The Western pattern diet is rich not only in fat and calories but also in phosphate. The negative effects of excessive fat and calorie intake on health are widely known, but the potential harms of excessive phosphate intake are poorly recognized. Here, we show the mechanism by which dietary phosphate damages the kidney. When phosphate intake was excessive relative to the number of functioning nephrons, circulating levels of FGF23, a hormone that increases the excretion of phosphate per nephron, were increased to maintain phosphate homeostasis. FGF23 suppressed phosphate reabsorption in renal tubules and thus raised the phosphate concentration in the tubule fluid. Once it exceeded a threshold, microscopic particles containing calcium phosphate crystals appeared in the tubule lumen, which damaged tubule cells through binding to the TLR4 expressed on them. Persistent tubule damage induced interstitial fibrosis, reduced the number of nephrons, and further boosted FGF23 to trigger a deterioration spiral leading to progressive nephron loss. In humans, the progression of chronic kidney disease (CKD) ensued when serum FGF23 levels exceeded 53 pg/mL. The present study identified calcium phosphate particles in the renal tubular fluid as an effective therapeutic target to decelerate nephron loss during the course of aging and CKD progression.

A randomized control trial was performed to test whether a lifestyle intervention program, carried out in a primary healthcare setting using existing resources, can reduce the incidence of type 2 diabetes in Japanese with impaired glucose tolerance (IGT). The results of 3 years' intervention are summarized. Through health checkups in communities and workplaces, 304 middle-aged IGT subjects with a mean body mass index (BMI) of 24.5 kg/m² were recruited and randomized to the intervention group or control group. The lifestyle intervention was carried out for 3 years by public health nurses using the curriculum and educational materials provided by the study group. After 1 year, the intervention had significantly improved body weight (-1.5 ± 0.7 vs. -0.7 ± 2.5 kg in the control; p = 0.023) and daily non-exercise leisure time energy expenditure (25 ± 113 vs. -3 ± 98 kcal; p = 0.045). Insulin sensitivity assessed by the Matsuda index was improved by the intervention during the 3 years. The 3-year cumulative incidence tended to be lower in the intervention group (14.8% vs.8.2%, log-rank test: p = 0.097). In a sub-analysis for the subjects with a BMI > 22.5 kg/m², a significant reduction in the cumulative incidence was found (p = 0.027). The present lifestyle intervention program using existing healthcare resources is beneficial in preventing diabetes in Japanese with IGT. This has important implications for primary healthcare-based diabetes prevention. UMIN000003136

Aim: Smoking and adiponectin are individually associated with cardiometabolic pathologies. The present systematic review was carried out in order to summarize the association between the smoking status and circulating adiponectin levels. Methods: Original articles, restricted to epidemiological studies (by a cross-sectional, case-control and cohort study design) and intervention studies for adult humans, were screened for the years 1995-2010. All of the research group members then selected the eligible literature and assessed the articles in a structured systematic review manner. Results: There were 11 key studies, which included 9 articles with a cross-sectional design and 2 articles with an intervention design. Most cross-sectional studies reported lower levels of adiponectin in current smokers than in non/never smokers and/or ex-smokers, while 2 studies reported a non-significant difference in adiponectin between male smokers and non-smokers. The two intervention studies, conducted in patients on 9-week bupropion treatment and 6-month non-pharmacological treatment, reported that smoking cessation increased the adiponectin levels. Conclusion: This review suggests that there is a decreased adiponectin level in current smokers and this reduction can be reversed by quitting smoking. More studies are required to confirm the findings and elucidate the biological mechanisms underlying the association between the smoking status and adiponectin levels.

Purpose: Osteopenia typically presents low bone mineral density (BMD) and has recently been reported as a prognostic factor in various cancers. However, the prognostic value of osteopenia in digestive tract cancers remains to be defined. We aimed to review the prognostic value of preoperative osteopenia in patients with digestive cancers. Methods: Cohort studies evaluating the prognostic value of preoperative osteopenia in digestive cancers (colorectal, esophageal, hepatic, bile duct, and pancreatic cancer) were searched using electronic databases and trial registries. The exposure was defined as low BMD estimated by computed tomography at 11^th thoracic vertebra, while comparator was normal BMD. The primary outcomes were overall survival and recurrence-free survival for osteopenia. Random effect meta-analyses were performed. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to assess the certainty of evidence. Results: A total of 11 studies (2230 patients) were included. Osteopenia was an independent risk factor for overall survival (hazard ratio [HR] = 2.02, 95% CI = 1.47 to 2.78; I² = 74%), along with sarcopenia. Osteopenia also predicted poor recurrence-free survival (HR = 1.96, 95% CI = 1.36 to 2.81; I² = 85%). In subgroup analyses, osteopenia predicted prognosis in colorectal, esophageal, hepatic, and bile duct cancers, but not in pancreatic cancer. The certainty of the evidence was low due to inconsistency and publication bias. Conclusion: Osteopenia may be independently associated with poor prognosis in patients with digestive tract cancer. Further studies are needed to establish the relevance of osteopenia in the operative prognosis of these patients.

Introduction: Helicobacter pylori (H. pylori) infection is positively associated with cardiovascular diseases, but the involvement of lipids in this association remains unclear. The present study reviewed the changes in circulating lipid levels following H. pylori eradication. Methods: A PubMed database was searched until December 2020 to identify randomized control trials (RCTs) and non-RCTs investigating the effect of H. pylori eradication on the lipid levels in inverse variance-weighted, random-effects meta-analyses. Results: A total of 24 studies (four RCTs and 20 non-RCTs) with 5270 participants were identified. The post-eradication levels were increased for high-density lipoprotein cholesterol (HDL-C; mean difference (MD) 2.28 mg/dL, 95% confidence interval (CI) 1.90 to 2.66) and triglyceride (TG; MD 3.22 mg/dL, 95% CI 1.13 to 5.31) compared with the pre-eradication levels. H. pylori eradication resulted in little to no difference in the low-density lipoprotein-cholesterol levels (MD −2.33 mg/dL, 95% CI −4.92 to 0.26). In the analyses of RCTs only, the findings for elevated HDL-C levels, but not TG, were robust. Conclusions: H. pylori eradication increases the HDL-C levels. Further studies are needed to elucidate the effects of lipid changes following H. pylori eradication on cardiovascular diseases.