Recently, obesity-induced insulin resistance, type 2 diabetes, and cardiovascular disease have become major social problems. We have previously shown that Astaxanthin (AX), which is a natural antioxidant, significantly ameliorates obesity-induced glucose intolerance and insulin resistance. It is well known that AX is a strong lipophilic antioxidant and has been shown to be beneficial for acute inflammation. However, the actual effects of AX on chronic inflammation in adipose tissue (AT) remain unclear. To observe the effects of AX on AT functions in obese mice, we fed six-week-old male C57BL/6J on high-fat-diet (HFD) supplemented with or without 0.02% of AX for 24 weeks. We determined the effect of AX at 10 and 24 weeks of HFD with or without AX on various parameters including insulin sensitivity, glucose tolerance, inflammation, and mitochondrial function in AT. We found that AX significantly reduced oxidative stress and macrophage infiltration into AT, as well as maintaining healthy AT function. Furthermore, AX prevented pathological AT remodeling probably caused by hypoxia in AT. Collectively, AX treatment exerted anti-inflammatory effects via its antioxidant activity in AT, maintained the vascular structure of AT and preserved the stem cells and progenitor’s niche, and enhanced anti-inflammatory hypoxia induction factor-2α-dominant hypoxic response. Through these mechanisms of action, it prevented the pathological remodeling of AT and maintained its integrity.

Objectives. A single-arm prospective study was conducted among Japanese patients with type 2 diabetes having preserved ejection fraction. The aim was to investigate (1) whether liraglutide therapy could improve B-type natriuretic peptide (BNP) levels and diastolic cardiac function assessed by the E -wave to E ′ ratio ( E / E ′ ) using transthoracic echocardiography (TTE), and (2) whether E / E ′ contributed to BNP improvement independent of bodyweight reduction (UMIN000005565). Methods. Patients with type 2 diabetes and left ventricular ejection fraction LVEF ≥ 40 % without heart failure symptoms were enrolled, and daily injection with liraglutide (0.9 mg) was introduced. Cardiac functions were assessed by TTE before and after 26 weeks of liraglutide treatment. Diastolic cardiac function was defined as septal E / E ′ ≥ 13.0 . Results. Thirty-one patients were analyzed. BNP and E / E ′ improved, with BNP levels declining from 36.8 ± 30.5 pg / mL to 26.3 ± 25.9 pg / mL ( p = 0.0014 ) and E / E ′ dropping from 12.7 ± 4.7 to 11.0 ± 3.3 ( p = 0.0376 ). The LVEF showed no significant changes. E / E ′ improved only in patients with E / E ′ ≥ 13.0 . Favorable changes in E / E ′ were canceled when adjusted for body mass index (BMI). Multivariate linear regression analysis revealed that the left ventricular diastolic diameter and ∆ E / E ′ /∆BMI contributed to ∆BNP/baseline BNP ( p = 0.0075 , R 2 = 0.49264 ). Conclusions. Liraglutide had favorable effects on BNP and E / E ′ but not on LVEF. E / E ′ improvement was only seen in patients with diastolic cardiac function. Body weight reduction affected the change of E / E ′ . The BMI-adjusted E / E ′ significantly contributed to the relative change of BNP. GLP-1 analog treatment could be considered a therapeutic option against diabetic diastolic cardiac dysfunction regardless of body weight. This trial is registered with the University Hospital Medical Information Network in Japan, with clinical trial registration number: UMIN000005565.

Aim The objective of the present study was to clarify the association of the type and number of first‐degree family history of diabetes (FHD) with the clinical characteristics, especially with residual β‐cell function, in type 2 diabetic patients (T2D). Material and methods A total of 1131 T2D were recruited and divided into four groups according to FHD information as follows: 1) patients without FHD (FHD‐), 2) those with at least 1 sibling having diabetes without parental diabetes (FHD+), and 3) those with one parent (FHD++) or 4) both parents (FHD+++) having diabetes with or without a diabetic sibling. Result The percentages of FHD‐, FHD+, FHD++, and FHD+++ groups were 49.4%, 13.4%, 34.0%, and 3.2%, respectively. Patients in the FHD++ and FHD+++ groups were significantly younger at the time of diabetes diagnosis (P<0.001) than those in the FHD‐ and FHD+ groups, even after adjusting for confounding factors. In addition, the levels of insulin secretion were significantly lower in the patients in the FHD+, FHD++, and FHD+++ groups than those in the FHD‐ group (P<0.05) after adjusting for confounding factors, and the patients in the FHD+++ group presented with the lowest levels of insulin secretion among the 4 groups. Conclusion Our results showed that in T2D patients, the degree of the associations between FHD and clinical characteristics differs according to the number and the type of FHD. Especially, FHD in both parents is most strongly associated with impaired residual β‐cell function.

Background: Depression has a significant effect on cardiovascular disease (CVD), but uncertainties persist regarding which modifiable risk factors mediate the causal effects. We aim to determine whether depression is causally linked to CVD and which modifiable risk factors play potential mediating roles. Methods: We used a two-sample Mendelian randomization (MR) approach and NHANES 2007–2018 data to estimate the effects of depression on various CVD cases and investigated 28 potential mediators of the association between depression and CVD. Results: The results of our MR analysis indicated that genetically determined depression was associated with increased risk of several CVD, including coronary heart disease (odds ratio (OR) = 1.14; 95% confidence interval (CI): 1.05,1.22), myocardial infarction (OR = 1.19; 95% CI, 1.09,1.31), atrial fibrillation (OR = 1.14; 95% CI, 1.06,1.22), and stroke (OR = 1.13; 95% CI, 1.05,1.22). However, there was no causal association between depression and heart failure. Four out of 28 cardiometabolic risk factors, including hyperlipidemia, hypertension, diabetes, and prescription opioid use, were identified as mediators of the association between depression and various CVDs. Observational association analyses from NHANES data yielded consistent results. Conclusion: Our findings demonstrated that depression has a causal detrimental effect on various CVDs. Four causal mediators (hyperlipidemia, hypertension, diabetes, and prescription opioid use) were screened to explain the causal effect. Implementing targeted management strategies for these risk factors may be warranted to mitigate the public health burden of CVD among individuals with depression.

Aims/Introduction: Fragmented QRS (fQRS) on electrocardiography is a marker of myocardial fibrosis and myocardial scar formation. This study aimed to clarify the relationship of fQRS with diabetes mellitus and metabolic syndrome (MetS) in Japanese patients.Materials and Methods: Approximately 702 individuals who had a routine health checkup at the Hokuriku Health Service Association (Toyama, Japan) in October 2014 were enrolled and categorized into one of the following four groups based on MetS and diabetes mellitus status: with diabetes mellitus (+) MetS+ (164 participants); diabetes mellitus+ without MetS (Mets−; 103 participants); diabetes mellitus− MetS+ (133 participants); and diabetes mellitus− MetS− (302 participants). fQRS was assessed using the results of electrocardiography.Results: The prevalence of fQRS was statistically higher in patients with diabetes mellitus+ MetS+ (37%) and diabetes mellitus+ MetS− (35%), than those with diabetes mellitus− MetS+ (14%) or diabetes mellitus− MetS− (10%; P < 0.0001). Significant differences were observed between the fQRS(+) and fQRS(–) groups for age, sex, waist circumference, heart rate, hypertension, hemoglobin A1c, total cholesterol, MetS and diabetes mellitus. The area under the receiver operating characteristic curve for traditional risk factors and diabetes mellitus was 0.72 (P = 0.0007, 95% confidence interval 0.67–0.76), and for traditional risk factors and MetS it was 0.67 (P = 0.28, 95% confidence interval 0.62–0.72). Patients with diabetes mellitus had more than threefold higher likelihood of showing fQRS (odds ratio 3.41; 95% confidence interval 2.25–5.22; P < 0.0001) compared with the reference group without diabetes mellitus, after adjusting for age, sex, dyslipidemia, hypertension and waist circumference.Conclusions: fQRS was observed more frequently in diabetes mellitus patients than in MetS and control individuals. Diabetes mellitus was the most significant determinant for fQRS among MetS and other traditional metabolic risk factors.

The stable fractions of glycated hemoglobin (Hb), particularly HbA(1c), and glycated albumin (GA) were measured to monitor chronic glycemic control. Haptoglobin (Hp) is a Hb-binding protein, which plays a major role in preventing free Hb-induced tissue oxidative damage. The aim of this study was to clarify the relationships of serum Hp concentration with HbA(1c) and GA concentrations. A cross-sectional study to determine the relationship of serum Hp concentration with GA and HbA(1c) concentrations was conducted. The subjects were 125 Japanese type 2 diabetic patients with stable HbA(1c) levels for more than 3 consecutive months. Patients with altered albumin and red blood cell turnover, which are observed in those with chronic renal failure, liver cirrhosis, and anemia among others, were excluded from the study. Serum Hp concentration positively correlated with HbA(1c) concentration (r=0.30, p<0.001), but not with GA concentration (r=0.15, p=0.10). There was a weak inverse correlation between serum Hp concentration and GA/HbA(1c) ratio (r=-0.19, p=0.03). Moreover, GA /HbA(1c) ratio inversely correlated with body mass index (BMI) (r=-0.31, p<0.001). In contrast, there was no significant correlation between Hb concentration and HbA(1c) (r=0.01, p=0.88) or GA (r=0.12, p=0.21) concentrations. We also analyzed the correlation of serum Hp concentration with GA and HbA(1c) concentrations in patients with the Hp 2-1 and Hp 2-2 genotypes, separately. Hp concentration positively correlated with HbA(1c) concentration in patients with the Hp 2-1 (r=0.32, p=0.03) and Hp 2-2 (r=0.29, p=0.02) phenotypes. Multiple regression analysis revealed that the observed correlation between Hp and HbA(1c) concentrations was significant after adjustment for age, gender, and BMI. In contrast, there was no significant correlation between GA and Hp concentrations in patients with either phenotype. Then, we analyzed how Hp concentration affects GA/HbA(1c) ratio in patients with these Hp phenotypes. There was an inverse correlation between Hp concentration and GA/HbA(1c) ratio in patients with Hp 2-1 (r=-0.44, p=0.003), but not in those with Hp 2-2 (r=-0.03, p=0.75). Multiple regression analysis revealed that the inverse correlation between Hp concentration and GA/HbA(1c) ratio in patients with Hp 2-1 was independent of age, gender, and BMI. Hp phenotype and concentration should be considered in interpreting HbA(1c) and GA levels as glycemic control indicators in diabetic patients. We suggest that in type 2 diabetic patients with Hp 2-1 and high Hp concentrations, HbA(1c) level may be overestimated relative to GA level.