Challenges associated with insulin therapy progression among patients with type 2 diabetes: Latin American MOSAIc study baseline data

Background: Poor glycemic control in patients with type 2 diabetes is commonly recorded worldwide; Latin America (LA) is not an exception. Barriers to intensifying insulin therapy and which barriers are most likely to negatively impact outcomes are not completely known. The objective was to identify barriers to insulin progression in individuals with type 2 diabetes mellitus (T2DM) in LA countries (Mexico, Brazil, and Argentina). Methods: MOSAIc is a multinational, non-interventional, prospective, observational study aiming to identify the patient-, physician-, and healthcare-based factors affecting insulin intensification. Eligible patients were ≥18 years, had T2DM, and were treated with insulin for ≥3 months with/without oral antidiabetic drugs (OADs). Demographic, clinical, and psychosocial data were collected at baseline and regular intervals during the 24-month follow-up period. This paper however, focuses on baseline data analysis. The association between glycated hemoglobin (HbA1c) and selected covariates was assessed. Results: A trend toward a higher level of HbA1c was observed in the LA versus non-LA population (8.40 ± 2.79 versus 8.18 ± 2.28; p ≤ 0.069). Significant differences were observed in clinical parameters, treatment patterns, and patient-reported outcomes in LA compared with the rest of the cohorts and between Mexico, Brazil, and Argentina. Higher number of insulin injections and lower number of OADs were used, whereas a lower level of knowledge and a higher level of diabetes-related distress were reported in LA. Covariates associated with HbA1c levels included age (-0.0129; p < 0.0001), number of OADs (0.0835; p = 0.0264), higher education level (-0.2261; p = 0.0101), healthy diet (-0.0555; p = 0.0083), self-monitoring blood glucose (-0.0512; p = 0.0033), hurried communication style in the process of care (0.1295; p = 0.0208), number of insulin injections (0.1616; p = 0.0088), adherence (-0.1939; p ≤ 0.0104), and not filling insulin prescription due to associated cost (0.2651; p = 0.0198). Conclusion: MOSAIc baseline data showed that insulin intensification in LA is not optimal and identified several conditions that significantly affect attaining appropriate HbA1c values. Tailored public health strategies, including education, should be developed to overcome such barriers.Centro de Endocrinología Experimental y Aplicad

Challenges associated with insulin therapy progression among patients with type 2 diabetes: Latin American MOSAIc study baseline data

Background: Poor glycemic control in patients with type 2 diabetes is commonly recorded worldwide; Latin America (LA) is not an exception. Barriers to intensifying insulin therapy and which barriers are most likely to negatively impact outcomes are not completely known. The objective was to identify barriers to insulin progression in individuals with type 2 diabetes mellitus (T2DM) in LA countries (Mexico, Brazil, and Argentina). Methods: MOSAIc is a multinational, non-interventional, prospective, observational study aiming to identify the patient-, physician-, and healthcare-based factors affecting insulin intensification. Eligible patients were ≥18 years, had T2DM, and were treated with insulin for ≥3 months with/without oral antidiabetic drugs (OADs). Demographic, clinical, and psychosocial data were collected at baseline and regular intervals during the 24-month follow-up period. This paper however, focuses on baseline data analysis. The association between glycated hemoglobin (HbA1c) and selected covariates was assessed. Results: A trend toward a higher level of HbA1c was observed in the LA versus non-LA population (8.40 ± 2.79 versus 8.18 ± 2.28; p ≤ 0.069). Significant differences were observed in clinical parameters, treatment patterns, and patient-reported outcomes in LA compared with the rest of the cohorts and between Mexico, Brazil, and Argentina. Higher number of insulin injections and lower number of OADs were used, whereas a lower level of knowledge and a higher level of diabetes-related distress were reported in LA. Covariates associated with HbA1c levels included age (-0.0129; p < 0.0001), number of OADs (0.0835; p = 0.0264), higher education level (-0.2261; p = 0.0101), healthy diet (-0.0555; p = 0.0083), self-monitoring blood glucose (-0.0512; p = 0.0033), hurried communication style in the process of care (0.1295; p = 0.0208), number of insulin injections (0.1616; p = 0.0088), adherence (-0.1939; p ≤ 0.0104), and not filling insulin prescription due to associated cost (0.2651; p = 0.0198). Conclusion: MOSAIc baseline data showed that insulin intensification in LA is not optimal and identified several conditions that significantly affect attaining appropriate HbA1c values. Tailored public health strategies, including education, should be developed to overcome such barriers.Centro de Endocrinología Experimental y Aplicad

Data from: Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE. Using expression-QTL mapping and -GWAS, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans. Multi-allelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicate that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (MITE) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds due to lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically-important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils

Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE. Using expression-QTL mapping and expression genome-wide association mapping, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans. Multiallelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicates that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (a miniature inverted repeat transposable element) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds as a result of lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils

Melo et al_2018_PNAS_QTL-GWAS dataset

This dataset includes SNP physical positions (pos in bp, v1.4 of the sorghum genome) and association P-values with Al tolerance (RNRG) and SbMATE expression (RQ) obtained from biparental mapping (QTL) and genome wide association mapping (GWAS) (Fig. 2). Data was generated with TASSEL. Quantitative trait mapping in recombinant inbred lines: QTL.csv. Genome wide association mapping: GWAS.csv. Al tolerance was measured as RNRG: relative net root growth (see supplementary methods) SbMATE expression: RQ - relative quantification using the ddCt method (see supplementary methods)

Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis

Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE. Using expression-QTL mapping and expression genome-wide association mapping, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans. Multiallelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicates that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (a miniature inverted repeat transposable element) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds as a result of lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils

Clinical phenotypes and outcomes in children with multisystem inflammatory syndrome across SARS-CoV-2 variant eras: a multinational study from the 4CE consortiumResearch in context

Summary: Background: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. It remains unclear how MIS-C phenotypes vary across SARS-CoV-2 variants. We aimed to investigate clinical characteristics and outcomes of MIS-C across SARS-CoV-2 eras. Methods: We performed a multicentre observational retrospective study including seven paediatric hospitals in four countries (France, Spain, U.K., and U.S.). All consecutive confirmed patients with MIS-C hospitalised between February 1st, 2020, and May 31st, 2022, were included. Electronic Health Records (EHR) data were used to calculate pooled risk differences (RD) and effect sizes (ES) at site level, using Alpha as reference. Meta-analysis was used to pool data across sites. Findings: Of 598 patients with MIS-C (61% male, 39% female; mean age 9.7 years [SD 4.5]), 383 (64%) were admitted in the Alpha era, 111 (19%) in the Delta era, and 104 (17%) in the Omicron era. Compared with patients admitted in the Alpha era, those admitted in the Delta era were younger (ES −1.18 years [95% CI −2.05, −0.32]), had fewer respiratory symptoms (RD −0.15 [95% CI −0.33, −0.04]), less frequent non-cardiogenic shock or systemic inflammatory response syndrome (SIRS) (RD −0.35 [95% CI −0.64, −0.07]), lower lymphocyte count (ES −0.16 × 109/uL [95% CI −0.30, −0.01]), lower C-reactive protein (ES −28.5 mg/L [95% CI −46.3, −10.7]), and lower troponin (ES −0.14 ng/mL [95% CI −0.26, −0.03]). Patients admitted in the Omicron versus Alpha eras were younger (ES −1.6 years [95% CI −2.5, −0.8]), had less frequent SIRS (RD −0.18 [95% CI −0.30, −0.05]), lower lymphocyte count (ES −0.39 × 109/uL [95% CI −0.52, −0.25]), lower troponin (ES −0.16 ng/mL [95% CI −0.30, −0.01]) and less frequently received anticoagulation therapy (RD −0.19 [95% CI −0.37, −0.04]). Length of hospitalization was shorter in the Delta versus Alpha eras (−1.3 days [95% CI −2.3, −0.4]). Interpretation: Our study suggested that MIS-C clinical phenotypes varied across SARS-CoV-2 eras, with patients in Delta and Omicron eras being younger and less sick. EHR data can be effectively leveraged to identify rare complications of pandemic diseases and their variation over time. Funding: None