HNF1A gene polymorphisms and cardiovascular risk factors in individuals with late-onset autosomal dominant diabetes: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a genetically heterogeneous disease, hepatocyte nuclear factor-1 homeobox A (<it>HNF1A</it>) single-nucleotide polymorphisms (SNPs) playing a minor role in its pathogenesis. <it>HNF1A </it>is a frequent cause of monogenic diabetes, albeit with early-onset. Some uncommon subgroups like late-onset autosomal dominant diabetes mellitus (LOADDM) may present peculiar inheritance patterns with a stronger familial component. This study aims to investigate the relationship of <it>HNF1A </it>SNPs with cardiovascular risk factors in this group, as well as to characterize them in contrast with classical T2DM (CT2DM).</p> <p>Methods</p> <p>eighteen LOADDM (age at onset > 40 y.o.; diabetes in 3 contiguous generations, uniparental lineage) along with 48 CT2DM patients and 42 normoglycemic controls (N group) have been evaluated for cardiovascular risk factors and SNPs of <it>HNF1A</it>.</p> <p>Results</p> <p>LOADDM showed significantly higher frequencies of SNPs A98V (22.2% vs 2.1%, p = 0.02) and S487N (72.2% vs 43.8%, p = 0.049) of <it>HNF1A </it>compared to CT2DM. I27L did not show significant difference (66.7% vs 45.8%), but associated with lower risk of hypertriglyceridemia (OR 0.16, 95% CI 0.04–0.65, p = 0.01). "Protective effect" was independent from other well-known predictive risk factors for hypertriglyceridemia, such as waist circumference (OR 1.09 per 1 cm increase, p = 0.01) and HDL (OR 0.01 per 1 mmol/l, p = 0.005), after logistic regression.</p> <p>Conclusion</p> <p>Late onset autosomal dominant diabetes mellitus is clinically indistinguishable from classical type 2 diabetes individuals. However, LOADDM group is enriched for common <it>HNF1A </it>polymorphisms A98V and S487N. I27L showed "protective effect" upon hypertriglyceridemia in this sample of individuals, suggesting a role for <it>HNF1A </it>on diabetic individuals' lipid profile. These data contribute to the understanding of the complex interactions between genes, hyperglycemia and cardiovascular risk factors development in type 2 diabetes mellitus.</p

Individuals with prediabetes identified by HbA1c undergoing coronary angiography have worse cardiometabolic profile than those identified by fasting glucose

Background: Type 2 diabetes mellitus has well known deleterious effects on coronary artery disease (CAD). the role of milder hyperglycemic states such as prediabetes (PD) on CAD is debatable. Glycated hemoglobin (HbA1c) has recently been advocated as a diagnostic tool for diabetes mellitus (DM) and PD. This study aims to assess the cardiometabolic risk profile and coronary lesions of patients with PD undergoing coronary angiography identified either by fasting plasma glucose (FPG) or HbA1c levels.Methods: We studied 514 individuals without previously known glucose disturbances. Their glycemic status was assessed by FPG and HbA1c (HPLC) and classified according to ADA guidelines, using each parameter independently, as having normal glucose tolerance (N), PD, or DM. CAD was defined as stenosis greater than 50% in one major coronary vessel or branch. Framingham score was calculated.Results: Subjects with PD had a similar frequency of CAD compared do N individuals by both FPG (61 vs. 59.3%) and HbA1c (55.4 vs 61.2%) (p non-significant for linear-by-linear association). PD individuals identified by FPG had worse HOMA2B (mean [95% CI] 65.4 [60.9-69.9] vs. 76.6 [71.4-81.9]) and HOMA2-IR (1.10 [0.98-1.22] vs. 0.80 [0.72-0.89]) when compared to N controls. PD individuals identified by HbA1c had higher frequency of Framingham risk above 20% (25.4 vs 11.8%), arterial hypertension (87.8 vs 72.6%), and dyslipidemia (83.8 vs 72%) compared to N individuals. PD associated with an increased number of coronary lesions only when diagnosed by HbA1c (median [interquartile interval] 2 [0-4] PD versus 1 [0-3.75] N, p = 0.03 for trend).Conclusions: HbA1c was more effective than FPG in identifying individuals with PD associated with high cardiovascular risk profile in a sample of individuals undergoing coronary angiography.Universidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilUniv Estado Bahia, Dept Ciencias Vida, Colegiado Med, BR-41150000 Salvador, BA, BrazilCtr Endocrinol Estado Bahia CEDEBA, Salvador, BA, BrazilUniversidade Federal de São Paulo, Endocrinol Unit, Diabet Ctr, São Paulo, BrazilWeb of Scienc

The common-866G > A variant in the promoter of UCP2 is associated with decreased risk of coronary artery disease in type 2 diabetic men

OBJECTIVE-Uncoupling protein 2 (UCP2) is a physiological downregulator of reactive oxygen species generation and plays an antiatherogenic role in the vascular wall. A common variant in the UCP2 promoter (-866G>A) modulates mRNA expression, with increased expression associated with the A allele. We investigated association of this variant with coronary artery disease (CAD) in two cohorts of type 2 diabetic subjects.RESEARCH DESIGN and METHODS-We studied 3,122 subjects from the 6-year prospective Non-Insulin-Dependent Diabetes, Hypertension, Microalbuminuria, Cardiovascular Events, and Ramipril (DIABHYCAR) Study (14.9% of CAD incidence at follow-up). An independent, hospital-based cohort of 335 men, 52% of whom had CAD, was also studied.RESULTS-We observed an inverse association of the A allele with incident cases of CAD in a dominant model (hazard risk 0.88 [95% CI 0.80-0.96]; P = 0.006). Similar results were observed for baseline cases of CAD. Stratification by sex confirmed an allelic association with CAD in men, whereas no association was observed in women. All CAD phenotypes considered-myocardial infarction, angina pectoris, coronary artery bypass graft (CABG), and sudden death-contributed significantly to the association. Results were replicated in a cross-sectional study of an independent cohort (odds ratio 0.47 [95% CI 0.25-0.89]; P = 0.02 for a recessive model).CONCLUSIONS-The A allele of the -866G>A variant of UCP2 was associated with reduced risk of CAD in men with type 2 diabetes in a 6-year prospective study. Decreased risk of myocardial infarction, angina pectoris, CABG, and sudden death contributed individually and significantly to the reduction of CAD risk. This association was independent of other common CAD risk factors.INSERM, Fac Med Xavier Bichat, U695, F-75018 Paris, FranceCochin Hosp, AP HP, Dept Immunol & Diabetol, Paris, FranceUniv São Paulo, Lab Cellular & Mol Endocrinol, São Paulo, BrazilUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilFed Fac Fdn Med Sci Porto Alegre, Post Grad Program Med Sci, Porto Alegre, RS, BrazilHop La Pitie Salpetriere, Dept Cardiol, AP HP, Paris, FranceUniv Paris 07, Paris, FranceUniv Paris 05, Paris, FranceUniversidade Federal de São Paulo, Mol Endocrinol Lab, São Paulo, BrazilWeb of Scienc

Association of classical risk factors and coronary artery disease in type 2 diabetic patients submitted to coronary angiography

Background: Coronary artery disease (CAD) is the leading cause of death among individuals with type 2 diabetes (T2DM). T2DM accelerates atherosclerosis alongside classical risk factors such as dyslipidemia and hypertension. This study aims to investigate the association of hyperglycemia and associated risk factors with CAD in outpatients with T2DM undergoing coronary angiography.Methods: 818 individuals referred to coronary angiography were evaluated for glucose disturbances. After exclusion of those with prediabetes, 347 individuals with T2DM and 94 normoglycemic controls were studied for BMI, blood pressure, fasting plasma glucose, HbA1c, lipids, HOMA, adiponectin, Framingham risk score, number of clinically significant coronary lesions (stenosis > 50%).Results: Among T2DM subjects, those with CAD (n = 237) had worse glycemic control (fasting glucose 162.3 + 69.8 vs. 143.4 + 48.9 mg/dL, p = 0.004; HbA1c 8.03 + 1.91 vs. 7.59 + 1.55%, p = 0.03), lower HDL (39.2 + 13.2 vs. 44.4 + 15.9 mg/dL, p = 0.003), and higher triglycerides (140 [106-204] vs. 121 [78.5-184.25] mg/dL, p = 0.002), reached more often therapeutic goals for LDL (63.4% vs. 51.4%, p = 0.037) and less often goals for HDL (26.6% vs. 37.3%, p = 0.04), when compared to CAD-free individuals (n = 110). the same differences were not seen in normoglycemic controls. in T2DM subjects HbA1c tertiles were associated with progressively higher number of significant coronary lesions (median number of lesions 2 [A1c 8.2%]; p = 0.01 for trend).Conclusions: Classic risk factors such as glycemic control and lipid profile were associated with presence of CAD in T2DM subjects undergoing coronary angiography. Glycemic control is progressively associated with number and extent of coronary lesions in patients with T2DM.Universidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilCEDEBA, BR-41820000 Salvador, BA, BrazilUniversidade Federal de São Paulo UNIFESP, Escola Paulista Med, Ctr Diabet, BR-04039002 São Paulo, BrazilWeb of Scienc

Climate Change and Management Impacts on Soybean N Fixation, Soil N Mineralization, N2O Emissions, and Seed Yield

Limited knowledge about how nitrogen (N) dynamics are affected by climate change, weather variability, and crop management is a major barrier to improving the productivity and environmental performance of soybean-based cropping systems. To fill this knowledge gap, we created a systems understanding of agroecosystem N dynamics and quantified the impact of controllable (management) and uncontrollable (weather, climate) factors on N fluxes and soybean yields. We performed a simulation experiment across 10 soybean production environments in the United States using the Agricultural Production Systems sIMulator (APSIM) model and future climate projections from five global circulation models. Climate change (2020–2080) increased N mineralization (24%) and N2O emissions (19%) but decreased N fixation (32%), seed N (20%), and yields (19%). Soil and crop management practices altered N fluxes at a similar magnitude as climate change but in many different directions, revealing opportunities to improve soybean systems’ performance. Among many practices explored, we identified two solutions with great potential: improved residue management (short-term) and water management (long-term). Inter-annual weather variability and management practices affected soybean yield less than N fluxes, which creates opportunities to manage N fluxes without compromising yields, especially in regions with adequate to excess soil moisture. This work provides actionable results (tradeoffs, synergies, directions) to inform decision-making for adapting crop management in a changing climate to improve soybean production systems

Soybean Management for Seed Composition: The Perspective of U.S. Farmers

The soybean [Glycine max (L.) Merr.] compositional quality is mainly provided by the seed concentration of protein and oil. These traits are critical for sustaining global use, and although there is demand for high protein soybean, no mechanism to differentiate production is in place. At the opposite end of the supply chain, farmers are remunerated on a mass basis without having any incentive regarding seed composition. This study evaluated farmers\u27 perspectives and knowledge on soybean quality and their propensity to adopt quality improvement technologies. Farmers from the main U.S. producing regions (n = 271) were investigated with a self-administrated survey containing 21 questions during 2020 and 2021. Our results show that 84% are unaware of the current protein and oil levels from their own production. A small portion (1.4%) make management decisions (e.g., choice of genotypes or monitor quality) based on the implications on seed quality. However, practices already in place are likely to enhance the quality of seed, namely N nutrition (via rhizobia [12.9%] or fertilizer [5.9%]) and late-season crop protection (17.1%). If farmers are financially rewarded by US$0.50 per bushel, a mindset change may occur. Based on these results, we concluded that shifts in the U.S. production system targeting protein or oil markets are possible, and the constraints are mainly related to on-farm management. However, the challenges for improving the U.S. soybean competitiveness in global or niche markets also rely upon other segments of the production chain, specifically breeders, technology suppliers, and logistical structure

Lime application effects on soil aggregate properties: Use of the mean weight diameter and synchrotron-based X-ray mu CT techniques

The hierarchical organization of aggregates in soil is responsible for the presence of inter and intra-aggregate pores. This research aimed to investigate effects of soil surface liming, considering lime rates of 0, 10 and 15 t ha(-1), on the intra-aggregate porous system of soil aggregates with equivalent diameters of 2-4 and 1-2 mm, from 0 to 10 (A) and 10 to 20 cm (B) soil layers. These aggregates were selected by the wet sieving method carried out for determination of the mean weight diameter. Synchrotron-based computed microtomography (mu CT) of aggregates was analyzed in terms of porosity, connectivity, tortuosity, and fractal dimension. Additionally, X-ray fluorescence was used to evaluate the elemental composition of the soil aggregates. All liming effects were concentrated at layer A, where calcium percentage was elevated in aggregates from 1-2 mm class as compared to those from 2-4 mm class. Accordingly, the physical parameters studied were generally more affected in the case of smaller aggregates (1-2 mm). Liming decreased total porosity, increased tortuosity of pores, and decreased fractal dimension for 1-2 mm aggregates, which was in line with the fact that larger pores were replaced by smaller ones in 1-2 mm aggregates, as found via both quantitative and qualitative analyses. On the other hand, liming did not affect pore connectivity under any of the circumstances