Lipids in health and disease.

United Kingdom Prospective Diabetes Study(UKPDS)からのメッセージとその解釈

Context Subacute thyroiditis (SAT) is a thyroid disease of viral or postviral origin. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that began in Wuhan, China, has spread rapidly worldwide and Italy has been severely affected by this outbreak. Objectives The objective of this work is to report the first case of SAT related to SARS-CoV-2 infection. Methods We describe the clinical, laboratory, and imaging features of an 18-year-old woman who came to our attention for fever, neck pain radiated to the jaw, and palpitations occurring 15 days after a SARS-CoV-2-positive oropharyngeal swab. Coronavirus disease 2019 (COVID-19) had been mild and the patient had completely recovered in a few days. Results At physical examination the patient presented with a slightly increased heart rate and a painful and enlarged thyroid on palpation. At laboratory exams free thyroxine and free triiodothyronine were high, thyrotropin undetectable, and inflammatory markers and white blood cell count elevated. Bilateral and diffuse hypoechoic areas were detected at neck ultrasound. One month earlier, thyroid function and imaging both were normal. We diagnosed SAT and the patient started prednisone. Neck pain and fever recovered within 2 days and the remaining symptoms within 1 week. Thyroid function and inflammatory markers normalized in 40 days. Conclusions We report the first case of SAT after a SARS-CoV-2 infection. We alert clinicians to additional and unreported clinical manifestations associated with COVID-19.

Subacute Thyroiditis After Sars-COV-2 Infection.

Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.

Vascular Calcification-New Insights Into Its Mechanism.

Background: Sodium glucose cotransporter 2 inhibitors may reduce kidney hyperfiltration, thereby preventing diabetic kidney disease progression, which may in turn reduce cardiovascular risk, includ...

https://ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.118.037418

Evaluation of Glomerular Hemodynamic Function by Empagliflozin in Diabetic Mice Using In Vivo Imaging.

IL-6 and sIL-6R induces STAT3-dependent differentiation of human VSMCs into osteoblast-like cells through JMJD2B-mediated histone demethylation of RUNX2.

Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins. The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels ≥80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment. The percent change of LDL-C was −31% in the combination group and −12% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level <80 mg/dL. As a result, add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C. Compared with increasing the dose of rosuvastatin, the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients, suggesting that this combination could suppress the progression of atherosclerosis. UMIN000011005

/pdf/efficacy-of-combination-of-ezetimibe-10-mg-and-rosuvastatin-3g0mc3y9rt.pdf

Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes

The rate of recurrence of subacute thyroiditis (SAT) during prednisolone (PSL) therapy is approximately 10 to 20%. However, there is little or no information on the time period to relapse following administration of a tapered dose of PSL and the factors associated with such relapse. The aim of this study was to determine the correlation between SAT recurrence and PSL tapering regimen used in the treatment of SAT. This study was a medical record-based retrospective study and involved 26 patients (3 men, 23 women) who received PSL therapy for SAT. The primary endpoint was the association between recurrence and number of days required to taper daily PSL dose to 5 mg. The secondary endpoint was the relationship between recurrence and several variables including age, clinical score, free thyroxine, inflammatory reaction, thyroglobulin, total treatment time, total dose of PSL and presence or absence of creeping thyroiditis. The SAT recurrence rate was 15.3%. There was no significant difference in the initial PSL dose between the non-recurrence and recurrence groups (27.5 mg vs 24.5 mg, P = 0.302). However, for the primary endpoint, significant differences were found between the two groups in time required for tapering PSL to 5 mg/day (non-recurrence: 44.3 ± 15.3 days, recurrence: 19.0 ± 11.9 days, P = 0.012). None of the clinical variables evaluated correlated significantly with SAT relapse. In conclusion, to prevent recurrence of SAT, consideration should be given to the period required for PSL tapering to 5 mg/day.

https://www.jstage.jst.go.jp/article/juoeh/37/2/37_103/_pdf

Prednisolone Dosing Regimen for Treatment of Subacute Thyroiditis

Objective Visceral fat obesity and metabolic syndrome correlate with atherosclerosis in part due to insulin resistance and various other factors The aim of this study was to determine the relationship between vascular endothelial dysfunction and excess visceral adipose tissue (VAT) in Japanese patients with type 2 diabetes mellitus (T2DM) Methods In 71 T2DM patients, the reactive hyperemia index (RHI) was measured using an Endo-PAT 2000, and VAT and subcutaneous adipose tissue (SAT) were measured via CT We also measured various metabolic markers, including high-molecular-weight adiponectin (HMW-AN) Results VAT correlated negatively with the natural logarithm of RHI (L_RHI), the primary endpoint (p=0042, r=-0242) L_RHI did not correlate with SAT, VAT/SAT, abdominal circumference, homeostasis model assessment for insulin resistance, urinary C-peptide reactivity, HMW-AN, or alanine amino transferase, the secondary endpoints A linear multivariate analysis via the forced entry method using age, sex, VAT, and smoking history as independent variables and L_RHI as the dependent variable revealed a lack of any determinants of L_RHI Conclusion Excess VAT worsens the vascular endothelial function, represented by RHI which was analyzed using Endo-PAT, in Japanese patients with T2DM

Excess Visceral Adipose Tissue Worsens the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus.

Aims/Introduction
The aim of this study was to determine the actual state of inter-day glycemic variability and identify the factors that affect glycemic variability in diabetic outpatients on insulin therapy.

Materials and Methods
The subjects were 45 outpatients with diabetes mellitus on insulin therapy. The mean plasma glucose (MPG) levels, intra-day glycemic variability (expressed by standard deviation [SD] and mean amplitude of glucose excursion [MAGE]), and inter-day glycemic variability (expressed by mean of daily differences in blood glucose levels [MODD]) were measured continuously over seven days with iPro2®. The primary outcome was the relationship between MODD and life variability index.

Results
MODD values were high in 93.3% of the subjects, and significantly higher in patients with lifestyle changes than in those without (higher in patients with high life variability index). MODD values were not associated with age, but significantly higher in women. MODD values correlated significantly with HbA1c and glycoalbumin levels, and negatively with 1,5-anhydroglucitol (1,5-AG) levels. MODD values were significantly higher in type 1 diabetes patients and not associated with duration of disease. MODD values correlated significantly with insulin dose. Multivariate analysis identified life variability index as a significant determinant of MODD.

Conclusions
iPro2® provided detailed information on glycemic profile in diabetic outpatients on insulin therapy. The results suggest that patients with large inter-day glycemic variability are unlikely to achieve improvement in HbA1c level. Treatment and instructions based on patient's characteristics, day-to-day glycemic variability and lifestyle are important to achieve good glycemic control. This clinical trial was registered with the University Hospital Medical Information Network (UMIN000019727).

This article is protected by copyright. All rights reserved.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/jdi.12551

Akira Kurozumi

Papers

IL-6 and sIL-6R induces STAT3-dependent differentiation of human VSMCs into osteoblast-like cells through JMJD2B-mediated histone demethylation of RUNX2.

Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes

Prednisolone Dosing Regimen for Treatment of Subacute Thyroiditis

Excess Visceral Adipose Tissue Worsens the Vascular Endothelial Function in Patients with Type 2 Diabetes Mellitus.

Factors influencing inter‐day glycemic variability in diabetic outpatients receiving insulin therapy