ABSTRACT
INTRODUCTION: Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage-SFN, LFN, and MFN-in T1DM-associated DPN, both with and without pain. RESEARCH DESIGN AND METHODS: In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests). RESULTS: MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern. CONCLUSIONS: DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Neuropathies , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetic Neuropathies/epidemiology , Diabetic Neuropathies/pathology , Diabetic Neuropathies/diagnosis , Diabetic Neuropathies/etiology , Male , Cross-Sectional Studies , Female , Adult , Middle Aged , Nerve Fibers/pathology , Prevalence , Case-Control Studies , Follow-Up Studies , Neural Conduction/physiology , Prognosis , Severity of Illness IndexABSTRACT
AIMS/HYPOTHESIS: Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes. METHODS: Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres. RESULTS: There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures. CONCLUSIONS/INTERPRETATION: Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetic Neuropathies , Humans , Diabetes Mellitus, Type 1/complications , Nerve Fibers/pathology , Peripheral Nerves/pathology , Schwann Cells/pathologyABSTRACT
BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetic Neuropathies , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/pathology , Diabetic Neuropathies/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/pathology , Skin/pathology , PainABSTRACT
Background: Low-intensity extracorporeal shockwave therapy (LI-ESWT) has been suggested as a treatment for vascular diseases such as ischemic heart disease, diabetic foot ulcers, and erectile dysfunction. Primarily, LI-ESWT is known for its ability to stimulate angiogenesis and activation of stem cells in target tissues. Application of LI-ESWT in chronic progressive renal diseases is a novel area. The aim of the present review was to summarize available data on the effects of LI-ESWT used in the setting of renal diseases. Methods: We systematically searched PubMed, Medline, and Embase databases for relevant studies. Our review included the results from preclinical animal experiments and clinical research. Results: Eleven animal studies and one clinical study were included in the review. In the animal studies, LI-ESWT was used for the treatment of hypertensive nephropathy (n=1), diabetic nephropathy (n=1), or various types of ischemic renal injury (ie, artery occlusion, reperfusion injury) (n=9). The clinical study was conducted in a single-arm cohort as a Phase 1 study with patients having diabetic nephropathy. In animal studies, the application of LI-ESWT was associated with several effects: LI-ESWT led to increased VEGF and endothelial cell proliferation and improved vascularity and perfusion of the kidney tissue. LI-ESWT reduced renal inflammation and fibrosis. LI-ESWT caused only mild side effects in the clinical study, and, similarly, there were no signs of kidney injury after LI-ESWT in the animal studies. Conclusion: LI-ESWT, as a non-invasive treatment, reduces the pathological manifestations (inflammation, capillary rarefaction, fibrosis, decreased perfusion) associated with certain types of renal disease. The efficacy of renal LI-ESWT needs to be confirmed in randomized clinical trials.
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Chronic ulcers are most often seen as a complication to venous leg ulcers, diabetic foot ulcers and pressure ulcers. Ulcers often display an underlying medical condition, which makes it mandatory to treat these individuals in a multidisciplinary setting. Modern ulcer therapy has changed over the latest decade, and as described in this review a number of new modalities have been included. The major group of ulcers often presents with well-defined features, but attention should be directed towards ulcers with atypic appearance such as ulcers related to calciphylaxis, hypertension (Martorell) and pyoderma.
Subject(s)
Calciphylaxis , Diabetic Foot , Hypertension , Leg Ulcer , Calciphylaxis/etiology , Calciphylaxis/therapy , Diabetic Foot/complications , Diabetic Foot/therapy , Humans , Hypertension/complications , Leg Ulcer/complications , Ulcer/complicationsABSTRACT
PURPOSE: Treatment with low-intensity shockwave therapy (LI-ESWT) is associated with angiogenesis and is suggested as a treatment for different types of vascular diseases. It was hypothesized that LI-ESWT improves the renal filtration barrier and halts the progression of GFR decline in diabetic kidney disease (DKD) potentially through VEGF and NO formation. We present the first data on LI-ESWT in human DKD. METHODS: The study was designed as an interventional, prospective, one-arm, Phase 1 study. We investigated change in GFR and albuminuria in 28 patients with DKD treated with six sessions of LI-ESWT over three weeks. The patients were followed for six months. Urine excretion of kidney injury markers, vascular endothelial growth factor (VEGF) and nitric oxide metabolites (NOx) was studied after LI-ESWT. RESULTS: There were no significant changes in GFR and albuminuria up to six months after LI-ESWT compared to baseline. Urine VEGF was transiently reduced one month after LI-ESWT, but there were no other significant changes in urine VEGF or NOx after LI-ESWT. Secondary analysis showed that NOx increased after LI-ESWT in patients who had low levels of NOx at baseline. Kidney injury marker trefoil factor 3 (TFF3) increased acutely after the first session of LI-ESWT indicating transient endothelial repair. Other markers of kidney injury were stable in relation to LI-ESWT. CONCLUSION: LI-ESWT treatment did not significantly improve kidney function and albumin excretion. It is concluded that LI-ESWT is not harmful. A randomized blinded study should be performed to clarify whether adjunctive treatment with LI-ESWT is superior to standard treatment of DKD.
ABSTRACT
BACKGROUND: Increased use of telemedicine in the healthcare system is a political goal in Denmark. Although the number of hospital patients using interventions such as the video consultation has increased in recent years only a small proportion of the outpatient and inpatient visits involve telemedicine. The TELEMED database (https://telemedicine.cimt.dk/) has been launched at the Center for Innovative Medical Technology in Denmark to ensure that hospital managers and healthcare professionals have access to information about telemedicine services and their effectiveness. This article describes the development and the content of the TELEMED database. METHODS: A structured literature search was made in the PubMed Database for randomised controlled trials or observational studies with a control group that investigated the effect of telemedicine interventions for hospital patients. Data were extracted from each article on the clinical effectiveness, patient perceptions, economic effects and implementation challenges. As the database should only provide inspiration to healthcare professionals regarding possibilities for use of telemedicine, the risk of bias in the studies was not assessed. RESULTS: The literature search resulted in 2825 hits. Based on full text assessment, 331 articles were included for data extraction and assessment. These articles present telemedicine services used in 22 different medical specialities. Forty-eight percent of the studies found a positive, statistically significant clinical effect, while 47% showed no statistically significant difference. In 48% of the studies, patients' experiences were examined and of these 68% found positive patient experiences. Fifty-four percent of the articles included information on the economic effects and, of these, 51% found reduction in healthcare utilization. In the majority of studies between two and four types of implementation challenges were found.Conclusions and recommendations: The TELEMED database provides an easily accessible overview of existing evidence-based telemedicine services for use by hospital managers and health professionals, who whish to to implement telemedicine. The database is freely available and expected to be continuously improved and broadened over time.
Subject(s)
Databases, Factual , Telemedicine , Delivery of Health Care , Health Personnel , Hospitals , Humans , OutpatientsABSTRACT
Diabetes is currently one of the major public health threats. The essential components for effective treatment of diabetes include early diagnosis and regular monitoring. However, health-care providers are often short of human resources to closely monitor populations at risk. In this work, a video-based eye-tracking method is proposed as a low-cost alternative for detection of diabetic neuropathy. The method is based on the tracking of the eye-trajectories recorded on videos while the subject follows a target on a screen, forcing saccadic movements. Upon extraction of the eye trajectories, representation of the obtained time-series is made with the help of heteroscedastic ARX (H-ARX) models, which capture the dynamics and latency on the subject's response, while features based on the H-ARX model's predictive ability are subsequently used for classification. The methodology is evaluated on a population constituted by 11 control and 20 insulin-treated diabetic individuals suffering from diverse diabetic complications including neuropathy and retinopathy. Results show significant differences on latency and eye movement precision between the populations of control subjects and diabetics, while simultaneously demonstrating that both groups can be classified with an accuracy of 95%. Although this study is limited by the small sample size, the results align with other findings in the literature and encourage further research.
Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Computers , Diabetic Neuropathies/diagnosis , Eye Movements , Eye-Tracking Technology , Humans , InsulinABSTRACT
Rubeosis faciei diabeticorum, caused by microangiopathy and characterized by a chronic facial erythema, is associated with diabetic neuropathy. In clinical practice, facial erythema of patients with diabetes is evaluated based on subjective observations of visible redness, which often goes unnoticed leading to microangiopathic complications. To address this major shortcoming, we designed a contactless, non-invasive diagnostic point-of-care-device (POCD) consisting of a digital camera and a screen. Our solution relies on (1) recording videos of subject's face (2) applying Eulerian video magnification to videos to reveal important subtle color changes in subject's skin that fall outside human visual limits (3) obtaining spatio-temporal tensor expression profile of these variations (4) studying empirical spectral density (ESD) function of the largest eigenvalues of the tensors using random matrix theory (5) quantifying ESD functions by modeling the tails and decay rates using power law in systems exhibiting self-organized-criticality and (6) designing an optimal ensemble of learners to classify subjects into those with diabetic neuropathy and those of a control group. By analyzing a short video, we obtained a sensitivity of 100% in detecting subjects diagnosed with diabetic neuropathy. Our POCD paves the way towards the development of an inexpensive home-based solution for early detection of diabetic neuropathy and its associated complications.
Subject(s)
Diabetic Neuropathies/diagnosis , Erythema/etiology , Face , Machine Learning , Skin , Aged , Diabetic Neuropathies/complications , Female , Humans , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
BACKGROUND AND OBJECTIVE: Diabetes mellitus is a common disorder amounting to 400 million patients worldwide. It is often accompanied by a number of complications, including neuropathy, nephropathy, and cardiovascular diseases. For example, peripheral neuropathy is present among 20-30% of diabetics before the diagnosis is substantiated. For this reason, a reliable detection method for diabetic complications is crucial and attracts a lot of research attention. METHODS: In this paper, we introduce a non-invasive detection framework for patients with diabetic complications that only requires short video recordings of faces from a standard commercial camera. We employed multiple image processing and pattern recognition techniques to process video frames, extract relevant information, and predict the health status. To evaluate our framework, we collected a dataset of 114 video files from diabetic patients, who were diagnosed with diabetes for years and 60 video files from the control group. Extracted features from videos were tested using two conceptually different classifiers. RESULTS: We found that our proposed framework correctly identifies patients with diabetic complications with 92.86% accuracy, 100% sensitivity, and 80% specificity. CONCLUSIONS: Our study brings a novel perspective on diagnosis procedures in this field. We used multiple techniques from image processing, pattern recognition, and machine learning to robustly process video frames and predict the health status of our subjects with high efficiency.
Subject(s)
Diabetes Complications , Diabetes Mellitus , Color , Diabetes Complications/diagnosis , Diabetes Mellitus/diagnosis , Humans , Image Processing, Computer-Assisted , Machine Learning , Video RecordingABSTRACT
BACKGROUND: Low-intensity shockwave therapy (LI-SWT) is suggested as a therapy for promoting tissue regeneration. In pigs, it was recently found that LI-SWT improved renal function after ischaemic injury. Our objectives were to study glomerular filtration rate (GFR) and albuminuria in diabetic nephropathy (DN) after treatment with LI-SWT. The present pilot study reports on the clinical safety of LI-SWT in DN. METHODS: A total of 14 patients with diabetes mellitus and Stage 3 chronic kidney disease were recruited for this prospective, one-arm Phase 1 study. The patients were treated with six sessions of LI-SWT during a 3-week period. At each session, 3000 shockwaves were applied to each kidney with 0.265 mJ/mm2, extended focal size and 4 Hz. Follow-up visits were performed at 1, 3 and 6 months. RESULTS: In general, the treatment was well tolerated. Transient macroscopic haematuria was observed in three patients immediately after LI-SWT. The majority of patients experienced lower back tenderness lasting up to 2 days after treatment. There was no need for analgesic treatment. LI-SWT showed no negative effect on GFR and albuminuria. At baseline, median (interquartile range) GFR was 33.5 mL/min/1.73 m2 (27.8-43.8) compared with 36.0 mL/min/1.73 m2 (27.5-52.0) at 6 months follow-up. In parallel, median albuminuria was 256 mg/24 h (79-619) at baseline and tended to decrease to 137 mg/24 h (41-404) 6 months after LI-SWT. There was no statistical difference between baseline and follow-up results. CONCLUSIONS: LI-SWT is a safe treatment for DN. Inclusion of more patients is needed to determine whether LI-SWT can improve renal functional outcomes.
Subject(s)
Diabetic Nephropathies/therapy , High-Energy Shock Waves/therapeutic use , Adolescent , Adult , Aged , Albuminuria , Diabetic Nephropathies/pathology , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: The MHC region harbors the strongest loci for latent autoimmune diabetes in adults (LADA); however, the strength of association is likely attenuated compared with that for childhood-onset type 1 diabetes. In this study, we recapitulate independent effects in the MHC class I region in a population with type 1 diabetes and then determine whether such conditioning in LADA yields potential genetic discriminators between the two subtypes within this region. RESEARCH DESIGN AND METHODS: Chromosome 6 was imputed using SNP2HLA, with conditional analysis performed in type 1 diabetes case subjects (n = 1,985) and control subjects (n = 2,219). The same approach was applied to a LADA cohort (n = 1,428) using population-based control subjects (n = 2,850) and in a separate replication cohort (656 type 1 diabetes case, 823 LADA case, and 3,218 control subjects). RESULTS: The strongest associations in the MHC class II region (rs3957146, ß [SE] = 1.44 [0.05]), as well as the independent effect of MHC class I genes, on type 1 diabetes risk, particularly HLA-B*39 (ß [SE] = 1.36 [0.17]), were confirmed. The conditional analysis in LADA versus control subjects showed significant association in the MHC class II region (rs3957146, ß [SE] = 1.14 [0.06]); however, we did not observe significant independent effects of MHC class I alleles in LADA. CONCLUSIONS: In LADA, the independent effects of MHC class I observed in type 1 diabetes were not observed after conditioning on the leading MHC class II associations, suggesting that the MHC class I association may be a genetic discriminator between LADA and childhood-onset type 1 diabetes.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Genes, MHC Class II/genetics , Genes, MHC Class I/genetics , Genetic Testing , Latent Autoimmune Diabetes in Adults/genetics , Adolescent , Adult , Age of Onset , Alleles , Case-Control Studies , Child , Child, Preschool , Chromosomes, Human, Pair 6/genetics , Cohort Studies , Diabetes Mellitus, Type 1/classification , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Diagnosis, Differential , Female , Genetic Association Studies , Genetic Testing/methods , Humans , Latent Autoimmune Diabetes in Adults/classification , Latent Autoimmune Diabetes in Adults/diagnosis , Male , Polymorphism, Single Nucleotide , Young AdultABSTRACT
AIM: (1) To quantify the invisible variations of facial erythema that occur as the blood flows in and out of the face of diabetic patients, during the blood pulse wave using an innovative image processing method, on videos recorded with a conventional digital camera and (2) to determine whether this "unveiled" facial red coloration and its periodic variations present specific characteristics in diabetic patients different from those in control subjects. METHODS: We video recorded the faces of 20 diabetic patients with peripheral neuropathy, retinopathy, and/or nephropathy and 10 nondiabetic control subjects, using a Canon EOS camera, for 240 s. Only one participant presented visible facial erythema. We applied novel image processing methods to make the facial redness and its variations visible and automatically detected and extracted the redness intensity of eight facial patches, from each frame. We compared average and standard deviations of redness in the two groups using t-tests. RESULTS: Facial redness varies, imperceptibly and periodically, between redder and paler, following the heart pulsation. This variation is consistently and significantly larger in diabetic patients compared to controls (p value < 0.001). CONCLUSIONS: Our study and its results (i.e., larger variations of facial redness with the heartbeats in diabetic patients) are unprecedented. One limitation is the sample size. Confirmation in a larger study would ground the development of a noninvasive cost-effective automatic tool for early detection of diabetic complications, based on measuring invisible redness variations, by image processing of facial videos captured at home with the patient's smartphone.
Subject(s)
Diabetes Complications/complications , Diabetes Complications/diagnosis , Erythema/etiology , Face/blood supply , Aged , Color , Female , Humans , Image Processing, Computer-Assisted , Male , Middle AgedABSTRACT
AIM: This case-control study aimed to examine impairments in glucose metabolism in non-diabetic carriers of the mitochondrial mutation m.3243A>G by evaluating insulin secretion capacity and sensitivity. METHODS: Glucose metabolism was investigated in 23 non-diabetic m.3243A>G carriers and age-, sex- and BMI-matched healthy controls with an extended 4-h oral glucose tolerance test (OGTT). Insulin sensitivity index and acute insulin response were estimated on the basis of the OGTT. This was accompanied by examination of body composition by dual-energy X-ray absorptiometry (DXA), maximum aerobic capacity and a Recent Physical Activity Questionnaire (RPAQ). RESULTS: Fasting p-glucose, s-insulin and s-c-peptide levels did not differ between m.3243A>G carriers and controls. Insulin sensitivity index (BIGTT-S1) was significantly lower in the m.3243A>G carriers, but there was no difference in the acute insulin response between groups. P-lactate levels were higher in carriers throughout the OGTT. VO2max, but not BMI, waist and hip circumferences, lean and fat body mass%, MET or grip strength, was lower in mutation carriers. BIGTT-S1 remained lower in mutation carriers after adjustment for multiple confounding factors including VO2max in regression analyses. CONCLUSIONS: Glucose metabolism in m.3243A>G carriers was characterized by reduced insulin sensitivity, which could represent the earliest phase in the pathogenesis of m.3243A>G-associated diabetes.
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BACKGROUND: Hospitals increasingly make decisions about early development of and investment in innovative medical technologies (IMTs), but at present often without an early assessment of their potential to ensure selection of the most promising candidates for further development. This paper explores how early assessment is carried out in different health organisations and then discusses relevant learning points for hospitals. METHODS: A qualitative study design with a structured interview guide covering four themes was used. Content analyses of interview notes were performed covering four predetermined themes: context, basis for decision-making, process and structure, and perceptions. A fifth theme, handling cognitive bias, was identified during data analysis. RESULTS: A total of 11 organisations participated; eight from the private health industry and three public hospitals. The interviews identified four areas in which early assessment is performed in similar manner across the studied organisations and four areas where differences exist between public hospitals and private organisations. Public hospitals indicate a lower degree of formalised early assessment and less satisfaction with how early assessment is performed, compared to private organisations. Based on the above findings, two learning points may carry promise for hospitals. First, having dedicated prioritising committees for IMTs making stop/go decisions. This committee is separate from the IMT development processes and involved staff. Secondly, the committee should base decisions on a transparent early assessment decision-support tool, which include a broad set of domains, is iterative, describes uncertainty, and minimise cognitive biases. CONCLUSIONS: Similarities and differences in the way early assessment is done in different health organisations were identified. These findings suggest promising learning points for the development of an early assessment model for hospitals.
Subject(s)
Technology Assessment, Biomedical , Therapies, Investigational , Biomedical Technology , Decision Making , Delivery of Health Care , Hospitals, Public , Humans , Qualitative ResearchABSTRACT
OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype. RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396). RESULTS: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes. CONCLUSIONS: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
Subject(s)
Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study , Immune System Phenomena/genetics , Latent Autoimmune Diabetes in Adults/genetics , Adult , Aged , Case-Control Studies , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/metabolism , Female , Glucose Intolerance/genetics , Glucose Intolerance/immunology , Glucose Intolerance/metabolism , Haplotypes , Humans , Insulin/metabolism , Latent Autoimmune Diabetes in Adults/immunology , Latent Autoimmune Diabetes in Adults/metabolism , Male , Middle Aged , Young AdultABSTRACT
To monitor wound healing, it is essential to obtain accurate and reliable wound measurements. Various methods have been used to measure wound size including three-dimensional (3D) measurement devices enabling wound assessment from a volume perspective. However, the currently available methods are inaccurate, costly, or complicated to use. As a consequence, we have developed a 3D-wound assessment monitor (WAM) camera, which is able to measure wound size in three-dimension and to assess wound characteristics. The aim of the study was to assess the intrarater and interrater reliability of the 3D wound measurements using the 3D camera and to compare these with traditional measurement methods. Four raters measured 48 wounds using the 3D camera, digital imaging method (2D area), and gel injection into the wound cavity (volume). The data were analyzed using linear mixed effect model. Intraclass and interclass correlation coefficient (ICC) and Bland-Altman plots were used to assess intrarater and interrater reliability for the 3D camera and agreement between the methods. The Bland-Altman plots for intrarater reliability showed minor differences between the measurements, especially the 3D area and perimeter measurements. Moreover, ICCs were very high for both the intrarater and interrater reliability for the 2D area, 3D area, and perimeter measurements (ICCs > 0.99), although slightly lower for the volume measurements (ICC = 0.946-0.950). Finally, a high agreement was found between the 3D camera and the traditional methods (2D area and volume) assessed by narrow 95% prediction intervals and high ICCs above 0.97. In conclusion, the 3D-WAM camera is an accurate and reliable method, which is useful for several types of wounds. However, the volume measurements were primarily useful in large, deep wounds. Moreover, the 3D images are based on digital technology and therefore carry the possibility for use in remote settings.
Subject(s)
Imaging, Three-Dimensional/instrumentation , Imaging, Three-Dimensional/standards , Photogrammetry/instrumentation , Photogrammetry/standards , Wound Healing/physiology , Wounds and Injuries/diagnostic imaging , Wounds and Injuries/pathology , Adult , Female , Humans , Male , Middle Aged , Observer Variation , Reproducibility of Results , Skin Physiological PhenomenaABSTRACT
BACKGROUND: Latent Autoimmune Diabetes in Adults (LADA) is the second most common form of diabetes, but data on its clinical course and prognosis are scarce. We compared long-term risk of mortality and cardiovascular outcomes in patients with LADA, type 2 diabetes mellitus (T2D), and insulin deficient diabetes (IDD). METHODS: We conducted a cohort study of 4368 adults with diabetes referred to the Department of Endocrinology, Odense University Hospital, Denmark, between 1997 and 2012. Data on comorbidity, cardiovascular outcomes and death were obtained from prospective medical databases. We compared adjusted hazard ratios (HRs) of mortality and cardiovascular outcomes for patients with LADA, T2D and IDD, respectively. RESULTS: We included 327 patients with LADA, 3539 with T2D and 502 with IDD. At diagnosis, patients with LADA were older (50â¯years (IQR 37-59)) than IDD patients (40â¯years (IQR 28-52)), but younger than patients with T2D (55â¯years (IQR 45-64)). During a median follow-up period of 6.6â¯years (IQR 3.4-9.4), patients with IDD had higher mortality than patients with LADA, age- and gender-adjusted HR 2.2 (95% CI, 1.5-3.2). T2D also conferred higher mortality than LADA, HR 1.4 (95% CI, 1.0-1.9). Compared with LADA patients, cardiovascular outcome rates were increased both with IDD, HR 1.2 (95% CI, 0.7-2.0) and T2D, HR 1.2 (95% CI, 0.8-1.8), with the strongest association observed for T2D vs. LADA and acute myocardial infarction HR 1.7 (95% CI, 0.8-3.5). CONCLUSION: LADA seems to be associated with lower mortality and lower risk of cardiovascular events, compared with both T2D and IDD.
Subject(s)
Diabetes Mellitus, Type 2/complications , Latent Autoimmune Diabetes in Adults/complications , Adult , Cardiovascular Diseases , Cohort Studies , Diabetes Mellitus, Type 2/mortality , Female , Humans , Latent Autoimmune Diabetes in Adults/mortality , Male , Middle Aged , Prospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
This study compared the cost-effectiveness of telemonitoring with standard monitoring for patients with diabetic foot ulcers. The economic evaluation was nested within a pragmatic randomised controlled trial. A total of 374 patients were randomised to either telemonitoring or standard monitoring. Telemonitoring consisted of two tele-consultations in the patient's own home and one consultation at the outpatient clinic; standard monitoring consisted of three outpatient clinic consultations. Total healthcare costs were estimated over a 6-month period at individual patient level, from a healthcare sector perspective. The bootstrap method was used to calculate the incremental cost-effectiveness ratio, and one-way sensitivity analyses were performed. Telemonitoring costs were found to be 2039 less per patient compared to standard monitoring; however, this difference was not statistically significant. Amputation rate was similar in the two groups. In conclusion, a telemonitoring service in this form had similar costs and effects as standard monitoring.