Introduction
Both body mass index (BMI) and waist circumference (WC) are associated with diabetes risk, and the difference between them in predictive ability for diabetes is still contentious. We ...conducted a population-based study to investigate and compare the association of them with diabetes by sex.
Methods
This study included a total of 4754 subjects aged 40–80 years with no diabetes at baseline between 2008 and 2017. Using multivariate Cox proportional hazards models, we calculated hazard ratios for diabetes according to tertiles of BMI or WC. Harrell's
C
statistics was applied to assess and compare the predictive ability of the models using BMI and WC.
Results
Both BMI and WC showed the significant positive trends with diabetes risk. In men, the extreme tertiles (BMI > 25.1 kg/m
2
and WC > 88.0 cm) provided 1.58-fold or 2.04-fold higher risk compared with the first tertiles (< 22.6 kg/m
2
and < 81.2 cm). In women, BMI > 24.4 kg/m
2
showed 3.28-fold higher risk than the first tertile (< 21.6 kg/m
2
), whereas WC ≥ 78.2 cm was more than twice as likely to suffer from diabetes as WC < 78.2 cm. BMI and WC showed a comparative performance in predicting diabetes in both sexes (
P
value 0.447 in men, and 0.337 in women).
Conclusion
Both BMI and WC showed a positive association with diabetes and offered a comparative predictive performance for diabetes in both sexes. The cut-off points, BMI 25.1 kg/m
2
and WC 88.0 cm in men and BMI 24.4 kg/m
2
and WC 78.2 cm in women, might contribute to the effective prevention strategies for diabetes.
Many studies have shown the feasibility of in vivo cardiac transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in animal experiments. However, nano-structural ...confirmation of the successful incorporation of the engrafted iPSC-CMs including electron microscopy (EM) has not been accomplished, partly because identification of graft cells in EM has proven to be difficult. Using APEX2, an engineered ascorbate peroxidase imaging tag, we successfully localized and analyzed the fine structure of sarcomeres and the excitation contraction machinery of iPSC-CMs 6 months after their engraftment in infarcted mouse hearts. APEX2 made iPSC-CMs visible in multiple imaging modalities including light microscopy, X-ray microscopic tomography, transmission EM, and scanning EM. EM tomography allowed assessment of the differentiation state of APEX2-positive iPSC-CMs and analysis of the fine structure of the sarcomeres including T-tubules and dyads.
Optical coherence tomography angiography (OCTA) is a new non-invasive imaging technique that does not require the use of contrast agents and that allows the visualization of the retinal ...microvasculature in a layer-by-layer manner without bright light. This merit allows us to obtain the fundus image in children. Retinal vessels are typically absent from the center of the fovea, an area known as the foveal avascular zone (FAZ). The purpose of the present case study was to evaluate the FAZ in a nanophthalmic pediatric patient with OCTA.
A 6-year-old girl was referred to the Hiroshima University Hospital because of her poor vision. She had a best-corrected visual acuity of 20/125 in the right eye and of 20/100 in the left eye. The refractive errors after the administration of atropine sulfate eye drops were +13.00D in the right eye and +14.00D in the left eye. The axial lengths were 17.03 mm in the right eye and 16.90 mm in the left eye. At 9 years of age, the patient was diagnosed with nanophthalmos and OCTA was used to investigate the superficial and deep retinal layers. We demonstrated that the FAZ could not be observed in either eye, whereas the FAZ was readily observed in both eyes of a control subject of similar age.
OCTA is a useful technique to reveal the absence of the FAZ in cases of nanophthalmos. Because OCTA is a non-invasive and rapid procedure that is ideal for use with children.
Background:TheSCN5Agene encodes the α subunit of the cardiac voltage-gated sodium channel, NaV1.5. The missense mutation, D1275N, has been associated with a range of unusual phenotypes associated ...with reduced NaV1.5 function, including cardiac conduction disease and dilated cardiomyopathy. Curiously, the reported biophysical properties ofSCN5A-D1275N channels vary with experimental system.Methods and Results:First, using a human embryonic kidney (HEK) 293 cell-based heterologous expression system, theSCN5A-D1275N channels showed similar maximum sodium conductance but a significantly depolarizing shift of activation gate (+10 mV) compared to wild type. Second, we generated human-induced pluripotent stem cells (hiPSCs) from a 24-year-old female who carried heterozygousSCN5A-D1275N and analyzed the differentiated cardiomyocytes (CMs). AlthoughSCN5Atranscript levels were equivalent between D1275N and control hiPSC-CMs, both the total amount of NaV1.5 and the membrane fractions were reduced approximately half in the D1275N cells, which were rescued by the proteasome inhibitor MG132 treatment. Electrophysiological assays revealed that maximum sodium conductance was reduced to approximately half of that in control hiPSC-CMs in the D1275N cells, and maximum upstroke velocity of action potential was lower in D1275N, which was consistent with the reduced protein level of NaV1.5.Conclusions:This study successfully demonstrated diminished sodium currents resulting from lower NaV1.5 protein levels, which is dependent on proteasomal degradation, using a hiPSC-based model forSCN5A-D1275N-related sodium channelopathy.
Background: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. Methods: A total of 4853 Japanese individuals without diabetes at ...baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. Results: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94–3.06) for the medium eating speed and 2.08 (95%CI 1.13–3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. Conclusion: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population.
Background: Limited data are available for sex-based differences in Japanese patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). Methods and ...Results: The study patients comprised 1,197 women and 3,182 men who underwent primary PCI for AMI in 2005–2007. Compared with the men, the women were significantly older, and had significantly longer onset-to-balloon time and lower rate of follow-up coronary angiography. In-hospital mortality was higher among women than men (8.7% vs. 4.9%, P<0.001). Although the cumulative incidence of all-cause death at 3 years was also higher for women (17.7% vs. 10.7%, P<0.001), the adjusted risk for all-cause death was comparable hazard ratio (HR, women vs. men)=0.94, 95% confidence interval (CI): 0.71–1.24, P=0.66. The incidence (12.1% vs. 12.4%, P=0.77) and the adjusted risk (HR=0.99, 95% CI 0.78–1.24, P=0.92) for any clinically-driven coronary revascularization were both comparable. However, regarding any non-clinically-driven coronary revascularization, the incidence (19.6% vs. 27.8%, P<0.001) and the adjusted risk (HR=0.79, 95% CI 0.65–0.95, P=0.012) were both lower in women relative to men. Conclusions: In current Japanese clinical practice for AMI, onset-to-balloon time was significantly longer in women than in men. Female sex was associated with lower follow-up coronary angiography rate and lower incidence of any non-clinically-driven coronary revascularization, whereas the incidence of any clinically-driven coronary revascularization was comparable between the sexes. (Circ J 2013; 77: 1508–1517)
There is uncertainty surrounding the causal relationship between serum uric acid and hypertension. The aim was to investigate the association between serum uric acid and prevalence of hypertension in ...a general population of Japanese.
This was a population-based cross-sectional study using health check-up data of the residents of the Iki City, Nagasaki Prefecture, Japan. A total of 7,484 participants aged 30 years or older were included in this study. Serum uric acid was classified into four groups: group 1 (< 357 µmol/L (< 6 mg/dL)), group 2 (357 - 415 µmol/L (6 - 6.9 mg/dL)), group 3 (416 - 475 µmol/L (7 - 7.9 mg/dL)) and group 4 (≥ 476 µmol/L (≥ 8 mg/dL)). Hypertension was defined as blood pressure (BP) levels of ≥ 140/90 mm Hg or use of BP lowering medications.
Hypertension was observed among 3,467 participants (prevalence 46.3%). The prevalence of hypertension increased with elevation of serum uric acid levels: 42.8% in group 1, 55.0% in group 2, 57.6% in group 3 and 59.8% in group 4 (P < 0.001 for trend). This association was significant even after adjustment for other risk factors including age, sex, current smoking, current alcohol intake, obesity, diabetes, dyslipidemia, estimated glomerular filtration rate and proteinuria: odds ratios (95% confidence intervals) were 1.50 (1.28 - 1.77) for group 2, 1.58 (1.25 - 1.99) for group 3 and 1.89 (1.36 - 2.64) for group 4 compared with the reference group of group 1 (P < 0.001 for trend).
Serum uric acid was clearly associated with prevalence of hypertension in a general population of Japanese.
The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of ...Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.
Background: Limited data are available for gender-based differences in patients undergoing coronary revascularization. This study aimed to identify gender-based differences in risk factor profiles ...and outcomes among Japanese patients undergoing coronary revascularization. Methods and Results: The subjects consisted of 2,845 women and 6,843 men who underwent first percutaneous coronary intervention or coronary artery bypass grafting in 2000-2002. The outcome measures were all-cause death, major adverse cardiovascular events (MACE) as the composite of cardiovascular death, myocardial infarction and stroke, and any coronary revascularization. The females were older than the males and more frequently had histories of heart failure, diabetes, hypertension, chronic kidney disease, anemia, and dyslipidemia. Unadjusted survival analysis revealed a significantly lower incidence of any revascularization in women (at 3 years: 28.2% vs. 31.2%, P=0.0037), although no significant gender-based differences were shown in the incidence of all-cause death (at 3 years: 8.8% vs. 8.5%, P=0.37) or MACE (at 3 years: 12.0% vs. 11.5%, P=0.61). Multivariate analysis revealed that female gender was associated with significantly lower risks of any revascularization (relative risk=0.93, 95% confidence interval CI=0.88-0.99, P=0.014) and all-cause death (relative risk=0.86, 95%CI=0.77-0.96, P=0.005). Conclusions: In Japanese patients undergoing first coronary revascularization, the coronary risk factor burden appeared greater in women than in men. Despite the greater modifiable risk factor accumulation, female gender was associated with a lower incidence of repeated revascularization relative to male gender. (Circ J 2011; 75: 1358-1367)
The cardiomyocyte (CM) subtypes in the mammalian heart derive from distinct lineages known as the first heart field (FHF), the anterior second heart field (aSHF), and the posterior second heart field ...(pSHF) lineages that are specified during gastrulation. We modeled human heart field development from human pluripotent stem cells (hPSCs) by using single-cell RNA-sequencing to delineate lineage specification and progression. Analyses of hPSC-derived and mouse mesoderm transcriptomes enabled the identification of distinct human FHF, aSHF, and pSHF mesoderm subpopulations. Through staged manipulation of signaling pathways identified from transcriptomics, we generated myocyte populations that display molecular characteristics of key CM subtypes. The developmental trajectory of the human cardiac lineages recapitulated that of the mouse, demonstrating conserved cardiovascular programs. These findings establish a comprehensive landscape of human embryonic cardiogenesis that provides access to a broad spectrum of cardiomyocytes for modeling congenital heart diseases and chamber-specific cardiomyopathies as well as for developing new therapies to treat them.
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•ScRNA-seq profiling of human heart field development spanning various stages•Comparisons of hPSC-derived, human fetal-, and mouse fetal-cardiac populations•Identification of pathways involved in the development of heart field lineages•Generation of functionally and transcriptionally distinct cardiomyocyte (CM) subtypes
We describe hPSC-derived models of FHF, aSHF, and pSHF development spanning the mesoderm, progenitor, and cardiomyocyte stages. Comparison between the hPSC-derived and the corresponding mouse populations revealed conserved developmental trajectories across the species. Access to cardiomyocyte subtypes derived from different heart fields enables modeling chamber-specific diseases and developing new therapies.
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