Impact of treatment cessation on incidence and progression of retinopathy in Japanese patients with type 2 diabetes mellitus: a retrospective cohort study.

Aims: This cohort study investigated the association between treatment cessation and incidence/progression of diabetic retinopathy (DR) in Japanese patients with type 2 diabetes mellitus (T2DM). Materials and methods: Data were extracted from electronic medical records at the University of the Ryukyu Hospital and the Tomishiro Central Hospital of Okinawa, Japan. We enrolled 417 diabetic patients without DR (N = 281) and with nonproliferative DR (N = 136) at the baseline. Treatment cessation was defined as failing to attend outpatient clinics for at least twelve months prior to the baseline. After a median follow-up of 7 years, we compared the incidence/progression rate of DR including nonproliferative and proliferative DR between patients with and without treatment cessation and calculated the odds ratio (OR) in the treatment cessation group using a logistic regression model. Results: The overall prevalence of treatment cessation was 13% in patients with T2DM. Characteristics of treatment cessation included relative youth (57 ± 11 years vs. 63 ± 12 years, P < 0.01). Treatment cessation was tightly associated with the incidence of DR (OR 4.20 [95% confidence interval [CI] 1.46-12.04, P < 0.01) and also incidence/progression of DR (OR 2.70 [1.28-5.69], P < 0.01), even after adjusting for age, sex, BMI, duration of T2DM, and HbA1c level. Conclusions: By considering major confounding factors, the present study demonstrates an independent association between treatment cessation and incidence of DR in patients with T2DM, highlighting treatment cessation as an independent risk for DR in T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-024-00724-7.

Peripheral Dopamine Suppression and Elevated Cystatin C in Early Diabetic Nephropathy in Spontaneously Diabetic Rats.

Intrarenal dopamine plays a protective role against the development of diabetic nephropathy during the early stages of the disease. In streptozotocin-induced diabetic mice with a renal-specific catechol-O-methyl transferase knockout, intrarenal dopamine was found to suppress glomerular hyperfiltration, reduce oxidative stress and inflammation, and inhibit fibrosis. However, while dopamine activation in streptozotocin-induced diabetic models has been shown to provide renal protection, the role of dopamine in models of naturally induced diabetes mellitus is still unclear. In the present study, we administered 10 mg/kg p.o. benserazide, a peripheral decarboxylase inhibitor, to Spontaneously Diabetic Torii rats daily, in order to investigate the activation of the renal dopaminergic system during diabetic nephropathy progression. Our findings show that peripheral dopamine decreased urinary 8-iso-prostaglandin F2a and suppressed increases in plasma cystatin C levels. This study demonstrates that a reduction in peripheral dopamine can exacerbate renal dysfunction, even in the early stages of diabetic nephropathy characterized by glomerular hyperfiltration, thereby clarifying the pivotal role of endogenous peripheral dopamine in modulating oxidative stress and kidney performance.

Machine learning-based reproducible prediction of type 2 diabetes subtypes.

AIMS/HYPOTHESIS: Clustering-based subclassification of type 2 diabetes, which reflects pathophysiology and genetic predisposition, is a promising approach for providing personalised and effective therapeutic strategies. Ahlqvist's classification is currently the most vigorously validated method because of its superior ability to predict diabetes complications but it does not have strong consistency over time and requires HOMA2 indices, which are not routinely available in clinical practice and standard cohort studies. We developed a machine learning (ML) model to classify individuals with type 2 diabetes into Ahlqvist's subtypes consistently over time. METHODS: Cohort 1 dataset comprised 619 Japanese individuals with type 2 diabetes who were divided into training and test sets for ML models in a 7:3 ratio. Cohort 2 dataset, comprising 597 individuals with type 2 diabetes, was used for external validation. Participants were pre-labelled (T2Dkmeans) by unsupervised k-means clustering based on Ahlqvist's variables (age at diagnosis, BMI, HbA1c, HOMA2-B and HOMA2-IR) to four subtypes: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD). We adopted 15 variables for a multiclass classification random forest (RF) algorithm to predict type 2 diabetes subtypes (T2DRF15). The proximity matrix computed by RF was visualised using a uniform manifold approximation and projection. Finally, we used a putative subset with missing insulin-related variables to test the predictive performance of the validation cohort, consistency of subtypes over time and prediction ability of diabetes complications. RESULTS: T2DRF15 demonstrated a 94% accuracy for predicting T2Dkmeans type 2 diabetes subtypes (AUCs ≥0.99 and F1 score [an indicator calculated by harmonic mean from precision and recall] ≥0.9) and retained the predictive performance in the external validation cohort (86.3%). T2DRF15 showed an accuracy of 82.9% for detecting T2Dkmeans, also in a putative subset with missing insulin-related variables, when used with an imputation algorithm. In Kaplan-Meier analysis, the diabetes clusters of T2DRF15 demonstrated distinct accumulation risks of diabetic retinopathy in SIDD and that of chronic kidney disease in SIRD during a median observation period of 11.6 (4.5-18.3) years, similarly to the subtypes using T2Dkmeans. The predictive accuracy was improved after excluding individuals with low predictive probability, who were categorised as an 'undecidable' cluster. T2DRF15, after excluding undecidable individuals, showed higher consistency (100% for SIDD, 68.6% for SIRD, 94.4% for MOD and 97.9% for MARD) than T2Dkmeans. CONCLUSIONS/INTERPRETATION: The new ML model for predicting Ahlqvist's subtypes of type 2 diabetes has great potential for application in clinical practice and cohort studies because it can classify individuals with missing HOMA2 indices and predict glycaemic control, diabetic complications and treatment outcomes with long-term consistency by using readily available variables. Future studies are needed to assess whether our approach is applicable to research and/or clinical practice in multiethnic populations.

Elevated resting heart rate is associated with mortality in patients with chronic kidney disease.

A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated. A total of 1353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate < 70/min, ≥ 70 and < 80/min, ≥ 80 and < 90/min, and ≥ 90/min). During the median observation period of 4.9 years, 123 participants died, and 163 cardiovascular events occurred. Compared with the reference level heart rate < 70/min group, the adjusted hazard ratios (HRs) for all-cause mortality were 1.74 (1.05-2.89) and 2.61 (1.59-4.29) for the heart rate ≥ 80 and < 90/min group and heart rate ≥ 90/min group, respectively. A significantly higher risk of cardiovascular events was observed in the heart rate ≥ 80/min and < 90/min group (adjusted HR 1.70, 1.10-2.62), but not in the heart rate ≥ 90/min group (adjusted HR 1.45, 0.90-2.34). In patients with non-dialysis-dependent CKD, a higher resting heart rate was associated with increased all-cause mortality.

Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

AIMS/INTRODUCTION: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. MATERIALS AND METHODS: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. RESULTS: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. CONCLUSIONS: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.

Association between specific human leukocyte antigen alleles and development of thyroid immune-related adverse event.

Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE. Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared. Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively). Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.

Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.

Circulating microRNA profile of long-lived Okinawans identifies novel potential targets for optimizing lifespan and health span.

Nonagenarians and centenarians serve as successful examples of aging and extended longevity, showcasing robust regulation of biological mechanisms and homeostasis. Given that human longevity is a complex field of study that navigates molecular and biological mechanisms influencing aging, we hypothesized that microRNAs, a class of small noncoding RNAs implicated in regulating gene expression at the post-transcriptional level, are differentially regulated in the circulatory system of young, middle-aged, and nonagenarian individuals. We sequenced circulating microRNAs in Okinawan males and females <40, 50-80, and >90 years of age accounting for FOXO3 genetic variations of single nucleotide polymorphism (SNP) rs2802292 (TT - common vs. GT - longevity) and validated the findings through RT-qPCR. We report five microRNAs exclusively upregulated in both male and female nonagenarians with the longevity genotype, play predictive functional roles in TGF-ß, FoxO, AMPK, Pi3K-Akt, and MAPK signaling pathways. Our findings suggest that these microRNAs upregulated in nonagenarians may provide novel insight into enhanced lifespan and health span. This discovery warrants further exploration into their roles in human aging and longevity.

Geriatric Nutritional Risk Index is associated with adverse outcomes in patients with hypertension: the Fukushima Cohort study.

Malnutrition is reportedly associated with adverse clinical outcomes in various populations. However, associations between nutritional status and adverse outcomes in patients with hypertension have not been sufficiently elucidated. We therefore aimed to investigate the impact of nutritional status as evaluated by the Geriatric Nutritional Risk Index (GNRI) on adverse outcomes in patients with hypertension. We conducted a retrospective cohort study of 1588 hypertensive patients enrolled in the Fukushima Cohort Study. Participants were categorized into tertiles (T1-T3) according to GNRI at baseline. The primary endpoint of the present study was a kidney event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease requiring kidney replacement therapy. Associations between GNRI and kidney events were assessed using Kaplan-Meier curves and multivariate Cox regression analyses. Median age was 64 years, 55% were men, median eGFR was 63.1 mL/min/1.73 m2, and median GNRI was 101.3. The lower GNRI group (T1) showed an increased incidence of kidney events in the Kaplan-Meier curve analysis. Compared to the highest GNRI group (T3), lower GNRI carried a higher risk of kidney events for both T2 (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.71-2.68) and T1 (HR 3.59, 95%CI 1.96-6.63). Similar relationships were observed for risks of all-cause death and cardiovascular events. Lower GNRI was associated with kidney events, all-cause death, and cardiovascular events in patients with hypertension. Nutritional status as evaluated by GNRI could offer a simple and useful predictor of adverse outcomes in this population.

Blood pressure reduction with empagliflozin in Japanese patients with type 2 diabetes and cardiovascular diseases: a post-hoc sub-analysis of the placebo-controlled randomized EMBLEM trial.

Detailed effect of sodium-glucose cotransporter 2 inhibitors on blood pressure (BP) in Japanese patients with type 2 diabetes (T2D) at a high risk of cardiovascular disease (CVD) is not fully understood. In this post-hoc sub-analysis of placebo-controlled randomized EMBLEM trial for Japanese patients with T2D and CVD, 105 participants (empagliflozin N = 52, placebo N = 53) were included, and office systolic/diastolic BPs and mean arterial pressure (MAP) over 24 weeks were estimated using mixed-effects models for repeated measures. Empagliflozin therapy, compared to placebo, reduced systolic/diastolic BPs (mean group difference in change from baseline to week 24; -5.9 [95% confidence interval (CI), -10.4 to -1.4] mmHg/-2.9 [95% CI, -6.2 to 0.4] mmHg) and MAP ( - 3.8 [95% CI, -7.0 to -0.7] mmHg). The systolic BP reduction was almost consistent across differing background clinical characteristics and usage status of anti-hypertensive medications.

Respiratory Displacement of the Right Adrenal Vein: Comparison of Inspiratory and Expiratory Computed Tomography With Catheter Venography.

OBJECTIVE: The aim of the study is to reveal the respiratory displacement of the right adrenal vein (RAV) to predict the exact location of the RAV during adrenal venous sampling (AVS). METHODS: Computed tomography (CT) scans obtained 45 seconds (breath-hold at inhalation) and 70 seconds (breath-hold at exhalation) after contrast material injection were compared to venograms of the RAV of patients with primary aldosteronism who underwent AVS between January 2016 and December 2020. The craniocaudal distance between the center of the Th11/12 disc and the RAV orifice was measured; the craniocaudal location of the RAV orifice was also specified relative to vertebral bodies and intervertebral discs on inspiratory phase CT (In-CT), expiratory phase CT (Ex-CT), and catheter venography. The transverse and vertical angles of the RAV and the position of the RAV orifice on the inferior vena cava (IVC) circumference were measured on In-CT and Ex-CT. RESULTS: In total, 51 patients (30 males, 21 females; mean age, 54.9 ± 11.1 years) were included. Craniocaudal distances between the center of the Th11/12 disc and RAV orifice were significantly different among the following 3 acquisitions: catheter venography versus In-CT (15.2 ± 8.4 mm); venography versus Ex-CT (5.6 ± 4.1 mm); and In-CT versus Ex-CT (19.6 ± 8.0 mm) (all, P < 0.001). The craniocaudal location of the RAV orifice on venography was significantly closer to that on Ex-CT than on In-CT (P < 0.001); measurements using venograms compared with In-CT and Ex-CT scans were within 1 level difference in 18 (35.3%) and 47 (92.2%) patients, respectively (P < 0.001). The vertical angle of the RAV was significantly more likely to be smaller on In-CT than on Ex-CT (P < 0.001). CONCLUSIONS: RAV locations and angles change with respiratory motion. It is crucial to consider the respiratory phase of CT because it can enable a more accurate prediction of the location of the RAV during AVS.

2023 Fukushima Medical University International Symposium on the Fukushima Health Management Survey, "Thinking Together about Health, Life, and our Future in Fukushima".

In response to the release of radioactive materials and evacuation of residents after the Tokyo Electric Power Company's Fukushima Daiichi Nuclear Power Plant accident, caused by the Great East Japan Earthquake, the Fukushima Health Management Survey (FHMS) began in June of 2011. This survey aims to provide long-term follow-up of the physical and mental health of Fukushima residents and to maintain and improve their health for the future. Every year since 2019, Fukushima Medical University (FMU) has organized the FHMS International Symposium to share survey results with people in Fukushima Prefecture and beyond. The fifth annual symposium convened at FMU's Ekimae Campus on Saturday, 4 March 2023, with the theme, "Thinking Together about Health, Life and our Future in Fukushima."

Novel protective effect of the FOXO3 longevity genotype on mechanisms of cellular aging in Okinawans.

The genetic association of FOXO3 genotypes with human longevity is well established, although the mechanism is not fully understood. We now report on the relationship of the FOXO3 longevity variant rs2802292 with telomere length, telomerase activity, FOXO3 expression, and inflammatory cytokine levels in men and women. In agreement with earlier work, the FOXO3 longevity variant conferred protection against telomere shortening of peripheral blood mononuclear cells from adults aged 55 years and older. This was accompanied by higher levels of telomerase activity in mononuclear cells for carriers of the longevity-associated FOXO3 G-allele of SNP rs2802292 (P = 0.015). FOXO3 mRNA expression increased slightly with age in both young (P = 0.02) and old (P = 0.08) G-allele carriers. Older female G-allele carriers displayed a modest decline in levels of pro-inflammatory cytokine IL-6 with age (P = 0.07). In contrast, older male G-allele carriers displayed an age-dependent increase in levels of anti-inflammatory cytokine IL-10 with age (P = 0.04). Thus, FOXO3 may act through several different pro-longevity mechanisms, which may differ by age and sex.

Role of perirenal adiposity in renal dysfunction among CKD individuals with or without diabetes: a Japanese cross-sectional study.

INTRODUCTION: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm3), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm3/m2). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m2 proteinuria onset, or both. RESULTS: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm2, the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM. CONCLUSIONS: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies.

Predicting CKD progression using time-series clustering and light gradient boosting machines.

Predicting the transition of kidney function in chronic kidney disease is difficult as specific symptoms are lacking and often overlooked, and progress occurs due to complicating factors. In this study, we applied time-series cluster analysis and a light gradient boosting machine to predict the trajectories of kidney function in non-dialysis dependent chronic kidney disease patients with baseline estimated glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m2. Based on 5-year changes in estimated GFR, participants were stratified into groups with similar trajectories by cluster analysis. Next, we applied the light gradient boosting machine algorithm and Shapley addictive explanation to develop a prediction model for clusters and identify important parameters for prediction. Data from 780 participants were available for analysis. Participants were classified into five classes (Class 1: n = 78, mean [± standard deviation] estimated GFR 100 ± 19.3 mL/min/1.73 m2; Class 2: n = 176, 76.0 ± 9.3 mL/min/1.73 m2; Class 3: n = 191, 59.8 ± 5.9 mL/min/1.73 m2; Class 4: n = 261, 52.7 ± 4.6 mL/min/1.73 m2; and Class 5: n = 74, 53.5 ± 12.0 mL/min/1.73 m2). Declines in estimated GFR were 8.9% in Class 1, 12.2% in Class 2, 4.9% in Class 3, 12.0% in Class 4, and 45.1% in Class 5 during the 5-year period. The accuracy of prediction was 0.675, and the top three most important Shapley addictive explanation values were 1.61 for baseline estimated GFR, 0.12 for hemoglobin, and 0.11 for body mass index. The estimated GFR transition of patients with preserved chronic kidney disease mostly depended on baseline estimated GFR, and the borderline for estimated GFR trajectory was nearly 50 mL/min/1.73 m2.

Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

Innate Immune System Regulated by Stimulator of Interferon Genes, a Cytosolic DNA Sensor, Regulates Endothelial Function.

Background Sterile inflammation caused by metabolic disorders impairs endothelial function; however, the underlying mechanism by which hyperglycemia induces inflammation remains obscure. Recent studies have suggested that stimulator of interferon genes (STING), a key cytosolic DNA sensor in the innate immune system, contributes to the pathogenesis of inflammatory diseases. This study examines the role of the STING in endothelial dysfunction in streptozotocin-induced diabetic mice. Methods and Results Injection of streptozotocin promoted the expression of STING and DNA damage markers in the aorta of wild-type mice. Streptozotocin elevated blood glucose and lipid levels in both wild-type and STING-deficient mice, which showed no statistical differences. Genetic deletion of STING ameliorated endothelial dysfunction as determined by the vascular relaxation in response to acetylcholine (P<0.001) and increased endothelial nitric oxide synthase phosphorylation in the aorta (P<0.05) in STZ-injected mice. Endothelium-independent vascular response to sodium nitroprusside did not differ. Treatment with a direct STING agonist, cyclic GMP-AMP, or mitochondrial DNA increased inflammatory molecule expression (eg, VCAM1 and IFNB) and decreased endothelial nitric oxide synthase phosphorylation in human umbilical vein endothelial cells, partially through the STING pathway. Cyclic GMP-AMP significantly impaired endothelial function of aortic segments obtained from wild-type mice, which was ameliorated in the presence of C-176, a STING inhibitor, or a neutralizing interferon-ß antibody. Furthermore, the administration of C-176 ameliorated endothelial dysfunction in STZ-induced diabetic mice (P<0.01). Conclusions The DNA damage response regulated by STING impairs endothelial function. STING signaling may be a potential therapeutic target of endothelial dysfunction caused by hyperglycemia.

Influence of post-disaster evacuation on childhood obesity and liver dysfunction: The Fukushima Health Management Survey.

BACKGROUND: After the Great East Japan Earthquake and subsequent Fukushima Daiichi Nuclear Power Plant accident in 2011, the Fukushima Prefectural Government launched a long-term health management survey for the population of Fukushima. Results of the Comprehensive Health Check (CHC) showed that some children aged 6-15 years, who resided in the evacuation area at the time of the disaster, had obesity, hyperlipidemia, liver dysfunction, and/or renal dysfunction from as early as 2011. The aim of the present study was to determine the long-term trend of obesity and hepatic enzyme abnormalities in Fukushima children. METHODS: We evaluated the changes in body mass index standard deviation score (BMI-SDS), aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase from 2011 to 2018. RESULTS: Obesity (BMI-SDS ≥ 2) was significantly associated with hepatobiliary enzyme abnormalities. The mean BMI-SDS was significantly higher in 2011 after the disaster, but then soon showed a gradual decrease. The frequency of obesity did not increase significantly after the disaster. There were no significant differences in the prevalence of hepatobiliary enzyme abnormalities in the children aged 6-15 years of either sex from 2011 to 2018. CONCLUSIONS: In the present study, we found that the increase in the mean BMI-SDS after the disaster was temporary, suggesting that the frequency of obesity and liver dysfunction might not have been significantly influenced by the disaster.

Blood data trends of children in Fukushima after the Great East Japan Earthquake: Fukushima health management survey.

BACKGROUND: After the Great East Japan Earthquake on March 11, 2011 and the subsequent accident at the Tokyo Electric Power Company-operated Daiichi Nuclear Power Plant, the Fukushima Prefecture government initiated the Fukushima Health Management Survey (FHMS) to assess the long-term health effects of the disaster on Fukushima residents. The blood tests of children aged ≤15 years between 2011 and 2012 did not reveal any changes regarding peripheral blood data; however, long-term monitoring is still necessary. Therefore, this study aimed to investigate the long-term health status of children aged ≤15 years who had evacuated the Fukushima Prefecture. METHODS: From 2011 to 2018, 71,250 evacuees aged 15 years or younger participated in the FMHS and were subjected to blood tests. By analyzing the data of the comprehensive health check survey managed by the FHMS, we examined the changes in hemoglobin (Hb) levels, white blood cell (WBC) counts, including fractions, and platelet (PLT) counts among children from 2011 to 2018. RESULTS: Minor fluctuations in Hb levels, PLT counts, and WBC counts were observed during the study period, but the central 95% intervals of distribution of the laboratory values were generally within previously reported reference intervals. In particular, there was no increase in the proportions of patients with anemia, polycythemia, or deviating WBC counts. CONCLUSION: From 2011 to 2018, there was no increase in the percentages of children with anemia, polycythemia, or deviating WBC counts among the Fukushima Prefecture evacuees.