Thermal biofeedback and lower extremity blood flow in adults with diabetes: is neuropathy a limiting factor?

Thermal biofeedback may be a useful adjunctive technique for enhancing cutaneous blood flow in patients with lower-extremity vascular complications of diabetes. However, autonomic, sensory, and/or motor neuropathies may impair vasomotion and limit the ability to alter blood flow and achieve significant foot warming with thermal biofeedback. We examined nerve function associated with four common types of diabetic neuropathy (sympathetic–autonomic, vagal–autonomic, sensory, and motor), hypothesizing that both sympathetic–autonomic and sensory neuropathies would limit the acquisition of biofeedback-mediated foot warming. Twenty-four participants with diabetes mellitus (19 with type II and 5 with type I) received a nerve conduction study and neurological evaluation of the upper and lower extremities. Hand temperature, foot temperature, and electrodermal gradient at the toes were monitored across six thermal biofeedback sessions. Participants were able to significantly raise p < .01) foot temperatures across sessions, an average of 2.2°F. Consistent with our hypotheses, 41% of the variance in foot warming was explained by lower-extremity sympathetic–autonomic and sensory nerve function tests. This study demonstrated that a general diabetic population, including patients with mild-to-moderate neuropathy, can increase skin perfusion with thermal biofeedback. As hypothesized, lower-extremity sympathetic–autonomic and sensory neuropathies interfered with foot warming.     

Corneal Confocal Microscopy Detects Neuropathy in Patients with Type 1 Diabetes without Retinopathy or Microalbuminuria

Objective

Corneal innervation is increasingly used as a surrogate marker of human diabetic peripheral neuropathy (DPN) however its temporal relationship with the other microvascular complications of diabetes is not fully established. In this cross-sectional, observational study we aimed to assess whether neuropathy occurred in patients with type 1 diabetes, without retinopathy or microalbuminuria.

Materials and Methods

All participants underwent detailed assessment of peripheral neuropathy [neuropathy disability score (NDS), vibration perception threshold (VPT), peroneal motor nerve conduction velocity (PMNCV), sural sensory nerve conduction velocity (SSNCV) and in vivo corneal confocal microscopy (IVCCM)], retinopathy (digital fundus photography) and albuminuria status [albumin: creatinine ratio (ACR)].

Results

53 patients with Type 1 diabetes with (n=37) and without retinopathy (n=16) were compared to control subjects (n=27). SSNCV, corneal nerve fibre (CNFD) and branch (CNBD) density and length (CNFL) were reduced significantly (p<0.001) in diabetic patients without retinopathy compared to control subjects. Furthermore, CNFD, CNBD and CNFL were also significantly (p<0.001) reduced in diabetic patients without microalbuminuria (n=39), compared to control subjects. Greater neuropathic severity was associated with established retinopathy and microalbuminuria.

Conclusions

IVCCM detects early small fibre damage in the absence of retinopathy or microalbuminuria in patients with Type 1 diabetes.     

Type 1 diabetes in pre-school children - long-term metabolic control, associated autoimmunity and complications

Diabet. Med. 29, 1291-1296 (2012) ABSTRACT: Aims To identify clinical characteristics and co-morbidity rates of children diagnosed with Type 1 diabetes mellitus at younger than 6?years of age. Methods Data were obtained from a retrospective chart review of 103 patients diagnosed with Type 1 diabetes at younger than 6?years (study group) and 220 patients at older than 6?years (comparison group). Measures of glycaemic control and occurrence of co-morbidities (coeliac disease, autoimmune thyroid disease, hypertension, nephropathy and retinopathy) were compared. Results The mean follow-up period was more than 8?years. For the study group, mean HbA(1c) levels ranged from 64?mmol/mol to 66?mmol/mol (8.0-8.2%) until age 10?years, and then rose to 73?mmol/mol (8.8%). The HbA(1c) levels were higher in the study than in the comparison group for comparable ages (P?=?0.003). After adjustment for duration of diabetes this difference was not significant. The overall rate of severe hypoglycaemic events was greater in the study group than in the comparison group (P?=?0.03). Kaplan-Meier diagnosis rates of celiac disease, 10?years after Type 1 diabetes diagnosis, were 14.4% and 4.2% in the study and comparison groups, respectively (P log-rank?=?0.03). There were no differences in rates of autoimmune thyroid disease, hypertension, nephropathy or retinopathy. Conclusions Children diagnosed with Type 1 diabetes before the age of 6?years were in greater risk of developing celiac disease, compared with children diagnosed after the age of 6?years. For children diagnosed with Type 1 diabetes aged under 6?years, good metabolic control was achievable until age 10?years, after which it deteriorated. Higher HbA(1c) levels observed in children diagnosed before the age of 6?years were associated with longer duration of disease.     

Diagnostic accuracy of heart-rate recovery after exercise in the assessment of diabetic cardiac autonomic neuropathy

Diabet. Med. 29, e312-e320 (2012) ABSTRACT: Aims Poor prognosis associated with blunted post-exercise heart-rate recovery may reflect autonomic dysfunction. This study sought the accuracy of post-exercise heart-rate recovery in the diagnosis of cardiac autonomic neuropathy, which represents a serious, but often unrecognized complication of Type?2 diabetes. Methods Clinical assessment of cardiac autonomic neuropathy and maximal treadmill exercise testing for heart-rate recovery were performed in 135 patients with Type?2 diabetes and negative exercise echocardiograms. Cardiac autonomic neuropathy was defined by abnormalities in ≥?2 of 7 autonomic function markers, including four cardiac reflex tests and three indices of short-term (5-min) heart-rate variability. Heart-rate recovery was defined at 1-, 2- and 3-min post-exercise. Results Patients with cardiac autonomic neuropathy (n?=?27; 20%) had lower heart-rate recovery at 1-, 2- and 3-min post-exercise (P?相似文献   

Electrophysiological changes in diabetic neuropathy: from subclinical alterations to disabling abnormalities

Clinical spectrum of diabetic neuropathy is variable; it may be asymptomatic, but once established as polyneuropathy, it is irreversible and may finally be disabling. To estimate the prevalence of subclinical diabetic polyneuropathy in the UAE, we undertook a pilot study by means of nerve conduction study (NCS) of peroneal motor and sural sensory studies in 60 diabetics with no symptoms of neuropathy. Neurological examination revealed clinical abnormalities suggesting polyneuropathy in 26 patients, 43% of the patients. NCS revealed abnormal values in 63% of the whole patients. Abnormal NCS was confirmed in 88% of the positive sign group. As to the negative sign group 44% had abnormalities in NCS. Prolonged F-wave latency was seen in 29% in no sign group and in 66% of the patients with positive signs. We found close association between neurological deficit score and abnormalities in NCS. Among various parameter of systemic nerve conduction study in subclinical patients, prolonged F-wave latency seems the commonest abnormality suggesting morphological changes in subclinical diabetic nerve. Decrease in amplitude of compound sensory action potential of sural nerve is another earlier abnormality, which is, then, accompanied by a fall in motor amplitude of peroneal nerve in advanced patients. Recently, our own group of Hirosaki has demonstrated that somatosensory central conduction time (CCT) between the spinal cord entry time and the arrival time to the sensory cortex is prolonged in diabetics. This abnormality might be partly responsible for the irreversible sensory deficits of diabetic neuropathy.     

Targeting Apoptosis Signalling Kinase-1 (ASK-1) Does Not Prevent the Development of Neuropathy in Streptozotocin-Induced Diabetic Mice

Apoptosis signal-regulating kinase-1 (ASK1) is a mitogen-activated protein 3 kinase (MAPKKK/MAP3K) which lies upstream of the stress-activated MAPKs, JNK and p38. ASK1 may be activated by a variety of extracellular and intracellular stimuli. MAP kinase activation in the sensory nervous system as a result of diabetes has been shown in numerous preclinical and clinical studies. As a common upstream activator of both p38 and JNK, we hypothesised that activation of ASK1 contributes to nerve dysfunction in diabetic neuropathy. We therefore wanted to characterize the expression of ASK1 in sensory neurons, and determine whether the absence of functional ASK1 would protect against the development of neuropathy in a mouse model of experimental diabetes. ASK1 mRNA and protein is constitutively expressed by multiple populations of sensory neurons of the adult mouse lumbar DRG. Diabetes was induced in male C57BL/6 and transgenic ASK1 kinase-inactive (ASK1n) mice using streptozotocin. Levels of ASK1 do not change in the DRG, spinal cord, or sciatic nerve following induction of diabetes. However, levels of ASK2 mRNA increase in the spinal cord at 4 weeks of diabetes, which could represent a future target for this field. Neither motor nerve conduction velocity deficits, nor thermal or mechanical hypoalgesia were prevented or ameliorated in diabetic ASK1n mice. These results suggest that activation of ASK1 is not responsible for the nerve deficits observed in this mouse model of diabetic neuropathy.     

The diabetic polyneuropathy. II. Polyneuropathy, angiopathy and nerve conduction velocity

789 patients with diabetes mellitus were studied by clinical and electroneurographical examination. Motor conduction velocity of the median and the tibial nerve and sensory conduction of the median nerve were determined. 81.1% of the patients we suffering from diabetes which began in childhood or adolescence, 13.9% were suffering from maturity onset diabetes. Average duration of the disease was 9.5 years, average age was 26.7 years. Clinical signs of polyneuropathy were found in 19.1%. Typical findings were pain and paraesthesia, lack or abolition of triceps surae reflexes, impaired pallaesthesia on lower extremities. 48.3% of 151 patients with clinical signs of polyneuropathy were suffering from combined angiopathy, 32.5% from microangiopathy, 7.9% from macroangiopathy. Severity of complicating retinopathy and macroangio,athy were found to be correlated with polyneuropathy. 58.2% of 323 diabetics with at least one delayed nerve conduction velocity exhibited signs of angiopathy. In nearly 30% of children and adolescents after comparatively short duration of the disease at least one conduction velocity was delayed. In diabetic children and adolescents metabolic disturbances are assumed to cause peripheral nerve dysfunction.     

Nerve conduction blocks and peripheral neuropathies

A motor nerve conduction block is defined as a reduction of either amplitude or area of the compound motor action potential elicited by proximal vs. distal motor nerve stimulation. The pathophysiological mechanisms leading to a figure of conduction block include segmental demyelination, recent axonal interruption, or various axonal excitability abnormalities due to ion channel dysfunction or membrane potential changes. These processes can be related to compressive, ischemic or dysimmune inflammatory causes. The etiologic diagnosis is established on the combination of clinical, electrophysiological, and biological data. Among the neuropathies that feature nerve conduction blocks, there is a group of particular dysimmune multifocal neuropathies characterized by long-term persistent conduction blocks, including pure motor forms and sensori-motor forms. The clinical, electrophysiological, biological, and therapeutic specificities of these two types of neuropathy will be discussed.     

Mononeuropathies of the radial nerve: clinical and neurographic findings in 91 consecutive cases.

Retrospective features of 91 consecutive cases (68 men, 23 women; mean age 44.4 years) of radial mononeuropathy diagnosed over the last 8 years in two electromyography (EMG) services are reported to define the clinical and electrophysiological findings of radial neuropathies in relation to traumatic and non-traumatic causes and site of injury. The occurrence of radial neuropathy was 0.65 x 100 first electromyographic examinations. The most frequent site of damage was the main trunk at the spiral groove of the humerus (36%); the most frequent cause was nerve trauma (70%) due to fracture (36%). In neuropathies of the main trunk and posterior interosseous (PI) nerve, "complete nerve injury" was observed in 36% of cases, conduction motor block in 33% and motor conduction velocity slowing in 46%. At least one of these findings was present in 51%, whereas motor neurography was normal in 13% of cases. Sensory action potential (SAP) anomalies were observed in 51% of cases. In neuropathy of the superficial radial nerve, no SAP was detected in 30% of cases; in all others except one, SAP was reduced in amplitude. Non-traumatic neuropathies showed severer conduction block and less severe anomalies of SAP than traumatic neuropathies. No differences were found between men and women. EMG is essential for confirming the site of injury and neurographic study may be helpful for diagnosis, providing information about lesion type and severity.     

Peripheral Nerve Dysfunction in Middle-Aged Subjects Born with Thalidomide Embryopathy

BackgroundPhocomelia is an extremely rare congenital malformation that emerged as one extreme of a range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous system dysfunction in the mal-developed limbs in later life.MethodsCase control study comparing TE subjects with upper limb anomalies and neuropathic symptoms with healthy controls using standard neurophysiological testing. Other causes of a peripheral neuropathy were excluded prior to assessment.ResultsClinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation] years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of upper limb compressive neuropathy in three-quarters of subjects. Additionally there were examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5 radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were electrophysiological changes consistent with a median large fibre neuropathic abnormality (mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95% CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p = 0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)).ConclusionsWe found a range of clinical features relevant to individuals with TE beyond upper limb compressive neuropathies supporting the need for a detailed neurological examination to exclude other treatable pathologies. The electrophysiological evidence of large and small fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of the original insult and merits further investigation.     

Protective effects of 4-amino1,8-napthalimide, a poly (ADP-ribose) polymerase inhibitor in experimental diabetic neuropathy

Peripheral diabetic neuropathy is a heterogeneous group of disorders, and is known to affect 50-60% of diabetic patients. Poly (ADP-ribose) polymerase (PARP) activation has been identified as one of the key components in the pathogenesis of diabetic neuropathy. In the present study we have targeted PARP overactivation in diabetic neuropathy using a known PARP inhibitor, 4 amino 1, 8-napthalimide (4-ANI). Streptozotocin induced diabetic rats developed neuropathy within 6 weeks, which was evident from significant reduction in motor nerve conduction velocity (MNCV), nerve blood flow (NBF) along with neuropathic pain and abnormal sensory perception. Six weeks after diabetes induction Sprague Dawley rats were treated with 4-ANI (3 and 10 mg/kg, p.o.) for a period of two weeks (seventh and eighth weeks). Two week treatment with 4-ANI showed improvement in nerve conduction, nerve blood flow and reduction in tail flick responses and mechanical allodynia in diabetic animals. 4-ANI also attenuated PAR immunoreactivity and NAD depletion in nerves of diabetic animals. Results of present study suggest the potential of PARP inhibitors like 4-ANI in the treatment of diabetic neuropathy.     

Hereditäre Optikusatrophien

Hereditary optic neuropathies comprise a group of clinically and genetically heterogeneous disorders, which can be divided into 2 subgroups: isolated hereditary optic atrophies and optic neuropathies as part of complex disorders. In the first group of isolated hereditary optic neuropathies, optic nerve dysfunction is typically the only manifestation of the disease. This group comprises autosomal dominant, autosomal recessive and X-linked recessive optic atrophy, and the mitochondrial inherited Leber’s hereditary optic neuropathy (LHON). In the second group of complex disorders, various neurologic and other systemic abnormalities are regularly observed. The most frequent cause in this group are mitochondrial DNA (mtDNA) mutations, inherited peripheral neuropathies, Charcot–Marie–Tooth disorders (CMT2A2, CMTX5), hereditary sensory neuropathy type 3 (HSAN3), Friedreich ataxia, leukodystrophies, sphingolipidoses, ceroid-lipofuscinoses, and neurodegeneration with brain iron accumulation (NBIA). In the present article, the clinical phenotypes and underlying genetic predispositions are described.     

Number and sex ratio of children and impact of parental diabetes in individuals with Type 1 diabetes

Diabet. Med. 29, 1268-1271 (2012) ABSTRACT: Objective To assess the number and sex ratio of children in individuals with Type?1 diabetes mellitus and the influence of parental diabetes on age at onset of Type?1 diabetes in our cohort. Methods In a cross-sectional study in a German region comprising 350?000 inhabitants, 697 subjects with Type?1 diabetes (364 women, 333 men) underwent a standardized assessment regarding the number and sex of their children and the family history of diabetes. Results Compared with 1.36 children per woman in the German background population, the total fertility rate in the calendar year of 2010 in our female cohort with Type?1 diabetes (age 18-49?years) was 0.88. Men with Type?1 diabetes had a fertility rate of 0.65. More men (51.1%) than women (35.7%; P?相似文献   

Normal blood flow but lower oxygen tension in diabetes of young rats: microenvironment and the influence of sympathectomy.

Studies of rats with experimental streptozotocin (STZ)-induced diabetes at 4 months have identified sciatic nerve trunk oligemia and hypoxia, but it is uncertain how early these abnormalities develop or which develops first. We studied young (4-week-old) rats after 6 or 16 weeks of STZ-induced diabetes (or after citrate buffer injection in controls) by recording multi-fiber conduction in three different nerve territories and by measuring sciatic endoneurial blood flow (NBF) and oxygen tension (PnO2) at end point. To evaluate the impact of sympathectomy on this diabetic model, separate animal groups were treated for 5 weeks with guanethidine monosulfate given at the onset of diabetes (group 1, end point 6 weeks) or after 6 weeks of diabetes (group 2, end point 16 weeks). Diabetes was associated with deficits in sensory and motor caudal conduction and increased resistance to ischemic conduction failure (RICF). NBF was comparable to control animals at both time points and was within the published normal range of NBF. In contrast, oxygen tensions were shifted to lower values in diabetic animals. Sympathectomy was associated with blunting of the RICF increase in group 2 but worsened caudal sensory conduction despite evidence of modest improvement in sciatic nerve oxygenation. Our findings support the concept that neuropathy occurs early in diabetes and that hypoxia develops before oligemia. Sympathectomy did not benefit this diabetic model.     

Sildenafil Ameliorates Long Term Peripheral Neuropathy in Type II Diabetic Mice

Diabetic peripheral neuropathy is a common complication of long-standing diabetes mellitus. To mimic clinical trials in which patients with diabetes enrolled have advanced peripheral neuropathy, we investigated the effect of sildenafil, a specific inhibitor of phosphodiesterase type 5 enzyme, on long term peripheral neuropathy in middle aged male mice with type II diabetes. Treatment of diabetic mice (BKS.Cg-m+/+Lepr^db/J, db/db) at age 36 weeks with sildenafil significantly increased functional blood vessels and regional blood flow in the sciatic nerve, concurrently with augmentation of intra-epidermal nerve fiber density in the skin and myelinated axons in the sciatic nerve. Functional analysis showed that the sildenafil treatment considerably improved motor and sensory conduction velocities in the sciatic nerve and peripheral thermal stimulus sensitivity compared with the saline treatment. In vitro studies showed that mouse dermal endothelial cells (MDE) cultured under high glucose levels exhibited significant down regulation of angiopoietin 1 (Ang1) expression and reduction of capillary-like tube formation, which were completely reversed by sildenafil. In addition, incubation of dorsal root ganglia (DRG) neurons with conditioned medium harvested from MDE under high glucose levels suppressed neurite outgrowth, where as conditional medium harvested from MDE treated with sildenafil under high glucose levels did not inhibit neurite outgrowth of DRG neurons. Moreover, blockage of the Ang1 receptor, Tie2, with a neutralized antibody against Tie2 abolished the beneficial effect of sildenafil on tube formation and neurite outgrowth. Collectively, our data indicate that sildenafil has a therapeutic effect on long term peripheral neuropathy of middle aged diabetic mice and that improvement of neurovascular dysfunction by sildenafil likely contributes to the amelioration of nerve function. The Ang1/Tie2 signaling pathway may play an important role in these restorative processes.     

Multifactorial risk factor intervention in patients with Type 2 diabetes improves arginine bioavailability ratios

Diabet. Med. 29, e365-e368 (2012) ABSTRACT: Aim Endothelial dysfunction is defined by reduced bioavailability of nitric oxide and has been shown to be associated with cardiovascular risk. The global arginine bioavailability ratio and the arginine to ornithine ratio have recently been shown to be associated with cardiovascular outcome in patients with coronary artery disease. The aim of our study was to investigate the impact of a multifactorial risk factor intervention in subjects with Type?2 diabetes on these two potential new cardiovascular surrogate parameters. Methods In a single-centre and prospective study, we investigated 41 patients with Type?2 diabetes not reaching treatment targets according to current local diabetes guidelines in two out of three of the following measurements: HbA(1c) LDL cholesterol 2.6 or blood pressure. Within 3?months, therapy was intensified according to current guidelines aiming to reach the treatment targets. At baseline and 3?months, arginine, ornithine and citrulline were chromatographically determined after pre-column-derivatization followed by fluorescent detection, and arginine bioavailability ratios were calculated. Results Intensified risk factor management significantly improved the global arginine bioavailability ratio (0.33?±?0.12 at baseline vs. 0.38?±?0.14 after 3?months; P?=?0.018). A significant improvement was only seen in patients with short diabetes duration (相似文献   

Diabetic polyneuropathy. 3. Electroneurographic findings in diabetics and their relationships to age and duration of diabetes

Nerve conduction velocities were determined in patients with diabetes mellitus: motor conduction of the median nerve in 778 patients, sensory conduction of the median nerve in 680 patients and motor conduction of the tibial nerve in 745 patients. In 40.9% out of 778 patients at least one of the three nerve conduction velocities were found within pathological ranges. 30.4% of 227 patients below 19 years of age in whom the duration of the disease did not exceed four years exhibited at least one delayed nerve conduction velocity. Clinical signs of polyneuropathy in children and in adolescents below 19 years of age are rare (0.6%). In contrast delayed nerve conduction velocities were found in 29.4%. Metabolic disturbance of peripheral nerve function is assumed to be responsible in these patients, for angiopathy in children and adolescents is very rare too.     

Early diagnosis of neuropathy in leprosy--comparing diagnostic tests in a large prospective study (the INFIR cohort study)

Background

Leprosy is the most frequent treatable neuromuscular disease. Yet, every year, thousands of patients develop permanent peripheral nerve damage as a result of leprosy. Since early detection and treatment of neuropathy in leprosy has strong preventive potential, we conducted a cohort study to determine which test detects this neuropathy earliest.

Methods and Findings

One hundred and eighty-eight multibacillary (MB) leprosy patients were selected from a cohort of 303 and followed for 2 years after diagnosis. Nerve function was evaluated at each visit using nerve conduction (NC), quantitative thermal sensory testing and vibrometry, dynamometry, monofilament testing (MFT), and voluntary muscle testing (VMT). Study outcomes were sensory and motor impairment detected by MFT or VMT. Seventy-four of 188 patients (39%) had a reaction, neuritis, or new nerve function impairment (NFI) event during a 2-year follow-up. Sub-clinical neuropathy was extensive (20%–50%), even in patients who did not develop an outcome event. Sensory nerve action potential (SNAP) amplitudes, compound motor action potential (CMAP) velocities, and warm detection thresholds (WDT) were most frequently affected, with SNAP impairment frequencies ranging from 30% (median) to 69% (sural). Velocity was impaired in up to 43% of motor nerves. WDTs were more frequently affected than cold detection thresholds (29% versus 13%, ulnar nerve). Impairment of SNC and warm perception often preceded deterioration in MF or VMT scores by 12 weeks or more.

Conclusions

A large proportion of leprosy patients have subclinical neuropathy that was not evident when only MFT and VMT were used. SNC was the most frequently and earliest affected test, closely followed by WDT. They are promising tests for improving early detection of neuropathy, as they often became abnormal 12 weeks or more before an abnormal monofilament test. Changes in MFT and VMT score mirrored changes in neurophysiology, confirming their validity as screening tests.     

Corneal Confocal Microscopy Detects Small Fibre Neuropathy in Patients with Upper Gastrointestinal Cancer and Nerve Regeneration in Chemotherapy Induced Peripheral Neuropathy

There are multiple neurological complications of cancer and its treatment. This study assessed the utility of the novel non-invasive ophthalmic technique of corneal confocal microscopy in identifying neuropathy in patients with upper gastrointestinal cancer before and after platinum based chemotherapy. In this study, 21 subjects with upper gastrointestinal (oesophageal or gastric) cancer and 21 healthy control subjects underwent assessment of neuropathy using the neuropathy disability score, quantitative sensory testing for vibration perception threshold, warm and cold sensation thresholds, cold and heat induced pain thresholds, nerve conduction studies and corneal confocal microscopy. Patients with gastro-oesophageal cancer had higher heat induced pain (P = 0.04) and warm sensation (P = 0.03) thresholds with a significantly reduced sural sensory (P<0.01) and peroneal motor (P<0.01) nerve conduction velocity, corneal nerve fibre density (CNFD), nerve branch density (CNBD) and nerve fibre length (CNFL) (P<0.0001). Furthermore, CNFD correlated significantly with the time from presentation with symptoms to commencing chemotherapy (r = -0.54, P = 0.02), and CNFL (r = -0.8, P<0.0001) and CNBD (r = 0.63, P = 0.003) were related to the severity of lymph node involvement. After the 3^rd cycle of chemotherapy, there was no change in any measure of neuropathy, except for a significant increase in CNFL (P = 0.003). Corneal confocal microscopy detects a small fibre neuropathy in this cohort of patients with upper gastrointestinal cancer, which was related to disease severity. Furthermore, the increase in CNFL after the chemotherapy may indicate nerve regeneration.     

How does physical activity and fitness influence glycaemic control in young people with Type 1 diabetes?

Diabet. Med. 29, e369-e376 (2012) ABSTRACT: Aims To assess physical activity and fitness levels of young people with Type?1 diabetes compared with siblings without diabetes, and to investigate the association between physical activity, physical fitness and glycaemic control (HbA(1c) ) in those young people with diabetes. Methods The study consisted of 97 young people aged 8 to 16?years (62% male) from a Paediatric Diabetes Service in South West England. Sixty participants (67% male) had Type?1 diabetes and 37 participants (54% male) were siblings without diabetes (control group). We measured weight, height and waist circumference, calculated BMI and waist-height ratio and recorded pubertal status, blood pressure and current insulin regimen information. We assessed physical activity by accelerometry, from which we calculated light and moderate-to-vigorous intensity activity. We measured physical fitness by multistage sub-maximal bicycle ergometer test. We obtained HbA(1c) by venipuncture. Results There were no differences between the young people with diabetes and siblings without diabetes in body composition, blood pressure, physical activity and fitness. Moderate-to-vigorous physical activity was associated with better glycaemic control, accounting for 30-37% (R(2) =?0.295-0.374) of the variance for HbA(1c) . Physical fitness was not associated with HbA(1c.) Conclusions Moderate-to-vigorous physical activity was associated with better glycaemic control while fitness was not. Findings suggest that developing strategies to increased moderate-to-vigorous physical activity may prove an effective method of improving glycaemic control in young people with diabetes.