Safety and tolerability of sodium-glucose cotransporter-2 inhibitors in children and young adults: a systematic review and meta-analysis.

PURPOSE: Sodium glucose cotransporter-2 inhibitors (SGLT2i) have been evaluated in children with type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), and several other nondiabetic conditions. Potential tolerability issues have prevented the routine use of SGLT2i in children with diabetes. However, no meta-analysis to date has evaluated the safety and tolerability of SGLT2i in children. This systematic review and meta-analysis aimed to address this knowledge gap. METHODS: Databases were searched for randomized controlled trials (RCTs), case control, and cohort studies involving children receiving SGLT2i in the intervention-arm. Primary outcome was occurrence of treatment emergent adverse events (TAEs). Secondary outcomes were evaluation of glycemic efficacy and occurrence of severe adverse events (SAEs), hypoglycemia, ketosis, genital or urinary infections, and any other adverse events. RESULTS: From the 27 articles initially screened, data from 4 RCTs (258 children) were analyzed. In children with T2DM, occurrence of TAEs (odds ratio [OR], 1.77; 95% confidence interval [CI], 0.93-3.36; P=0.08; I2=0%), SAEs (OR, 0.45; 95% CI, 0.08-2.54; P=0.37; I2=0%), ketoacidosis (OR, 0.33; 95% CI, 0.01-8.37; P=0.50), urinary tract infections (OR, 2.34; 95% CI, 0.44-12.50; P=0.32; I2=0%), and severe hypoglycemia (OR, 4.47; 95% CI, 0.21-96.40; P=0.34) were comparable among the SGLTi group and placebo. Compared to placebo, T2DM children receiving SGLTi had significantly lower glycosylated hemoglobin at 24-26 weeks (mean difference [MD], -0.79%; 95% CI, -1.33 to -0.26; P=0.004; I2=0%). In T1DM children, ß-hydroxybutyrate levels were significantly higher in the SGLTi group than the placebo group (MD, 0.11 mmol/L; 95% CI, 0.05-0.17; P=0.0005; I2=53%). In T1DM, there was not a single report of an SAE, ketoacidosis, or severe hypoglycemia in either the placebo or treatment groups, but time-in-range was considerably greater in the SGLT2i group than the placebo group (68%±6% vs. 50%±13%, P<0.001). CONCLUSION: SGLT2i use in children and young adults appears to be both safe and tolerable based on our meta-analyses and review of the literature.

Management of anxiety using eye movement desensitization and reprocessing therapy in children undergoing extraction: a randomized controlled pilot study.

Background: Eye movement desensitization and reprocessing (EMDR) therapy has been reported to be very efficacious for treating post-traumatic stress disorder (PTSD) and other anxiety-related conditions. However, a review of the literature reveals the sparse use of this therapy in the field of pediatric dentistry. This study aimed to evaluate anxiety trends in pediatric dental patients during local anesthesia and extraction with and without EMDR therapy. Methods: Children in the age range of 8-12 years who required dental extractions were assigned randomly into two groups: an EMDR group (group 1) and a routine behavior management therapy group (group 2; receiving more traditional interventions such as tender love and care behavioral modeling, and distraction). Anxiety scores were recorded at four levels using the visual facial anxiety scale (VFAS) preoperatively, after therapy, after the administration of local anesthesia (LA), and after extraction. Results: Reduced anxiety was observed after the delivery of EMDR therapy, after LA administration, and post-extraction in the EMDR group compared to pre-operative anxiety scores of anxiety (P < 0.001; unpaired Student's t and Mann-Whitney U tests). In the control group, mild reductions in anxiety after routine behavior management therapy were observed, accompanied by spikes in anxiety levels after LA and extractions. Conclusion: EMDR therapy was found to be valuable for reducing anxiety among pediatric dental patients during tooth extraction procedures.

Geriatric Goalposts: Of Independence And Interdependence.

Our elder population has a unique set of needs and necessities, challenges and concerns. This reflects in the approach of geriatric medicine, which aims to ensure functional freedom and independence, as well as healthy ageing, of older citizens. We propose another, higher, aim of geriatric medicine: that is interdependence. This creates a spirit of optimism, in persons of geriatric age group as well as in their health care providers, who are able to interpret goals of medical care in a broader perspective.

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.

Efficacy and safety of novel dual glucokinase activator dorzagliatin in type-2 diabetes A meta-analysis.

BACKGROUND & AIMS: Glucokinase has a critical role in regulating glucose homeostasis in humans, and has been a target for diabetes drug development since 1990s. Dorzagliatin is a novel allosteric dual glucokinase activator targeting both pancreatic and hepatic glucokinase. No meta-analysis has analysed the efficacy and safety of dorzagliatin in type-2 diabetes (T2DM). We undertook this meta-analysis to address this knowledge-gap. METHODS: Electronic databases were searched for RCTs involving T2DM patients receiving dorzagliatin in intervention arm, and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in blood glucose parameters, lipids, insulin-resistance and adverse events. RESULTS: From initially screened 17 articles, data from 3 RCTs (1333 patients) was analysed. Over 12-24 weeks use, dorzagliatin had significantly higher lowering of HbA1c [MD -0.66% (95%CI: -0.74 to -0.59); P < 0.01; I2 = 99%], fasting glucose [MD -32.03 mg/dl (95%CI: 45.12 to -18.94); P < 0.01; I2 = 100%], 2-h post-prandial glucose [MD -43.49 mg/dl (95%CI: -46.26 to -40.72); P < 0.01; I2 = 90%] along with greater number of patients achieving HbA1c<7% [OR 6.01 (95% CI: 2.50-14.46); P < 0.01; I2 = 83%], as compared to placebo. Dorzagliatin was associated with significant elevation of triglycerides [MD 0.43 mmol/L (95%CI:0.30-0.56); P < 0.01; I2 = 0%], greater occurrence of hyperlipidaemia [RR 1.52 (95% CI:1.05-2.18); P = 0.03; I2 = 0%], and increase in body-weight [MD 0.40 kg (95%CI:0.06-0.75); P = 0.03; I2 = 0%], compared to placebo. The occurrence of total-adverse-events [RR 1.43 (95%CI:1.11-1.83); P < 0.01; I2 = 0%] but not severe adverse-events [RR 0.92 (95%CI:0.54-1.57); P = 0.76; I2 = 0%] was significantly higher with dorzagliatin. CONCLUSION: Dorzagliatin has good glycaemic efficacy and well tolerated over 6-months use. Mild increase in body-weight, serum triglycerides and overall adverse events remain issues of concern warranting further evaluation in longer clinical trials with active controls.

A Rare Case of Shprintzen-Goldberg craniosynostosis syndrome with Hirschsprung disorder: Dental characteristics and its Clinical Management.

Shprintzen-Goldberg syndrome (SGS) is an autosomal dominant syndrome caused by de novo gene mutations. It is characterized by a number of congenital defects such as craniofacial, skeletal, neurological, and connective tissue abnormalities. It is characterized by craniosynostosis and marfanoid features. To our knowledge, approximately 75 shprintzen-goldberg syndrome cases have been documented since it was first described in 1982. Rare cases of shprintzen-goldberg syndrome have been reported in which the mutated gene was inherited from an unaffected parent through their germline cells i.e., egg or sperm cells. This is a case report of a 6-year-old boy with clinically diagnosed Shprintzen-Goldberg Syndrome with Hirschsprung disease. Patient reported with multiple caries and malpositioned teeth. The treatment initiated with awareness about cariogenic foods, oral hygiene instructions and diet counselling. Subsequently, comprehensive rehabilitation was done. Key words:Dental management, Craniosynostosis, Hirschsprung disorder.

An In Vitro Study to Compare the Release of Fluoride from Glass Ionomer Cement (Fuji IX) and Zirconomer.

Mercury toxicity from amalgam dental fillings and their potential for creating problems in the environment and for human health have prompted the development of new restorative materials. The leading alternatives among these are glass ionomer cements. According to current understanding, restorative materials that slowly release fluoride exert a local cariostatic effect. For this purpose, glass ionomer cements have desirable properties in that they help prevent recurrence of caries by releasing fluoride over a long period. Thus, they function in accord with the major cariostatic mechanism of fluoride, which is believed to be its action to promote remineralization and to influence the morphology of teeth by reducing enamel solubility and by suppressing oral cariogenic bacteria. Although the minimum local concentration of fluoride release required to inhibit demineralization has not been determined, it is reported that the cariostatic ability of fluoride releasing restorative materials is significant. Zirconomer defines a new class of restorative that promises the strength and durability of amalgam with the protective benefits of glass ionomer while completely eliminating the hazards of mercury. The inclusion of specially micronized zirconia fillers in the glass component of zirconomer reinforces the structural integrity of the restoration and imparts superior mechanical properties for the restoration of load-bearing permanent teeth. Combination of outstanding strength, durability, and sustained fluoride protection deems it ideal for multiple applications. The aim of the present study was to determine the fluoride release from glass ionomer cements and compare it with new material zirconomer. Materials and methods: Sample preparation: Tablets of glass-ionomer cements and zirconomer were prepared. A dental floss was incorporated into the tablets during fabrication to allow suspension into the test medium. Each disk specimen was immersed in airtight polyethylene bottle containing 20 mL of deionized water and incubated at 37°C and stored for 24 hours. Determination of fluoride ion release: Fluoride ion measurement was performed after 6 hours, 24 hours, 48 hours, 7 days, and 14 days under normal atmospheric conditions by fluoride ion selective electrode connected to an ion selective electrode meter. Result and conclusion: Both the material tested in the study had the ability to release fluoride but higher fluoride release was observed by zirconomer as compared to GIC at all time intervals. Clinical significance: From a clinical point of view, both the restorative materials release fluoride at all time intervals; however, addition of zirconia particles in zirconomer increases its strength and provides superior mechanical properties. Therefore, due to the combination of both good structural integrity and fluoride releasing properties, zirconomer can be used for restoration of load bearing teeth. How to cite this article: Kukreja R, Singla S, Bhadoria N, et al. An In Vitro Study to Compare the Release of Fluoride from Glass Ionomer Cement (Fuji IX) and Zirconomer. Int J Clin Pediatr Dent 2022;15(1):35-37.

Expert opinion on the preoperative medical optimization of adults with diabetes undergoing metabolic surgery.

Diabetes mellitus (DM) and obesity are interrelated in a complex manner, and their coexistence predisposes patients to a plethora of medical problems. Metabolic surgery has evolved as a promising therapeutic option for both conditions. It is recommended that patients, particularly those of Asian origin, maintain a lower body mass index threshold in the presence of uncontrolled DM. However, several comorbidities often accompany these chronic diseases and need to be addressed for successful surgical outcome. Laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) are the most commonly used bariatric procedures worldwide. The bariatric benefits of RYGB and LSG are similar, but emerging evidence indicates that RYGB is more effective than LSG in improving glycemic control and induces higher rates of long-term DM remission. Several scoring systems have been formulated that are utilized to predict the chances of remission. A glycemic target of glycated hemoglobin < 7% is a reasonable goal before surgery. Cardiovascular, pulmonary, gastrointestinal, hepatic, renal, endocrine, nutritional, and psychological optimization of surgical candidates improves perioperative and long-term outcomes. Various guidelines for preoperative care of individuals with obesity have been formulated, but very few specifically focus on the concerns arising from the presence of concomitant DM. It is hoped that this statement will lead to the standardization of presurgical management of individuals with DM undergoing metabolic surgery.

Comparative Evaluation of Marginal Integrity of Three Esthetic Restorative Materials - An In-vitro Study.

CONTEXT: Microleakage is the major cause for the failure of dental restorations, especially in Class V cavities, as margins of such restorations are generally located in dentin or cementum. Microleakage evaluation is necessary as a means of evaluation of the marginal integrity of restorative materials. This would assist in developing techniques and materials that would reduce damage caused by the failure of the restorative marginal seal. AIM: The aim of this study is to analyze and compare the marginal integrity among three esthetic restorative materials, namely GC Fuji II LC, GC G-Aenial anterior composite resin, and GC Equia forte fil. SETTING AND DESIGN: Sixty orthodontically extracted caries-free premolar teeth with Class V restorations were divided into three groups. Microleakage was measured using an ordinal scale of 0-4, as given by Khera and Chan, in increasing order of dye penetration, which was observed under a microscope. MATERIALS AND METHODS: Study was conducted in sound human extracted premolars in which Standardized Class V cavities were prepared. Teeth were randomly and equally assigned to three groups (GC Fuji II LC, GC G-Aenial anterior composite resin, and GC Equia forte fil). Teeth were sectioned longitudinally into two halves using diamond discs and the sectioned halves of the teeth were evaluated for dye penetration under stereomicroscope. STATISTICAL ANALYSIS USED: Intergroup comparison of mean dye penetration scores were compared using the Kruskal-Wallis test along with post hoc pairwise comparison by Mann Whitney U test. The level of statistical significance was set at 0.05. RESULTS AND CONCLUSION: All the three groups (GC Fuji II LC, GC G-Aenial anterior composite resin, and GC Equia forte fil) tested showed microleakage at the tooth restoration interface. It was evident that microleakage was found to be highest with the Fuji II LC, both at occlusal and cervical levels. GC Equia forte exhibited the best performance in limiting microleakage around the restoration margins.

Efficacy and safety of novel sodium glucose cotransporter-2 inhibitor remogliflozin in the management of type 2 diabetes mellitus: A systematic review and meta-analysis.

BACKGROUND AND AIMS: No meta-analysis has analysed efficacy and safety of remogliflozin. We undertook this meta-analysis to address this gap in knowledge METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving remogliflozin as compared to controls. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in glycaemia, lipids and adverse events. RESULTS: Data from 3 RCTs involving 535 patients was analysed [2 having pioglitazone and 1 having dapagliflozin as active comparator]. Over 12-24 weeks use, Hba1c [mean difference (MD) -0.13% (95% CI: 0.35 - 0.09%); P = 0.24; I2 = 99%] and fasting glucose [MD 3.67 mg/dl (95% CI: 0.53 - 7.88 mg/dl); P = 0.09; I2 = 52%]. reduction with remogliflozin was not significantly different from controls. Remogliflozin was inferior to dapagliflozin with regards to reduction in post-prandial glucose [MD+12.17 mg/dl (95%CI:10.79-13.55 mg/dl); P < 0.001].Remogliflozin use was associated with a significantly greater decline in body weight [MD -2.79 kg (95% CI: 3.07 to -2.51 kg); P < 0.001; I2 = 30%]. Total adverse events [Risk ratio (RR) 1.21 (95% CI: 0.62-2.64); P = 0.58; I2 = 59%] were comparable among groups. CONCLUSION: Remogliflozin had HbA1c and fasting glucose reduction comparable to pioglitazone and dapagliflozin. The paradox with regard to post-prandial glucose reduction needs further evaluation. The current analysis is limited by considerable data heterogeneity and low certainty of evidence for most primary and secondary outcomes. There remains urgent need for high quality RCTs evaluating long-term outcomes with remogliflozin.

Effect of yoga on glycemia and lipid parameters in type-2 diabetes: a meta-analysis.

PURPOSE: Prior systematic reviews on yoga and diabetes have given conflicting results. They have been limited by inclusion of uncontrolled unblinded single group observational studies. No reviews are available which have used the Cochrane methodology and GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. This meta-analysis evaluated the efficacy of yoga on glycaemia and lipids in T2DM using the Cochrane methodology and GRADE approach. METHODS: Major repositories were searched to pick randomized controlled trials involving T2DM patients receiving yoga. Primary outcome was to evaluate changes in fasting plasma glucose (FPG) and glycated haemoglobin (HbA1c). Secondary outcomes were to evaluate changes in post-prandial plasma glucose (PPG), total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Sub-group analysis involving people undergoing structured exercise regimen (SER) versus those undergoing standard diabetes care in controls was done. RESULTS: Data from 13 studies involving 1440 patients were analysed. Compared to controls, individuals doing yoga had significantly lower FPG [mean difference (MD) -17.22 mg/dl (95% CI: -26.19 - -8.26 mg/dl); p < 0.01; considerable heterogeneity (CH); low certainty of evidence (LCE)], PPG [MD -27.77 mg/dl (95% CI: -35.73 - -19.81 mg/dl); p < 0.01; low heterogeneity; moderate certainty of evidence (MCE)], TC [MD -19.48 mg/dl (95% CI: -31.97 - -6.99 mg/dl); p < 0.01; CH; LCE], triglycerides [MD -12.99 mg/dl (95% CI: -23.74 - -2.25 mg/dl); p < 0.01; CH; LCE], LDL-C [MD -11.71 mg/dl (95% CI: -17.49 - -5.93 mg/dl); p < 0.01; I2 = 69% CH; LCE] and significantly higher HDL-C [MD 4.58 mg/dl (95% CI: 3.98-5.18 mg/dl); p < 0.01; low heterogeneity; MCE]. On sub-group analysis, where yoga was compared to SER, FPG was significantly lower in yoga group. CONCLUSION: Yoga improves glycaemia and lipid parameters in T2DM with additional benefits seen both in people doing/not doing structured exercise. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-021-00751-0.

Thyroid Dysfunction and Dysmetabolic Syndrome: The Need for Enhanced Thyrovigilance Strategies.

Thyroid dysfunction (TD) is common in metabolic disorders such as diabetes mellitus (DM), cardiovascular disease (CVD), obesity, dyslipidemia, hyperuricemia, kidney and liver dysfunctions, and polycystic ovary syndrome (PCOS). Subclinical hypothyroidism (SHypo) worsens glycemic control in patients with DM, and these patients, especially those with Type-1DM, have higher prevalence of TD. Both TD and DM increase CVD risk. Even minor alteration in thyroid hormone (TH) levels can alter cardiovascular function. While hyperthyroidism increases systolic blood pressure and leads to high-output heart failure, hypothyroidism increases diastolic blood pressure and leads to low-output heart failure. Chronic subclinical hyperthyroidism (SHyper) and SHypo both increase the risk of hypertension, coronary artery disease (CAD) events, CAD deaths, and total deaths. SHyper alters cardiac morphology and function. SHypo causes dyslipidemia and endothelial dysfunction and increases the risk for weight gain and obesity. Overweight and obese patients often have hyperleptinemia, which increases the secretion of thyroid stimulating hormone (TSH) and induces TD. Dyslipidemia associated with TD can increase serum uric acid levels. Hyperuricemia promotes inflammation and may increase the risk for dyslipidemia, atherosclerosis, and CVD. TD increases the risk for developing chronic kidney disease. In nephrotic syndrome, proteinuria is associated with urinary loss of TH leading to TD. Some correlation between TD and severity of liver disease is also seen. TD and PCOS have common risk factors and pathophysiological abnormalities. Hypothyroidism must be excluded before diagnosing PCOS. Current guidelines do not strongly recommend thyroid screening in the presence of all metabolic disorders. However, pragmatic thyrovigilance is required. Clinicians must stay alert to signs and symptoms of TD, maintain high clinical suspicion, and investigate thoroughly. Drug-induced TD should be considered when TH levels do not match clinical findings or when patients are on medications that can alter thyroid function.

Efficacy and Safety of the Novel Dipeptidyl Peptidase-4 Inhibitor Gemigliptin in the Management of Type 2 Diabetes: A Meta-Analysis.

BACKGROUND: No meta-analysis has holistically analysed and summarised the efficacy and safety of gemigliptin in type 2 diabetes. The meta-analysis addresses this knowledge gap. METHODS: Electronic databases were searched for randomised controlled trials (RCTs) involving diabetes patients receiving gemigliptin in the intervention arm and placebo/active comparator in the control arm. The primary outcome was change in haemoglobin A1c (HbA1c). The secondary outcomes were alterations in glucose, glycaemic targets, lipids, insulin resistance, and adverse events. RESULTS: Data from 10 RCTs involving 1,792 patients were analysed. Four had an active control group (ACG), with metformin/dapagliflozin/sitagliptin/glimepiride as the active comparator; six had a passive control group (PCG), with placebo/rosuvastatin as controls. HbA1c reduction by gemigliptin at 24 weeks was comparable to ACG (mean difference [MD], 0.09%; 95% confidence interval [CI], -0.06 to 0.23; P=0.24; I2=0%; moderate certainty of evidence [MCE]), but superior to PCG (MD, -0.91%; 95% CI, -1.18 to -0.63); P<0.01; I2=89%; high certainty of evidence [HCE]). Gemigliptin was superior to PCG regarding achieving HbA1c <7% (12 weeks: odds ratio [OR], 5.91; 95% CI, 1.34 to 26.08; P=0.02; I2=74%; 24 weeks: OR, 4.48; 95% CI, 2.09 to 9.60; P<0.01; I2=69%; HCE). Gemigliptin was comparable to ACG regarding achieving HbA1c <7% after 24 weeks (OR, 0.92; 95% CI, 0.52 to 1.63; P=0.77; I2=66%; MCE). Adverse events were similar between the gemigliptin and control groups (risk ratio [RR], 1.06; 95% CI, 0.82 to 1.36; P=0.66; I2=35%; HCE). The gemigliptin group did not have increased hypoglycaemia (RR, 1.19; 95% CI, 0.62 to 2.28; P=0.61; I2=19%; HCE). CONCLUSION: Gemigliptin has good glycaemic efficacy and is well-tolerated over 6 months of use.

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

Clinical practice recommendations for the detection and management of hyperglycemia in pregnancy from South Asia, Africa and Mexico during COVID-19 pandemic.

The human coronavirus disease 2019 (COVID-19) pandemic has affected overall healthcare delivery, including prenatal, antenatal and postnatal care. Hyperglycemia in pregnancy (HIP) is the most common medical condition encountered during pregnancy. There is little guidance for primary care physicians for providing delivery of optimal perinatal care while minimizing the risk of COVID-19 infection in pregnant women. This review aims to describe pragmatic modifications in the screening, detection and management of HIP during the COVID- 19 pandemic. In this review, articles published up to June 2021 were searched on multiple databases, including PubMed, Medline, EMBASE and ScienceDirect. Direct online searches were conducted to identify national and international guidelines. Search criteria included terms to extract articles describing HIP with and/or without COVID-19 between 1st March 2020 and 15th June 2021. Fasting plasma glucose, glycosylated hemoglobin (HbA1c) and random plasma glucose could be alternative screening strategies for gestational diabetes mellitus screening (at 24-28 weeks of gestation), instead of the traditional 2 h oral glucose tolerance test. The use of telemedicine for the management of HIP is recommended. Hospital visits should be scheduled to coincide with obstetric and ultrasound visits. COVID-19 infected pregnant women with HIP need enhanced maternal and fetal vigilance, optimal diabetes care and psychological support in addition to supportive measures. This article presents pragmatic options and approaches for primary care physicians, diabetes care providers and obstetricians for GDM screening, diagnosis and management during the pandemic, to be used in conjunction with routine antenatal care.

Cardiometabolic vigilance in COVID-19 and resource husbandry in resource-challenged times: Clinical practice- based expert opinion.

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.

Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis.

BACKGROUND AND AIMS: Saroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia. METHODS: Electronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)]. RESULTS: Following 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: -123.67 to -19.66 mg/dl); P < 0.01; I2 = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: -84.55-9.79 mg/dl; P = 0.12; I2 = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: -44.13 to -5.09 mg/dl); P = 0.01; I2 = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: -33.1-6.10 mg/dl; P = 0.18; I2 = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04-0.21 mg/dl); P < 0.01; I2 = 29% (low heterogeneity); high certainty of evidence]. CONCLUSION: This meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.