Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Inhibitory action of B-type natriuretic peptide on adrenocorticotropic hormone in patients with acute coronary syndrome.

In addition to the classical actions of hemodynamic regulation, natriuretic peptides (NPs) interact with various neurohumoral factors that are deeply involved in the pathophysiology of cardiovascular diseases. However, their effects on the hypothalamic-pituitary-adrenal (HPA) axis, which is activated under acute high-stress conditions in acute coronary syndrome (ACS), remain largely unknown. We investigated the impact of plasma B-type NP (BNP) on plasma adrenocorticotropic hormone (ACTH)-cortisol levels during the acute phase of ACS ischemic attacks. The study population included 436 consecutive patients with ACS for whom data were collected during emergency cardiac catheterization. Among them, biochemical data after acute-phase treatment were available in 320 cases, defined as the ACS-remission phase (ACS-rem). Multiple regression analyses revealed that plasma BNP levels were significantly negatively associated with plasma ACTH levels only during ACS attacks (P < 0.001), but not in ACS-rem, whereas plasma BNP levels were not significantly associated with plasma cortisol levels at any point. Accordingly, covariance structure analyses were performed to clarify the direct contribution of BNP to ACTH by excluding other confounding factors, confirming that BNP level was negatively correlated with ACTH level only during ACS attacks (ß = -0.152, P = 0.002), whereas BNP did not significantly affect ACTH in ACS-rem. In conclusion, despite the lack of a significant direct association with cortisol levels, BNP negatively regulated ACTH levels during the acute phase of an ACS attack in which the HPA axis ought to be activated. NP may alleviate the acute stress response induced by severe ischemic attacks in patients with ACS.NEW & NOTEWORTHY BNP negatively regulates ACTH during a severe ischemic attack of ACS in which hypothalamic-pituitary-adrenal axis ought to be activated, indicating an important role of natriuretic peptides as a mechanism of adaptation to acute critical stress conditions in humans.

Predicting dry weight change in Hemodialysis patients using machine learning.

BACKGROUND: Machine Learning has been increasingly used in the medical field, including managing patients undergoing hemodialysis. The random forest classifier is a Machine Learning method that can generate high accuracy and interpretability in the data analysis of various diseases. We attempted to apply Machine Learning to adjust dry weight, the appropriate volume status of patients undergoing hemodialysis, which requires a complex decision-making process considering multiple indicators and the patient's physical conditions. METHODS: All medical data and 69,375 dialysis records of 314 Asian patients undergoing hemodialysis at a single dialysis center in Japan between July 2018 and April 2020 were collected from the electronic medical record system. Using the random forest classifier, we developed models to predict the probabilities of adjusting the dry weight at each dialysis session. RESULTS: The areas under the receiver-operating-characteristic curves of the models for adjusting the dry weight upward and downward were 0.70 and 0.74, respectively. The average probability of upward adjustment of the dry weight had sharp a peak around the actual change over time, while the average probability of downward adjustment of the dry weight formed a gradual peak. Feature importance analysis revealed that median blood pressure decline was a strong predictor for adjusting the dry weight upward. In contrast, elevated serum levels of C-reactive protein and hypoalbuminemia were important indicators for adjusting the dry weight downward. CONCLUSIONS: The random forest classifier should provide a helpful guide to predict the optimal changes to the dry weight with relative accuracy and may be useful in clinical practice.

The safety and feasibility of retrograde balloon aortic valvuloplasty using the INOUE-BALLOON with severe aortic stenosis.

In the transcatheter aortic valve implantation (TAVI) era, the indications for balloon aortic valvuloplasty (BAV) are increasing. Previously, the INOUE-BALLOON® (IB) was used only for antegrade BAV, but recently, it has also been used for retrograde BAV. However, the safety and feasibility of retrograde BAV using an IB are not fully understood. In this study, we investigated the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe aortic stenosis (AS). We compared 39 cases of retrograde BAV using an IB performed from June 2018 to September 2020 and 34 cases of antegrade BAV using an IB performed from August 2013 to May 2018. The total number of complications was lower in retrograde BAV than in antegrade BAV (p = 0.020). The procedure time was significantly shorter in retrograde BAV than in antegrade BAV (p < 0.001), and the maximum balloon size and number of balloon inflations were smaller in retrograde BAV than in antegrade BAV (p = 0.002 and p < 0.001, respectively). There was no significant difference in the degree of improvement in the aortic valve area or ejection fraction between retrograde and antegrade BAV. In conclusion, the present study showed the safety and feasibility of retrograde BAV using an IB in elderly Japanese patients with severe AS compared with antegrade BAV using an IB.

Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia-Reperfusion Injury in Diet-Induced Obesity.

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

Cardiac ischemia-reperfusion injury under insulin-resistant conditions: SGLT1 but not SGLT2 plays a compensatory protective role in diet-induced obesity.

BACKGROUND: Recent large-scale clinical trials have shown that SGLT2-inhibitors reduce cardiovascular events in diabetic patients. However, the regulation and functional role of cardiac sodium-glucose cotransporter (SGLT1 is the dominant isoform) compared with those of other glucose transporters (insulin-dependent GLUT4 is the major isoform) remain incompletely understood. Given that glucose is an important preferential substrate for myocardial energy metabolism under conditions of ischemia-reperfusion injury (IRI), we hypothesized that SGLT1 contributes to cardioprotection during the acute phase of IRI via enhanced glucose transport, particularly in insulin-resistant phenotypes. METHODS AND RESULTS: The hearts from mice fed a high-fat diet (HFD) for 12 weeks or a normal-fat diet (NFD) were perfused with either the non-selective SGLT-inhibitor phlorizin or selective SGLT2-inhibitors (tofogliflozin, ipragliflozin, canagliflozin) during IRI using Langendorff model. After ischemia-reperfusion, HFD impaired left ventricular developed pressure (LVDP) recovery compared with the findings in NFD. Although phlorizin-perfusion impaired LVDP recovery in NFD, a further impaired LVDP recovery and a dramatically increased infarct size were observed in HFD with phlorizin-perfusion. Meanwhile, none of the SGLT2-inhibitors significantly affected cardiac function or myocardial injury after ischemia-reperfusion under either diet condition. The plasma membrane expression of GLUT4 was significantly increased after IRI in NFD but was substantially attenuated in HFD, the latter of which was associated with a significant reduction in myocardial glucose uptake. In contrast, SGLT1 expression at the plasma membrane remained constant during IRI, regardless of the diet condition, whereas SGLT2 was not detected in the hearts of any mice. Of note, phlorizin considerably reduced myocardial glucose uptake after IRI, particularly in HFD. CONCLUSIONS: Cardiac SGLT1 but not SGLT2 plays a compensatory protective role during the acute phase of IRI via enhanced glucose uptake, particularly under insulin-resistant conditions, in which IRI-induced GLUT4 upregulation is compromised.

Obstructive sleep apnea is associated with increased coronary plaque instability: an optical frequency domain imaging study.

Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk for myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non-OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non-OSA patients. Compared with the non-OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P = 0.014) and microchannels (86% vs. 55%, P = 0.014); a significantly higher mean lipid index (1392 ± 982 vs. 817 ± 699, P = 0.021), macrophage grade (8.4 ± 6.4 vs. 4.8 ± 4.5, P = 0.030), and maximum number of microchannels (1.5 ± 1.0 vs. 0.7 ± 0.7, P = 0.001); and a significantly lower mean minimum fibrous cap thickness (69.4 ± 28.7 vs. 96.1 ± 51.8 µm, P = 0.008). This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.

Predictors of oxygenation impairment in medical treatment for type B acute aortic dissection.

Lung oxygenation impairment often occurs in patients with type B acute aortic dissection (AAD), necessitating mechanical ventilation. Patients receiving mechanical ventilation are at risk of complications, so a low-oxygen condition requiring mechanical ventilation should be avoided. We explored the predictors of oxygenation impairment. We enrolled 46 patients with type B AAD who had been medically treated and underwent computed tomography. Blood was sampled to measure markers of inflammation, such as the C-reactive protein (CRP) levels and white blood cell count. The arterial partial pressure of oxygen/fraction of inspired oxygen ratio (PaO2/FiO2) was calculated to quantify the severity of respiratory failure. Spearman's rank correlation analysis revealed that the minimum PaO2/FiO2 ratio was significantly correlated with gender, age, and current smoker, and the peak CRP, body temperature, and D-dimer values. A multivariate regression analysis revealed that younger age, male sex, and the peak CRP level were significant predictors of the minimum PaO2/FiO2 ratio (P = 0.01, 0.035 and 0.005, respectively). A covariance structure analysis showed that a younger age and the peak CRP level were significant predictors of oxygenation impairment in type B AAD. Oxygenation impairment in type B AAD is correlated with younger age and a higher peak CRP level. This will enable the identification of patients whose respiratory condition is susceptible to worsening and help prevent mechanical ventilation, leading to the provision of appropriate therapy.

Stent thrombosis caused by metal allergy complicated by protein S deficiency and heparin-induced thrombocytopenia: a case report and review of the literature.

A 43-year-old woman recipient of a bare metal coronary stent during an acute anterior myocardial infarction was repeatedly hospitalized with recurrent stent thrombosis (ST) over the following 3 years. Emergent coronary angiography showed a thrombus in the in-stent segment of the proximal left anterior descending artery. We repeatedly aspirated the thrombus, which immediately reformed multiple times. The discontinuation of heparin and administration of thrombolytics and argatroban, followed by repeated balloon dilatations, ended the formation of new thrombi. The patient was found to be allergic to nickel, protein S deficient and carrier of heparin-induced thrombocytopenia antibody. We discuss this case in the context of a) literature pertaining to acute coronary syndromes in the young, and b) the detailed investigations needed to identify thrombotic risk factors. Steroids may be effective to prevent recurrent ST caused by stent allergy.

Sodium-glucose cotransporter 2 inhibitor therapy reduces the administration frequency of steroid injection in patients with diabetic macular edema: A cohort study using the Japanese health insurance claims database.

AIMS/INTRODUCTION: Severe diabetic macular edema (DME) is often resistant to anti-vascular endothelial growth factor therapy. Steroids are particularly effective at reducing edema by suppressing inflammation; they are also used as an alternative to expensive anti-vascular endothelial growth factor therapy in some patients. Therefore, the use of steroids in DME reflects an unmet need for anti-vascular endothelial growth factor therapy. Notably, triamcinolone acetonide (TA) injections are widely used in Japan. Here, we evaluated the frequency of TA as an indicator of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in DME treatment using a health insurance claims database. MATERIALS AND METHODS: In this cohort study, we retrospectively analyzed the health insurance claims data of 11 million Japanese individuals from 2005 to 2019. The frequency and duration of TA injection after the initiation of SGLT2is or other antidiabetic drugs were analyzed. RESULTS: Among the 2,412 matched patients with DME, the incidence rate of TA injection was 63.8 times per 1,000 person-years in SGLT2i users and 94.9 times per 1,000 person-years in non-users. SGLT2is reduced the risk for the first (P = 0.0024, hazard ratio 0.66, 95% confidence interval 0.50-0.87), second (P = 0.0019, hazard ratio 0.53, 95% confidence interval 0.35-0.80) and third TA (P = 0.0053, hazard ratio 0.44, 95% confidence interval 0.25-0.80) injections. A subanalysis of each baseline characteristic of the patients showed that SGLT2is were effective regardless of the background factors. CONCLUSIONS: The use of SGLT2is reduced the frequency of TA injection in patients with DME. Therefore, SGLT2i therapy might be a novel, noninvasive and low-cost adjunctive therapy for DME.

Increased urinary aldosterone excretion is associated with subcutaneous not visceral, adipose tissue area in obese individuals: a possible manifestation of dysfunctional subcutaneous adipose tissue.

BACKGROUND: Aldosterone is reported to be associated with obesity and is a risk factor for metabolic syndrome. Metabolic abnormalities are more strongly associated with visceral adipose tissue (VAT) than with subcutaneous adipose tissue (SAT). OBJECTIVE: We examined whether aldosterone is more closely associated with VAT area than with SAT area in obese individuals. METHODS: We enrolled 81 Japanese patients (46 men, mean age 43 ± 13 years and 35 women, mean age 53 ± 10 years) suspected of metabolic disorders and measured plasma and 24-h urinary aldosterone, as well as SAT and VAT areas. SAT and VAT areas were measured at the umbilical level by computed tomography. RESULTS: Spearman's rank correlation analysis showed that urinary aldosterone was significantly and positively correlated with body mass index, waist circumference, SAT area, alanine aminotransferase, C-reactive protein, plasma immune-reactive insulin, plasma renin activity and estimated glomerular filtration rate, and negatively correlated with age and blood glucose. Urinary aldosterone was not correlated with VAT area (r = 0·013, P = 0·906). Multivariate regression analyses revealed that log SAT area, age and diastolic blood pressure were significant (P = 0·001, 0·001 and 0·032, respectively) predictors of log urinary aldosterone excretion rate. CONCLUSION: Our results indicate that urinary aldosterone excretion is positively associated with SAT but not with VAT area in the middle-aged obese individuals.Urinary aldosterone is also negatively correlated with age.

Cardiac production of B-type natriuretic peptide is inversely related to the plasma level of free fatty acids in obese individuals - possible involvement of the insulin resistance -.

B-type natriuretic peptide (BNP) is produced by the heart and its plasma level is increased with the severity of left ventricular (LV) dysfunction/hypertrophy. The normal heart preferentially utilizes fatty acids as energy substrates. Plasma BNP levels are reported to be lower in obese individuals. We examined the relationship between BNP production and plasma free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and LV dysfunction/ hypertrophy. We examined the plasma BNP levels and FFA at the aortic root (AO) and coronary sinus (CS) as well as hemodynamic parameters in 62 patients (38 men and 24 women, 62.5±11.7 yrs) who underwent cardiac catheterization. Log BNP (AO) had a significant positive correlation with log BNP (CS-AO) (r=0.877, P<0.001). Log BNP(CS-AO) had a significant negative correlation with BMI (r=-0.558, P<0.001), waist circumference (WC) (r=-0.574, P<0.001), log FFA(AO) (r=-0.643, P<0.001), log triglyceride (r=-0.431, P<0.001), and log HOMA-IR (r=-0.463, P<0.001) and a significant positive correlation with left ventricular mass index (LVMI) (r=0.403, P=0.001). The multivariable regression analyses including log HOMA-IR, LVMI, and age as an independent variable revealed that HOMA-IR and LVMI were significant predictors of log BNP (CS-AO) or BNP production (P=0.001 and 0.004, respectively). We conclude that plasma BNP levels are determined primarily by cardiac production and that insulin resistance is a significant predictor of cardiac BNP production independent of LV hypertrophy in obese individuals.

Effects of angiotensin receptor-neprilysin inhibitor on insulin resistance in patients with heart failure.

AIMS: Although the haemodynamic effects of angiotensin receptor-neprilysin inhibitor (ARNI) on patients with heart failure have been demonstrated, the effect on glucose metabolism has not been fully elucidated. We retrospectively investigated the effect of ARNI on abnormal glucose metabolism in patients with stable chronic heart failure using an additional structural equation model (SEM) analysis. METHODS: We analysed 34 patients who regularly visited to the outpatient department of our institute with heart failure from October 2021 and July 2022 and who were taking angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). Seventeen patients switched from ACE inhibitors or ARBs to an ARNI (ARNI group), and the other 17 patients continued treatment with ACE inhibitors or ARBs (control group). RESULTS: At baseline, although the ARNI group included fewer patients with heart failure with preserved ejection fraction in comparison with the control group (P = 0.004), patients with heart failure with mildly reduced ejection fraction, and heart failure with reduced ejection fraction were mostly biased towards the ARNI group (although not statistically significant). The baseline insulin resistance in the ARNI group was already significantly higher in comparison with the control group [fasting blood insulin, 9.7 (7.4, 11.6) vs. 7.8 (5.2, 9.2) µU/mL, P = 0.033; homoeostasis model assessment of insulin resistance (HOMA-IR), 3.10 (1.95, 4.19) vs. 2.02 (1.56, 2.42), P = 0.014]. Three months later, the fasting blood insulin and the HOMA-IR levels were both found to have decreased in comparison with the baseline values [baseline to 3 months: insulin, 9.7 (7.4, 11.6) to 7.3 (4.6, 9.4) µU/mL, P < 0.001; HOMA-IR, 3.10 (1.95, 4.19) to 1.96 (1.23, 3.09), P < 0.001]. An additional SEM analysis demonstrated that the initiation of ARNI had caused a reduction in the fasting blood insulin and the HOMA-IR levels at 3 months independently of the baseline fasting blood insulin and HOMA-IR levels, respectively. Similarly, the initiation of ARNI resulted in a significant reduction in serum uric acid levels (6.28 ± 0.35 to 5.80 ± 0.30 mg/dL, P = 0.008). CONCLUSIONS: In conclusion, even in a short period of only 3 months, the administration of ARNI improved insulin resistance and consequently reduced the serum uric acid levels in patients with stable chronic heart failure. Although the ARNI group already had high insulin resistance at baseline, an additional SEM analysis revealed that the decreased insulin resistance was truly due to the effect of ARNI.

URAT1 is expressed in cardiomyocytes and dotinurad attenuates the development of diet-induced metabolic heart disease.

We recently reported that the selective inhibition of urate transporter-1 (URAT1), which is primarily expressed in the kidneys, ameliorates insulin resistance by attenuating hepatic steatosis and improving brown adipose tissue function in diet-induced obesity. In this study, we evaluated the effects of dotinurad, a URAT1-selective inhibitor, on the hearts of high-fat diet (HFD)-fed obese mice for 16-20 weeks and on neonatal rat cardiomyocytes (NRCMs) exposed to palmitic acid. Outside the kidneys, URAT1 was also expressed in cardiomyocytes and indeed worked as a uric acid transporter. Dotinurad substantially attenuated HFD-induced cardiac fibrosis, inflammatory responses, and cardiac dysfunction. Intriguingly, among various factors related to the pathophysiology of diet-induced obesity, palmitic acid significantly increased URAT1 expression in NRCMs and subsequently induced apoptosis, oxidative stress, and inflammatory responses via MAPK pathway, all of which were reduced by dotinurad. These results indicate that URAT1 is a potential therapeutic target for metabolic heart disease.

Paralytic Ileus during Treatment of Pulmonary and Renal Tuberculosis in a Non-Human Immunodeficiency Virus Patient: An Unusual Presentation of Tuberculosis-immune Reconstitution Inflammatory Syndrome.

Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.

[Abnormalities of magnesium (Mg) metabolism and therapeutic significance of Mg administration in patients with metabolic syndrome, type 2 diabetes, heart failure and chronic hemodialysis].

Magnesium (Mg) , one of the fundamental minerals acting the co-factor of about 300 kinds of enzymes and natural Ca channel blocker, plays an important role of cardiovascular, neurological, and metabolic functions in physiological, and pathophysiological conditions. Common abnormal Mg metabolism is an absolute or relative deficiency of Mg due to an attenuated Mg intake and an enhanced urinary Mg excretion, particularly in the metabolic syndrome (MetS) , type 2 diabetes (DM) , chronic heart failure (CHF) and hemodialysis (HD) patients with diabetes. It has been reported the Mg deficiency relating to enhanced risk of MetS and type 2 DM, and to fatal cardiac events in CHF and an atherosclerotic, vascular calcification in HD patients. On the otherhand, severe and fatal hypermagnesemia is very rare, except for the condition associated with high dose administration of Mg, renal failure and an abnormally enhanced Mg absorption from damaged intestine in the mesenteric ischemia/infarction, severe constipation or ileus. In this paper, we conduct to review and discuss the pathophysiological and pathogenetical role of the abnormal Mg metabolism focused on Mg deficiency, and the protective and therapeutic significance of Mg administration in the MetS, type 2 DM, CHF and diabetic HD patients.

Heart Failure Treatments Such As Angiotensin Receptor/Neprilysin Inhibitor Improve Heart Failure Status and Glucose Metabolism.

A recent study suggested that angiotensin receptor/neprilysin inhibitor (ARNI; sacubitril/valsartan) can improve functional capacity and cardiac reverse remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Another study suggested that ARNI reduced glycated hemoglobin (HbA1c) in patients with diabetes and HFrEF; however, the details of its efficacy are unknown. We herein report a case of HFrEF with abnormal glucose metabolism in which ARNI was initiated. On the 7th day of admission (before the initiation of ARNI), blood tests showed an abnormal glucose metabolism as follows: fasting blood glucose 134 mg/dL; and fasting blood insulin 11.4 µU/mL (homeostasis model assessment of insulin resistance (HOMA-IR) index 3.77; homeostasis model assessment of ß-cell function (HOMA-ß), 57.8%). On the 23rd day after the initiation of ARNI, even though the patient was not using hypoglycemic drugs, his fasting blood glucose markedly decreased to 70 mg/dL without hypoglycemic symptoms, and his fasting blood insulin decreased to 5.4 µU/mL (HOMA-IR decreased to 0.93, HOMA-ß increased to 277.7%). These results imply that ARNI has the potential to improve insulin resistance and the islet beta-cell function in patients with heart failure, in addition to the original effect of improving the hemodynamics, although the effect of improving the glucose metabolism is also considered to have been influenced by the improvement of the heart failure status and other drugs that the patient was taking.