A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia: design, results and future prospects

The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites

Association of sleep duration and insulin resistance in Taiwanese vegetarians

<p>Abstract</p> <p>Background</p> <p>Short sleep duration has been reported to associate with increased insulin resistance. However, no studies have investigated whether such association exists in vegetarians. The aim of this study was to investigate the association between sleep duration and insulin resistance in Taiwanese vegetarians.</p> <p>Methods</p> <p>A total of 1290 individuals were recruited from a regional hospital in south Taiwan during their regular routine physical examination. Only individuals who described themselves as Buddhist vegetarians were included in the study. Demographic information and clinical characteristics were collected and multiple logistic regression analysis was used to evaluate the association between sleep duration and insulin resistance.</p> <p>Results</p> <p>A total of 433 vegetarians were included in the study. Results from univariate logistic regression indicated that insulin resistance was significantly associated with male sex, greater waist circumference, higher triglyceride levels, lower high-density lipoprotein cholesterol levels, higher plasma creatinine levels, higher alanine transaminase levels, greater energy expenditure, and sleep duration of more than 8 hours per night. Multiple logistic regression revealed that insulin resistance was significantly and independently associated with sleep duration of more than 8 hours per night (odd ratios = 2.27, 95% confidence interval = 1.24, 4.11) after adjusting for waist circumference and levels of alanine transaminase.</p> <p>Conclusions</p> <p>Sleep duration of more than 8 hours per night is an independent risk factor associated with increased insulin resistance in vegetarians.</p

Capacidade aeróbia de ratos alimentados com dieta rica em frutose Aerobic capacity of rats fed with fructose rich diet

INTRODUÇÃO: Evidências apontam que a ingestão exacerbada de frutose pode desencadear distúrbios característicos da síndrome metabólica. OBJETIVOS: Analisar os efeitos da ingestão de dieta rica em frutose sobre aspectos metabólicos de ratos da linhagem Wistar. Adicionalmente, verificar a capacidade aeróbia através da identificação da máxima fase estável de lactato (MFEL). MÉTODOS: Dezesseis ratos foram separados em dois grupos de oito animais: a) controle, alimentados com dieta balanceada, e b) frutose, alimentados com dieta rica em frutose. Foram analisadas a tolerância à glicose (área sob a curva de glicose durante teste de tolerância à glicose), sensibilidade à insulina (taxa de remoção da glicose sérica após sobrecarga exógena de insulina), perfil lipídico sérico e concentração de lactato sanguíneo [lac]s durante exercício na intensidade da MFEL. RESULTADOS: Teste t não pareado (p < 0,05) revelou diferença para a tolerância à glicose e triglicérides, porém não houve diferença na sensibilidade à insulina e na [lac]s. Anova one way com post hoc de Newman-Keuls (p < 0,05) revelou diferença para a cinética da glicose durante o teste de tolerância, mas não para a cinética do lactato durante exercício na MSSL. CONCLUSÃO: As Alterações fisiológicas provocadas pela dieta rica em frutose e inerentes à síndrome metabólica não prejudicam a capacidade aeróbia de ratos.<br>INTRODUCTION: Evidence points that exacerbated ingestion of fructose may trigger disturbs characteristic of the metabolic syndrome. OBJECTIVES: To analyze the effects of a fructose rich diet on metabolic aspects of Wistar lineage rats. Additionally, to verify the aerobic capacity, through the identification of the maximal lactate steady state (MSSL). PROCEDURES: Sixteen rats were separated in two groups of eight animals: a) Control, fed a balanced diet, and b) fructose, fed a fructose-rich diet. The glucose tolerance, (area under serum glucose during a glucose tolerance test), insulin sensibility (glucose disappearance rate after exogenous insulin administration), serum lipid profile and blood lactate concentration [lac]b during exercise at MSSL intensity, have been analyzed. RESULTS: Non-paired t test (p<0.05) revealed difference between groups in the area under the curve of glucose and serum triglycerides, no difference in insulin sensibility or in [lac]b was detected, though. One-way ANOVA with Newman Keuls post hoc revealed difference in the glucose kinetics during tolerance test, but not in the lactate kinetics during the MSSL. CONCLUSION: The physiological alterations promoted by fructose-rich diet and intrinsic to the metabolic syndrome do not harm the aerobic capacity of rats