Sodium-Glucose Cotransporter-2 Inhibitor Suppresses Endoplasmic Reticulum Stress and Oxidative Stress in Diabetic Nephropathy Through Nrf2 Signaling: A Clinical and Experimental Study.

Diabetic nephropathy (DN), a severe complication of type 2 diabetes mellitus (T2DM), is marked by heightened endoplasmic reticulum stress (ERS) and oxidative stress (OS) due to protein misfolding and free radical generation. We investigated the sodium-glucose co-transporter-2 inhibitor (SGLT2i), canagliflozin (Cana), in alleviating ERS and OS in DN patients and THP-1 cells under hyperglycemic condition. A total of 120 subjects were divided into four groups, with 30 subjects in each group: healthy controls, T2DM individuals, DN patients receiving standard treatment, and those treated with Cana. The control group had no history of diabetes, cardiovascular or renal diseases, or other comorbidities. Cana was administered at doses of either 100 or 300 mg per day based on the estimated glomerular filtration rate (eGFR) value of DN individuals, with a mean follow-up of 6 months. Additionally, THP-1 monocytes were exposed to HGM (33.3 mM glucose with a cytokine cocktail of TNF-α and IFN-γ at 50 ng/mL each) to evaluate the relative levels of ERS, OS markers, and nuclear factor erythroid 2-related factor 2 (Nrf2), the transcription factor regulating cellular redox, which is downregulated in diabetes. Our results revealed that ERS markers GRP78 and PERK, as well as OS markers TXNIP and p22phox, were elevated in both DN patients and HGM-treated THP-1 monocytes and were reduced by Cana intervention. Furthermore, Cana regulated the phosphorylation of Nrf2, Akt, and EIF2α in HGM-treated monocytes. In conclusion, our findings highlight the role of Cana in activating Nrf2, thereby attenuating ERS and OS to mitigate DN progression.

Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review.

Background: The field of precision medicine endeavors to transform the healthcare industry by advancing individualised strategies for diagnosis, treatment modalities, and predictive assessments. This is achieved by utilizing extensive multidimensional biological datasets encompassing diverse components, such as an individual's genetic makeup, functional attributes, and environmental influences. Artificial intelligence (AI) systems, namely machine learning (ML) and deep learning (DL), have exhibited remarkable efficacy in predicting the potential occurrence of specific cancers and cardiovascular diseases (CVD). Methods: We conducted a comprehensive scoping review guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) framework. Our search strategy involved combining key terms related to CVD and AI using the Boolean operator AND. In August 2023, we conducted an extensive search across reputable scholarly databases including Google Scholar, PubMed, IEEE Xplore, ScienceDirect, Web of Science, and arXiv to gather relevant academic literature on personalised medicine for CVD. Subsequently, in January 2024, we extended our search to include internet search engines such as Google and various CVD websites. These searches were further updated in March 2024. Additionally, we reviewed the reference lists of the final selected research articles to identify any additional relevant literature. Findings: A total of 2307 records were identified during the process of conducting the study, consisting of 564 entries from external sites like arXiv and 1743 records found through database searching. After 430 duplicate articles were eliminated, 1877 items that remained were screened for relevancy. In this stage, 1241 articles remained for additional review after 158 irrelevant articles and 478 articles with insufficient data were removed. 355 articles were eliminated for being inaccessible, 726 for being written in a language other than English, and 281 for not having undergone peer review. Consequently, 121 studies were deemed suitable for inclusion in the qualitative synthesis. At the intersection of CVD, AI, and precision medicine, we found important scientific findings in our scoping review. Intricate pattern extraction from large, complicated genetic datasets is a skill that AI algorithms excel at, allowing for accurate disease diagnosis and CVD risk prediction. Furthermore, these investigations have uncovered unique genetic biomarkers linked to CVD, providing insight into the workings of the disease and possible treatment avenues. The construction of more precise predictive models and personalised treatment plans based on the genetic profiles of individual patients has been made possible by the revolutionary advancement of CVD risk assessment through the integration of AI and genomics. Interpretation: The systematic methodology employed ensured the thorough examination of available literature and the inclusion of relevant studies, contributing to the robustness and reliability of the study's findings. Our analysis stresses a crucial point in terms of the adaptability and versatility of AI solutions. AI algorithms designed in non-CVD domains such as in oncology, often include ideas and tactics that might be modified to address cardiovascular problems. Funding: No funding received.

Prevention of diabetes from prediabetes in real world setting in South India.

AIM: The aim was to explore the effect of lifestyle modification in a real world situation to prevent the progression to diabetes in India. METHODS: Participants who underwent OGTT from August 2017-2022 and were diagnosed as having Prediabetes (n = 200) were assigned into control (group1, n = 100) received standard care and intervention (group2, n = 100) received intensive counseling on physical activity (PA) and diet. PA included walking for 150 min/week and personalized advice based on the profession. OGTTs were repeated once every 6 months for 5 years and primary outcome was development of DM. RESULTS: The conversion rate was significantly higher in the control group than the intervention group (44.6 vs.7.9 %, p < 0.0001). Individuals who reverted back to normal was significantly higher in Group2 compared to Group1 (34.9 vs.6.2 %; p < 0.001). A significant increase in weight, BMI and waist circumference in group1 and significant reduction in glucose and HbA1c was noted in group2. Mean (95%CI) survival time for Group1 was 25.4 (20.8-29.9) and Group2 was 36.4months (32.6-40.1; p < 0.001). The factors which influenced the conversion of prediabetes to DM were averaged BMI, fasting and 2hr glucose levels of all follow up visit measurements. CONCLUSION: We can prevent diabetes in individuals with prediabetes using real world strategies in India.

Undernourished Household Contacts Are at Increased Risk of Tuberculosis (TB) Disease, but not TB Infection- a Multicenter Prospective Cohort Analysis.

Undernutrition is the leading risk factor for tuberculosis (TB) globally and in India. This multicenter prospective cohort analysis from India suggests that undernutrition is associated with increased risk of TB disease but not TB infection among household contacts of persons with TB.

Effectiveness of interventions to enhance healing of chronic foot ulcers in diabetes: A systematic review.

BACKGROUND: It is critical that interventions used to enhance the healing of chronic foot ulcers in diabetes are backed by high-quality evidence and cost-effectiveness. In previous years, the systematic review accompanying guidelines published by the International Working Group of the Diabetic Foot performed 4-yearly updates of previous searches, including trials of prospective, cross-sectional and case-control design. AIMS: Due to a need to re-evaluate older studies against newer standards of reporting and assessment of risk of bias, we performed a whole new search from conception, but limiting studies to randomised control trials only. MATERIALS AND METHODS: For this systematic review, we searched PubMed, Scopus and Web of Science databases for published studies on randomised control trials of interventions to enhance healing of diabetes-related foot ulcers. We only included trials comparing interventions to standard of care. Two independent reviewers selected articles for inclusion and assessed relevant outcomes as well as methodological quality. RESULTS: The literature search identified 22,250 articles, of which 262 were selected for full text review across 10 categories of interventions. Overall, the certainty of evidence for a majority of wound healing interventions was low or very low, with moderate evidence existing for two interventions (sucrose-octasulfate and leucocyte, platelet and fibrin patch) and low quality evidence for a further four (hyperbaric oxygen, topical oxygen, placental derived products and negative pressure wound therapy). The majority of interventions had insufficient evidence. CONCLUSION: Overall, the evidence to support any other intervention to enhance wound healing is lacking and further high-quality randomised control trials are encouraged.

The sound of silent RNA in tuberculosis and the lncRNA role on infection.

Tuberculosis (TB) is one of the leading causes of death worldwide, and Diabetes Mellitus is one of the major comorbidities (TB/DM) associated with the disease. A total of 103 differentially expressed ncRNAs have been identified in the TB and TB/DM comparisons. A machine learning algorithm was employed to identify the most informative lncRNAs: ADM-DT, LINC02009, LINC02471, SOX2-OT, and GK-AS1. These lncRNAs presented substantial accuracy in classifying TB from HC (AUCs >0.85) and TB/DM from HC (AUCs >0.90) in the other three countries. Genes with significant correlations with the five lncRNAs enriched common pathways in Brazil and India for both TB and TB/DM. This suggests that lncRNAs play an important role in the regulation of genes related to the TB immune response.

Guidelines on offloading foot ulcers in persons with diabetes (IWGDF 2023 update).

AIMS: Offloading mechanical tissue stress is arguably the most important of multiple interventions needed to heal diabetes-related foot ulcers. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on offloading interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the PICO (Patient-Intervention-Control-Outcome) format, undertaking a systematic review and meta-analyses, developing summary of judgement tables and writing recommendations and rationales for each question. Each recommendation is based on the evidence found in the systematic review, expert opinion where evidence was not available, and a careful weighing of GRADE summary of judgement items including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability. RESULTS: For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, use a non-removable knee-high offloading device as the first-choice offloading intervention. If contraindications or patient intolerance to non-removable offloading exist, consider using a removable knee-high or ankle-high offloading device as the second-choice offloading intervention. If no offloading devices are available, consider using appropriately fitting footwear combined with felted foam as the third-choice offloading intervention. If such a non-surgical offloading treatment fails to heal a plantar forefoot ulcer, consider an Achilles tendon lengthening, metatarsal head resection, joint arthroplasty, or metatarsal osteotomy. For healing a neuropathic plantar or apex lesser digit ulcer secondary to flexibile toe deformity, use digital flexor tendon tenotomy. For healing rearfoot, non-plantar or ulcers complicated with infection or ischaemia, further recommendations have been outlined. All recommendations have been summarised in an offloading clinical pathway to help facilitate the implementation of this guideline into clinical practice. CONCLUSION: These offloading guideline recommendations should help healthcare professionals provide the best care and outcomes for persons with diabetes-related foot ulcers and reduce the person's risk of infection, hospitalisation and amputation.

Imperatorin from the aerial parts of Cleome viscosa L.: a characterization study and evaluation of the antibacterial activity.

Cleome viscosa L., a member of the family Cleomaceae, is a potential medicinal plant, known for several bioactive properties such as: anticancer, antidiabetic, antioxidant, anti-inflammatory, antimicrobial, wound healing, etc. Our study aimed to isolate a bioactive compound and assess its antibacterial activity. The crystal compound imperatorin was isolated and reported for the first time from the aerial parts of C. viscosa. The isolation was made using silica gel (100-200 mesh) column chromatography. The structure of imperatorin was investigated through single-crystal XRD, unit cell molecules, FTIR, and ESI-MS spectral analysis. The results validated imperatorin's triclinic crystal structure and P2i/c distance group. The electronic structure was also calculated (4.28/6.21 D) along with the frontier molecular orbital, dipole moment, atomic charges, and electrostatic map of particles in gaseous stage and active site. Imperatorin showed highest activity at 40 µg/mL concentration against Gram + ve bacteria: Staphylococcus aureus (3 ± 0.2 mm), Bacillus subtilis (3 ± 0.6 mm), and Gram -ve bacteria: Klebsiella pneumoniae (3 ± 0.2 mm), Escherichia coli (5 ± 0.2 mm). The study highlights that the compound can be isolated in larger quantities as the plant is easily available across the tropics.

Guidelines on interventions to enhance healing of foot ulcers in people with diabetes (IWGDF 2023 update).

AIMS: Principles of wound management, including debridement, wound bed preparation, and newer technologies involving alternation of wound physiology to facilitate healing, are of utmost importance when attempting to heal a chronic diabetes-related foot ulcer. However, the rising incidence and costs of diabetes-related foot ulcer management necessitate that interventions to enhance wound healing of chronic diabetes-related foot ulcers are supported by high-quality evidence of efficacy and cost effectiveness when used in conjunction with established aspects of gold-standard multidisciplinary care. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on wound healing interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline. MATERIALS AND METHODS: We followed the GRADE approach by devising clinical questions and important outcomes in the Patient-Intervention-Control-Outcome (PICO) format, undertaking a systematic review, developing summary of judgements tables, and writing recommendations and rationale for each question. Each recommendation is based on the evidence found in the systematic review and, using the GRADE summary of judgement items, including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability, we formulated recommendations that were agreed by the authors and reviewed by independent experts and stakeholders. RESULTS: From the results of the systematic review and evidence-to-decision making process, we were able to make 29 separate recommendations. We made a number of conditional supportive recommendations for the use of interventions to improve healing of foot ulcers in people with diabetes. These include the use of sucrose octasulfate dressings, the use of negative pressure wound therapies for post-operative wounds, the use of placental-derived products, the use of the autologous leucocyte/platelet/fibrin patch, the use of topical oxygen therapy, and the use of hyperbaric oxygen. Although in all cases it was stressed that these should be used where best standard of care was not able to heal the wound alone and where resources were available for the interventions. CONCLUSIONS: These wound healing recommendations should support improved outcomes for people with diabetes and ulcers of the foot, and we hope that widescale implementation will follow. However, although the certainty of much of the evidence on which to base the recommendations is improving, it remains poor overall. We encourage not more, but better quality trials including those with a health economic analysis, into this area.

New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

Polygenic Risk Score for Cardiovascular Diseases in Artificial Intelligence Paradigm: A Review.

Cardiovascular disease (CVD) related mortality and morbidity heavily strain society. The relationship between external risk factors and our genetics have not been well established. It is widely acknowledged that environmental influence and individual behaviours play a significant role in CVD vulnerability, leading to the development of polygenic risk scores (PRS). We employed the PRISMA search method to locate pertinent research and literature to extensively review artificial intelligence (AI)-based PRS models for CVD risk prediction. Furthermore, we analyzed and compared conventional vs. AI-based solutions for PRS. We summarized the recent advances in our understanding of the use of AI-based PRS for risk prediction of CVD. Our study proposes three hypotheses: i) Multiple genetic variations and risk factors can be incorporated into AI-based PRS to improve the accuracy of CVD risk predicting. ii) AI-based PRS for CVD circumvents the drawbacks of conventional PRS calculators by incorporating a larger variety of genetic and non-genetic components, allowing for more precise and individualised risk estimations. iii) Using AI approaches, it is possible to significantly reduce the dimensionality of huge genomic datasets, resulting in more accurate and effective disease risk prediction models. Our study highlighted that the AI-PRS model outperformed traditional PRS calculators in predicting CVD risk. Furthermore, using AI-based methods to calculate PRS may increase the precision of risk predictions for CVD and have significant ramifications for individualized prevention and treatment plans.

A Pharmaceutical Paradigm for Cardiovascular Composite Risk Assessment Using Novel Radiogenomics Risk Predictors in Precision Explainable Artificial Intelligence Framework: Clinical Trial Tool.

BACKGROUND: Cardiovascular disease (CVD) is challenging to diagnose and treat since symptoms appear late during the progression of atherosclerosis. Conventional risk factors alone are not always sufficient to properly categorize at-risk patients, and clinical risk scores are inadequate in predicting cardiac events. Integrating genomic-based biomarkers (GBBM) found in plasma/serum samples with novel non-invasive radiomics-based biomarkers (RBBM) such as plaque area, plaque burden, and maximum plaque height can improve composite CVD risk prediction in the pharmaceutical paradigm. These biomarkers consider several pathways involved in the pathophysiology of atherosclerosis disease leading to CVD. OBJECTIVE: This review proposes two hypotheses: (i) The composite biomarkers are strongly correlated and can be used to detect the severity of CVD/Stroke precisely, and (ii) an explainable artificial intelligence (XAI)-based composite risk CVD/Stroke model with survival analysis using deep learning (DL) can predict in preventive, precision, and personalized (aiP3) framework benefiting the pharmaceutical paradigm. METHOD: The PRISMA search technique resulted in 214 studies assessing composite biomarkers using radiogenomics for CVD/Stroke. The study presents a XAI model using AtheroEdgeTM 4.0 to determine the risk of CVD/Stroke in the pharmaceutical framework using the radiogenomics biomarkers. CONCLUSIONS: Our observations suggest that the composite CVD risk biomarkers using radiogenomics provide a new dimension to CVD/Stroke risk assessment. The proposed review suggests a unique, unbiased, and XAI model based on AtheroEdgeTM 4.0 that can predict the composite risk of CVD/Stroke using radiogenomics in the pharmaceutical paradigm.

Telemedicine for diabetes management during COVID-19: what we have learnt, what and how to implement.

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine's advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient's glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

Effect of prediabetes on tuberculosis treatment outcomes: A study from South India.

BACKGROUND AND AIMS: The aim was to assess the effect of prediabetes on tuberculosis(TB) treatment outcomes. METHODS: This is a prospective observational cohort study of 569 eligible new smear positive cases screened for DM between 2014 and 2018 in TB units in North Chennai, South India. Based on study criteria, a total of 187 subjects were included and categorised into two groups: TB with normoglycaemia (groupI) (HbA1c<5.7%) and TB with prediabetes (group II) (HbA1c = 5.7-6.4%) and followed them at 3rd and 6th month and treatment outcomes were assessed at the end of the TB treatment. RESULTS: Total cure rate was 72.7% with no significant difference between the groups. Higher proportion of deaths occurred in group II (6.3%) compared to group I (1.3%) (p = 0.09). At the end of intensive phase of directly observed therapy (DOTS) treatment, about 23.8% were observed to have positive sputum smear in group II compared to 8.6% in group I(p = 0.019). The estimated relative risk to remain as sputum smear positive among people with prediabetes at the end of intensive phase was 3.0(95% CI: 1.2-7.6). There was a significant association found with HbA1c at enrollment and unfavourable TB treatment outcomes (ß = 1.38, [odds ratio (95% CI) 3.98(1.65-9.64); p = 0.007]. CONCLUSION: Death rate was high and there was a delay in sputum conversion among TB patients with prediabetes at the end of the intensive phase of TB treatment. HbA1c at the time of diagnosis of prediabetes was significantly associated with unfavourable TB treatment outcomes.

Topical Esmolol Hydrochloride as a Novel Treatment Modality for Diabetic Foot Ulcers: A Phase 3 Randomized Clinical Trial.

Importance: Preclinical and phase 1/2 studies with esmolol hydrochloride suggest its potential role in treatment of diabetic foot ulcers (DFUs). Objective: To study the efficacy of topical esmolol for healing of uninfected DFUs. Design, Setting, and Participants: A randomized, double-blind, multicenter, phase 3 clinical trial was conducted from December 26, 2018, to August 19, 2020, at 27 referral centers across India. Participants included adults with DFUs. Interventions: Participants were randomized after a run-in phase (1 week) to receive esmolol, 14%, gel with standard of care (SoC), SoC only, or vehicle with SoC (3:3:1 proportion) for 12 weeks (treatment phase) and followed up subsequently until week 24. Main Outcomes and Measures: The primary outcome was the proportion of wound closure within the 12-week treatment phase in the esmolol with SoC and SoC only groups. Analysis was conducted using an intention-to-treat safety evaluable population, full analysis set or efficacy-evaluable population, and per-protocol population comparing the esmolol plus SoC and SoC only treatment groups. Results: In the study, 176 participants (122 men [69.3%]; mean [SD] age, 56.4 [9.0] years; mean [SD] hemoglobin A1c level, 8.6% [1.6%]) with DFUs classified as University of Texas Diabetic Wound Classification system grade IA and IC (mean [SD] ulcer area, 4.7 [2.9] cm2) were randomized to the 3 groups. A total of 140 participants were analyzed for efficacy. The proportion of participants in the esmolol with SoC group who achieved target ulcer closure within 12 weeks was 41 of 68 (60.3%) compared with 30 of 72 (41.7%) participants in the SoC only group (odds ratio [OR], 2.13; 95% CI, 1.08-4.17; P = .03). A total of 120 participants completed the end of study visit which were analyzed. Target ulcer closure by the end of the study (week 24) was achieved in 44 of 57 (77.2%) participants in the esmolol with SoC group and 35 of 63 (55.6%) participants in the SoC only group (OR, 2.71; 95% CI, 1.22-5.99; P = .01). The median time for ulcer closure was 85 days for the esmolol with SoC group and was not estimable for SoC only group. Significant benefits of Esmolol with SoC were seen in patients with factors that impede the healing of DFU. Treatment-emergent adverse events were noted in 18.8% of the participants, but most (87.3%) of these events were not attributable to the study drug. Conclusions and Relevance: In this multicenter, randomized, double-blind clinical trial, the addition of esmolol to SoC was shown to significantly improve the healing of DFUs. With these results, topical esmolol may be an appropriate addition to SoC for treating DFUs. Trial Registration: ClinicalTrials.gov Identifier: NCT03998436; Clinical Trial Registry, India CRI Number: CTRI/2018/11/016295.

A multi-center, prospective cohort study of whole blood gene expression in the tuberculosis-diabetes interaction.

Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, with or without diabetes mellitus (DM) from sites in Brazil and India. RNA sequencing (RNAseq) performed at baseline and during TB treatment. Publicly available baseline RNAseq data from South Africa and Romania reported by the TANDEM Consortium were also analyzed. Across the sites, differentially expressed genes varied for each condition (DM, TB, and TBDM) and no pattern classified any one group across all sites. A concise signature of TB disease was identified but this was expressed equally in TB and TBDM. Pathway enrichment analysis failed to distinguish TB from TBDM, although there was a trend for greater neutrophil and innate immune pathway activation in TBDM participants. Pathways associated with insulin resistance, metabolic dysfunction, diabetic complications, and chromosomal instability were positively correlated with glycohemoglobin. The immune response to pulmonary TB as reflected by whole blood gene expression is substantially similar with or without comorbid DM. Gene expression pathways associated with the microvascular and macrovascular complications of DM are upregulated during TB, supporting a syndemic interaction between these coprevalent diseases.

Precision of Michigan Neuropathy Screening Instrument (MNSI) Tool for the Diagnosis of Diabetic Peripheral Neuropathy Among People with Type 2 Diabetes-A Study from South India.

Diabetic peripheral neuropathy (DPN) is one of the risk factors for foot-related complications among people with type 2 diabetes mellitus (T2DM). Hence, we aimed to validate the Michigan Neuropathy Screening Instrument (MNSI) tool against biothesiometer with a cut-off value of ≥25 V and also to determine the cut-off point of MNSI score for the diagnosis of diabetic neuropathy among people with T2DM in India. A cross-sectional study was conducted among 357 people with T2DM in a tertiary care centre for diabetes in Chennai, South India. The eligible study participants underwent testing with a biothesiometer and the MNSI tool was administered. The patient version tool of MNSI was translated to the local language, Tamil. The MNSI scores (1, 1.5, 2, and 2.5) were compared with biothesiometer value. For the MNSI scores of less than 1, 1.5, 2, and 2.5, sensitivities were 97.6%, 97.6%, 96.8%, and 77.8% and specificities were 76.6%, 77.9%, 85.7%, and 88.3% respectively. The cut-off value of MNSI score was derived as two with AUC of 0.934. The sensitivity was 96.8% and the specificity was 85.7% with 89.6% accuracy. The high sensitivity indicates the positive cases are diagnosed correctly. There is no validated tool available for detection of DPN in Indian population. The Indian version of MNSI tool was found to be effective for screening diabetic neuropathy among people with T2DM. The MNSI tool was found to be reliable, convenient, and non-invasive for diagnosis of DPN and can be used in routine clinical settings.

Chitinase and indoleamine 2, 3-dioxygenase are prognostic biomarkers for unfavorable treatment outcomes in pulmonary tuberculosis.

Introduction: Chitinase, Indoleamine 2,3-dioxygenesae-1 (IDO-1) and heme oxygenase-1 (HO-1) are candidate diagnostic biomarkers for tuberculosis (TB). Whether these immune markers could also serve as predictive biomarkers of unfavorable treatment outcomes in pulmonary TB (PTB) is not known. Methods: A cohort of newly diagnosed, sputum culture-positive adults with drug-sensitive PTB were recruited. Plasma chitinase protein, IDO protein and HO-1 levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death, or recurrence) and 108 control individuals who had recurrence-free cure. Results: Plasma chitinase and IDO protein levels but not HO-1 levels were lower in cases compared to controls. The low chitinase and IDO protein levels were associated with increased risk of unfavourable outcomes in unadjusted and adjusted analyses. Receiver operating characteristic analysis revealed that chitinase and IDO proteins exhibited high sensitivity and specificity in differentiating cases vs controls as well as in differentiating treatment failure vs controls and recurrence vs controls, respectively. Classification and regression trees (CART) were used to determine threshold values for these two immune markers. Discussion: Our study revealed a plasma chitinase and IDO protein signature that may be used as a tool for predicting adverse treatment outcomes in PTB.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.