Corneal confocal microscopy detects early nerve regeneration after pharmacological and surgical interventions: Systematic review and meta-analysis.

Corneal confocal microscopy (CCM) is an ophthalmic imaging technique that enables the identification of corneal nerve fibre degeneration and regeneration. To undertake a systematic review and meta-analysis of studies utilizing CCM to assess for corneal nerve regeneration after pharmacological and surgical interventions in patients with peripheral neuropathy. Databases (EMBASE [Ovid], PubMed, CENTRAL and Web of Science) were searched to summarize the evidence from randomized and non-randomized studies using CCM to detect corneal nerve regeneration after pharmacological and surgical interventions. Data synthesis was undertaken using RevMan web. Eighteen studies including 958 patients were included. CCM identified an early (1-8 months) and longer term (1-5 years) increase in corneal nerve measures in patients with peripheral neuropathy after pharmacological and surgical interventions. This meta-analysis confirms the utility of CCM to identify nerve regeneration following pharmacological and surgical interventions. It could be utilized to show a benefit in clinical trials of disease modifying therapies for peripheral neuropathy.

Earlier diagnosis of peripheral neuropathy in primary care: A call to action.

Peripheral neuropathy (PN) often remains undiagnosed (~80%). Earlier diagnosis of PN may reduce morbidity and enable earlier risk factor reduction to limit disease progression. Diabetic peripheral neuropathy (DPN) is the most common PN and the 10 g monofilament is endorsed as an inexpensive and easily performed test for DPN. However, it only detects patients with advanced neuropathy at high risk of foot ulceration. There are many validated questionnaires to diagnose PN, but they can be time-consuming and have complex scoring systems. Primary care physicians (PCPs) have busy clinics and lack access to a readily available screening method to diagnose PN. They would prefer a short, simple, and accurate tool to screen for PN. Involving the patient in the screening process would not only reduce the time a physician requires to make a diagnosis but would also empower the patient. Following an expert meeting of diabetologists and neurologists from the Middle East, South East Asia and Latin America, a consensus was formulated to help improve the diagnosis of PN in primary care using a simple tool for patients to screen themselves for PN followed by a consultation with the physician to confirm the diagnosis.

Longitudinal Studies of Wearables in Patients with Diabetes: Key Issues and Solutions.

Glucose monitoring is key to the management of diabetes mellitus to maintain optimal glucose control whilst avoiding hypoglycemia. Non-invasive continuous glucose monitoring techniques have evolved considerably to replace finger prick testing, but still require sensor insertion. Physiological variables, such as heart rate and pulse pressure, change with blood glucose, especially during hypoglycemia, and could be used to predict hypoglycemia. To validate this approach, clinical studies that contemporaneously acquire physiological and continuous glucose variables are required. In this work, we provide insights from a clinical study undertaken to study the relationship between physiological variables obtained from a number of wearables and glucose levels. The clinical study included three screening tests to assess neuropathy and acquired data using wearable devices from 60 participants for four days. We highlight the challenges and provide recommendations to mitigate issues that may impact the validity of data capture to enable a valid interpretation of the outcomes.

Distinctive Microbial Signatures and Gut-Brain Crosstalk in Pediatric Patients with Coeliac Disease and Type 1 Diabetes Mellitus.

Coeliac disease (CD) and Type 1 diabetes mellitus (T1DM) are immune-mediated diseases. Emerging evidence suggests that dysbiosis in the gut microbiome plays a role in the pathogenesis of both diseases and may also be associated with the development of neuropathy. The primary goal in this cross-sectional pilot study was to identify whether there are distinct gut microbiota alterations in children with CD (n = 19), T1DM (n = 18) and both CD and T1DM (n = 9) compared to healthy controls (n = 12). Our second goal was to explore the relationship between neuropathy (corneal nerve fiber damage) and the gut microbiome composition. Microbiota composition was determined by 16S rRNA gene sequencing. Corneal confocal microscopy was used to determine nerve fiber damage. There was a significant difference in the overall microbial diversity between the four groups with healthy controls having a greater microbial diversity as compared to the patients. The abundance of pathogenic proteobacteria Shigella and E. coli were significantly higher in CD patients. Differential abundance analysis showed that several bacterial amplicon sequence variants (ASVs) distinguished CD from T1DM. The tissue transglutaminase antibody correlated significantly with a decrease in gut microbial diversity. Furthermore, the Bacteroidetes phylum, specifically the genus Parabacteroides was significantly correlated with corneal nerve fiber loss in the subjects with neuropathic damage belonging to the diseased groups. We conclude that disease-specific gut microbial features traceable down to the ASV level distinguish children with CD from T1DM and specific gut microbial signatures may be associated with small fiber neuropathy. Further research on the mechanisms linking altered microbial diversity with neuropathy are warranted.

Rapid Improvement in Weight, Body Composition, and Glucose Variability With Semaglutide in Type 1 Diabetes.

The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) in type 2 diabetes mellitus is well-established. GLP1-RAs are not approved for use in type 1 diabetes mellitus (T1DM). A 34-year-old woman with a 23-year history of T1DM presented for review for weight gain (weight 63 kg, BMI 26.9 kg/m2) and increased HbA1c (8.3%) and glycemic variability. Subcutaneous semaglutide (1 mg weekly) was commenced. After two months, there was decrease in weight by 12 kg, body fat percent by 15%, visceral fat by 7%, and a reduction in insulin dose, glycemic variability, and HbA1c. Semaglutide could be an important adjunct to insulin treatment in T1DM.

Case report: Nerve fiber regeneration in children with melanocortin 4 receptor gene mutation related obesity treated with semaglutide.

Melanocortin 4 receptor (MC4R) mutations are the commonest cause of monogenic obesity through dysregulation of neuronal pathways in the hypothalamus and prefrontal cortex that regulate hunger and satiety. MC4R also regulates neuropathic pain pathways via JNK signaling after nerve injury. We show evidence of corneal small fiber degeneration in 2 siblings carrying a heterozygous missense variant c.508A>G, p.Ille170Val in the MC4R gene. Both children were treated with once weekly semaglutide for 6 months with no change in weight, and only a minor improvement in HbA1c and lipid profile. However, there was evidence of nerve regeneration with an increase in corneal nerve fiber density (CNFD) [child A (13.9%), child B (14.7%)], corneal nerve branch density (CNBD) [child A (110.2%), child B (58.7%)] and corneal nerve fiber length (CNFL) [child A (21.5%), child B (44.0%)].

Introducing Group Open-Book Exams as a Learning and Assessment Strategy in the Clinical Biochemistry Course for Medical Students.

BACKGROUND: Teachers constantly strive to obtain reliable and appropriate teaching and assessment methods to maximize the learning experience. This study aimed to introduce combined modified team-based learning and open-book exams (TBL/OBEs) as learning and assessment strategies in clinical biochemistry for medical students and assess students' perceptions. METHODS: Second-year medical students enrolled in the clinical biochemistry course were included in this study and subjected to TBL/OBE assessment. The assessment included two parts: the open-book format for half of the questions and the closed-book format for the other as a control. Upon completing the combined TBL/OBE session, the students were required to complete a structured survey to evaluate their perception of the experience. The data were gathered and analyzed. Data were presented as mean±standard error of the mean (SEM), and a p-value ≤0.05 was considered statistically significant. RESULTS: A total of 358 students completed the TBL/OBE and closed-book exam (CBE) and responded to the survey. Of these students, 76% preferred the OBE, and 84% thought it was a suitable learning method. On the one hand, the mean difficulty of the OBE format was 92.7±1.5 SEM, while, for the CBE, the mean difficulty was 88.7±1.9 SEM (p=0.015). On the other hand, the mean discrimination factor for OBE was 0.26±0.04 and, for the CBE, 0.41±0.04 SEM (p=0.0016). Males found the OBE questions easier (p=0.025) and less stressful (p=0.01). CONCLUSION: A combined model of modified TBL and OBE is a successful learning and assessment strategy in clinical biochemistry for medical students.

Single-Center Experience of Using Liraglutide in Adolescents With Obesity +/- Type 2 Diabetes.

Background Childhood obesity is recognized as a chronic illness with limited therapeutic options. Tackling obesity (BMI; the weight in kilograms divided by the square of the height in meters, at the 95th percentile or higher) with lifestyle interventions, especially in adolescents, has proven to be a daunting task, yielding only modest results. Research on the use of liraglutide for weight reduction in pediatric patients has yielded conflicting results. Notably, there is a lack of studies in the Middle East reporting on the outcomes of glucagon-like peptide 1 (GLP-1) receptor agonists in treating obesity in children and adolescents, with or without diabetes. This study, conducted in the Middle East, represents the first investigation into the utilization of liraglutide for weight reduction in this pediatric population. Methods This retrospective study collected data on 22 consecutive participants, aged 12 to 19 years, who were diagnosed with obesity (defined as having a BMI greater than the 95th percentile for their age and sex) and had either type 2 diabetes mellitus (T2DM) or were non-diabetic who attended endocrine clinics in Sidra Medicine, Doha, Qatar, between 2020 and 2022. The study protocol involved a liraglutide treatment period spanning 18 months (72 weeks), with scheduled follow-up appointments at six-month intervals. The primary endpoints were changes in weight and BMI from baseline to the 72-week mark. Secondary endpoints were safety measures and changes in HbA1c.  Results Out of the initial cohort of 22 patients, 12 completed the full 72-week duration of the study, while 10 patients either discontinued treatment or did not adhere to the prescribed medication regimen due to side effects. Among the 12 patients who completed the study, six had a diagnosis of T2DM. At baseline, the weight, standard deviation score (SDS), BMI, and BMI standard deviation (SD) were 113.9 kg, 2.9, 40.9 kg/m2, and 2.6 respectively. At the 18-month follow-up, the weight, SDS, BMI, and BMI SD were 117.8kg, 2.6, 39kg/m2, and 2.5, respectively. Thus, no statistically significant change in the weight parameters was evident at 18 months compared to baseline. Dropout from the study and poor compliance were high (10 out of 22 patients) due to side effects, mainly gastrointestinal (nausea, abdominal pain, diarrhea, and vomiting). No statistically significant differences were observed between obese vs. obese with T2DM. No significant change in HbA1c was found between baseline and treatment follow-up in the diabetes patients. No adverse effects in terms of impairment of liver and kidney function or pancreatitis were observed. Conclusions The administration of liraglutide to adolescents with obesity, regardless of whether they had T2DM or not, in a real-life setting, did not yield statistically significant reductions in BMI/weight parameters, and HbA1c levels at the 72-week mark. Nevertheless, the study findings indicate that liraglutide is deemed safe for utilization within this age group, despite the presence of mild gastrointestinal side effects.

Corneal confocal microscopy demonstrates sensory nerve loss in children with autism spectrum disorder.

Autism spectrum disorder (ASD) is a developmental disorder characterized by difficulty in communication and interaction with others. Postmortem studies have shown cerebral neuronal loss and neuroimaging studies show neuronal loss in the amygdala, cerebellum and inter-hemispheric regions of the brain. Recent studies have shown altered tactile discrimination and allodynia on the face, mouth, hands and feet and intraepidermal nerve fiber loss in the legs of subjects with ASD. Fifteen children with ASD (age: 12.00 ± 3.55 years) and twenty age-matched healthy controls (age: 12.83 ± 1.91 years) underwent corneal confocal microscopy (CCM) and quantification of corneal nerve fiber morphology. Corneal nerve fibre density (fibers/mm2) (28.61 ± 5.74 vs. 40.42 ± 8.95, p = 0.000), corneal nerve fibre length (mm/mm2) (16.61 ± 3.26 vs. 21.44 ± 4.44, p = 0.001), corneal nerve branch density (branches/mm2) (43.68 ± 22.71 vs. 62.39 ± 21.58, p = 0.018) and corneal nerve fibre tortuosity (0.037 ± 0.023 vs. 0.074 ± 0.017, p = 0.000) were significantly lower and inferior whorl length (mm/mm2) (21.06 ± 6.12 vs. 23.43 ± 3.95, p = 0.255) was comparable in children with ASD compared to controls. CCM identifies central corneal nerve fiber loss in children with ASD. These findings, urge the need for larger longitudinal studies to determine the utility of CCM as an imaging biomarker for neuronal loss in different subtypes of ASD and in relation to disease progression.

Where Art Thou O treatment for diabetic neuropathy: the sequel.

INTRODUCTION: Having lived through a pandemic and witnessed how regulatory approval processes can evolve rapidly; it is lamentable how we continue to rely on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. AREAS COVERED: Small (Aδ and C) fibers are key to the genesis of pain, regulate skin blood flow, and play an integral role in the development of diabetic foot ulceration but continue to be ignored. This article challenges the rationale for the FDA insisting on symptoms/signs and nerve conduction as primary endpoints for clinical trials in DPN. EXPERT OPINION: Quantitative sensory testing, intraepidermal nerve fiber density, and especially corneal confocal microscopy remain an after-thought, demoted at best to exploratory secondary endpoints in clinical trials of diabetic neuropathy. If pharma are to be given a fighting chance to secure approval for a new therapy for diabetic neuropathy, the FDA needs to reassess the evidence rather than rely on 'opinion' for the most suitable endpoint(s) in clinical trials of diabetic neuropathy.

Prevalence and Factors Associated with Metabolic Syndrome among Non-Diabetic Saudi Adults: A Cross-Sectional Study.

(1) Introduction: given the high prevalence of metabolic syndrome (MetS) in Saudi Arabia, especially in Jeddah, this study aims to understand the dietary and lifestyle-related risk factors among Jeddah's non-diabetic adults. (2) Material and Methods: Employing a cross-sectional design, non-diabetic adults were sourced from public healthcare centers. Demographics, lifestyle, and dietary habits were surveyed. Blood pressure, anthropometrics, and fasting blood samples measuring plasma glucose, serum triglycerides, and HDL cholesterol were collected. The age cut-off for MetS was ascertained using the receiver operating characteristic curve. Variables influencing MetS were evaluated using univariate logistic regression, and consequential factors underwent multivariate analysis, adjusted for age and sex. (3) Results: Among 1339 participants, 16% had MetS, with age being the strongest predictor (p < 0.001). The optimal age cut-off was 32 years. For those <32, elevated BP in men and waist circumference (WC) in women were most prevalent. For those >32, elevated WC was dominant in both sexes. Univariate logistic regression revealed that higher income and education correlated with lower MetS prevalence, while marriage and smoking were risk factors. Adjusting for age and sex, only very high income had a significant low-risk association (p = 0.034). (4) Conclusion: MetS is notable in the studied group, with age as the pivotal predictor. High income reduces MetS risk, while marital status and smoking could increase it. Since this was a cross-sectional study, cohort studies are needed to validate our findings.

Cardiovascular autonomic neuropathy is associated with increased glycemic variability driven by hyperglycemia rather than hypoglycemia in patients with diabetes.

AIM: Cardiac autonomic neuropathy (CAN) has been suggested to be associated with hypoglycemia and impaired hypoglycemia unawareness. We have assessed the relationship between CAN and extensive measures of glucose variability (GV) in patients with type 1 and type 2 diabetes. METHODS: Participants with diabetes underwent continuous glucose monitoring (CGM) to obtain measures of GV and the extent of hyperglycemia and hypoglycemia and cardiovascular autonomic reflex testing. RESULTS: Of the 40 participants (20 T1DM and 20 T2DM) (aged 40.70 ± 13.73 years, diabetes duration 14.43 ± 7.35 years, HbA1c 8.85 ± 1.70%), 23 (57.5%) had CAN. Despite a lower coefficient of variation (CV) (31.26 ± 11.87 vs. 40.33 ± 11.03, P = 0.018), they had a higher CONGA (8.42 ± 2.58 vs. 6.68 ± 1.88, P = 0.024) with a lower median LBGI (1.60 (range: 0.20-3.50) vs. 4.90 (range: 3.20-7.40), P = 0.010) and percentage median time spent in hypoglycemia (4 (range:4-13) vs. 1 (range:0-5), P = 0.008), compared to those without CAN. The percentage GRADEEuglycemia (3.30 ± 2.78 vs. 5.69 ± 3.09, P = 0.017) and GRADEHypoglycemia (0.3 (range: 0 - 3.80) vs. 1.8 (range: 0.9-6.5), P = 0.036) were significantly lower, while the percentage median GRADEHyperglycemia (95.45 (range:93-98) vs. 91.6 (82.8-95.1), P = 0.013) was significantly higher in participants with CAN compared to those without CAN. CONCLUSION: CAN was associated with increased glycemic variability with less time in euglycemia attributed to a greater time in hyperglycemia but not hypoglycemia.

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study.

Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) (n = 68) or secondary progressive MS (SPMS) (n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-µm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls (n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD (p = 0.004) and RNFL thickness (p < 0.001) were lower, and CNBD (p = 0.003) was higher. In patients with SPMS compared with controls, CNFD (p < 0.001), CNFL (p = 0.04) and RNFL thickness (p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD (p = 0.04), CNBD (p = 0.001), CNFL (p = 0.008) and RNFL (p = 0.002) in RRMS; in CNFD (p = 0.04) and CNBD (p = 0.002) in SPMS; and in CNBD (p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study.

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) (n = 45) or secondary progressive MS (SPMS) (n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls (n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP (p < 0.001 and p < 0.001, respectively) and DCF (p < 0.001 and p = 0.005) were higher and NCF (p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP (p = 0.01) was significantly reduced, and NCP (p = 0.004) and NCF (p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher (p = 0.04-0.05) in patients who switched disease-modifying treatment, and baseline NCP (p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

Corneal nerve loss predicts dementia in patients with mild cognitive impairment.

OBJECTIVES: This study compared the utility of corneal nerve measures with brain volumetry for predicting progression to dementia in individuals with mild cognitive impairment (MCI). METHODS: Participants with no cognitive impairment (NCI) and MCI underwent assessment of cognitive function, brain volumetry of thirteen brain structures, including the hippocampus and corneal confocal microscopy (CCM). Participants with MCI were followed up in the clinic to identify progression to dementia. RESULTS: Of 107 participants with MCI aged 68.4 ± 7.7 years, 33 (30.8%) progressed to dementia over 2.6-years of follow-up. Compared to participants with NCI (n = 12), participants who remained with MCI (n = 74) or progressed to dementia had lower corneal nerve measures (p < 0.0001). Progressors had lower corneal nerve measures, hippocampal, and whole brain volume (all p < 0.0001). However, CCM had a higher prognostic accuracy (72%-75% vs 68%-69%) for identifying individuals who progressed to dementia compared to hippocampus and whole brain volume. The adjusted odds ratio for progression to dementia was 6.1 (95% CI: 1.6-23.8) and 4.1 (95% CI: 1.2-14.2) higher with abnormal CCM measures, but was not significant for abnormal brain volume. INTERPRETATION: Abnormal CCM measures have a higher prognostic accuracy than brain volumetry for predicting progression from MCI to dementia. Further work is required to validate the predictive ability of CCM compared to other established biomarkers of dementia.

Corneal confocal microscopy for the diagnosis of diabetic peripheral neuropathy: A systematic review and meta-analysis.

INTRODUCTION: Corneal confocal microscopy (CCM) is a rapid non-invasive ophthalmic imaging technique that identifies corneal nerve fiber damage. Small studies suggest that CCM could be used to assess patients with diabetic peripheral neuropathy (DPN). AIM: To undertake a systematic review and meta-analysis assessing the diagnostic utility of CCM for sub-clinical DPN (DPN- ) and established DPN (DPN+ ). DATA SOURCES: Databases (PubMed, Embase, Central, ProQuest) were searched for studies using CCM in patients with diabetes up to April 2020. STUDY SELECTION: Studies were included if they reported on at least one CCM parameter in patients with diabetes. DATA EXTRACTION: Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and inferior whorl length (IWL) were compared between patients with diabetes with and without DPN and controls. Meta-analysis was undertaken using RevMan V.5.3. DATA SYNTHESIS: Thirty-eight studies including ~4,000 participants were included in this meta-analysis. There were significant reductions in CNFD, CNBD, CNFL, and IWL in DPN- vs controls (P < 0.00001), DPN+ vs controls (P < 0.00001), and DPN+ vs DPN- (P < 0.00001). CONCLUSION: This systematic review and meta-analysis shows that CCM detects small nerve fiber loss in subclinical and clinical DPN and concludes that CCM has good diagnostic utility in DPN.

Effect of Ramadan fasting in patients with type 2 diabetes mellitus treated with sodium-glucose cotransporter 2 inhibitors: A systematic review and meta-analysis.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) improve glycemic control and weight, but might be associated with dehydration, hypotension and ketoacidosis, especially in patients with type 2 diabetes mellitus who fast during Ramadan. This meta-analysis evaluates the effects of Ramadan fasting on patients with type 2 diabetes mellitus treated with SGLT-2i. MATERIALS AND METHODS: A literature search was carried out in PubMed, Embase and the Cochrane Library. Quality assessment was carried out using the ROBINS-I and Cochrane tools for risk of bias, and analyses were carried out using RevMan version 5.3. RESULTS: A total of five studies were included in this meta-analysis. During Ramadan, there was a significant reduction in glycated hemoglobin (P < 0.00001) and diastolic blood pressure (P = 0.006), with a non-significant trend for a reduction in weight (P = 0.44) and systolic blood pressure (P = 0.67). The number and severity of hypoglycemic episodes was lower in patients with type 2 diabetes mellitus treated with SGLT-2i compared with sulfonylureas. There was no significant change in estimated glomerular filtration rate, ß-hydroxybutyrate, bicarbonate or anion gap. However, we identified considerable heterogeneity among studies, and a lack of head-to-head studies with structured outcome reporting on the risks and benefits of SGLT-2i during Ramadan. CONCLUSIONS: This systematic review and meta-analysis shows that patients with type 2 diabetes treated with SGLT2i's during Ramadan have an improvement in HbA1c, less hypoglycemia and no major adverse effects.

Sense and Learn: Recent Advances in Wearable Sensing and Machine Learning for Blood Glucose Monitoring and Trend-Detection.

Diabetes mellitus is characterized by elevated blood glucose levels, however patients with diabetes may also develop hypoglycemia due to treatment. There is an increasing demand for non-invasive blood glucose monitoring and trends detection amongst people with diabetes and healthy individuals, especially athletes. Wearable devices and non-invasive sensors for blood glucose monitoring have witnessed considerable advances. This review is an update on recent contributions utilizing novel sensing technologies over the past five years which include electrocardiogram, electromagnetic, bioimpedance, photoplethysmography, and acceleration measures as well as bodily fluid glucose sensors to monitor glucose and trend detection. We also review methods that use machine learning algorithms to predict blood glucose trends, especially for high risk events such as hypoglycemia. Convolutional and recurrent neural networks, support vector machines, and decision trees are examples of such machine learning algorithms. Finally, we address the key limitations and challenges of these studies and provide recommendations for future work.

Retinal vessel multifractals predict pial collateral status in patients with acute ischemic stroke.

OBJECTIVES: Pial collateral blood flow is a major determinant of the outcomes of acute ischemic stroke. This study was undertaken to determine whether retinal vessel metrics can predict the pial collateral status and stroke outcomes in patients. METHODS: Thirty-five patients with acute stroke secondary to middle cerebral artery (MCA) occlusion underwent grading of their pial collateral status from computed tomography angiography and retinal vessel analysis from retinal fundus images. RESULTS: The NIHSS (14.7 ± 5.5 vs 10.1 ± 5.8, p = 0.026) and mRS (2.9 ± 1.6 vs 1.9 ± 1.3, p = 0.048) scores were higher at admission in patients with poor compared to good pial collaterals. Retinal vessel multifractals: D0 (1.673±0.028vs1.652±0.025, p = 0.028), D1 (1.609±0.027vs1.590±0.025, p = 0.044) and f(α)max (1.674±0.027vs1.652±0.024, p = 0.019) were higher in patients with poor compared to good pial collaterals. Furthermore, support vector machine learning achieved a fair sensitivity (0.743) and specificity (0.707) for differentiating patients with poor from good pial collaterals. Age (p = 0.702), BMI (p = 0.422), total cholesterol (p = 0.842), triglycerides (p = 0.673), LDL (p = 0.952), HDL (p = 0.366), systolic blood pressure (p = 0.727), HbA1c (p = 0.261) and standard retinal metrics including CRAE (p = 0.084), CRVE (p = 0.946), AVR (p = 0.148), tortuosity index (p = 0.790), monofractal Df (p = 0.576), lacunarity (p = 0.531), curve asymmetry (p = 0.679) and singularity length (p = 0.937) did not differ between patients with poor compared to good pial collaterals. CONCLUSIONS: This is the first translational study to show increased retinal vessel multifractal dimensions in patients with acute ischemic stroke and poor pial collaterals. A retinal vessel classifier was developed to differentiate between patients with poor and good pial collaterals and may allow rapid non-invasive identification of patients with poor pial collaterals.

Corneal nerve loss in patients with TIA and acute ischemic stroke in relation to circulating markers of inflammation and vascular integrity.

Vascular and inflammatory mechanisms are implicated in the development of cerebrovascular disease and corneal nerve loss occurs in patients with transient ischemic attack (TIA) and acute ischemic stroke (AIS). We have assessed whether serum markers of inflammation and vascular integrity are associated with the severity of corneal nerve loss in patients with TIA and AIS. Corneal confocal microscopy (CCM) was performed to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fiber length (CNFL) in 105 patients with TIA (n = 24) or AIS (n = 81) and age matched control subjects (n = 56). Circulating levels of IL-6, MMP-2, MMP-9, E-Selectin, P-Selectin and VEGF were quantified in patients within 48 h of presentation with a TIA or AIS. CNFL (P = 0.000, P = 0.000), CNFD (P = 0.122, P = 0.000) and CNBD (P = 0.002, P = 0.000) were reduced in patients with TIA and AIS compared to controls, respectively with no difference between patients with AIS and TIA. The NIHSS Score (P = 0.000), IL-6 (P = 0.011) and E-Selectin (P = 0.032) were higher in patients with AIS compared to TIA with no difference in MMP-2 (P = 0.636), MMP-9 (P = 0.098), P-Selectin (P = 0.395) and VEGF (P = 0.831). CNFL (r = 0.218, P = 0.026) and CNFD (r = 0.230, P = 0.019) correlated with IL-6 and multiple regression analysis showed a positive association of CNFL and CNFD with IL-6 (P = 0.041, P = 0.043). Patients with TIA and AIS have evidence of corneal nerve loss and elevated IL6 and E-selectin levels. Larger longitudinal studies are required to determine the association between inflammatory and vascular markers and corneal nerve fiber loss in patients with cerebrovascular disease.