The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese.</p> <p>Methods</p> <p>Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.</p> <p>Results</p> <p>We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (<it>P </it>< 0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (<it>P </it>< 0.0001 for trend), but not in the obese/overweight group (<it>P </it>= 0.88 for trend).</p> <p>Conclusions</p> <p>Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.</p

Dependency of lactose absorption on lactase activity in starved rats

The effects of starvation on intestinal disaccharidase activities and disaccharide absorption were studied in rats. Adult male rats were starved for either 16 or 72 h and the specific activity of lactase and sucrase was determined together with the absorption of lactose, sucrose, and glucose in vitro by the everted sac technique. The specific activity of lactase was significantly higher and the specific activity of sucrase was lower in the 72-h starved animals when compared with the 16-h starved group. The higher specific lactase activity in the 72-h starved animals was reflected in enhanced absorption of lactose as determined by the transfer of the constituent monosaccharides into the serosal fluid. The transfer of glucose into the serosal fluid by the glucose sac was also higher in the 72-h starved rats but not to the same extent as that of lactose. The absorption of sucrose was not significantly different between the two groups of animals. This study shows that the increase of intestinal lactase activity induced by starvation of adult rats correlates with in vitro increased lactose absorption

The combined effects of genetic variation in the <it>SIRT1</it> gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study

<p>Abstract</p> <p>Background</p> <p>Dyslipidemia due to high total cholesterol, LDL-cholesterol, triglycerides, or low HDL-cholesterol is an important risk factor for coronary heart disease (CHD). Both SIRT1 and PUFAs can influence the expression of genes for nuclear receptors and transcription factors related to lipid metabolism such as LXRα, LXRβ, PPARα, SREBP-1c.</p> <p>Methods</p> <p>A total of 707 Japanese males and 723 females were randomly selected from the participants who visited a medical center for routine medical check-ups. We analyzed the combined effects of the genotype/haplotype of the <it>SIRT1</it> gene and dietary n-6/n-3 PUFA intake ratio on the determination of serum lipid levels.</p> <p>Results</p> <p>We found that the <it>SIRT1</it> gene marked with haplotype 2 was associated with decreased serum LDL-cholesterol and increased HDL-cholesterol levels. In addition, the associations between the <it>SIRT1</it> haplotype 2 and decreased LDL-C and increased HDL-C levels were only observed in the low n-6/n-3 PUFA intake ratio group, but not in the high n-6/n-3 PUFA intake ratio group.</p> <p>Conclusions</p> <p>Our findings indicate that the combination of genetic variation in the <it>SIRT1</it> gene and dietary n-6 and/or n-3 PUFA intake influence the determination of inter-individual variations of serum levels of LDL-C and HDL-C.</p

Bioavailability of isoflavones from soy products in equol producers and non-producers in Japanese women

Background: The estimated intake of soy isoflavones from a meal has been based on the content in a food, but the health effects of soy isoflavones are possibly affected by their bioavailability. In this study we have evaluated the isoflavone bioavailability after the intake of three kinds of soy foods and a commercial soy isoflavone supplement, and examined whether the isoflavone bioavailability is different between equol producers and non-producers. Methods: Healthy female subjects (n = 20; 9 equol producers, 11 equol non-producers) aged between 20 and 26 y participated in this study. To assess the bioavailability of isoflavones, equol producers and non-producers consumed three kinds of soy foods (tofu, fermented soybeans: natto in Japanese, soy milk) and a soy isoflavone supplement containing 75 mg isoflavones together with breakfast. Urine was collected for 24 h, and the amounts of urinary excretions of daidzein, genistein, and the metabolite equol were measured. The intra- and inter-individual variations in the bioavailability of isoflavones were also examined. Results: The bioavailability of daidzein following the consumption of tofu, natto, soy milk, and soy isoflavone supplement were 66.9%, 45.2%, 65.7%, and 57.9%, respectively, and the bioavailability of genistein following the consumption of these soy products were 33.7%, 24.4%, 31.2%, and 17.7%, respectively. The bioavailability of daidzein and genistein was significantly greater in equol non-producers than equol producers, especially following the consumption of soymilk. In the equol producers, the 24 h urinary excretion of equol was significantly greater after the intake of soy isoflavone supplement than after the intake of natto or soymilk. The analysis of relative reliability of intra- and inter-individual variations suggested that bioavailability of isoflavones is less variable following soymilk intake than soy isoflavone supplement. Conclusions: The results in this study suggest that bioavailability of isoflavones are different between equol producers and non-producers, because the 24 h urinary excretion of equol in the equol producers were significantly lower than those in the equol non-producers