Objectives: The incidence of type 2 diabetes mellitus (DM2) is on the rise worldwide. The primary objective was to determine the prevalence of nutrient inadequacy and excessiveness in persons with DM2 with and without diabetic peripheral neuropathy (DPN). Study Design: A validated semi-quantitative food frequency questionnaire was used to determine the prevalence of inadequacy of nutrients with an estimated average requirement; the mean intake of nutrients with an adequate intake; and the proportion of persons not meeting the recommendations for the acceptable macronutrient distribution range (AMDR). Results: Differences were observed in the prevalence of inadequacy of vitamin A and the proportion of persons not meeting the AMDR for total fat, linoleic acid and carbohydrate. Conclusion: The aforementioned nutrients may have a significant role in the progression/development of DPN and should be studied in further detail. We recommend a balanced diet and use of a multi-vitamin for persons with DM2.

Objectives: The incidence of type 2 diabetes mellitus (DM2) is on the rise worldwide. The primary objective was to determine the prevalence of nutrient inadequacy and excessiveness in persons with DM2 with and without diabetic peripheral neuropathy (DPN). Study Design: A validated semi-quantitative food frequency questionnaire was used to determine the prevalence of inadequacy of nutrients with an estimated average requirement; the mean intake of nutrients with an adequate intake; and the proportion of persons not meeting the recommendations for the acceptable macronutrient distribution range (AMDR). Results: Differences were observed in the prevalence of inadequacy of vitamin A and the proportion of persons not meeting the AMDR for total fat, linoleic acid and carbohydrate. Conclusion: The aforementioned nutrients may have a significant role in the progression/development of DPN and should be studied in further detail. We recommend a balanced diet and use of a multi-vitamin for persons with DM2.

Yes / Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the nerve structures can assist the early diagnosis of this disease. This paper proposes a robust, fast and fully automatic nerve segmentation and morphometric parameter quantification system for corneal confocal microscope images. The segmentation part consists of three main steps. First, a preprocessing step is applied to enhance the visibility of the nerves and remove noise using anisotropic diffusion filtering, specifically a Coherence filter followed by Gaussian filtering. Second, morphological operations are applied to remove unwanted objects in the input image such as epithelial cells and small nerve segments. Finally, an edge detection step is applied to detect all the nerves in the input image. In this step, an efficient algorithm for connecting discontinuous nerves is proposed. In the morphometric parameters quantification part, a number of features are extracted, including thickness, tortuosity and length of nerve, which may be used for the early diagnosis of diabetic polyneuropathy and when planning Laser-Assisted in situ Keratomileusis (LASIK) or Photorefractive keratectomy (PRK). The performance of the proposed segmentation system is evaluated against manually traced ground-truth images based on a database consisting of 498 corneal sub-basal nerve images (238 are normal and 260 are abnormal). In addition, the robustness and efficiency of the proposed system in extracting morphometric features with clinical utility was evaluated in 919 images taken from healthy subjects and diabetic patients with and without neuropathy. We demonstrate rapid (13 seconds/image), robust and effective automated corneal nerve quantification. The proposed system will be deployed as a useful clinical tool to support the expertise of ophthalmologists and save the clinician time in a busy clinical setting.

A neuropatia periférica (NP) causada por diabetes mellitus é uma das complicações mais comuns do diabetes, atingindo cerca de 50% dos pacientes portadores da doença. Dentre os diversos sintomas da Neuropatia Periférica Diabética (NPD), destaca-se o desenvolvimento de dor crônica, que acomete, principalmente, as extremidades, manifestando-se como respostas exacerbadas para estímulos nocivos (hiperalgesia) e dor em resposta a estímulos leves ou não dolorosos (alodínia). Os tratamentos convencionais disponíveis para a neuropatia em geral, incluindo a dor associada, ainda são inadequados, insatisfatórios e beneficiam apenas uma pequena parcela dos pacientes. Na clínica, o uso de laser de baixa intensidade (LBI) torna-se cada vez mais popular, uma vez que, por promover regeneração nervosa precoce, resulta em significativa melhora das incapacidades motoras e sensitivas geradas por diversos tipos de lesões em nervos periféricos. No entanto, embora os efeitos sejam satisfatórios, os mecanismos pelos quais estes acontecem são ainda desconhecidos. Neste estudo, o efeito da laserterapia (660 nm, 30 mW, 1,6 J/cm2, 15 seg, 0.28 cm2) no tratamento da dor induzida por NPD e danos nos nervos periféricos foram avaliados em um modelo experimental de neuropatia diabética induzida por estreptozotocina em camundongos. O LBI induziu antinocicepção em camundongos com dor neuropática dependente da liberação central de opióides. Após 21 aplicações consecutivas, o LBI aumentou os níveis do fator de crescimento do nervo (NGF) e induziu a recuperação estrutural, aumentando o conteúdo mitocondrial e regulando a proteína Parkin no nervo isquiático de camundongos com NPD. Em conjunto, esses dados fornecem novos esclarecimentos sobre os mecanismos envolvidos na laserterapia, enfatizando seu potencial terapêutico no tratamento da NPD. / Peripheral neuropathy (PN) caused by diabetes mellitus is one of the most common complications of diabetes, affecting about 50% of patients. Among the many symptoms of Diabetic Peripheral Neuropathy (DPN), stands out the development of chronic pain, which affects mainly the extremities, presenting itself as exacerbated responses to noxious stimuli (hyperalgesia) and as pain in response to light or not painful stimuli (allodynia). Conventional treatments available for neuropathy, including the associated pain, are still inadequate, unsatisfactory and benefit only a small number of patients. In clinical practice, the low level laser therapy (LLLT) becomes increasingly popular, once it promotes early nerve regeneration, resulting in significant improvement of motor and sensory disabilities caused by various types of lesions in peripheral nerves. Although the effects are satisfactory, the mechanisms by which these effects occur are still unknown. In this study, the effects of lasertherapy (660 nm, 30 mW, 1.6 J/cm2, 15 sec, 0.28 cm2) on the treatment of DPN-induced pain and nerve damage was assessed in an experimental model of streptozotocin - induced diabetic neuropathy in mice. LLLT induced antinociception in neuropathic pain-mice dependent on the central release of opioids. After 21 consecutive applications, LLLT increased nerve growth factor (NGF) levels and induced structural recovery, increasing mitochondrial content and regulating Parkin in the sciatic nerve of mice with DPN. Together, these data provide further insights into the mechanisms involved in lasertherapy, emphasizing its therapeutic potential in the treatment of DPN.

The present study is a retrospective cohort analysis which sought to examine adherence to medications used in managing painful diabetic peripheral neuropathy (PDPN) and to determine their association with oral antidiabetic (OAD) medication adherence using the Texas Medicaid prescription claims database. The study objectives were to: 1) provide a description of PDPN and OAD medication use among the study subjects; 2) determine if PDPN medication adherence differs among individual PDPN agents (i.e., tricyclic antidepressants, gabapentin, pregabalin and duloxetine); 3) determine if pre-index OAD and post-index OAD medication adherence differs among mono, dual, and triple OAD therapies; and 4) determine if PDPN medication adherence is related to post-index OAD medication adherence while controlling for covariates. Study participants were adult (≥18 years) Medicaid beneficiaries prescribed OAD and PDPN medications. The index date was the first PDPN prescription. Data were extracted from June 1, 2003 to October 31, 2009 and prescription claims were analyzed over an 18-month study period (i.e., 6 months pre-index and 12 months post index period). Medication possession ratio (MPR) was used as a proxy measure of medication adherence. An MPR less than 80 percent was regarded as being non-adherent to prescribed medication, while an MPR greater than or equal to 80 percent was regarded as being adherent to prescribed medication. Objective 1 was addressed using descriptive statistics (i.e., mean, standard deviation, frequency). Univariate analysis (ANOVA) was employed to address Objectives 2 and 3. Multivariate analyses (i.e., multiple linear regression and logistic regression) were conducted to address Objective 4. For the logistic regression MPR was dichotomized at the cut-off value of 80 percent. A total of 4,277 patients met the study’s inclusion criteria. The overall mean MPR (±SD) for PDPN medications was 75.4 percent (±23.9). Mean MPR (±SD) was highest for duloxetine (85.6% ±18.2) and was lowest for pregabalin (69.4% ±24.9). Mean MPR differed significantly among individual PDPN medications (p<0.0001). The overall mean MPR (±SD) for OAD medications in the pre and post-index period was 73.0 percent (±24.3) and 64.5 percent (±25.6) respectively. In both pre and post-index periods, mean MPR differed significantly among mono, dual, and triple OAD therapies (p<0.0001). In the pre-index period, mean MPR (±SD) was highest for monotherapy users (75.4% ±24.7) and was lowest for triple therapy users (63.9% ±22.9). Similarly, mean MPR (±SD) was highest for monotherapy users (69.0% ±26.1) and was lowest for triple therapy users (52.9% ±21.8) in the post-index period. After controlling for the covariates, PDPN adherence (i.e., MPR) was statistically significant (p<0.0001) and positively related to post-index OAD adherence (i.e., MPR). PDPN patients who were non-adherent (i.e., MPR<80%) to their PDPN medications (or neuropathic pain medications), compared to those who were adherent (MPR≥80%), were significantly less likely to be adherent to their OAD medications [Odds Ratio (OR) = 0.626, 95% CI=0.545-0.719]. In addition, post-index OAD adherence (i.e., MPR) did not differ significantly (p>0.05) when pregabalin, duloxetine and gabapentin users were individually compared to tricyclic antidepressants users. In conclusion, PDPN patients who were adherent (i.e., MPR≥80%) to their PDPN medications, compared to those who were not adherent (i.e., MPR<80%), were more adherent to their OAD medications. Also, adherence to OAD medications was independent of the type of PDPN medication used. PDPN patients need to be educated regularly that neuropathic pain medications only relieve the pain associated with the neuropathy but achieving adequate glycemic control remains the only established approach for slowing down the progression of the neuropathy and other complications associated with the diabetes. / text

Yes / Confocal microscopy is employed as a fast and non-invasive way to capture a sequence of images from different layers and membranes of the cornea. The captured images are used to extract useful and helpful clinical information for early diagnosis of corneal diseases such as, Diabetic Peripheral Neuropathy (DPN). In this paper, an automatic corneal subbasal nerve registration system is proposed. The main aim of the proposed system is to produce a new informative corneal image that contains structural and functional information. In addition a colour coded corneal image map is produced by overlaying a sequence of Cornea Confocal Microscopy (CCM) images that differ in their displacement, illumination, scaling, and rotation to each other. An automatic image registration method is proposed based on combining the advantages of Fast Fourier Transform (FFT) and phase correlation techniques. The proposed registration algorithm searches for the best common features between a number of sequenced CCM images in the frequency domain to produce the formative image map. In this generated image map, each colour represents the severity level of a specific clinical feature that can be used to give ophthalmologists a clear and precise representation of the extracted clinical features from each nerve in the image map. Moreover, successful implementation of the proposed system and the availability of the required datasets opens the door for other interesting ideas; for instance, it can be used to give ophthalmologists a summarized and objective description about a diabetic patient’s health status using a sequence of CCM images that have been captured from different imaging devices and/or at different times

Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the corneal epithelium nerve structures and the corneal endothelial cell can assist early diagnosis of this disease and other corneal diseases, which can lead to visual impairment and then to blindness. In this thesis, fully-automated segmentation and quantification algorithms for processing and analysing sub-basal epithelium nerves and endothelial cells are proposed for early diagnosis of diabetic neuropathy in Corneal Confocal Microscopy (CCM) images. Firstly, a fully automatic nerve segmentation system for corneal confocal microscope images is proposed. The performance of the proposed system is evaluated against manually traced images with an execution time of the prototype is 13 seconds. Secondly, an automatic corneal nerve registration system is proposed. The main aim of this system is to produce a new informative corneal image that contains structural and functional information. Thirdly, an automated real-time system, termed the Corneal Endothelium Analysis System (CEAS) is developed and applied for the segmentation of endothelial cells in images of human cornea obtained by In Vivo CCM. The performance of the proposed CEAS system was tested against manually traced images with an execution time of only 6 seconds per image. Finally, the results obtained from all the proposed approaches have been evaluated and validated by an expert advisory board from two institutes, they are the Division of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and the Manchester Royal Eye Hospital, Centre for Endocrinology and Diabetes, UK.