Publications by authors named "Jose C Florez"
Aims: To evaluate the predictive value of a contemporary type 2 diabetes (T2D) polygenic score (PGS) in detecting incident diabetes across a range of diabetes risk factors.
Materials And Methods: We analysed participants in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial (ClinicalTrials.gov, number NCT0176463), which compared the efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab versus placebo in lowering cardiovascular outcomes in participants with stable atherosclerotic cardiovascular disease and LDL cholesterol levels of 70 mg/dL (1.
Background: DNA methylation differences are associated with kidney function and diabetic kidney disease (DKD), but prospective studies are scarce. Therefore, we aimed to study DNA methylation in a prospective setting in the Finnish Diabetic Nephropathy Study type 1 diabetes (T1D) cohort.
Methods: We analysed baseline blood sample-derived DNA methylation (Illumina's EPIC array) of 403 individuals with normal albumin excretion rate (early progression group) and 373 individuals with severe albuminuria (late progression group) and followed-up their DKD progression defined as decrease in eGFR to <60 mL/min/1.
Article Synopsis
- The All of Us Research Program (AoU) aims to collect a diverse dataset from over one million people in the USA to enhance research on human diseases, focusing on genetic and phenotypic information.
- This study developed and validated algorithms to identify cases of type 1 and type 2 diabetes using electronic health records and survey data, striving for improved accuracy in case-control studies.
- The results showed the EHR-only algorithm had a better association with type 1 diabetes genetic scores, while the EHR+ algorithm was superior for type 2 diabetes, identifying significantly more cases than previous definitions and providing new validated definitions for both diabetes types.
Article Synopsis
- Type 2 diabetes (T2D) genome-wide association studies (GWASs) typically miss rare genetic variants due to limitations in previous imputation methods and insufficient whole-genome sequencing data.
- In a large-scale study involving over half a million individuals, researchers uncovered 12 new genetic variants linked to T2D, including a rare enhancer variant near the LEP gene that significantly increases risk.
- The study also analyzed ClinVar variants related to monogenic diabetes, identifying additional rare variants that affect T2D risk and offering new insights into the pathogenicity of certain variants previously deemed uncertain.
Article Synopsis
- Genome-wide association studies have found numerous genetic loci linked to glycemic traits, but connecting these loci to specific genes and biological pathways remains a challenge.
- Researchers conducted meta-analyses of exome-array studies across four glycemic traits, analyzing data from over 144,000 participants, which led to the identification of coding variant associations in more than 60 genes.
- The study revealed significant pathways related to insulin secretion, zinc transport, and fatty acid metabolism, enhancing understanding of glycemic regulation and making data available for further research.
Importance: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care; however, accompanying immune-related adverse events (irAEs) confer substantial morbidity and occasional mortality. Life-threatening irAEs may require permanent cessation of ICI, even in patients with positive tumor response. Therefore, it is imperative to comprehensively define the spectrum of irAEs to aid individualized decision-making around the initiation of ICI therapy.
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- * The study analyzed data from nearly 30,000 type 2 diabetes patients to see how genetic factors, particularly a specific variant, correlated with retinopathy risk, regardless of measured HbA1c levels.
- * Findings revealed that those in the lowest genetic risk group experienced 20%-50% more retinopathy compared to higher-risk individuals, suggesting that genetic factors should inform personalized HbA1c targets for better diabetes management across different ancestries.
Partitioned polygenic scores (pPS) have been developed to capture pathophysiologic processes underlying type 2 diabetes (T2D). We investigated the association of T2D pPS with diabetes-related traits and T2D incidence in the Diabetes Prevention Program. We generated five T2D pPS (β-cell, proinsulin, liver/lipid, obesity, lipodystrophy) in 2,647 participants randomized to intensive lifestyle, metformin, or placebo arms.
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- - The study evaluates the effectiveness of polygenic scores (PGS) in predicting type 2 diabetes (T2D) risk in diverse populations within US healthcare systems, focusing on patients who may seem low-risk based on their clinical traits.
- - Researchers analyzed data from nearly 15,000 patients over 16 years, exploring how PGS correlates with T2D incidence under different clinical scenarios that included various health metrics and lifestyle factors.
- - Findings indicate that PGS is a significant predictor of T2D risk, identifying individuals at high risk even when clinical evaluations suggest they are low risk, thus highlighting the potential of genetic information in patient assessments.
Article Synopsis
- The study aimed to find genetic risk factors for cardiovascular disease (CVD) in individuals with type 2 diabetes (T2D) through a genome-wide association approach.
- Out of 49,230 T2D participants, 8,956 experienced incident CVD events, revealing three new genetic loci associated with increased CVD risk and confirming five known coronary artery disease variants.
- The findings suggest both novel and established genetic factors contribute to CVD risk in T2D patients, highlighting the importance of genetic screening in this population.
Reduced insulin sensitivity (insulin resistance) is a hallmark of normal physiology in late pregnancy and also underlies gestational diabetes mellitus (GDM). We conducted transcriptomic profiling of 434 human placentas and identified a positive association between insulin-like growth factor binding protein 1 gene (IGFBP1) expression in the placenta and insulin sensitivity at ~26 weeks gestation. Circulating IGFBP1 protein levels rose over the course of pregnancy and declined postpartum, which, together with high gene expression levels in our placenta samples, suggests a placental or decidual source.
View Article and Find Full Text PDFDiabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.
Lancet Reg Health Am
May 2024
Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys.
Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years).
Article Synopsis
- Type 2 diabetes (T2D) has a strong genetic component, and this study examined genetic data from over 1.4 million individuals across diverse populations to identify genetic clusters related to T2D.
- Researchers used 650 T2D-related genetic variants to categorize individuals into 12 genetic clusters associated with different cardiometabolic traits, revealing variations in risk factors across populations including African, East Asian, and European ancestry.
- The findings suggest that T2D risk varies by genetic background, with East Asians needing a lower body mass index (BMI) to have a similar T2D risk as Europeans, highlighting the complexity of genetic factors influencing T2D across different ancestries.
Article Synopsis
- Type 2 diabetes (T2D) is a complex disease influenced by various genetic factors and molecular mechanisms that vary by cell type and ancestry.
- In a large study involving over 2.5 million individuals, researchers identified 1,289 significant genetic associations linked to T2D, including 145 new loci not previously reported.
- The study categorized T2D signals into eight distinct clusters based on their connections to cardiometabolic traits and showed that these genetic profiles are linked to vascular complications, emphasizing the role of obesity-related processes across different ancestry groups.
Article Synopsis
- * A study examined genetic sequences from over 3,000 youth-onset T2D patients, finding specific gene variants and associations related to obesity and diabetes.
- * The research indicates that youth-onset T2D shares genetic factors with adult-onset T2D but shows a higher prevalence of rare variants, suggesting it is a diverse condition that falls between monogenic diabetes and adult-onset T2D.
Background: Insulin resistance (IR) is a major risk factor for Alzheimer's disease (AD) dementia. The mechanisms by which IR predisposes to AD are not well-understood. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus improving our understanding of the biological and regulatory mechanisms linking IR and AD.
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- - The study identified various genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from different populations, not just those of European descent.
- - Researchers found twelve distinct genetic clusters linked to T2D, each associated with unique cardiometabolic traits, and observed differences in polygenic risk scores based on ancestry— notably higher lipodystrophy-related risk in East Asians.
- - T2D risk was shown to be influenced by BMI thresholds, with East Asians needing a lower BMI for equivalent T2D risk compared to Europeans; adjusting for genetic risk revealed significant differences in BMI thresholds between the groups.
Context: Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations.
Objective: We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort.
Article Synopsis
- - The study investigated the link between a type 1 diabetes (T1D) polygenic score and the risk of developing type 2 diabetes (T2D) using large datasets from the CHARGE consortium and MGB Biobank.
- - Researchers found no significant association between the T1D polygenic score and T2D prevalence in both biobanks, although a specific human leukocyte antigen score showed a slight association with T2D in one cohort.
- - While the T1D score had a weak association with insulin use among T2D cases in one dataset, the overall results suggest that a common variant score for T1D does not reliably predict T2D risk, highlighting the need for further studies
We identified genetic subtypes of type 2 diabetes (T2D) by analyzing genetic data from diverse groups, including non-European populations. We implemented soft clustering with 650 T2D-associated genetic variants, capturing known and novel T2D subtypes with distinct cardiometabolic trait associations. The twelve genetic clusters were distinctively enriched for single-cell regulatory regions.
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- A meta-analysis was conducted on data from 51,256 cases and 370,487 controls to identify rare genetic variants linked to type 2 diabetes (T2D), discovering 52 novel variants with significant associations.
- This study highlighted a specific rare missense variant, p.Arg114Trp, that has a strong connection to diabetes risk, influenced by other common genetic risk factors.
- The findings also indicated that a subset of variants previously listed as possible disease-causing mutations might actually be benign, suggesting a need for reevaluation of these genetic markers in relation to T2D.