Metabolic syndrome (MetS) consists of 5 metabolic components, which are recognized as risk factors for cerebral infarction. The present study was to evaluate the relative influence of individual metabolic component on incident cerebral infarction. Using a data of 209,339 Koreans registered in National Health Information Corporation, we evaluated the risk for incident cerebral infarction according to the number of metabolic component and each metabolic component for 4.37 years’ follow-up. Cox proportional hazards model was used to calculate hazard ratios (HRs) for cerebral infarction and their confidence interval (CI). The more metabolic components accompanied the worse metabolic profile, leading increased incidence of cerebral infarction. The risk of cerebral infarction increased proportionally to the number of present metabolic components (number 0: reference, number 1: 1.78 [1.42–2.23], number 2: 2.20 [1.76–2.74], number 3: 2.61 [2.09–3.25] and number 4–5: 3.18 [2.54–3.98]). Compared to subjects without metabolic component, the impact of each component on cerebral infarction was relatively higher in elevated fasting glucose (1.56 [1.14–2.13]) and elevated BP (2.13 [1.66–2.73]), indicating no statistical significance in low HDL-cholesterol (1.53 [0.96–2.44]), high triglyceride (1.24 [0.84–1.84]) and abdominal obesity (1.05 [0.63–1.73]). Proportional relationship was found between the number of metabolic component and risk of cerebral infarction. Out of metabolic components, fasting glucose and BP are more powerful predictor for cerebral infarction.

Werner syndrome, also called adult progeria, is a heritable autosomal recessive human disorder characterized by the premature onset of numerous age-related diseases including juvenile cataracts, dyslipidemia, diabetes mellitus (DM), osteoporosis, atherosclerosis, and cancer. Werner syndrome is a segmental progeroid syndrome whose presentation resembles accelerated aging. The most common causes of death for WS patients are atherosclerosis and cancer. A 40-year-old female presented with short stature, bird-like facies, canities with alopecia, scleroderma-like skin changes, and non-healing foot ulcers. The patient reported a history of delayed puberty, abortion, hypertriglyceridemia, and juvenile cataracts. A clinical diagnosis of WS was made and subsequently confirmed. We discovered two WRN gene mutations in the patient, Variant 1 was the most common WRN mutation, nonsense mutation (c.1105C>T:p.R369Ter) in exon 9, which caused a premature termination codon (PTC) at position 369. Variant 2 was a frameshift mutation (c.1134delA:p.E379KfsTer5) in exon 9, which caused a PTC at position 383 and has no published reports describing. Patients with WS can show a wide variety of clinical and biological manifestations in endocrine-metabolic systems (DM, thyroid dysfunction, and hyperlipidemia). Doctors must be cognizant of early manifestations of WS and treatment options.

Rathke’s cleft cyst (RCC) is a common incidental tumor in the hypothalamic-pituitary region. Some reports have shown that the clinical symptoms and endocrine functions of symptomatic RCCs are temporarily improved by glucocorticoid administration. However, it is still unknown whether glucocorticoid treatment is effective for symptomatic RCCs according to long-term observations. In this study, we describe the long-term clinical outcomes of two cases of glucocorticoid-treated biopsy-proven secondary hypophysitis caused by RCCs. We summarize the symptoms, imaging findings, and endocrine evaluations of two symptomatic RCC patients with concomitant hypophysitis before and after prednisolone treatment. In both evaluated cases, visual impairments and altered endocrine parameters were present due to chiasm and stalk compression; these outcomes improved after shrinkage of RCCs in response to prednisolone administration, and partial recovery of anterior pituitary hormone secretion was observed. However, in both cases, the deficits in anterior pituitary hormone secretion recurred, possibly due to persistent inflammatory infiltration in the RCCs and pituitary glands. After relapse of hypophysitis, anterior hormone secretion did not fully recover. In our cases of secondary hypophysitis caused by RCCs, prednisolone administration had an early effect of cyst shrinkage, followed by partial improvements in clinical symptoms and pituitary functions. However, long-term observation showed that prednisolone treatment did not contribute to complete improvement in anterior pituitary hormone dysfunction.

Diabetes mellitus (DM) is widely considered to be associated with the risk of diverse cancers; however, the association between DM and the risk of leukemia is still controversial. Thus, a detailed meta-analysis of cohort studies was conducted to elucidate this association. Eligible studies were screened through the electronic searches in PubMed, Web of Science, and Embase from their inception to August 11, 2020. Summary relative risks (RRs) and 95% confidence intervals (CIs) were computed through the random-effects model. Eighteen articles involving 10,516 leukemia cases among a total of 4,094,235 diabetic patients were included in this meta-analysis. Overall, twenty-five RRs were synthesized for type 2 diabetes mellitus (T2DM) and yielded a summary RR of 1.33 (95%CI, 1.21–1.47; p < 0.001). For type 1 diabetes mellitus (T1DM), 7 RRs were combined, however, the pooled RR was insignificant (RR, 1.08; 95%CI, 0.87–1.34; p = 0.48). Interestingly, the summary RR for East Asia (RR, 1.83, 95%CI, 1.63–2.06) was significantly higher than that for Europe (RR, 1.11, 95%CI, 1.06–1.15), Western Asia (RR, 1.40, 95%CI, 1.25–1.54), North America (RR, 1.14, 95%CI, 1.08–1.20), and Australia (RR, 1.47, 95%CI, 1.25–1.71). Moreover, we found that patients with a shorter T2DM duration (1–5 years) had a higher risk of leukemia compared to those with a longer duration (5.1–10 years). Overall, this meta-analysis suggests there is a moderately increased risk of leukemia among T2DM patients, but not in T1DM patients. Further investigation is warranted.

Type 2 diabetes is associated with sarcopenia. Resistance training and appropriate nutritional therapy are reported to be effective for muscle strength and mass. This study aimed to evaluate the effect of resistance training using elastic bands at home combined with a leucine-rich amino acid supplement on muscle strength, physical function, and muscle mass in elderly type 2 diabetes. We conducted a 48-week prospective single-center randomized controlled trial in 60 patients who were randomly allocated to one of three groups: control (C), resistance exercise (R), and resistance exercise plus supplement (RL). R and RL groups performed daily bodyweight resistance training with elastic bands exercises at home, and the RL group also took 6 g of a leucine-rich amino acid supplement daily. Knee extension strength (muscle strength), grip strength, usual gait speed (physical function), muscle mass, and cognitive function were assessed at 0 and 48 weeks. Although the change in knee extension strength from baseline was significantly increased by 6.4 Nm (95% CI 1.0, 11.7) in the RL group (p = 0.036), no significant difference was observed among the three groups (p = 0.090). Physical function, muscle mass, and cognitive function also had no changes during the study period among the three groups. No additive effect of a leucine-rich amino acid supplement on muscle strength or mass was observed. Although a post hoc analysis comparing with or without resistance training (C group vs. R + RL group) found that knee extension strength was significantly increased (p = 0.028), and cognitive decline was less (p = 0.046) than in the C group.

Primary aldosteronism (PA) is the most common cause of secondary hypertension, and a simpler non-invasive method for identification of aldosterone-producing adenoma (APA) is required to improve the standard of medical treatment for PA patients. We retrospectively analyzed the clinical data of hypertensive patients with an aldosterone/renin ratio (ARR) ≥30 (ng/dL)/(ng/mL/h), and surgical and/or adrenal venous sampling (AVS) results served as the gold standard for APA diagnosis. The study aimed to determine whether positive CCT and SIT results plus a unilateral adrenal nodule found by CT allow unambiguous identification of an APA with high diagnostic specificity. Clinical data from 71 APA and 47 non-APA patients were collected, and logistic regression analysis was performed to construct models. Receiver operating characteristic (ROC) curves were used to analyze the efficacy of diagnostic tests. The areas under the ROC curves (AUCs) were similar between the post-SIT plasma aldosterone concentration (PAC) and post-CCT PAC (p > 0.05). The optimal post-SIT and post-CCT PAC cutoff values were 17.2 and 21.2 ng/dL, respectively. Positive CT findings combined with a post-SIT PAC >17.2 ng/dL or post-CCT PAC >21.2 ng/dL provided specificities of 97.8% and 95.7% for predicting APA, respectively. Logistic diagnostic models 1 (M1, CT finding + post-SIT PAC) and 2 (M2, CT finding + post-CCT PAC) were built, which showed equivalent diagnostic value (AUC = 0.959 and 0.932, respectively) (p > 0.05). The models combining CT findings with post-SIT PACs or post-CCT PACs represent an easier method to distinguish APA patients from other hypertensive patients with positive upright ARR results, especially in primary care where AVS may be unavailable.

Testosterone deficiency is associated with poor prognosis among patients with chronic heart failure (HF). Physiological testosterone improves the exercise capacity of patients with HF. In this study, we evaluated whether treatment with physiological testosterone contributes to anti-fibrogenesis by modifying calcium homeostasis in cardiac fibroblasts and we studied the underlying mechanisms. Nitric oxide (NO) analyses, calcium (Ca²⁺) fluorescence, and Western blotting were performed in primary isolated rat cardiac fibroblasts with or without (control cells) testosterone (10, 100, 1,000 nmol/L) treatment for 48 hours. Physiological testosterone (10 nmol/L) increased NO production and phosphorylation at the inhibitory site of the inositol trisphosphate (IP3) receptor, thereby reducing Ca²⁺ entry, phosphorylated Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) expression, type I and type III pro-collagen production. Non-physiological testosterone-treated fibroblasts exhibited similar NO and collagen production capabilities as compared to control (testosterone deficient) fibroblasts. These effects were blocked by co-treatment with NO inhibitor (L-NG-nitro arginine methyl ester [L-NAME], 100 μmol/L). In the presence of the IP3 receptor inhibitor (2-aminoethyl diphenylborinate [2-APB], 50 μmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar phosphorylated CaMKII expression. When treated with 2-APB or CaMKII inhibitor (KN93, 10 μmol/L), testosterone-deficient and physiological testosterone-treated fibroblasts exhibited similar type I, and type III collagen production. In conclusion, physiological testosterone activates NO production, and attenuates the IP3 receptor/Ca²⁺ entry/CaMKII signaling pathway, thereby inhibiting the collagen production capability of cardiac fibroblasts.

The purpose of this study was to explore the impact of maternal thyroid hormone dysfunction in late pregnancy on birth outcomes in a Chinese population. We retrospectively examined hospitalisation records and laboratory data between April 2016 and March 2017 and obtained results from 11,564 consecutive pregnant women with singleton births in which serum thyroid hormone had been examined together with birth outcomes. We assessed the association between maternal thyroid level and dysfunction with adverse birth outcomes based on regression analysis. Hyperthyroidism was associated with an increased risk of preterm birth (PTB, adjusted OR: 2.41, 95% CI: 1.83–3.17) and hypothyroidism was associated with an increased risk of small for gestational age (SGA, adjusted OR: 1.56, 95% CI: 1.10–2.22), while hyperthyroxinaemia was associated with a decreased risk of large for gestational age (LGA, adjusted OR: 0.64, 95% CI: 0.45–0.90). In addition, compared to women with normal FT3 and TSH (≥the 5^th and ≤the 95^th percentiles), women with high free triiodothyronine (FT3 >the 95^th percentile) and low thyroid-stimulating hormone (TSH <the 95^th percentile) had a 4.02- fold higher risk of PTB (95% CI: 2.05–7.88), and women with low FT3 and high TSH had a 4.22- fold greater risk of SGA (95% CI: 1.59–11.23). Our study supports associations between multiple types of maternal thyroid dysfunction in late pregnancy and adverse birth outcomes.

This study was aimed to evaluate the effects of intensive exercise in addition to the administration of sodium-glucose cotransporter 2 inhibitor dapagliflozin (DAPA) on body composition, including fat-free mass, in type 2 diabetes. We randomly assigned 146 patients to 24 weeks of treatment with intensive exercise, including resistance training, plus 5 mg (up to 10 mg) of DAPA daily (IT group) or DAPA alone (CT group). The primary endpoint was the difference in the change in fat-free mass from baseline to 24 weeks between the groups. The skeletal muscle mass index (SMI); metabolic profile, including HbA1c; and regional fat mass were also determined. ANCOVA was used for the group comparison, with least squares mean (LSM) differences and 95% confidence interval (CI). There was no significant difference in the change in fat-free mass (LSM difference –0.1 kg (95% CI: –0.5 to 0.4) and SMI (LSM difference –0.1 kg (95% CI: –0.2 to 0.1) between the groups. In contrast, the reduction of trunk fat mass was significantly higher in the IT group than in the CT group ((LSM difference –0.5 kg [95% CI –0.9 to –0.1]). Higher adherence to the resistance training tended to be associated with changes in HbA1c and high-sensitivity CRP levels. Our study suggests that intensive exercise do not prevent the reduction of fat-free mass after administration of SGLT2 inhibitors but can increase the reduction in abdominal fat, presumably leading to further improvements of hyperglycemia and chronic inflammation than DAPA alone in type 2 diabetes patients.

In recent times, the role of fibroblast growth factor 21 (FGF21) in patients with gestational diabetes mellitus (GDM) has been increasingly investigated. However, to our knowledge, no systematic analysis has been conducted yet to evaluate the relationship between FGF21 levels and GDM. Confirmed studies related to circulating FGF21 levels and GDM were searched from the databases of PubMed, ISI Web of Science, MEDLINE and EMBASE. Data were reported as standard mean difference (SMD) and associated 95% confidence intervals (CIs). Analysis were performed with Review Manager 5.2 and Stata version 11.0. A total of 392 cases and 435 controls in nine articles were included in this meta-analysis. The circulating FGF21 levels in pregnant women with GDM was higher than that in controls (random effects MD [95% CI] = 0.46, [0.07–0.86], p = 0.02). The result of multivariate meta-regression showed that sample size and point of sample collection contributed to heterogeneity (p = 0.033 and p = 0.047, respectively). Additionally, the results showed that there was no publication bias in this meta-analysis (Z = 1.36, p = 0.175; t = 1.24, p = 0.256, respectively). To conclude, this meta-analysis provides evidence that circulating FGF21 levels are higher in GDM subjects than controls, and it is important to clarify the relationship between circulating FGF21 levels and pregnant women with GDM in accurate prediction of GDM.

Many previous studies including ours have reported that athyreotic patients on levothyroxine (LT₄) have relatively low serum free triiodothyronine (FT₃) levels, whereas patients with large goitrous diseases often have high serum FT₃ levels. Here we investigated Hashimoto thyroiditis (HT) patients on LT₄ to study the relationship between thyroid volume (TV) and thyroid hormone status in hypothyroid patients on LT₄. We retrospectively studied 408 euthyroid HT patients treated with LT₄ for hypothyroidism; divided them as per TV and compared serum levels of free thyroxine (FT₄) and FT₃ and the FT₃/FT₄ ratio in each patient group with those in euthyroid matched control group. We also evaluated the association between serum FT₃ level and FT₃/FT₄ ratio and TV among HT patients on LT₄. In patients with TV <15 mL, serum FT₃ levels were significantly lower than those in controls. In patients with TV 15–80 mL, serum FT₃ levels were equivalent to those in controls. In patients with TV ≥80 mL, the serum FT₃ levels were significantly higher than those in controls. The serum FT₃ level (r = 0.35, p < 0.01) and FT₃/FT₄ ratio (r = 0.42, p < 0.01) showed a positive correlation with TV. TVs in HT patients on LT₄ caused differences in serum thyroid hormone balance, as increasing volume increases the serum FT₃ level and FT₃/FT₄ ratio. Serum thyroid hormone balance in HT patients with smaller thyroids was similar to that in athyreotic patients. Mild thyrotropin suppression with LT₄ is needed to achieve normal FT₃ levels in such patients.

The present study used intermittently scanned continuous glucose monitoring (isCGM) in 10 patients with type 1 diabetes mellitus (T1DM) to evaluate the efficacy and safety of 7-day outpatient treatment with the combination of intensive insulin therapy and sodium-glucose transporter 2 inhibitor (SGLT2-I). All participants wore isCGM and were treated with either 50 mg/day ipragliflozin or 5 mg/day dapagliflozin. The primary outcome, percent time with glucose at 70–180 mg/dL (TIR: time in range), improved significantly following the addition of SGLT2-I (p = 0.005). TIR increased from 36.0% before addition of SGLT2-I to 70.7% on day 7. Although none of the patients achieved TIR of 70% or higher before the addition of SGLT2-I, 6 patients met that criteria TIR on day 7. The secondary outcome measures, standard deviation (SD) of glucose, average plasma glucose, percent time with glucose at >180 mg/dL (TAR: time above range), maximum plasma glucose, high blood glucose index (HBGI) and average nocturnal plasma glucose (midnight to 05:59 AM) detected by isCGM, also improved significantly by SGLT2-I. There were no significant differences in percent time with glucose at <70 mg/dL (TBR: time below range), minimum plasma glucose and low blood glucose index (LBGI). Our results using isCGM in an actual clinical setting showed that 7-day use of SGLT2-I with intensive insulin therapy improved plasma glucose fluctuations and mean plasma glucose levels without inducing hypoglycemia in patients with T1DM.

Postpartum thyroiditis (PPT) is characterized by mild thyrotoxicosis occurring within one year of parturition commonly followed by transient hypothyroidism. Having genetic background of autoimmune thyroid disorders is a risk factor for it because the immune reactivation during postpartum period is a trigger for PPT. Pandemic of COVID-19: caused by SARS-CoV-2 infection is a global health problem, and occurrence of Graves’ disease and Hashimoto’s thyroiditis after the viral infection have been reported but occurrence of PPT with COVID-19 has never been reported. A 29-year-old woman developed general fatigue four and a half months after parturition, and was diagnosed as having PPT: one month before, she had COVID-19. Hereafter, we define the date of delivery as Day 0 to make timeline clear. SARS-CoV-2 infection was diagnosed by PCR on Day 103, its disappearance from the upper airway confirmed on Day 124, and the thyroiditis diagnosed on Day 136. She had been euthyroid on Day 0 and 95, but thyrotoxic on Day 136. Serum thyroglobulin (Tg) concentration was normal in the presence of anti-Tg antibody, other thyroid-related autoantibodies were negative, and by ultrasonography, the thyroid gland was normal in size and no evidence of increased vascularity. Thyroid function returned to normal by Day 172 without any specific drug therapy. In conclusion, although a clear causal relationship could not be found, we documented the world’s first case of PPT developed following COVID-19.