Jordi Merino

Massachusetts General Hospital | MGH · Diabetes Unit, Center for Genomic Medicine

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 part...

OBJECTIVE To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association wi...

Hyperinsulinemia is a complex and heterogeneous phenotype that characterizes molecular alterations that precede the development of type 2 diabetes (T2D). It results from a complex combination of molecular processes, including insulin secretion and insulin sensitivity, that differ between individuals. To better understand the physiology of hyperinsu...

BACKGROUND Type 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular compli...

Few studies have demonstrated reproducible gene–diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient–glycemia relationship...

OBJECTIVE Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity. RESEARCH DESIGN AND METHODS Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T...

Dietary intake is a major contributor to the global obesity epidemic and represents a complex behavioural phenotype that is partially affected by innate biological differences. Here, we present a multivariate genome-wide association analysis of overall variation in dietary intake to account for the correlation between dietary carbohydrate, fat and...

Background: Liver steatosis is considered the onset of the non-alcoholic fatty liver disease (NAFLD), a major public health challenge. Nevertheless, NAFLD detection and diagnosis remain a difficult task. Fatty acid binding protein 4 (FABP4) has been proposed as potential biomarker for the ectopic fat accumulation in non-adipose tissues, although it...

Objective: LDL cholesterol (LDLc)-lowering drugs modestly increase body weight and type 2 diabetes risk, but the extent to which the diabetogenic effect of lowering LDLc is mediated through increased BMI is unknown. Research design and methods: We conducted summary-level univariable and multivariable Mendelian randomization (MR) analyses in 921,...

Background - Carbohydrate responsive element binding protein (ChREBP) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) concentrations. We hypothesized SSB...

Genetics and socioeconomic status (SES) are key drivers of increased type 2 diabetes (T2D) risk, but the extent to which they impact disease in an additive or non-additive manner is unknown. We examined T2D prevalence using cross-sectional electronic health record (EHR) data from 27,771 participants of European ancestry in the Mass General Brigham...

Polygenic scores (PS) of T2D genetic variants based on pathophysiologic mechanisms underlying diabetes have been developed. We investigated whether T2D cluster PS influences response to interventions for diabetes prevention. We examined 2,647 DPP participants with impaired glucose tolerance and genetic data randomized to intensive lifestyle, metfor...

Patients with type 2 diabetes (T2D) are at two-fold increased risk of cardiovascular disease (CVD). CVD is the leading cause of T2D morbidity and mortality. The aim of this study was to identify genetic risk factors associated with incident CVD in patients with T2D. We performed survival genome-wide association study (GWAS) with patients with T2D i...

Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the di...

Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested f...

Objective To investigate whether the genetic burden of type 2 diabetes modifies the association between the quality of dietary fat and the incidence of type 2 diabetes. Design Individual participant data meta-analysis. Data sources Eligible prospective cohort studies were systematically sourced from studies published between January 1970 and Febr...

Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-dia...

Background: Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits. Objectives: The aim of this study w...

Background: The carbohydrate-insulin model of obesity postulates that hyperinsulinemia induces weight gain through increased hunger and lower energy expenditure. We investigated the extent to which genetic risk for hyperinsulinemia associates with energy intake and dietary composition. Methods: We conducted a population-based study of 148,494 unrel...

Dietary intake, a major contributor to the global obesity epidemic, is a complex phenotype partially affected by innate physiological processes. However, previous genome-wide association studies (GWAS) have only implicated a few loci in variability of dietary composition. Here, we present a multi-trait genome-wide association meta-analysis of inter...

Objective: Observational studies show that higher hemoglobin A1c (A1C) predicts coronary artery disease (CAD). It remains unclear whether this association is driven entirely by glycemia. We used Mendelian randomization (MR) to test whether A1C is causally associated with CAD through glycemic and/or nonglycemic factors. Research design and methods...

Aims/hypothesis: Identifying the metabolite profile of individuals with normal fasting glucose (NFG [<5.55 mmol/l]) who progressed to type 2 diabetes may give novel insights into early type 2 diabetes disease interception and detection. Methods: We conducted a population-based prospective study among 1150 Framingham Heart Study Offspring cohort...

Metabolic disorders present a public health challenge of staggering proportions. In diabetes, there is an urgent need to better understand disease heterogeneity, clinical trajectories, and related comorbidities. A pressing and timely question is whether we are ready for precision medicine in diabetes. Some biological insights that have emerged duri...

Background: Type 2 diabetes (T2D) is a complex disease driven by lifestyle and genetic factors. The extent to which dietary fat quality may modify T2D genetic burden on the incidence of T2D is unknown. Methods: We used Cox proportional-hazards models to calculate adjusted hazard ratios (HRs) for T2D among 103,2participants of European descent from...

Suboptimal diets are associated with increased risk of type 2 diabetes, cardiovascular disease and cancer. Genome-wide association studies (GWAS) for individual macronutrients have facilitated the discovery of two relevant loci (FGF-21, FTO), however a single-nutrient approach may preclude the discovery of additional relevant loci. Here, we conduct...

The increasing prevalence in polygenic diseases, such as obesity, cardiovascular disease, and type 2 diabetes, observed over the past few decades is more likely linked to a rapid transition in lifestyle rather than to changes in the sequence of the nuclear genome. In the new era of precision medicine, nutritional genomics holds the promise to be tr...

Type 2 diabetes (T2D) is widespread, affecting the health of hundreds of millions worldwide. The disease results from the complex interplay of lifestyle factors acting on a backdrop of inherited DNA risk variants. Detecting and understanding biomarkers, whether genotypes or other downstream biological features that dictate a person's phenotypic res...

Background Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease. Objective The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data S...

The Mediterranean diet (MedDiet) is actually a lifestyle encompassing nutrition, physical exercise, social companionship, and traditional family celebrations. Diet itself is based on preferential consumption of fruits, vegetables, legumes, oils, cereals, nuts, fish, poultry, eggs, and small amounts of red meat. The pattern involves low ingestion of...

Objective: The rs7903146 T allele in transcription-factor-7-like-2 (TCF7L2) is strongly associated with type 2 diabetes (T2D), but the mechanisms for increased risk remain unclear. We evaluated the physiologic and hormonal effects of TCF7L2 genotype before and after interventions that influence glucose physiology. Research design and methods: We...

Purpose of review: The purpose of this review was to summarize and reflect on advances over the past decade in human genetic and metabolomic discovery with particular focus on their contributions to type 2 diabetes (T2D) risk prediction. Recent findings: In the past 10 years, a combination of advances in genotyping efficiency, metabolomic profil...

Dietary polyphenols come mainly from plant-based foods including fruits, vegetables, whole grains, coffee, tea, and nuts. Polyphenols may influence glycemia and type 2 diabetes (T2D) through different mechanisms, such as promoting the uptake of glucose in tissues, and therefore improving insulin sensitivity. This review aims to summarize the eviden...

Objective: This study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease (CAD) risk separately from the risk conferred by type 2 diabetes as a whole. Research design and methods: We conducted a Mendelian randomization (MR) analysis using summary-level statistics from the largest published meta-analyses...

Background and aim: Clinical data on the role as a lipokine of de novo lipogenesis-derived palmitoleic acid (C16:1n-7cis) in serum non-esterified fatty acids (palmitoleate) are scarce. We aimed to assess whether palmitoleate relates to cardiometabolic risk. Methods and results: In this cross-sectional study we included 358 individuals aged 30-65...

Because it has been suggested that food rich in g-aminobutyric acid (GABA) or angiotensin-converting enzyme inhibitor (ACEI) peptides have beneficial effects on blood pressure (BP) and other cardiovascular risk factors, we tested the effects of low-sodium bread, but rich in potassium, GABA, and ACEI peptides on 24-hour BP, glucose metabolism, and e...

Background: Erectile dysfunction (ED) affects more than 100 million men worldwide, with a wide variability in prevalence. An overall association of cardiovascular risk factors, lifestyle and diet in the context of ED in a Mediterranean population is lacking. Aims: To assess ED prevalence and associated factors in a Mediterranean cohort of non-di...

Circulating FABP4 is strongly associated with metabolic and cardiovascular risk (CVR) and has been proposed as a new risk biomarker. Several FABP4 gene polymorphisms have been associated with protein expression in vitro and metabolic and vascular alterations in vivo. The aim of this study is to evaluate the impact of FABP4 polymorphisms on FABP4 pl...

Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). It is unknown whether decreasing sodium intake to <2300 mg/d has an effect on CVD or all-cause mortality. The objective was to assess whether reductions in sodium intake to <2300 mg/d were associated with either an increased or a decre...

Mounting evidence supports the hypothesis that functional foods containing physiologically-active components may be healthful. Longitudinal cohort studies have shown that some food classes and dietary patterns are beneficial in primary prevention, and this has led to the identification of putative functional foods. This field, however, is at its ve...

Background and Aims Obesity is associated with increased cardiovascular risk. However, the impact of morbid obesity on vascular structure and function is not well understood. This study was designed to appraise subclinical atherosclerosis markers, including carotid intima media thickness (cIMT), endothelial function, and arterial wall stiffness, an...

Abstract Evidence-based medicine (EBM) is the conscientious, explicit and judicious use of current best evidence in making decisions about the care of individual patients. The introduction of EBM was a conceptual and practical milestone in the history of medicine, with far-reaching impact yet to be fully realized. EBM has limitations, including ina...

Raised low-density lipoprotein cholesterol (LDLc) plasma concentration is a major risk factor for atherosclerotic cardiovascular disease. Despite international recommendations on hypercholesterolemia management the percentage of individuals with LDLc plasma concentration above goals according to their global cardiovascular risk remains high, and ad...

Introducción Los niveles moderados de actividad física (AF), 30 min al día de caminar, reducen el riesgo cardiovascular. No existe evidencia si los niveles bajos de actividad física, por debajo de las recomendaciones internacionales, afectan la salud cardiovascular. Objetivo Estudiar el efecto de los niveles bajos de actividad física sobre la salu...

Low carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or metabolic syndrome (MS), their net effect on vascular function remains unclear. Evaluate the relation between dietary macronutrient composition and the small artery reactive hyp...

Introduction: The first line of treatment for hypertriglyceridemic (HTG) includes a well-balanced diet, although the association of dietary components with triglyceride (TG) concentrations in hypertriglyceridemic patients is not fully understood. Objective: To describe the main dietary patterns in a cohort of hypertriglyceridaemic patients and t...

Background and objectiveTo describe clinical and epidemiological characteristics of patients with very high hypertriglyceridemia (HTG) who were attended in lipid units of the Spanish Society of Atherosclerosis (SEA).Patients and methodPatients of the HTG Registry of SEA with at least one triglyceride concentration greater than 1,000 mg/dL (n = 298,...

Objective: Some individuals with cardiovascular risk are unable to achieve even the lower internationally recommended level of physical activity (PA). We aimed to study the impact of a lower-than-advised level of PA on small artery vascular function and oxidative stress in overweight and obese postmenopausal women. Methods: Forty-seven overweigh...

Aim: Our objective was to assess the number of patients with an indication for lipid-lowering therapy according to their non-HDL cholesterol (N-HDL-C) (>130 mg/dL) concentrations despite on-target LDL (≤100 mg/dL) values determined using ultracentrifugation (UC) or direct enzymatic methods (DM). Methods: In 1590 patients we studied the lipid pro...

IntroductionFamilial hypercholesterolemia (FH) is a genetic disease of lipoprotein metabolism conferring a high cardiovascular risk (CVR) to patients. Arterial wall properties and function study are of interest in FH subjects. Arterial stiffness is associated with a higher CVR. The aim of our study was to determine the arterial stiffness in FH pati...

Background: Endothelial dysfunction is a major underlying mechanism for the elevated cardiovascular risk associated with increased body weight. We aimed to assess the impact of weight loss induced by an intensive very-low-calorie diet (VLCD) on arterial wall function in severely obese patients (SOP). Methods: Thirty-four SOP were admitted to the...

Low-carbohydrate diets have become increasingly popular for weight loss. Although they may improve some metabolic markers, particularly in type 2 diabetes mellitus (T2D) or the metabolic syndrome (MS), their net effect on arterial wall function remains unclear. The objective was to evaluate the relation between dietary macronutrient composition and...

IntroductionTherapeutic lifestyle changes (TLSC) reduce CV risk, but the impact on EF is unknown. In this study, we aimed to prospectively assess the effects of TLSC on EF in increased CV risk patients with abdominal obesity (AO).MethodsA hundred and fifty patients with AO at increased CV risk were randomized to groups receiving a one-year interven...

Introduction and objectivesTo analyze the impact of lifestyle changes on adipocyte fatty acid-binding protein (FABP4) plasma levels in patients with cardiovascular risk.MethodsA 1-year prospective study enrolled 140 patients with cardiovascular risk but without previous cardiovascular disease to evaluate the impact of therapeutic lifestyle changes...

Abdominal obesity (AO) is associated with endothelial function (EF) alteration and increased global cardiovascular (CV) risk. Therapeutic lifestyle changes (TLSC) reduce CV risk, but the impact on EF assessed by peripheral artery tonometry (PAT) is unknown. In this study, we aimed to prospectively assess the effects of TLSC on EF measured by PAT in...

To analyze the impact of lifestyle changes on adipocyte fatty acid-binding protein (FABP4) plasma levels in patients with cardiovascular risk. A 1-year prospective study enrolled 140 patients with cardiovascular risk but without previous cardiovascular disease to evaluate the impact of therapeutic lifestyle changes on cardiovascular risk, focusing...

In heterozygous familial hypercholesterolaemic (FH) patients, study of the arterial wall and its function are of particular interest. Arterial stiffness has been shown to be associated with increased cardiovascular risk (CVR). In this study, we examined arterial stiffness in FH patients and its association with biochemical and vascular parameters....

Objective Adipocyte fatty acid binding protein (FABP4) plasma levels are higher in type 2 diabetes (T2D), obesity and metabolic syndrome. Endothelial dysfunction is a common feature in the development of vascular diseases associated with metabolic disturbances. We have investigated the relationship between circulating FABP4 levels and endothelial f...

The use of methods based on reactive hyperaemia of small distal arteries to assess endothelial function (EF) is increasing; however, the mechanisms regulating vascular function in large and small arteries are probably different. We studied the correlations between the hyperaemia reactivity of small peripheral arteries determined by peripheral arter...

Reactive hyperaemia after shear stress is a surrogate marker of endothelial function. However, the mechanisms controlling the dilation capacity of small peripheral resistance arteries are not well characterised. We evaluated reactive hyperaemia by peripheral artery tonometry (PAT) in the acral arteries and studied their clinical and biochemical det...

Background Circulating FABP4 levels have been associated with metabolic alterations and have been considered a predictive biomarker of the development of metabolic syndrome (MS), independently of adiposity and insulin resistance in non-diabetic Asians.

Adipocyte fatty acid-binding protein (FABP4) plasma levels are higher in type 2 diabetes (T2D). Endothelial dysfunction is also common in T2D. We have investigated the relationship between circulating FABP4 levels and endothelial function in diabetic patients. In 257 patients (105 diabetic and 152 non-diabetic) at increased risk of cardiovascular d...

To describe clinical and epidemiological characteristics of patients with very high hypertriglyceridemia (HTG) who were attended in lipid units of the Spanish Society of Atherosclerosis (SEA). Patients of the HTG Registry of SEA with at least one triglyceride concentration greater than 1,000mg/dL (n=298, HTG severe group) and those whose baseline t...