Association between ANGPTL3, 4, and 8 and lipid and glucose metabolism markers in patients with diabetes.

Lipid management, especially with respect to triglyceride (TG) metabolism, in patients with diabetes is not sufficient with current therapeutic agents, and new approaches for improvement are needed. Members of the angiopoietin-like protein (ANGPTL) family, specifically ANGPTL3, 4, and 8, have been reported as factors that inhibit lipoprotein lipase (LPL) activity and affect TGs. The present study investigated the association between lipid and glucose metabolism markers and the mechanism by which these proteins affect lipid metabolism. A total of 84 patients hospitalized for diabetes treatment were evaluated. Lipid and glucose metabolism markers in blood samples collected before breakfast, on the day after hospitalization, were analyzed. ANGPTL8 showed a significant positive correlation with TG values. HDL-C values displayed a significant positive correlation with ANGPTL3 but a negative correlation with ANGPTL4 and ANGPTL8. The results did not indicate a significant correlation among ANGPTL3, 4, and 8 levels. Thus, it is possible that the distribution of these proteins differs among patients. When patients were divided into groups according to the levels of ANGPTL3 and ANGPTL8, those with high levels of both ANGPTL3 and ANGPTL8 also had high levels of TG and small dense LDL-C/LDL-C (%). Multiple regression analysis indicated that low LPL, high ApoC2, high ApoC3, high ApoE, and high ANGPTL8 levels were the determinants of fasting hypertriglyceridemia. By contrast, no clear association was observed between any of the ANGPTLs and glucose metabolism markers, but ANGPTL8 levels were positively correlated with the levels of HOMA2-IR and BMI. Patients with high levels of both ANGPTL3 and ANGPTL8 had the worst lipid profiles. Among ANGPTL3, 4, and 8, ANGPTL8 is more important as a factor determining plasma TG levels. We anticipate that the results of this research will facilitate potential treatments targeting ANGPTL8 in patients with diabetes.

Relationship between basal sodium intake and the effects of dapagliflozin in albuminuric diabetic kidney disease.

We investigated the impact of basal dietary sodium intake on the dapagliflozin-induced changes in albuminuria and blood pressure (BP) measured at home in patients with diabetic kidney disease (DKD).This was a secondary analysis of the Y-AIDA Study, in which DKD patients with estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine were administered dapagliflozin for 24 weeks, and dapagliflozin significantly improved albuminuria levels and home BP profiles. The effects on UACR, home-measured BP, and eGFR were compared between high- and low-sodium intake groups (HS and LS groups), which were created using baseline urinary sodium-to-creatinine ratio of 84 participants with available basal sodium-to-creatinine ratios. At baseline, clinic-/home-measured BPs, UACR, and eGFR, were comparable in the two groups. After 24 weeks, the reductions from baseline in ln-UACR were comparable in the two groups. In contrast, the reductions in evening home systolic BP and eGFR from baseline were larger in HS than in LS (BP: - 13 ± 2.08 vs. - 6 ± 1.88, P = 0.020; eGFR: - 3.33 ± 1.32 vs. 0.37 ± 1.29, P = 0.049). The home BP-lowering effects of dapagliflozin are larger in HS than LS, concomitant with a larger reduction in eGFR, suggesting a dapagliflozin-induced improvement in glomerular relative hyperfiltration in HS.

Improved home BP profile with dapagliflozin is associated with amelioration of albuminuria in Japanese patients with diabetic nephropathy: the Yokohama add-on inhibitory efficacy of dapagliflozin on albuminuria in Japanese patients with type 2 diabetes study (Y-AIDA study).

BACKGROUND: The Y-AIDA study was designed to investigate the renal- and home blood pressure (BP)-modulating effects of add-on dapagliflozin treatment in Japanese individuals with type 2 diabetes mellitus (T2DM) and albuminuria. METHODS: We conducted a prospective, multicenter, single-arm study. Eighty-six patients with T2DM, HbA1c 7.0-10.0%, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2, and urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine (gCr) were enrolled, and 85 of these patients were administered add-on dapagliflozin for 24 weeks. The primary and key secondary endpoints were change from baseline in the natural logarithm of UACR over 24 weeks and change in home BP profile at week 24. RESULTS: Baseline median UACR was 181.5 mg/gCr (interquartile range 47.85, 638.0). Baseline morning, evening, and nocturnal home systolic/diastolic BP was 137.6/82.7 mmHg, 136.1/79.3 mmHg, and 125.4/74.1 mmHg, respectively. After 24 weeks, the logarithm of UACR decreased by 0.37 ± 0.73 (P < 0.001). In addition, changes in morning, evening, and nocturnal home BP from baseline were as follows: morning systolic/diastolic BP - 8.32 ± 11.42/- 4.18 ± 5.91 mmHg (both P < 0.001), evening systolic/diastolic BP - 9.57 ± 12.08/- 4.48 ± 6.45 mmHg (both P < 0.001), and nocturnal systolic/diastolic BP - 2.38 ± 7.82/- 1.17 ± 5.39 mmHg (P = 0.0079 for systolic BP, P = 0.0415 for diastolic BP). Furthermore, the reduction in UACR after 24 weeks significantly correlated with an improvement in home BP profile, but not with changes in other variables, including office BP. Multivariate linear regression analysis also revealed that the change in morning home systolic BP was a significant contributor to the change in log-UACR. CONCLUSIONS: In Japanese patients with T2DM and diabetic nephropathy, dapagliflozin significantly improved albuminuria levels and the home BP profile. Improved morning home systolic BP was associated with albuminuria reduction. Trial registration The study is registered at the UMIN Clinical Trials Registry (UMIN000018930; http://www.umin.ac.jp/ctr/index-j.htm ). The study was conducted from July 1, 2015 to August 1, 2018.

Cancer Prevalence in Aichi, Japan for 2012: Estimates Based on Incidence and Survival Data from Population-Based Cancer Registry

Background: Cancer is the leading cause of death among both men and women in Japan. Monitoring cancer prevalence is important because prevalence data play a critical role in the development and implementation of health policy. We estimated cancer prevalence in 2012 based on cancer incidence and 5-year survival rate in Aichi Prefecture using data from a population-based cancer registry, the Aichi Cancer Registry, which covers 7.4 million people. Methods: The annual number of incident cases between 2008 and 2012 was used. Survival data of patients diagnosed in 2006­2008 and followed up until the end of 2012 were selected for survival analysis. Cancer prevalence was estimated from incidence and year-specific survival probabilities. Cancer prevalence was stratified by sex, cancer site (25 major cancers), and age group at diagnosis. Results: The estimated prevalence for all cancers in 2012 was 68,013 cases among men, 52,490 cases among women, with 120,503 cases for both sexes. Colorectal cancer was the most incident cancer with 6,654 cases, accounting for 16.0% of overall incident cases, followed by stomach cancer with 5,749 cases (13.8%) and lung cancer with 5,593 cases (13.4%). Prostate cancer was the most prevalent among men, accounting for 21.5%, followed by colorectal and stomach cancers. Breast cancer was the most prevalent among women, accounting for 28.6%, followed by colorectal, stomach, and uterine cancers. Conclusion: This study provides cancer prevalence data that could serve as useful essential information for local governments in cancer management, to carry out more practical and reasonable countermeasures for cancer.

The Effects of Bazedoxifene on Bone, Glucose, and Lipid Metabolism in Postmenopausal Women With Type 2 Diabetes: An Exploratory Pilot Study.

BACKGROUND: Selective estrogen receptor modulators (SERMs) decrease homocysteine and cross-linking of pentosidine and reduce low-density lipoprotein cholesterol (LDL-C), and they are expected to improve bone quality and atherosclerosis. Therefore, the potential effects of bazedoxifene on bone (bone resorption, bone formation, and bone quality), as well as on glucose and lipid metabolism markers, were examined in Japanese postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: Eligible patients received 20 mg of bazedoxifene tablets once daily and were followed up for 12 weeks. Bone resorption markers including tartrate-resistant acid phosphatase 5b (TRACP-5b), bone formation markers and bone quality markers such as homocysteine and serum pentosidine, total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and HbA1c were all measured. RESULTS: Twenty patients completed this study. All bone resorption markers decreased significantly 4 weeks after bazedoxifene treatment. In particular, TRACP-5b decreased significantly at 12 weeks (median percent change: -20.6%), and the minimum significant change (MSC) achievement rate of TRACP-5b was 65%. Bazedoxifene also decreased bone formation markers. However, bazedoxifene did not improve bone quality markers. LDL-C, HDL-C, and non-HDL-C were decreased, but TG was unchanged. Glucose metabolism was not changed after bazedoxifene treatment. In a subgroup analysis, the group of patients in whom the percent change in TRACP-5b exceeded the MSC had no change in pentosidine levels at 12 weeks. However, in the group of patients in whom the percent change in TRACP-5b did not exceed the MSC, pentosidine levels tended to increase. CONCLUSIONS: Bazedoxifene may improve bone resorption markers and LDL-C without affecting glucose metabolism in Japanese postmenopausal women with T2DM.

Metabolic factors accelerate colorectal adenoma recurrence.

BACKGROUND: Metabolic factors have been reported to increase the prevalence of colorectal adenomas, however, whether metabolic factors might also accelerate the recurrence after removal of adenomas has not yet been discussed. In this retrospective multicenter study, we clarified the risk factors for adenoma recurrence focusing on metabolic factors. METHODS: We analyzed the medical records of 43,195 patients who had undergone colonoscopy between January 2005 and December 2011 at 5 hospitals in Japan. Of these, the data of 1111 patients who had undergone removal of adenomas at the first screening colonoscopy, and then been followed up by colonoscopy 1 year and 2 years later were analyzed. RESULTS: The following 8 factors were demonstrated with a multivariate analysis as being associated with colorectal adenomas recurrence: for adenoma-related factors, 5 factors (villous features, grade of dysplasia, location and size of the largest removed adenoma, and number of the removed adenomas) were identified; for metabolic factors and other factors, 3 factors (age, body mass index (BMI), and fasting blood glucose (FBG)) were identified. A risk score (0-10 points) was developed based on these 8 factors. The risk of adenoma recurrence increased as the risk score increased. When the risk score was ≥3 (3-10) points, the odds ratio relative to <3 (0-2) points was 7.07 (95% CIs 5.30-9.43). CONCLUSIONS: In addition to adenoma-related factors (villous features, grade of dysplasia, location, size and number), 3 factors (age, BMI and FBG) were demonstrated to influence the recurrence rate of colorectal adenoma. When the risk score was ≥3, the risk of recurrence was significantly elevated.

Relationship between coronary artery disease and retinopathy in patients with type 2 diabetes mellitus.

OBJECTIVE: To examine risk factors for coronary artery disease (CAD) and retinopathy in patients with type 2 diabetes mellitus (DM) and assess the relationship between CAD and retinopathy. METHODS: A total of 1,003 outpatients with type 2 DM (578 men and 425 women) were classified into two groups according to the presence (based on ischemic findings on a resting electrocardiogram or a history of angina or myocardial infarction) or absence of CAD and four retinopathy stages based on the International Clinical Classification of Diabetic Retinopathy. RESULTS: Stepwise multiple regression analyses showed that independent risk factors for CAD were age, the triglyceride (TG) level and smoking, while those for retinopathy included age, age of DM diagnosis, the HbA1c level and a female gender. The prevalence of CAD increased in association with the progression of retinopathy (p<0.01). CONCLUSION: Since it is difficult to distinguish macrovascular and microvascular diseases, diabetic vascular disorders require comprehensive approaches to assessment and treatment.

Risk factors for first acute myocardial infarction attack assessed by cardiovascular disease registry data in Aichi Prefecture.

Recently, in Western countries, metabolic syndrome as well as such classical risk factors as hypertension and smoking has been considered to be closely associated with the occurrence of acute myocardial infarction (AMI). Therefore, we conducted a case-control study to investigate how the co-morbidity of obesity or thinness with hypertension, hyperlipidemia and diabetes mellitus would affect AMI occurrence among Japanese aged 30 to 69. Cases were comprised of 788 patients (590 men and 198 women) registered in the "Aichi Prefecture Cardiovascular Disease Registry Program" during hospitalization due to their first AMI attack. Controls were 2,300 randomly sampled inhabitants (1,142 men and 1,158 women) who responded to the questionnaire survey on lifestyle. We decided BMI < 18.5 as thin, 18.5 < or = BMI < 25.0 as normal, and BMI > or = 25.0 as obese, then divided subjects into six groups according to the presence or absence of histories of the above-mentioned three diseases in connection with their physique. In both sexes, multivariately adjusted odds ratios of first AMI attacks were much higher in groups with such histories (men, 4.14 to approximately 5.07; women, 5.62 to approximately 15.24) than in those without them (men, 0.90 to approximately 1.13; women, 1.54 to approximately 3.03) regardless of physique. Only in women, obesity uncombined with histories was significantly associated with AMI occurrence and not obesity but thinness intensified the association between histories and AMI. Among the six groups, population attributable risk percent was highest in the normal physique group with histories. It was suggested that persons with disease histories should be carefully treated irrespective of the presence or absence of obesity.