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Background There is a high incidence of type 2 diabetes in Asian adults, even those with a normal body mass index (BMI) (23 kg/m2) at middle age is a risk factor for type 2 diabetes in Asians. In this historical cohort study, we investigated whether a slightly increased BMI at college age was also a risk factor for future diabetes in Japanese men. Methods Six hundred and sixty-one male alumni who graduated from a physical education school between 1971 and 1991 and who responded to follow-up investigation between 2007 and 2017 were included in this study. Participants were categorized into four categories: college BMI of

Background Hypertension is developed easily in Asian adults with normal body mass index (BMI) (~23 kg/m2), compared with other ethnicities with similar BMI. This study tested the hypothesis that slightly increased BMI at young age is a risk factor for future hypertension in Japanese men by historical cohort study. Methods The study participants were 636 male alumni of the physical education school. They had available data on their physical examination at college age and follow-up investigation between 2007 and 2011. The participants were categorized into six categories: BMI at college age of

The molecular clock of neutral mutations, which represents linear mutation fixation over generations, is theoretically explained by genetic drift in fitness-steady evolution or hitchhiking in adaptive evolution. The present study is the first experimental demonstration for the molecular clock of neutral mutations in a fitness-increasing evolutionary process. The dynamics of genome mutation fixation in the thermal adaptive evolution of Escherichia coli were evaluated in a prolonged evolution experiment in duplicated lineages. The cells from the continuously fitness-increasing evolutionary process were subjected to genome sequencing and analyzed at both the population and single-colony levels. Although the dynamics of genome mutation fixation were complicated by the combination of the stochastic appearance of adaptive mutations and clonal interference, the mutation fixation in the population was simply linear over generations. Each genome in the population accumulated 1.6 synonymous and 3.1 non-synonymous neutral mutations, on average, by the spontaneous mutation accumulation rate, while only a single genome in the population occasionally acquired an adaptive mutation. The neutral mutations that preexisted on the single genome hitchhiked on the domination of the adaptive mutation. The successive fixation processes of the 128 mutations demonstrated that hitchhiking and not genetic drift were responsible for the coincidence of the spontaneous mutation accumulation rate in the genome with the fixation rate of neutral mutations in the population. The molecular clock of neutral mutations to the fitness-increasing evolution suggests that the numerous neutral mutations observed in molecular phylogenetic trees may not always have been fixed in fitness-steady evolution but in adaptive evolution., Author Summary Mutations that have little influence on biological function are referred to as neutral mutations and frequently appear in molecular phylogenetic analyses. The fixation of neutral mutations in populations has been attributed to genetic drift in fitness-steady evolutionary processes or hitchhiking in adaptive evolution. We examined the fitness-increasing evolution of Escherichia coli for thermal adaptation to observe the fixation dynamics of genome-wide mutations. In the adaptive evolution, all genomes in the population equally accumulated neutral mutations by replication errors. The infrequent occurrence of an adaptive mutation on one of the genomes by chance resulted in the fixation of the neutral mutations that had pre-accumulated in the same genome by hitchhiking. Via successive hitchhiking events, the neutral mutations were fixed in the population linearly over generations at the same rate as the spontaneous mutation accumulation rate in the genome. The molecular clock of neutral mutations thus functions even in adaptive evolution. The evolutionary period characterized by the accumulation of numerous neutral mutations observed in molecular phylogenetic trees may not be specific to neutral evolution but may occur in adaptive evolution as well.

Introduction While individuals tend to show accumulation of certain lifestyle patterns, the effect of such patterns in real daily life on cardio-renal—metabolic parameters remains largely unknown. This study aimed to assess clustering of lifestyle patterns and investigate the relationships between such patterns and cardio-renal-metabolic parameters. Participants and methods The study participants were 726 Japanese type 2 diabetes mellitus (T2DM) outpatients free of history of cardiovascular diseases. The relationship between lifestyle patterns and cardio-renal-metabolic parameters was investigated by linear and logistic regression analyses. Results Factor analysis identified three lifestyle patterns. Subjects characterized by evening type, poor sleep quality and depressive status (type 1 pattern) had high levels of HbA1c, alanine aminotransferase and albuminuria. Subjects characterized by high consumption of food, alcohol and cigarettes (type 2 pattern) had high levels of γ-glutamyl transpeptidase, triglycerides, HDL-cholesterol, blood pressure, and brachial-ankle pulse wave velocity. Subjects characterized by high physical activity (type 3 pattern) had low uric acid and mild elevation of alanine aminotransferase and aspartate aminotransferase. In multivariate regression analysis adjusted by age, gender and BMI, type 1 pattern was associated with higher HbA1c levels, systolic BP and brachial-ankle pulse wave velocity. Type 2 pattern was associated with higher HDL-cholesterol levels, triglycerides, aspartate aminotransferase, ɤ- glutamyl transpeptidase levels, and diastolic BP. Conclusions The study identified three lifestyle patterns that were associated with distinct cardio-metabolic-renal parameters in T2DM patients. Trial registration UMIN000010932