Transition from pre-diabetes to diabetes and predictors of risk in Mexican-Americans

Background: No studies have examined risk factors for the transition from pre-diabetes to diabetes in populations with widespread obesity and diabetes. We determined proximal changes and factors affecting the transition among Mexican-Americans with pre-diabetes. Methods: Participants with pre-diabetes (n=285) were recruited from our randomly sampled population-based Cameron County Hispanic Cohort. These participants were followed for an average of 27 months with repeat examination every 3 to 4 months. Metabolic health was defined as having less than 2 metabolic abnormalities (e.g., hypertension, elevated low-density lipoprotein, etc). Diabetes was identified as fasting blood glucose ≥126 mg/dL, glycated hemoglobin ≥6.5% and/or on hypoglycemic medication. Results: Ninety-six of 285 (33.7%) participants transitioned to overt diabetes. The increased risk of diabetes in the metabolically unhealthy varying with follow-up time was 81% (adjusted odds ratio [OR]: 1.81; 95% CI: 1.09–3.02). The risk of diabetes increased 8% for each kg/m2 of increase in body mass index (BMI, OR: 1.08; 95% CI: 1.05–1.11) independent of covariates. Transition to diabetes was accompanied by a mean increase in BMI of 0.28 kg/m2, and deterioration in metabolic health of 9% (OR: 1.09; 95% CI: 1.003–1.18) compared with those who did not transition. Conclusions: Deteriorating metabolic health and/or increasing BMI significantly raises the risk of transitioning from pre-diabetes to diabetes. Transition itself was accompanied by further increase in BMI and deterioration in metabolic health. These data underline the importance of improving metabolic health and avoiding weight gain in pre-diabetes as simple but clear diabetes prevention targets, and emphasize the importance of lifestyle management

Depression in Mexican Americans with Diagnosed and Undiagnosed Diabetes

Background: Depression and diabetes commonly co-occur; however, the strength of the physiological effects of diabetes as mediating factors towards depression is uncertain. Method: We analyzed extensive clinical, epidemiological and laboratory data from n = 2081 Mexican Americans aged 35-64 years, recruited from the community as part of the Cameron County Hispanic Cohort (CCHC) divided into three groups: Diagnosed (self-reported) diabetes (DD, n = 335), Undiagnosed diabetes (UD, n = 227) and No diabetes (ND, n = 1519). UD participants denied being diagnosed with diabetes, but on testing met the 2010 American Diabetes Association and World Health Organization definitions of diabetes. Depression was measured using the Center for Epidemiological Studies - Depression (CES-D) scale. Weighted data were analyzed using dimensional and categorical outcomes using univariate and multivariate models. Results: The DD group had significantly higher CES-D scores than both the ND and UD (p ⩽ 0.001) groups, whereas the ND and UD groups did not significantly differ from each other. The DD subjects were more likely to meet the CES-D cut-off score for depression compared to both the ND and UD groups (p = 0.001), respectively. The UD group was also less likely to meet the cut-off score for depression than the ND group (p = 0.003). Our main findings remained significant in models that controlled for socio-demographic and clinical confounders. Conclusions: Meeting clinical criteria for diabetes was not sufficient for increased depressive symptoms. Our findings suggest that the \u27knowing that one is ill\u27 is associated with depressive symptoms in diabetic subjects

Depression, Obesity, and Metabolic Syndrome: Prevalence and Risks of Comorbidity in a Population-Based Study of Mexican Americans

Introduction: We examined the prevalence of depression, obesity, and metabolic syndrome and associations between them in a population-based representative cohort of Mexican Americans living on the United States-Mexico border. Method: The sample in this cross-sectional analysis consisted of 1,768 Mexican American adults (≥ 18 years of age) assessed between the years 2004 and 2010, with whom we tested our central hypothesis of a significant relationship between obesity and depression. Depression was measured using the Center for Epidemiologic Studies-Depression scale (CES-D) with a cutoff score of ≥ 16 for depression and a cutoff score of ≥ 27 for severe depression. We categorized body mass index (BMI) values as obese (≥ 30kg/m(2)) and later subdivided the obese subjects into obese (30-39 kg/m(2)[inclusive]) and morbidly obese (≥ 40 kg/m(2)). Metabolic syndrome was defined using the American Heart Association definition requiring at least 3 of the following: increased waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL) cholesterol, elevated blood pressure, and elevated fasting glucose. Weighted data were analyzed to establish prevalence of depression, obesity, and metabolic syndrome. Univariate and multivariable weighted regression models were used to test potential associations between these disorders. Results: Using weighted prevalence, we observed high rates of depression (30%), obesity (52%), and metabolic syndrome (45%). Univariate models revealed female gender (P = .0004), low education (P = .003), low HDL level (P = .009), and increased waist circumference (P = .03) were associated with depression. Female gender (P = .01), low education (P = .003), and morbid obesity (P = .002) were risk factors for severe depression and remained significant in multivariable models. Conclusions: In this large cohort of Mexican Americans, obesity, female gender, and low education were identified risk factors for depression. These indicators may serve as targets for early detection, prevention, and intervention in this population

Effects of Atmospheric CO2 Level on the Metabolic Response of Resistant and Susceptible Wheat to Fusarium graminearum Infection.

Rising atmospheric CO2 concentrations and associated climate changes are thought to have contributed to the steady increase of Fusarium head blight (FHB) on wheat. However, our understanding of precisely how elevated CO2 influences the defense response of wheat against Fusarium graminearum remains limited. In this study, we evaluated the metabolic profiles of susceptible (Norm) and moderately resistant (Alsen) spring wheat in response to whole-head inoculation with two deoxynivalenol (DON)-producing F. graminearum isolates (DON+), isolates 9F1 and Gz3639, and a DON-deficient (DON−) isolate (Gzt40) at ambient (400 ppm) and elevated (800 ppm) CO2 concentrations. The effects of elevated CO2 were dependent on both the Fusarium strain and the wheat variety, but metabolic differences in the host can explain the observed changes in F. graminearum biomass and DON accumulation. The complexity of abiotic and biotic stress interactions makes it difficult to determine if the observed metabolic changes in wheat are a result of CO2-induced changes in the host, the pathogen, or a combination of both. However, the effects of elevated CO2 were not dependent on DON production. Finally, we identified several metabolic biomarkers for wheat that can reliably predict FHB resistance or susceptibility, even as atmospheric CO2 levels rise

Involvement of Trichoderma Trichothecenes in the Biocontrol Activity and Induction of Plant Defense-Related Genes

[EN] Trichoderma species produce trichothecenes, most notably trichodermin and harzianum A (HA), by a biosynthetic pathway in which several of the involved proteins have significant differences in functionality compared to their Fusarium orthologues. In addition, the genes encoding these proteins show a genomic organization differing from that of the Fusarium tri clusters. Here we describe the isolation of Trichoderma arundinaceum IBT 40837 transformants which have a disrupted or silenced tri4 gene, a gene encoding a cytochrome P450 monooxygenase that oxygenates trichodiene to give rise to isotrichodiol, and the effect of tri4 gene disruption and silencing on the expression of other tri genes. Our results indicate that the tri4 gene disruption resulted in a reduced antifungal activity against Botrytis cinerea and Rhizoctonia solani and also in a reduced ability to induce the expression of tomato plant defense-related genes belonging to the salicylic acid (SA) and jasmonate (JA) pathways against B. cinerea, in comparison to the wild-type strain, indicating that HA plays an important function in the sensitization of Trichoderma-pretreated plants against this fungal pathogen. Additionally, the effect of the interaction of T. arundinaceum with B. cinerea or R. solani and with tomato seedlings on the expressions of the tri genes was studiedSIResearch project funding was obtained from Junta de Castilla y León (GR67) and the Spanish Ministry of Science and Innovation (AGL2006-05660, AGL2009-13431-C01, and AGL2009-13431-C02). M. G. Malmierca was granted an FPU fellowship by the Spanish Ministry of Science and Innovation (AP2007-02835

Requirement of Two Acyltransferases for 4-O-Acylation during Biosynthesis of Harzianum A, an Antifungal Trichothecene Produced by Trichoderma arundinaceum

Trichothecenes are sesquiterpenoid toxins produced by multiple fungi, including plant pathogens, entomopathogens, and saprotrophs. Most of these fungi have the acyltransferase-encoding gene tri18. Even though its function has not been determined, tri18 is predicted to be involved in trichothecene biosynthesis because of its pattern of expression and its location near other trichothecene biosynthetic genes. Here, molecular genetic, precursor feeding, and analytical chemistry experiments indicate that in the saprotroph Trichoderma arundinaceum the tri18-encoded acyltransferase (TRI18) and a previously characterized acyltransferase (TRI3) are required for conversion of the trichothecene biosynthetic intermediate trichodermol to harzianum A, an antifungal trichothecene analog with an octa-2,4,6-trienedioyl acyl group. On the basis of the results, we propose that TRI3 catalyzes trichothecene 4-O-acetylation, and subsequently, TRI18 catalyzes replacement of the resulting acetyl group with octa-2,4,6-trienedioyl to form harzianum A. Thus, the findings provide evidence for a previously unrecognized two-step acylation process during trichothecene biosynthesis in T. arundinaceum and possibly other fungiSIThe Spanish Ministry of Economy and Competitiveness supported this work (MINECO-AGL2015-70671-C2-2-R to S.G.), and the University of León granted L.L. a fellowshi

Analysis of substrate specificity of cytochrome P450 monooxygenases involved in trichothecene toxin biosynthesis

[EN]Trichothecenes are a structurally diverse family of toxic secondary metabolites produced by certain species of multiple fungal genera. All trichothecene analogs share a core 12,13-epoxytrichothec-9-ene (EPT) structure but differ in presence, absence and types of substituents attached to various positions of EPT. Formation of some of the structural diversity begins early in the biosynthetic pathway such that some producing species have few trichothecene biosynthetic intermediates in common. Cytochrome P450 monooxygenases (P450s) play critical roles in formation of trichothecene structural diversity. Within some species, relaxed substrate specificities of P450s allow individual orthologs of the enzymes to modify multiple trichothecene biosynthetic intermediates. It is not clear, however, whether the relaxed specificity extends to biosynthetic intermediates that are not produced by the species in which the orthologs originate. To address this knowledge gap, we used a mutant complementation-heterologous expression analysis to assess whether orthologs of three trichothecene biosynthetic P450s (TRI11, TRI13 and TRI22) from Fusarium sporotrichioides, Trichoderma arundinaceum, and Paramyrothecium roridum can modify trichothecene biosynthetic intermediates that they do not encounter in the organism in which they originated. The results indicate that TRI13 and TRI22 could not modify the intermediates that they do not normally encounter, whereas TRI11 could modify an intermediate that it does not normally encounter. These findings indicate that substrate promiscuity varies among trichothecene biosynthetic P450s. One structural feature that likely impacts the ability of the P450s to use biosynthetic intermediates as substrates is the presence and absence of an oxygen atom attached to carbon atom 3 of EPT.SIOpen Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Challenges and strategies for recruitment of minorities to clinical research and trials

Minority populations are largely absent from clinical research trials. The neglect of these populations has become increasingly apparent, with escalating cancer burdens and chronic disease. The challenges to recruitment of minorities in the United States are multiple including trust or lack thereof. Keys to successful recruitment are responding to community issues, its history, beliefs, and its social and economic pressures. The strategy we have used in many low-income, sometimes remote, communities is to recruit staff from the same community and train them in the required basic research methods. They are the first line of communication. After our arrival in the Texas Rio Grande Valley in 2001, we applied these principles learned over years of global research, to studies of chronic diseases. Beginning in 2004, we recruited and trained a team of local women who enrolled in a cohort of over five thousand Mexican Americans from randomly selected households. This cohort is being followed, and the team has remained, acquiring not only advanced skills (ultrasound, FibroScan, retinal photos, measures of cognition, etc.) but capacity to derive key health information. Currently, we are participating in multiple funded studies, including an NIH clinical trial, liver disease, obesity, and diabetes using multiomics aimed at developing precision medicine approaches to chronic disease prevention and treatment

Effects of Trichothecene Production on the Plant Defense Response and Fungal Physiology: Overexpression of the Trichoderma arundinaceum tri4 Gene in T. harzianum

[EN] Trichothecenes are fungal sesquiterpenoid compounds, the majority of which have phytotoxic activity. They contaminate food and feed stocks, resulting in potential harm to animals and human beings. Trichoderma brevicompactum and T. arundinaceum produce trichodermin and harzianum A (HA), respectively, two trichothecenes that show different bioactive properties. Both compounds have remarkable antibiotic and cytotoxic activities, but in addition, trichodermin is highly phytotoxic, whileHAlacks this activity when analyzed in vivo. Analysis of Fusarium trichothecene intermediates led to the conclusion that most of them, with the exception of the hydrocarbon precursor trichodiene (TD), have a detectable phytotoxic activity which is not directly related to the structural complexity of the intermediate. In the present work, theHAintermediate 12,13-epoxytrichothec-9-ene (EPT) was produced by expression of the T. arundinaceum tri4 gene in a transgenic T. harzianum strain that already produces TD after transformation with the T. arundinaceum tri5 gene. Purified EPT did not show antifungal or phytotoxic activity, while purified HA showed both antifungal and phytotoxic activities. However, the use of the transgenic T. harzianum tri4 strain induced a downregulation of defense-related genes in tomato plants and also downregulated plant genes involved in fungal root colonization. The production of EPT by the transgenic tri4 strain raised levels of erg1 expression and reduced squalene accumulation while not affecting levels of ergosterol. Together, these results indicate the complex interactions among trichothecene intermediates, fungal antagonists, and host plantsSIThis research was supported by grants from MICINN and MINECO (grants AGL2009-13431-C02 and AGL2012-40041-C02-02) and from the Junta de Castilla y León (grant LE125A12-2). M. G. Malmierca was granted an FPU fellowship by the Spanish Ministry of Science and Innovation (grant AP2007-02835