Genetic Signature for the Causation of Charcot Neuro-osteoarthropathy of Foot in Diabetes: A Systematic Review.

Charcot neuro-osteoarthropathy (CNO) is a complication of diabetes occurring in people with diabetic neuropathy with a prevalence of 0.5% to 1% that may culminate to foot deformity, amputation, and early mortality. However, it is not known why only certain patients with diabetic neuropathy develop CNO. Hence, early recognition of risk factors, timely diagnosis, and appropriate intervention of CNO is pertinent. Recent understanding of the pathophysiology of CNO has expanded to suggest the involvement of RANKL-OPG pathways. But pharmaco-therapeutic interventions targeting bone metabolism predominantly inhibiting RANKL were not found to be useful. Moreover, there are not enough markers to help identify patients with diabetes who are at a higher risk of developing CNO. Hence, we explored the literature in the present systematic review of mainly case-control studies to identify genetic factors that could help in understanding the pathophysiology and risk factors for the development of CNO. We could identify 7 relevant studies identifying single nucleotide polymorphism of OPG and RANK genes. There is an isolated study identifying alterations of micro RNA associated with RANKL-OPG pathway. Another study found epigenetic alterations by performing whole methylome sequencing in people with CNO compared to control. These genetic factors can be used as a diagnostic marker and their functional counterparts as targets for future therapeutic interventions. However, we found that literature is sparse on the genetic risk factors for CNO in people with diabetic neuropathy and there is still a lot of scope for future studies towards finding the molecular and genetic markers for CNO.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

Understanding the diabetes self-care behaviour in rural areas: Perspective of patients with type 2 diabetes mellitus and healthcare professionals.

BACKGROUND: Diabetes self-care behaviour plays a crucial role in managing the diabetes effectively and preventing complications. Patients with type 2 diabetes mellitus (T2DM) and health care professionals (HCPs) of rural areas often face unique challenges when it comes to diabetes self-care practices (SCPs). Therefore, this study aim to explore the perspectives of patients with T2DM and HCPs on diabetes SCPs. METHODS: Eight focus group discussions (FGDs) among individuals with T2DM and In-depth interviews (IDIs) with 15 HCPs were conducted in rural areas of Punjab, North India. Capability, Opportunity, Motivation, and Behaviour model (COM-B) was employed for thematic framework analyses. RESULTS: The study participants perceived that a limited understanding of diabetes mellitus (DM), beliefs in alternative therapies, drug side effects, attitudes towards DM (psychological capability), comorbidities (physical capability), family support (social opportunity), financial and time constraints, and weather conditions (physical opportunity) contributed to lack of DM SCPs. Physicians' guidance and support were motivating them to adhere to SCPs, especially when aligned with their sense of self-efficacy (reflective motivation). HCPs constraints in providing patient-centred care are due to training limitations (psychological capability) and a lack of essential resources (physical opportunities). Participants expressed need for comprehensive diabetes care (automatic motivation) through structured diabetes education intervention to improve diabetes SCPs. CONCLUSIONS: The study findings indicate that various factors influence diabetes SCPs from the perspectives of both patients with T2DM and HCPs and emphasizes the need for a multi-faceted approach to improve diabetes SCPs in rural areas. Implementing a structured diabetes self-care intervention strategy in rural areas may help for preventing and mitigating the impact of diabetes-related complications in rural areas.

Second Malignancy Masquerading as Recurrence of Neuroendocrine Tumor.

Neuroendocrine tumors (NETs) may mimic many endocrine syndromes, including Cushing syndrome (CS) secondary to ectopic ACTH secretion. Radiotherapy (RT) is often used as adjuvant therapy for such persistent or recurrent NETs. However, RT may predispose a susceptible person to a second malignancy. Here, we reported the story of a 37-year-old male, who presented with progressive weight loss, bone pain, and shortness of breath in the emergency department. He was diagnosed with CS secondary to a carcinoid tumor in the bronchopulmonary tree a decade previous and underwent total bilateral adrenalectomy. He also underwent lobectomy, and subsequent RT for a primary NET and was in clinical remission. His presenting symptoms were considered a recurrence of pulmonary NETs. However, the biopsy suggested high-grade mucoepidermoid carcinoma (MEC). MEC of the lung is a rare tumor with a prevalence of <1% of all lung malignancies. MEC of the lung after RT for bronchial NET-causing ectopic CS has not yet been reported in the literature. The present patient did not survive despite achieving remission of CS and primary tumor because of the aggressive second malignancy attributed to RT, which was given for the primary tumor.

Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S).

BACKGROUND: efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. OBJECTIVE: effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. METHODS: participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. OUTCOMES: primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. RESULTS: in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10-16) and 13 (12-18) ng/ml (P = 0.06) at baseline; and 60 (55-65) ng/ml and 4 (1-7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2-5) versus 5 (95% CI, 3-7), P = 0.01, intergroup difference - 2 (95% CI, -4 to -0.01); r = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P = 0.046)] was observed with vitamin D. CONCLUSIONS: single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov id: NCT04952857 registered dated 7 July 2021. What is already known on this topic-vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds-high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy-vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced.

A paradigm shift for cardiovascular outcome evaluation in diabetes: Major adverse cardiovascular events (MACE) to major adverse vascular events (MAVE).

BACKGROUND AND AIMS: Drugs for diabetes are required to demonstrate cardiovascular safety through CV outcome trials (CVOT). The pre-defined end-points for cardiovascular outcome studies may not be sufficient to capture all clinically relevant atherosclerotic cardio vascular disease (ASCVD) events particularly peripheral arterial disease (PAD). METHODS: We planned a scoping review and searched database to identify CVOT conducted in population with diabetes measuring lower limb events due to PAD as the primary outcome measure. We also searched CVOT for reported differential cardiovascular outcomes in population with PAD. RESULTS: We identified that CV outcomes are measured as 3 point major adverse cardiovascular outcomes (3P-MACE) that includes nonfatal MI and nonfatal stroke or 4P-MACE that included additional unstable angina which is further expanded to 5P-MACE by the inclusion of hospitalization for heart failure (HHF). These CV end points are captured as surrogate for CV mortality based on the biological plausibility of relation between the surrogate and final outcome from pathophysiological studies. We found the prevalence of PAD is no lesser than other CV events in people with diabetes. Moreover, PAD contributes to the significant morbidity associated with diabetes as a surrogate for mortality. However, none of the CVOT with anti-diabetic drugs include PAD events as primary outcome measure despite the inclusion of 6-25 % participants with PAD in major CVOT. PAD outcomes are objectively measurable with tibial arterial waveforms and clinical end-point as lower extremity amputation. PAD outcomes do improve with treatment including intensive glycemic control and novel oral anticoagulants. We suggest the inclusion of PAD to MACE as a pre-specified outcome for a comprehensive capture of major adverse vascular event in future studies for people with diabetes. CONCLUSIONS: MACE should be expanded to include PAD event as major adverse vascular event in cardiovascular outcome studies since PAD is clinically relevant and objectively measurable in diabetes.

Normative Data on Dehydroepiandrosterone Sulphate (DHEAS) and its Attributes in Healthy Indian Children and Adolescents.

Dehydroepiandrosterone sulphate (DHEAS), the biochemical indicator of adrenarche and pubarche, is of paramount importance in the evaluation of puberty-related disorders. The reference range of DHEAS should be ethnicity, age, sex, pubarche and Tanner stage specific. Anthropometry, puberty assessment and hormonal parameters were estimated using electrochemiluminescence assay. Bone age was estimated using the BoneXpert software. Of 2191 healthy Indian children aged 5-18 y screened at Chandigarh, 1919 were included in the final analysis (994 boys). The median DHEAS levels at pubarche stage P2 were 82.10 (55.0-129.0) g/dl in girls and 132.50 (95.12-205.50) g/dl in boys. By ROC analysis, the level of DHEAS at pubarche was 63.7 g/dl (sensitivity 72.6%, specificity 64.4%) in girls and 82.2 g/dl (sensitivity 81.8%, specificity 68.8%) in boys. The median age at adrenarche was 9.5 y in both sexes. On multivariate regression analysis; bone age, body mass index (BMI), gonadal steroids, and insulin-like growth factor-1 (IGF-1) significantly correlated with serum DHEAS levels in either sex.

Study protocol for a multicenter randomized controlled trial to compare radiofrequency ablation with surgical resection for treatment of pancreatic insulinoma.

BACKGROUND: Insulinoma is the most common functional pancreatic neuroendocrine tumor and treatment is required to address symptoms associated with insulin hypersecretion. Surgical resection is effective but burdened by high rate of adverse events (AEs). Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) demonstrated encouraging results in terms of safety and efficacy for the management of these tumors. However, studies comparing surgery and EUS-RFA are lacking. AIMS: The primary aim is to compare EUS-RFA with surgery in term of safety (overall rate of AEs). Secondary endpoints include: (a) severe AEs rate; (b) clinical effectiveness; (c) patient's quality of life; (d) length of hospital stay; (e) rate of local/distance recurrence; (f) need of reintervention; (g) rate of endocrine and exocrine pancreatic insufficiency; (h) factors associated with EUS-RFA related AEs and clinical effectiveness. METHODS: ERASIN-RCT is an international randomized superiority ongoing trial in four countries. Sixty patients will be randomized in two arms (EUS-RFA vs surgery) and outcomes compared. Two EUS-RFA sessions will be allowed to achieve symptoms resolution. Randomization and data collection will be performed online. DISCUSSION: This study will ascertain if EUS-RFA can become the first-line therapy for management of small, sporadic, pancreatic insulinoma and be included in a step-up approach in case of clinical failure.

Region-wise severity analysis of diabetic plantar foot thermograms.

OBJECTIVES: Diabetic foot ulcers (DFU) can be avoided if symptoms of diabetic foot complications are detected early and treated promptly. Early detection requires regular examination, which might be limited for many reasons. To identify affected or potentially affected regions in the diabetic plantar foot, the region-wise severity of the plantar foot must be known. METHODS: A novel thermal diabetic foot dataset of 104 subjects was developed that is suitable for Indian healthcare conditions. The entire plantar foot thermogram is divided into three parts, i.e., forefoot, midfoot, and hindfoot. The division of plantar foot is based on the prevalence of foot ulcers and the load on the foot. To classify the severity levels, conventional machine learning (CML) techniques like logistic regression, decision tree, KNN, SVM, random forest, etc., and convolutional neural networks (CNN), such as EfficientNetB1, VGG-16, VGG-19, AlexNet, InceptionV3, etc., were applied and compared for robust outcomes. RESULTS: The study successfully developed a thermal diabetic foot dataset, allowing for effective classification of diabetic foot ulcer severity using the CML and CNN techniques. The comparison of different methods revealed variations in performance, with certain approaches outperforming others. CONCLUSIONS: The region-based severity analysis offers valuable insights for targeted interventions and preventive measures, contributing to a comprehensive assessment of diabetic foot ulcer severity. Further research and development in these techniques can enhance the detection and management of diabetic foot complications, ultimately improving patient outcomes.

Dose-dependent renoprotection efficacy of sglt2 inhibitors in type 2 diabetes: systematic review and network meta-analysis.

AIM: To compare the relative effects of different dosages of sodium-glucose cotransport inhibitors (SGLT2i) for renoprotection in Type 2 diabetes mellitus. METHODS: The study searched different databases (PubMed, Embase, Scopus, and Web of Science) for studies comparing dose-dependent renoprotective efficacy defined as a decline in eGFR with the different "-flozins namely Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Ipragliflozin, Luseogliflozin, Remogliflozin and Sotagliflozin. The studies were compared with the Bayesian approach of network meta-analysis coupled with the random-effect model using the Cochrane risk of bias tool (RoB 2.0), and the surface under the cumulative ranking curve (SUCRA) score was allotted to each dosage of different SGLT-2i. RESULTS: A total of 43,434 citations were identified, out of which forty-five randomized trials with 48,067 patients, mentioning the flozin dose and eGFR as an endpoint, were found to be eligible for further analysis. The median duration of the follow-up in the trials was 12 months (IQR 5.5-16 months). Canagliflozin 100 mg demonstrated distinct eGFR benefit with an odds ratio of 2.3 (CI 0.72-3.9) compared to placebo. A statistically non-significant eGFR benefit was observed with all other "-flozins." Canagliflozin 100 mg drug dose category showed the highest sucra rank probability score of 93%, followed by the Canagliflozin 300 mg and Dapagliflozin 5 mg with sucra rank probability scores of 69% and 65%, respectively. The Flozin-dose assessment against eGFR was similar to the albumin-creatinine ratios as the secondary endpoint in the SUCRA ranking. CONCLUSION: The renoprotective efficacy of SGLT2i is independent of the incremental doses suggesting lower doses may suffice for renal 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.

Incidence and risk factors for dysglycaemia in Asian-Indians: a 10-year population-based prospective cohort study.

BACKGROUND: Diabetes prevalence estimates suggest an increasing trend in South-East Asia region, but studies on its incidence are limited. The current study aims to estimate the incidence of type 2 diabetes and pre-diabetes in a population-based cohort from India. METHODS: A subset of Chandigarh Urban Diabetes Study cohort (n=1878) with normoglycaemia or pre-diabetes at baseline was prospectively followed after a median of 11 (0.5-11) years. Diabetes and pre-diabetes were diagnosed as per WHO guidelines. The incidence with 95% CI was calculated in 1000 person-years and Cox proportional hazard model was used to find the association between the risk factors and progression to pre-diabetes and diabetes. RESULTS: The incidence of diabetes, pre-diabetes and dysglycaemia (either pre-diabetes or diabetes) was 21.6 (17.8-26.1), 18.8 (14.8-23.4) and 31.7 (26.5-37.6) per 1000 person-years, respectively. Age (HR 1.02, 95% CI 1.01 to 1.04), family history of diabetes (HR 1.56, 95% CI 1.09 to 2.25) and sedentary lifestyle (HR 1.51, 95% CI 1.05 to 2.17) predicted conversion from normoglycaemia to dysglycaemia, while obesity (HR 2.43, 95% CI 1.21 to 4.89) predicted conversion from pre-diabetes to diabetes. CONCLUSION: A high incidence of diabetes and pre-diabetes in Asian-Indians suggests a faster conversion rate to dysglycaemia, which is partly explained by sedentary lifestyle and consequent obesity in these individuals. The high incidence rates call for a pressing need for public health interventions targeting modifiable risk factors.

Autonomous growth hormone secretion due to McCune Albright syndrome in paediatric age group: an ominous triad.

PURPOSE: The current study aimed to report cases of McCune Albright syndrome (MAS) with growth hormone (GH) hyper secretion along with a systematic review of literature to elucidate challenges and intricacies in its diagnosis and management. METHODS: It was a single centre study carried out in individuals with MAS and autonomous GH secretion (AGHS). In addition, a systematic search of literature across three databases (PubMed, Scopus and EMBASE) was performed from inception until May 31, 2021 to identify cases of MAS with AGHS in the pediatric age group (<18 years). RESULTS: Three cases from authors centre and 42 cases identified from systematic literature review were analysed. Precocious puberty was the most common presenting endocrinopathy seen in 56.8% (25/44) cases, followed by hyperthyroidism (10/45), hypophosphatemia (4/45), and hypercortisolism (2/45). Cranio-facial fibrous dysplasia (CFFD) was seen in all while polyostotic fibrous dysplasia and Café au lait macule was seen in 40/45 (88.9%) and 35/45 (77.8%), respectively. Pituitary adenoma (58.3% microadenoma) was localized in 53.3% (24/45) cases on pituitary imaging. Biochemical and clinical remission of AGHS was achieved in 61.5% (24/45) cases with medical therapy. CONCLUSION: Diagnosing AGHS in MAS is challenging because of concomitant presence of CFFD, non-GH endocrinopathies associated height spurt and elevated serum IGF-1. GH-GTT should be performed in presence of elevated growth velocity and serum IGF-1 (>1 X ULN) despite adequate control of non-GH endocrinopathies. Medical management can lead to disease control in substantial number of cases and often entails use of multiple agents.

Body fat patterning in lean Asian Indians with diabetes: Case-control study.

AIM: To perform body fat patterning in Asian-Indian individuals with T2D. METHODS: A total of 53 patients with recent-onset diabetes and 106 non-diabetic controls were included from screened 261 individuals. Data was divided into 2 groups; overweight/obese [(BMI ≥23 kg/m2); 45 diabetic, 84 non-diabetic] and lean [(BMI <23 kg/m2); 8 diabetic, 22 non-diabetic]. Anthropometry (weight, height, BMI, waist, hip circumference, waist-hip ratio) and lipids, adiponectin and hsCRP were measured. Body composition (BC) was assessed by bioimpedance analysis (BIA) and Dual Energy X-ray absorptiometry (DEXA). We analyzed the association of visceral adipose tissue (VAT) with anthropometric measures to identify predictors of diabetes. RESULTS: Total body fat percentage was comparable between patients with T2D and non-diabetic controls in both, obese [35.0 ± 9.1% vs 36.8 ± 8.4%, p = 0.29 (BIA), 40.1 ± 6.7 vs 46.6 ± 4.1%, p = 0.052 (DEXA) and lean [25.1 ± 5.6% vs 26.0 ± 6.7%, p = 0.74 (BIA), 35.3 ± 4.8% vs 34.1 ± 6.3%, p = 0.72 (DEXA) study group. Individuals of T2D (obese or lean) had significantly higher visceral fat rating (BIA), VAT area, volume, mass and VAT corrected for total body fat percentage (DEXA). Obese T2D had lower muscle mass (57.0 ± 6.4% vs 60.0 ± 5.5%, p = 0.03) than obese controls. Intra-abdominal visceral fat (IAVF) [(VFR, VAT (mass/area/volume) and VAT mass corrected for body fat)] had the best sensitivity (71%) for incident diabetes. CONCLUSION: Higher Intra-abdominal visceral fat and not total body fat is associated with incident diabetes independent of BMI. IAVF estimation by either BIA or DEXA should be performed to predict diabetes especially in lean individuals.

Urinary exosomal miRNA-663a shows variable expression in diabetic kidney disease patients with or without proteinuria.

Heterogeneity in the Diabetic Kidney Disease (DKD) diagnosis makes its rational therapeutics challenging. Although albuminuria characterizes DKD, reports also indicate its prevalence among non-proteinuric. Recent understanding of disease progression has thus inclined the focus on proximal tubular cell damage besides the glomeruli. A non-invasive approach exploiting exosomal miRNA derived from human kidney proximal tubular cell line was, hence, targeted. Upon miRNA profiling, three miRNAs, namely, hsa-miR-155-5p, hsa-miR-28-3p, and hsa-miR-425-5p were found to be significantly upregulated, while hsa-miR-663a was downregulated under diabetic conditions. Among these, hsa-miR-663a downregulation was more pronounced in non-proteinuric than proteinuric DKD subjects and was thus selected for the bioinformatics study. Ingenuity Pathway Analysis (IPA) narrowed on to IL-8 signaling and inflammatory response as the most enriched 'canonical pathway' and 'disease pathway' respectively, during DKD. Further, the putative gene network generated from these enriched pathways revealed experimentally induced diabetes, renal tubular injury, and decreased levels of albumin as part of mapping under 'disease and function'. Genes target predictions and annotations by IPA reiterated miR-663a's role in the pathogenesis of DKD following tubular injury. Overall, the observations might offer an indirect reflection of the underlying mechanism between patients who develop proteinuria and non-proteinuria.

Incidence and predictors of metabolic syndrome in Asian-Indians: a 10-year population-based prospective cohort study.

Background: Metabolic syndrome represents aggregation of risk factors associated with an increased risk of developing type 2 diabetes mellitus (DM) and atherosclerotic cardiovascular disease (ASCVD). Assessing its incidence is an effective way for estimating the future burden of DM and ASCVD and understanding their secular trends and effect of public health measures on halting the evolution of risk factors. The present study aimed to estimate the incidence of metabolic syndrome and its predictors using a population-based cohort. Methods: A subset of Chandigarh Urban Diabetes Study cohort (n = 1023) without diabetes or metabolic syndrome was prospectively evaluated after a mean of 10.7 years. Metabolic syndrome was defined as per International Diabetes Federation criteria and diabetes as per American Diabetes Association standards. The incidence was calculated in 1000 person years, and multivariate logistic regression was used to estimate the strength of association between incident metabolic syndrome and risk factors. Results: In the followed-up individuals (n = 303), incidence of metabolic syndrome was 32.1 per 1000 person years (95% CI 26.3-38.7 per 1000 person years). Amongst those developing metabolic syndrome, ≥4 components were present in 52% individuals, with low HDL-C being the most common abnormality. Those with metabolic syndrome had a five-time higher risk of diabetes (OR: 4.94; 95% CI: 2.27-9.96; p < 0.001) and a threefold higher risk of hypertension (OR: 2.67; 95% CI: 1.30-5.48; p = 0.006). Conclusion: Asian-Indians have a high incidence rate of metabolic syndrome, which is associated with sedentary lifestyle and consequent central obesity.

Novel Topical Esmolol Hydrochloride (Galnobax) for Diabetic Foot Wound: Phase 1/2, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Parallel-Group Study.

We aimed to assess safety and dose-finding efficacy of esmolol hydrochloride (Galnobax) for healing of diabetic foot ulcer (DFU). This is phase 1/2 multicenter, randomized, double-blind vehicle-controlled study. Participants having diabetes and noninfected, full-thickness, neuropathic, grade I or II (Wagner classification) DFU, area 1.5-10 cm2, and unresponsive to standard wound care (at least 4 weeks) were randomized to receive topical Galnobax 14% twice daily (BID), Galnobax 20% BID, Galnobax 20% once daily (OD)+vehicle, or vehicle BID with standard of care. The primary efficacy end point was the reduction in area and volume of target ulcer from baseline to week 12 or wound closure, whichever was earlier. The wound duration was 12.5 weeks (5-49.1 weeks) and wound area 4.10 ± 2.41 cm2 at baseline. The ulcer area reduction was 86.56%, 95.80%, 80.67%, and 82.58% (p = 0.47) in the Galnobax 14%, Galnobax 20%, Galnobax20%+vehicle, and vehicle only groups, respectively. Ulcer volume reduction was 99.40% in the Galnobax14%, 83.36% in Galnobax20%, 55.41% in the Galnobax20%+vehicle, and 84.57% in vehicle group (p = 0.86). The systemic concentration of esmolol was below the quantification limit (10 ng/mL) irrespective of doses of Galnobax (Cmax esmolol acid 340 ng/mL for 14% Galnobax, AUC 2.99 ± 4.31 h*µg/mL after single dose). This is the first clinical study of the short acting beta blocker esmolol hydrochloride used as novel formulation for healing of DFU. We found that esmolol when applied topically over wounds had minimal systemic concentration establishing its safety for wound healing in patients with diabetes. Esmolol hydrochloride is a safe novel treatment for DFU.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Early and Intensive Glycemic Control for Diabetic Foot Ulcer Healing: A Prospective Observational Nested Cohort Study.

We aimed to assess the effect of glycemic control on diabetic foot ulcer (DFU) healing. A prospective nested cohort study was employed of individuals with poorly controlled diabetes (glycated hemoglobin [HbA1c] >9%) and neuropathic DFU of >2-week duration. All individuals received standard diabetes and ulcer interventions for 12 weeks. Baseline demographic characteristics, ulcer area (automated assessment by wound zoom camera), and biochemical parameters were analyzed. The cohort was stratified into ulcer healed and unhealed groups. Ulcer area and glycemic parameters at 4 and 12 weeks on follow up were compared. Forty-three individuals (47 DFU) with baseline HbA1c 11.6% and ulcer area 9.87 cm2 were enrolled. After 12 weeks, mean HbA1c was 7.2%, 17 ulcers closed (healed group) and 30 ulcers did not close (unhealed group). The median time to ulcer healing was 10 weeks. Individuals in the healed group had lower fasting blood glucose (P = .010), postprandial blood glucose (P = .006), and HbA1c at 4 weeks (P = .001), and 12 weeks (0.018) compared to the unhealed group. Cox-regression analysis that revealed lower baseline ulcer area (P = .013) and HbA1c at 4 weeks (P = .009) significantly predicted DFU healing by 12 weeks. Baseline ulcer area of >10.58 cm2 and HbA1c at 4 weeks of >8.15% predicted delayed DFU healing. In conclusion, early and intensive glycemic control in the first 4 weeks of treatment initiation is associated with greater healing of DFU independent of initial ulcer area.

Ankle Charcot Mimics: Tubercular Rheumatism to Complex Regional Pain Syndrome.

Charcot Foot is often misdiagnosed because of its varied presentation that mimics other common disorders including tubercular rheumatism, complex regional pain syndrome or gout. We present a case of ankle swelling and discuss the differential diagnosis, radiological findings, and management. We also discuss the approach to diagnosis and provide differences in clinical presentations, magnetic resonance imaging,and bone scan findings for various differentials considered for Charcot foot.