Aims/hypothesis Calcium and vitamin D have been implicated in the development of type 2 diabetes, but epidemiological evidence is limited. We examined prospectively the relation of calcium and vitamin D intake to type 2 diabetes risk in a Japanese cohort. Methods Participants were 59,796 middle-aged and older men and women, who participated in the Japan Public Health Center-based Prospective Study and had no history of type 2 diabetes or other serious diseases. Dietary intake of calcium and vitamin D were estimated using a validated food frequency questionnaire. Logistic regression was used to assess the association between intake of these nutrients and self-reported newly diagnosed type 2 diabetes. Results During a 5 year follow-up, 1,114 cases of type 2 diabetes were documented. Overall, calcium intake was not associated with a significantly lower risk of type 2 diabetes; the multivariable odds ratio for the highest vs lowest quartiles was 0.93 (95% CI 0.71-1.22) in men and 0.76 (95% CI 0.56-1.03) in women. However, among participants with a higher vitamin D intake, calcium intake was inversely associated with diabetes risk; the odds ratio for the highest vs lowest intake categories was 0.62 (95% CI 0.41-0.94) in men and 0.59 (95% CI 0.38-0.91) in women. Dairy food intake was significantly associated with a lower risk of type 2 diabetes in women only. Conclusions/interpretation Calcium and vitamin D may not be independently associated with type 2 diabetes risk. Our finding suggesting a joint action of these nutrients against type 2 diabetes warrants further investigation.

Isoflavones have been shown to improve glucose metabolism, but epidemiologic data are limited. We prospectively investigated the relationship between soy product and isoflavone intake and the risk of developing type 2 diabetes among Japanese adults. Participants were 25,872 men and 33,919 women aged 45-75 y, who participated in the second survey of the Japan Public Health Center-Based Prospective Study and had no history of diabetes. Soy product and isoflavone intakes were ascertained using a 147-item FFQ. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over 5 y were estimated using logistic regression analysis. A total of 1114 new cases of type 2 diabetes were self-reported. Intakes of soy products and isoflavones were not significantly associated with type 2 diabetes in either men or all women. However, among overweight women (BMI > or = 25 kg/m(2)), a higher intake of soy products was associated with a lower risk of type 2 diabetes; multivariable-adjusted odds ratios (95% CI) for the lowest through highest quintiles of soy product intake were 1.00 (reference), 0.78 (0.52-1.18), 0.79 (0.52-1.20), 0.62 (0.39-0.99), and 0.89 (0.55-1.44), respectively, and we found a similar risk pattern for daidzein and genistein intakes. Overall, our results suggest that there are no benefits of soy product or isoflavone intake with respect to risk of type 2 diabetes in either men or women. The possible protective associations of soy and isoflavone intakes among overweight women deserves further investigation.

The cytoplasmic regulatory protein p62 (Sequestosome 1/A170) is known to modulate various receptor-mediated intracellular signaling pathways. p62 deficiency was shown to result in mature-onset obesity in mice, but the mechanisms underlying this abnormality remained unclear. Here we report that hyperphagia due to central leptin resistance is the cause of obesity in p62 Ϫ/Ϫ mice. We found that these mice show hyperphagia. Restriction of food to the amount eaten by wild-type mice prevented excess body weight gain and fat accumulation, suggesting that overfeeding is the primary cause of obesity in p62 Ϫ/Ϫ mice. Brain-specific p62 deficiency caused mature-onset obesity to the same extent as in p62 Ϫ/Ϫ mice, further supporting a neuronal mechanism as the major cause of obesity in these mice. Immunohistochemical analysis revealed that p62 is highly expressed in hypothalamic neurons, including POMC neurons in the arcuate nucleus. Central leptin resistance was observed even in young preobese p62 Ϫ/Ϫ mice. We found a defect in intracellular distribution of the transcription factor Stat3, which is essential for the action of leptin, in p62 Ϫ/Ϫ mice. These results indicate that brain p62 plays an important role in bodyweight control by modulating the central leptin-signaling pathway and that lack of p62 in the brain causes leptin resistance, leading to hyperphagia. Thus, p62 could be a clinical target for treating obesity and metabolic syndrome.

This study examined the association between magnesium intake and type II diabetes risk among Japanese adults. Participants were 25 872 men and 33 919 women aged 45-75 years who had no history of diabetes. Magnesium intake was ascertained using a 147-item food frequency questionnaire. Odds ratio of self-reported physician-diagnosed type II diabetes over 5 years was estimated using logistic regression analysis. A total of 1114 new cases of type II diabetes were self-reported. Magnesium intake was not significantly associated with type II diabetes in either men or women. The multivariable-adjusted odds ratios (95% confidence intervals) of type II diabetes for the highest versus lowest quintile of magnesium intake were 0.86 (0.63-1.16) and 0.92 (0.66-1.28) for men and women, respectively. Although a small effect cannot be excluded in men, magnesium intake may not be appreciably associated with risk of type II diabetes for Japanese adults.

Dietary intake of magnesium was associated with a reduced risk of type 2 diabetes in Japanese populations.