment and prevention of diabetic neuropathy. The aim of the present study was to evaluate the function of nitric oxide (NO) and stress proteins (HSP72) in insulin-dependent diabetes complicated by polyneuropathy and possible contribution of these systems to the therapeutic effects of alpha-lipoic acid. Plasma content of nitrites and nitrates in diabetic patients was almost 2-fold below the normal. The treatment with alpha-lipoic acid completely normalized the plasma content of these stable NO metabolites. The majority of patients had also low level of HSP72. Positive clinical effects of alpha-lipoic acid were accompanied by normalization of HSP72 synthesis. Thus, activation of the NO and HSP protective systems is involved in the therapeutic effect of alpha-lipoic acid in diabetic patients (type 1 diabetes mellitus) with polyneuropathy.
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PMID:The function of endogenous protective systems in patients with insulin-dependent diabetes mellitus and polyneuropathy: effect of antioxidant therapy. 1117 1

This study was performed to clarify if diabetic complications are associated with liver enzyme activities in type 1 diabetic outpatients. Elevated activities of serum aminotransferases are a common sign of liver disease and are observed more frequently among people with diabetes than in the general population. Many studies have shown an association between specific diabetic complications and disturbances in various tissues, such as diabetic nephropathy and cardiovascular diseases, but only limited data are available on the possible association between diabetic complications and liver function. We studied 28 patients with type 1 diabetes. Mean age was 43.4+/-9.5 (S.D.), and duration of diabetes 25.2+/-9.7. Limited joint mobility (LJM) was assessed by the Rosenbloom's method. Background and proliferative retinopathy, and peripheral symmetrical polyneuropathy were also assessed. Activities of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in serum were determined. The metabolic control of the diabetes was evaluated by the glycosylated haemoglobin A(1c) (HbA(1c)) level and lipid values were also measured. ALT activity was associated with LJM (P<0.01) and with neuropathy (P<0.01). Association between GGT activity and LJM (P<0.01) and neuropathy (P<0.01) were also found. GGT activity was also associated with the severity of retinopathy (P<0.01). None of these associations was explained by confounding effects of diabetes duration, age, body mass index (BMI), HbA(1c) or alcohol consumption. In conclusion, diabetic complications such as LJM, retinopathy and neuropathy are associated with liver enzyme activities independent of alcohol consumption, BMI and metabolic control of diabetes.
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PMID:Diabetic complications are associated with liver enzyme activities in people with type 1 diabetes. 1131 65

With the purpose of studying the condition of the neuromuscular apparatus, an electroneuromuscular myographic investigation was conducted in 36 patients with freshly detected type I diabetes mellitus in the state of compensation with no neurologic complaints. The study made showed 100% affection of the peripheral portion of the nervous system (subclinical form of polyneuropathy) which has been shown to be more manifest in the lower extremites. The secured results corroborate the symmetry theory of affection of the peripheral nervous system in type I diabetes mellitus.
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PMID:[Electrophysiological diagnosis of diabetic polyneuropathy in patients with newly detected diabetes Type I]. 1169 90


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