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NerveCheck for the Detection of Sensory Loss and Neuropathic Pain in Diabetes.
Ponirakis, G, Odriozola, MN, Odriozola, S, Petropoulos, IN, Azmi, S, Ferdousi, M, Fadavi, H, Alam, U, Marshall, A, Jeziorska, M, et al
Diabetes technology & therapeutics. 2016;(12):800-805
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Abstract
BACKGROUND Accurate and economic detection of nerve damage in diabetes is key to more widespread diagnosis of patients with diabetic peripheral neuropathy (DPN) and painful diabetic neuropathy. This study examined the diagnostic performance of NerveCheck, an inexpensive ($500) quantitative sensory testing (QST) device. METHODS One hundred forty-four subjects (74 with and 70 without diabetes) underwent assessment with NerveCheck, neuropathy disability score (NDS), nerve conduction studies (NCS), intraepidermal and corneal nerve fiber density (IENFD and CNFD), and McGill questionnaire for neuropathic pain. RESULTS Of the 74 subjects with diabetes, 41 were diagnosed with DPN based on the NDS. The NerveCheck scores for vibration perception threshold (VPT), cold perception threshold (CPT), and warm perception threshold (WPT) were significantly lower (P ≤ 0.0001) in diabetic patients with DPN compared to patients without DPN. The diagnostic accuracy of VPT was high with reference to NCS (area under the curve [AUC]: 82%-84%) and moderate for IENFD, CNFD, and neuropathic pain (AUC: 60%-76%). The diagnostic accuracy of CPT and WPT was moderate with reference to NCS, IENFD, and CNFD (AUC: 69%-78%) and low for neuropathic pain (AUC: 63%-65%). CONCLUSIONS NerveCheck is a low-cost QST device with good diagnostic utility for identifying sensory deficits, comparable to established tests of large and small fiber neuropathy and for the severity of neuropathic pain.
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The association between skin collagen glucosepane and past progression of microvascular and neuropathic complications in type 1 diabetes.
Monnier, VM, Sell, DR, Strauch, C, Sun, W, Lachin, JM, Cleary, PA, Genuth, S, ,
Journal of diabetes and its complications. 2013;(2):141-9
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PURPOSE We determined the association between novel and acid-labile skin collagen-linked advanced glycation endproducts (AGEs) and the progression of microvascular and neuropathic complications from baseline to near study closeout in the Diabetes Control and Complications Trial (DCCT). METHODS From a skin biopsy obtained near the close of the DCCT, proteolytic collagen digests were analyzed by liquid chromatography/mass spectrometry (LC/MS/MS) for glucosepane (GSPNE), glyoxal and methylglyoxal hydroimidazolones (G-H1 and MG-H1) and the glycation product fructose-lysine (FL) using isotope dilution method. RESULTS GSPNE and MG-H1 correlated with age and diabetes duration (P<0.02), while GSPNE and FL correlated with the history of glycemia expressed as mean A1c (P≤0.003). Age and duration-adjusted GSPNE and FL levels were lower in intensive (INT) vs. conventional (CONV) treatment subjects in the primary prevention DCCT cohort (P<0.0001), and FL was lower in INT in the secondary intervention cohort (P<0.0001). GSPNE was associated with increased incidence of retinopathy progression (odds ratio (OR) / unit increase in GSPNE 2.5 for 3 step progression on the ETDRS scale, P=0.003) and sustained≥3 microaneurysms (MA) (OR=4.8, P<0.0001) from DCCT baseline up to the time of the biopsy, and prevalence of microalbuminuria or AER>40mg/24h (OR=5.3, P<0.0001), and confirmed clinical neuropathy (OR=3.4, P=0.015) at the time of the biopsy. GSPNE adjusted for mean A1c remained significant for ≥3 MA (P=0.0252) and AER (P=0.0006). The strong association of complications with A1c was reduced or eliminated when adjusted for GSPNE. CONCLUSIONS Glucosepane is a novel AGE marker of diabetic complications that is robustly associated with nephropathic, retinopathic and neuropathic outcomes despite adjustment for A1c, suggesting that it could be one mediator of these complications with possible diagnostic implications.
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Alpha lipoic acid and glycaemic control in diabetic neuropathies at type 2 diabetes treatment.
Ibrahimpasic, K
Medical archives (Sarajevo, Bosnia and Herzegovina). 2013;(1):7-9
Abstract
INTRODUCTION Diabetes mellitus is a metabolic, chronic and incurable disease which reduces span and quality of life. Over 50% of diabetic patients have clinical manifestations of diabetic neuropathy. AIM: To show a positive influence of alpha lipoic acid on clinically manifested diabetic neuropathy symptoms as well as the effect of alpha lipoic acid in patients glycaemic control. MATERIAL AND METHODS Testing has been conducted in Cantonal Hospital"Irfan Ljubijankic MD" in Bihac and included 20 diabetes type 2 patients who were diagnosed with clinically manifested diabetic neuropathy. All the patients' conditions were evaluated by: medical history, clinical parameters, detailed internal examination, laboratory analyses for glycaemic control assessment and mono filament test. They were treated with oral anti-diabetics and insulin as well as with alpha lipoic acid preparation in duration of four months. They were divided into two groups, with good (HbA1c < 7%) and poor (HbAc > or = 7%) glycaemic control. Medical control has been conducted four months after the research started. RESULTS Twenty patients took part in the research, 7 male and 13 female. The average age of the patients was 58.6 in the first and 55.6 years in the second group. The average patients' disease duration was 13.4 +/- 6.6 years in the first and 11.2 +/- 5.4 years in the second group. The difference in gender, average age and disease duration in both groups statistically is not significant (p < or = 0.05). The number of negative points after the therapy has been reduced for 56.4% in the first and 43.1% for the second group (p < or = 0.05). Prior to the treatment, all the patients in both groups had paresthesia. At medical checkup, there were 40% less patients in the first group and 10% in the second one (p < or = 0.01). The difference is statistically significant (p < or = 0.05) in night pain occurrence between two groups of patients after alpha lipoic acid treatment (40% more patients had night pain in the second group after the treatment). The same number of patients in both groups, 40% had muscle atrophy and difficulty in walking. At medical checkup, 30% in first group and 20% less patients had discomforts (p > or = 0.05). Regression of subjective sensations in both groups of patients after alpha lipoic acid treatment has been noted. CONCLUSION Alfa lipoic acid is an effective drug in the treatment of diabetic distal sensory-motor neuropathy and its therapeutic effect is more effective in patients with good glycaemic control.
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Correlation of diabetic retinopathy and corneal neuropathy using confocal microscopy.
Nitoda, E, Kallinikos, P, Pallikaris, A, Moschandrea, J, Amoiridis, G, Ganotakis, ES, Tsilimbaris, M
Current eye research. 2012;(10):898-906
Abstract
PURPOSE/AIM: To employ corneal confocal microscopy to assess differences in the extent of corneal nerve fiber alterations between diabetic patients classed according to retinopathy status and nondiabetic patients. MATERIALS AND METHODS Two hundred seventy-eight corneas of 139 patients with type 2 diabetes mellitus and 94 corneas of 47 age-matched control participants were scanned using corneal confocal microscopy. Images of the subbasal nerve plexus were collected and analyzed for nerve fiber density (NFD), nerve branch density (NBD), nerve fiber length (NFL), and nerve fiber tortuosity (NFT). Diabetic patients were categorized into three groups according to the classification of diabetic retinopathy (DR) proposed in the Early Treatment of Diabetic Retinopathy Study, based on indirect fundoscopy, fundus photography, and fluorescein angiography findings. A separate classification into four groups according to the severity of peripheral diabetic neuropathy (DN) was also used, based on the results of clinical and electrodiagnostic examinations. RESULTS Average NFD, NBD, and NFL differed significantly according to DR status and were found to be lower, whereas NFT was found to be higher in diabetic patients than control participants. A positive correlation between diabetic corneal neuropathy and peripheral DN was also found. CONCLUSIONS Nerve fiber alterations of the subbasal nerve plexus of diabetic corneas appear to progress in parallel with DR and peripheral DN. Corneal confocal microscopy could possibly represent a promising adjuvant technique for the early diagnosis and assessment of human DN.
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[Biological age and the pain syndrome at diabetic polyneuropathy].
Galkin, VV, Nesterova, MV, Emel'ianov, VV
Advances in gerontology = Uspekhi gerontologii. 2011;(2):303-7
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Patients with diabetic polyneuropathy were examined to study their biological age, rate of aging and pain syndrome. More rapid rate of aging was revealed in patients with diabetic polyneuropathy and pain syndrome. Using Duloxetin and Gabapentin is reliable to decrease the display of pain syndrome in diabetic polyneuropathy patients. Against the background of pain syndrome therapy the rate of aging is noticed to decrease along with the regression of pain syndrome. The medicines of Duloxetin and Gabapentin which are used during depression and epilepsy protect against aging.
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Effects of pentoxifylline and pentosan polysulphate combination therapy on diabetic neuropathy in type 2 diabetes mellitus.
Laczy, B, Cseh, J, Mohás, M, Markó, L, Tamaskó, M, Koszegi, T, Molnár, GA, Wagner, Z, Wagner, L, Wittmann, I
Acta diabetologica. 2009;(2):105-11
Abstract
Vascular dysfunction, including impaired perfusion has a pivotal role in the pathogenesis of microvascular complications in diabetes mellitus. Both pentoxifylline (PF) and pentosan polysulphate (PPS) are known to improve microcirculation. Antioxidant and antiproteinuric effects of PF are also known. In a placebo-controlled study, we determined the possible efficacy of PF-PPS combination therapy on diabetic neuropathy and nephropathy in type 2 diabetic patients. Patients in Verum group (n = 77) received PF-PPS infusions (100-100 mg/day) for 5 days. Control diabetics (Placebo group; n = 12) were given only saline infusions. Specialized cardiovascular autonomic reflex tests, vibration threshold values and urinary albumin excretion were assessed before and after therapy. In Verum group, autonomic score, indicating the severity of cardiac autonomic dysfunction, decreased after therapy (p < or = 0.001). Of the reflexes, deep breath and handgrip tests also improved after therapy (p < or = 0.001). Vibration threshold values, an indicator of the loss of sensory nerve function, were increased after therapy (p < or = 0.001). Results of cardiac autonomic tests and vibration threshold values remained unaltered in Placebo group. Majority of patients had normalbuminuria, which was not affected by PF-PPS. In conclusion, short-term PF-PPS therapy was effective on cardiovascular autonomic function and vibration perception, whereas it failed to reduce albuminuria within normal range in type 2 diabetic patients.
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Sixty-one patients with diabetic peripheral neuropathy treated by tongluo yangyin recipe.
Xu, WG
Chinese journal of integrative medicine. 2007;(3):190-4
Abstract
OBJECTIVE To observe the therapeutic effect of tongluo yangyin recipe (TLYYR) in patients with diabetic peripheral neuropathy (DPN). METHODS Ninety-nine patients with diabetes mellitus type 2 were assigned, according to the order of their visit, to two groups: 61 in the treated group and 38 in the control group. They were given the same information about diabetes mellitus and treated with the same therapy: strict diet control and Western drugs for hypoglycemia. In addition, the treated group received one dose (200 mL) of TLYYR in water decoction every day in two portions, while the control group had vitamin B1 100 mg and vitamin B12 250 microg administered daily via intramuscular injection. The course for all patients was 28 days. RESULTS The treated group experienced a therapeutic effect superior to that of the control group, with the difference between the total effective rates and the markedly effective rates (P<0.05, P<0.01). The blood levels of total cholesterol (TC) and triglyceride (TG) fell, the hemorrheological manner improved, the transmission velocity of the median nerve and common peroneal nerve significantly increased in the treated group after treatment (P<0.05), although the treatment showed no significant influence on blood glucose level (P>0.05). CONCLUSION TLYYR could promote blood microcirculation, improve nutritional metabolism of peripheral nerve, and thus accelerating DPN repair.
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Validation of a novel screening device (NeuroQuick) for quantitative assessment of small nerve fiber dysfunction as an early feature of diabetic polyneuropathy.
Ziegler, D, Siekierka-Kleiser, E, Meyer, B, Schweers, M
Diabetes care. 2005;(5):1169-74
Abstract
OBJECTIVE To validate a handheld screening device (NeuroQuick) for an early detection of diabetic distal symmetric polyneuropathy (DSP) by quantitative testing of cold sensation based on the wind chill factor (NeuroQuick threshold [NQT]). RESEARCH DESIGN AND METHODS NQT was measured on the dorsum of the foot in 160 healthy subjects as well as 60 and 128 diabetic patients without and with DSP, respectively. DSP was diagnosed by a neurological examination, motor and sensory nerve conduction velocity, vibration perception threshold, and warm and cold thermal perception threshold (TPT) (TPT Medoc). In addition, a C-64 Hz tuning fork and TipTherm device were used as screening instruments. RESULTS In the diabetic cohort, NQT correlated significantly with all nerve function tests, with the highest correlation coefficients being found on the foot versus Medoc warm TPT (r = 0.618, P < 0.001) and cold TPT (r = 0.529, P < 0.001). Among patients with DSP, NQT was abnormal, whereas Medoc warm TPT was normal in 34%, whereas only 5% showed the opposite constellation (P < 0.05). Likewise, the corresponding percentages for Medoc cold TPT were 32 and 11%, for TipTherm 47 and 2%, and for the tuning fork 29 and 10% (all P < 0.05), whereas no significant differences were noted when comparing NQT with peroneal motor nerve conduction velocity, sural sensory nerve conduction velocity, and malleolar vibration perception threshold. The coefficients of variation for repeated NQT measurements in 41 control and 41 diabetic subjects were 20.4 and 8.5%, respectively. CONCLUSIONS The NeuroQuick is a valid and reliable screening tool for quantitative assessment of small nerve fiber dysfunction. This device appears to be more sensitive in detecting early diabetic polyneuropathy than both elaborate thermal testing and screening tests such as the tuning fork.
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Role of C-nociceptive fibers in the nerve axon reflex-related vasodilation in diabetes.
Caselli, A, Rich, J, Hanane, T, Uccioli, L, Veves, A
Neurology. 2003;(2):297-300
Abstract
OBJECTIVE To evaluate the role of the C-nociceptive nerve fibers in nerve axon reflex-related vasodilation. METHODS Skin vascular reactivity, in response to iontophoresis of acetylcholine and sodium nitroprusside, was evaluated at both the forearm and the foot levels in 13 diabetic neuropathic (DN),11 nonneuropathic (D), and 9 healthy control (C) subjects. The total and nerve axon reflex-related vasodilation were measured by two single-point laser probes. A topical anesthetic was applied on the contralateral forearm and foot, and all the measurements were repeated. RESULTS Dermal anesthesia resulted in a reduction of the nerve axon reflex-related vasodilation at the forearm in all three groups (C 70.7 +/- 12%, D 59.7 +/- 7%, and DN 73.5 +/- 14%; percentage of reduction over preanesthesia response, mean +/- SEM; p < 0.001) and at the foot in the two nonneuropathic groups (C 74 +/- 10% and D 68.9 +/- 9%; p < 0.001 versus before anesthesia). This reduction was absent at the foot of the neuropathic patients (DN -4 +/- 21%; p = NS versus before anesthesia). A correlation was found between the nerve axon reflex-related response and measurements of nerve function (neuropathy disability score, r = -0.425, p < 0.017; vibration perception threshold, r = -0.527, p < 0.002; Semmes-Weinstein monofilament perception, r = -0.619, p < 0.001). CONCLUSION The nerve axon reflex-related vasodilation is directly related to the function of the C-nociceptive fibers and is significantly associated with other nerve function measurements. As this is an objective measurement, it has the potential to be used as an alternative to currently employed techniques to evaluate small-fiber function.
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Role of vasopressin in 24-hour blood pressure regulation in diabetic patients with autonomic neuropathy.
Monteagudo, PT, Gavras, H, Gavras, I, Kohlmann, O, Ribeiro, AB, Zanella, MT
American journal of hypertension. 2002;(1 Pt 1):42-7
Abstract
To evaluate the role of vasopressin (AVP) on blood pressure (BP) in diabetic patients with autonomic neuropathy (AN), 10 patients were studied on a fixed sodium and potassium diet. On days 4 and 7, a 24-h BP monitoring, as well as blood and urine samples for sodium, potassium, creatinine, and osmolality determinations were obtained for every 4-h period; either placebo or an AVP-V1-antagonist (d(CH2)5Tyr(me)AVP; 0.5 mg; AVPi) were given iv at 1 PM. On placebo, systolic BP (SBP) showed a progressive elevation during the day, declining after 12 PM (8 AM to 12 AM 122+/-9; 12 AM to 4 PM 125+/-11; 4 PM to 8 PM 134+/-14; 8 PM to 12 PM 136+/-14; 12 PM to 8 AM 131+/-17 mm Hg). On AVPi this rise in SBP was blunted: 8 AM to 12 AM 125+/-122; 12 AM to 4 PM 121+/-21; 4 PM to 8 PM 126+/-16; 8 PM to 12 PM 129+/-14; 12 PM to 8 AM 124+/-12 mm Hg. Creatinine clearance and diureses were greater during the night, both with placebo and AVPi. Plasma osmolality did not change on either day, although serum sodium decreased after AVPi, reaching the lowest values at 4 PM to 8 PM period (137+/-4.7 v 131+/-3.8 mEq/L; P < .05). With placebo, fractional excretion of sodium (FENa) increased from 0.43%+/-0.32% during 12 h of orthostasis to 0.92%+/-1.05% during 12 h of recumbency (P < .02). With AVPi, the FENa on orthostasis did not differ from that with placebo, although BP values were lower and did not increase with recumbency (0.58+/-0.57 v 0.73%+/-0.49%; NS). In conclusion, our results show that in diabetic patients with AN, vasopressin participates in BP control by stimulating vascular and renal V1 receptors, which results in vasoconstriction and sodium reabsorption.