Impact of Glucocorticoid Replacement Therapy on Nocturnal Hypoglycemia in Adrenal Insufficiency: An Analysis of Multiple Case Studies.

BACKGROUND AND AIM: Adrenal insufficiency (AI) is a hormonal disorder characterized by insufficient glucocorticoid production. Nocturnal hypoglycemia (NH) occurs in patients with AI. However, the effect of glucocorticoid replacement therapy (GCRT) on AI and NH remains unclear. This study aimed to investigate the relationship between AI and NH by evaluating the impact of GCRT on NH in patients newly diagnosed with AI. METHODS: The present study was conducted between October 2018 and December 2022 at the Department of Diabetes, Metabolism and Endocrinology of the Tokyo Rosai Hospital, Japan. In total, 15 patients aged ≥18 years with newly diagnosed AI or NH were included in this study. The NH frequency was measured using continuous glucose monitoring (CGM). The primary outcome was the change in NH frequency before and after the GCRT intervention. RESULTS: GCRT significantly decreased NH frequency. Severe NH frequency and minimum nocturnal glucose levels changed significantly while fasting blood glucose and glycated hemoglobin levels did not change significantly. GCRT intervention improved CGM profiles' time below range, time in range, and average daily risk range. CONCLUSIONS:  The present study suggests that GCRT can help newly diagnosed patients with AI manage NH. These findings show that CGM can detect NH in patients with newly diagnosed AI, determine the optimal GCRT dosage, and hence prevent an impaired quality of life and even serious adverse effects in these patients. Further large multicenter studies should validate these findings and delve deeper into the mechanistic link between AI and NH.

Clinical insights of pregnancy management, adrenal insufficiency as a possible cause of elevated TSH: a pilot study of case series.

BACKGROUND: The upper limit for thyroid-stimulating hormone has been strictly defined for pregnancy management, at which point levothyroxine replacement therapy will been initiated. However, it is essential to exclude adrenal insufficiency, including subclinical adrenal insufficiency, when initiating levothyroxine replacement therapy. However, in pregnancy management, it has rarely reported the incidence, clinical course, and characteristics of adrenal insufficiency as a possible cause of elevated thyroid-stimulating hormone. METHODS: This case series study included pregnant patients undergoing thyroid-stimulating hormone management in a single-center diabetes endocrinology department between 2017 and 2020. The primary study outcome was the incidence of newly diagnosed adrenal insufficiency. We reported the clinical course and assessed the adrenal insufficiency characteristics at baseline and delivery and compared them with those of hypothyroidism. RESULT: Fifteen pregnant women were included for thyroid-stimulating hormone management; and nine were below the basal serum cortisol level, and four were newly diagnosed as having adrenal insufficiency (26.7%) with the endocrinological stimulation test. Among them, two cases exhibited nausea and hypoglycemic symptoms after the start of levothyroxine replacement therapy. In cases of adrenal insufficiency, the patients were successfully treated with appropriate steroid coverage. CONCLUSIONS: In the management of elevated thyroid-stimulating hormone levels during pregnancy, the frequency of adrenal insufficiency suspecting hypothyroidism may be higher than expected; therefore, we must be careful about starting levothyroxine replacement therapy for hypothyroidism. These clinical insights can have a significant impact on the pregnancy outcomes.

Ceftriaxone-associated Biliary Pseudolithiasis with Elderly Type 1 Diabetes Mellitus: Two Case Reports.

Biliary pseudolithiasis is a ceftriaxone (CTRX)-induced complication, but the risk in cases of elderly type 1 diabetes mellitus (T1DM) is unclear. Case 1: A 78-year-old woman with T1DM complicated by diabetic autonomic neuropathy was admitted with pneumonia and treated with CTRX. On day 8, biliary pseudolithiasis and cholecystitis were observed. Case 2: an 80-year-old woman with T1DM was suspected of having a urinary tract infection and treated with CTRX. After a week, she developed asymptomatic biliary pseudolithiasis with gastroparesis. CTRX-associated biliary pseudolithiasis was thus noted in these cases of elderly T1DM. CTRX should be cautiously administered, especially in elderly T1DM patients with diabetic autonomic neuropathy.

A comprehensive risk assessment for nocturnal hypoglycemia in geriatric patients with type 2 diabetes: A single-center case-control study.

AIMS: To evaluate the overall association between clinically significant nocturnal hypoglycemia (CsNH) and risk factors in geriatric patients with type 2 diabetes. METHODS: Overall, 606 geriatric with type 2 diabetes were evaluated for CsNH using Freestyle Libre Pro® (Abbott Diabetes Care, Tokyo, Japan) during October 2018-February 2020. We defined CsNH as blood glucose level <54 mg/dL (3.0 mmol/L). We investigated clinical characteristics and efficacies of hypoglycemic agents and insulin and analyzed CsNH risk factors using univariate and multivariate logistic regression analyses. RESULTS: We enrolled 152 patients each for the CsNH and non-nocturnal hypoglycemia groups. Insulin use (OR = 3.77 [95 % CI: 1.92-7.67]; P = 0.0002), age (OR = 1.06 [95 % CI: 1.01-1.12]; P = 0.0492), estimated glomerular filtration rate (OR = 0.97 [95 % CI: 0.95-0.98]; P = 0.0492), and fasting blood glucose level (OR = 0.94 [95 % CI: 0.91-0.94]; P < 0.0001) were independent CsNH risk factors. The combined results demonstrated a higher predictability of CsNH than each of the individual risk factors. CONCLUSIONS: We identified risk factors that could help predict CsNH in geriatric patients with type 2 diabetes and demonstrated a comprehensive risk factor assessment.

Different Life Histories and Life Styles in Spatangoid Echinoids Living in the Shallow Sublittoral Zone in the Oki-Islands, Japan.

The growth rate, reproduction, recruitment and feeding of four spatangoid species in the Okiislands in the Japan Sea were investigated over five years. Nacospatangus alta, which inhabits unstable surface sediments, grows rapidly, reaches sexual maturity early, and has a short life span, indicating that it should be a ruderal, whereas Metalia spatagus and Brissus agassizii, which inhabit relatively stable deep sediment, grow slowly, reach sexual maturity late, and have a long life span, suggesting that they are stress-tolerators. Lovenia elongata, however, inhabits unstable surface sediment but has an exceptional life history; it grows rapidly, but does not reach sexual maturity early and has a long life span, likely because the specific morphology of its spines and tubercles allow it to cope with surface disturbances caused by storms. Lovenia elongata seems to be a competitive ruderal. A trade-off between test formation and gonad development may occur; N. alta constructs a fragile test with very thin plates, allowing the echinoid to allocate energy to increasing test size and developing the gonad to sexual maturity within a year. Lovenia elongata, with thick plates supporting the specific stout spines and tubercles, needs 2 years to reach sexual maturity with a similar rate of test growth to that of N. alta; M. spatagus and B. agassizii construct robust tests with thick plates, presumably necessary for these species, which burrow and live deep in sand under high pressure from surrounding sand. These echinoids do not reach sexual maturity until over 2 years of age. The flexible trade-off related to stress and disturbance associated with burrowing depth in different habitats allows the spatangoids to have different life-history strategies.

Sustained fasting glucose oxidation and postprandial lipid oxidation associated with reduced insulin dose in type 2 diabetes with sodium-glucose cotransporter 2 inhibitor: A randomized, open-label, prospective study.

AIMS/INTRODUCTION: Hyperglycemia impairs energy substrate oxidation as a result of glucotoxicity. We examined whether the reduction of plasma glucose using a sodium-glucose cotransporter 2 inhibitor, in inpatient diabetes management, has any effect on: (i) treatment period and basal-bolus dosage of insulin that achieve euglycemia; (ii) fasting/postprandial energy expenditure (EE); and (iii) energy substrate oxidation. MATERIALS AND METHODS: This was a randomized, open-label, 7-day prospective study. Participants were type 2 diabetes patients with hyperglycemia, aged >20 years, with glycated hemoglobin >10%, daily mean preprandial blood glucose >11 mmol/L (200 mg/dL) and no previous antidiabetic medication. A total of 18 type 2 diabetes patients were randomized (1:1) to basal-bolus insulin titration algorithm (INS) alone or INS + dapagliflozin 5 mg/day (INS/DAPA). The main outcome measures were total daily insulin dose to achieve euglycemia, as well as EE and respiratory quotient during fasting and postprandial states, measured by indirect calorimetry. RESULTS: The rate of euglycemia was higher in the INS/DAPA compared with INS group (100 vs 55.6%, P = 0.04), whereas the total daily dose of insulin was 19% lower and was accompanied by a decreased basal-bolus ratio (P = 0.02). Fasting and postprandial EE elevation were similar in both groups. The post-treatment fasting respiratory quotient significantly increased in the INS/DAPA group (0.72 ± 0.05 vs 0.79 ± 0.08, P = 0.04), and the postprandial respiratory quotient elevation was abolished; the opposite trend was observed in the INS group (P < 0.02). CONCLUSIONS: INS/DAPA sustained fasting carbohydrate oxidation, postprandial lipid-derived EE (failed to increase carbohydrate-derived EE) and reduced basal insulin requirement might be related to further bodyweight loss. CLINICAL TRIAL REGISTRY: National University Hospital Medical Information Network UMIN000018997.

Glycemic Variability in Type 1 Diabetes Compared with Degludec and Glargine on the Morning Injection: An Open-label Randomized Controlled Trial.

INTRODUCTION: Optimal adjustment of basal insulin to overcome hypoglycemia and glycemic variability (GV) depends on its duration of action and peak-less profile. Owing to the ability of long-acting basal insulin to avoid hypoglycemia, we titrated pre-meal glucose to normal fasting blood glucose, 80-110 mg/dL (4.5-6.1 mmol/L), and post-meal glucose to 80-140 mg/dL (4.5-7.8 mmol/L). The purpose of this study was to evaluate two basal insulin analogues degludec (IDeg) and glargine (IGlar), injected in the morning, for GV using continuous glucose monitoring (CGM) in type 1 diabetes (T1DM). METHODS: In this crossover study, 20 Japanese patients with T1DM (age 54 ± 16 years, disease duration 16 ± 8 years, BMI 24 ± 4 kg/m2, HbA1c 7.4 ± 0.8%) were randomized into one of two different starting regimens, and CGM was conducted on three consecutive days during the last week of each 12-week titration period. Treatment satisfaction was assessed at the end of each treatment period using the Diabetes Therapy-Related Quality of Life Questionnaire (DTR-QOL). RESULTS: There were no differences in HbA1c, total insulin dosage, body weight changes, and basal to bolus ratio between the IDeg and IGlar arms. The day-to-day variability in fasting interstitial GV on the CGM curves was significantly less in the IDeg than IGlar treatment period (25.9 ± 22.0 vs. 43.8 ± 30.1 mg/dl, p = 0.04). Other markers of GV, calculated by the EasyGV software, including mean amplitude of glycemic excursions (MAGE), J-index, total and nocturnal hypoglycemia were not different between the two treatment periods. The score of "satisfaction with treatment", a subdomain of the DTR-QOL system, was higher in the IDeg period. CONCLUSION: Thus, the morning injection of the two long-acting insulin analogues seemed similar with regard to the magnitude of hypoglycemia in T1DM, but treatment with IDeg was associated with lower day-to-day variation in glucose level. These results suggest that IDeg is safe with minimal morning GV in patients with T1DM. CLINICAL TRIAL REGISTRATION: Japanese Clinical Trials Registry, UMIN000012358.

Attractive interaction between Mn atoms on the GaAs(110) surface observed by scanning tunneling microscopy.

Scanning tunneling microscopy/spectroscopy (STM/STS) was carried out to investigate the structures of Mn atoms deposited on a GaAs(110) surface at room temperature to directly observe the characteristics of interactions between Mn atoms in GaAs. Mn atoms were paired with a probability higher than the random distribution, indicating an attractive interaction between them. In fact, re-pairing of unpaired Mn atoms was observed during STS measurement. The pair initially had a new structure, which was transformed during STS measurement into one of those formed by atom manipulation at 4 K. Mn atoms in pairs and trimers were aligned in the <110> direction, which is theoretically predicted to produce a high Curie temperature.

Dynamic probe of ZnTe(110) surface by scanning tunneling microscopy.

The reconstructed surface structure of the II-VI semiconductor ZnTe (110), which is a promising material in the research field of semiconductor spintronics, was studied by scanning tunneling microscopy/spectroscopy (STM/STS). First, the surface states formed by reconstruction by the charge transfer of dangling bond electrons from cationic Zn to anionic Te atoms, which are similar to those of IV and III-V semiconductors, were confirmed in real space. Secondly, oscillation in tunneling current between binary states, which is considered to reflect a conformational change in the topmost Zn-Te structure between the reconstructed and bulk-like ideal structures, was directly observed by STM. Third, using the technique of charge injection, a surface atomic structure was successfully fabricated, suggesting the possibility of atomic-scale manipulation of this widely applicable surface of ZnTe.

Real space probe of short-range interaction between Cr in a ferromagnetic semiconductor ZnCrTe.

The short-range interaction between Cr atoms was directly examined by scanning tunneling microscopy measurements on a Zn(0.95)Cr(0.05)Te film. Our measurements revealed that a Cr atom formed a localized state within the bandgap of ZnTe and this state was broadened for a pair of Cr atoms within a distance of ∼ 1 nm.

New method for liquid-medication filling systems.

For the systems used to fill large numbers of containers with liquid medication, a permissible relative error is ±1.0%. Here, a medication filling and estimating system was designed to improve cycle time. The nonlinear least squares (NLS) method was used with the proposed system, and the results succeeded in providing the medication fill ration meeting certain specifications and below the permissible relative error. The proposed method also realizes medication filling accuracy comparable to that achieved by the conventional method, but additionally made it possible to shorten the time needed to compute the weight value by approx 60%. Moreover, since a low-pass filter does not need to be used with the proposed method, the new method is not subject to the influence of a time delay.

Scanning tunneling microscopy/spectroscopy on self-assembly of a glycine/Cu(111) nanocavity array.

The step-by-step analysis of a hierarchical self-assembly revealed the incorporation of nanocavity blocks in a metastable orientation to stabilize the organized array. The confinement of 2D electrons by a quantum corral was verified. Furthermore, manipulation of an isolated C(60) molecule was realized using nanocavities of ∼1.3 nm diameter as a template.

Optical doping: active control of metal-insulator transition in nanowire.

The reversible control of metal-insulator transition (MIT) in In/Si(111) nanowires is demonstrated by tuning the band filling of the one-dimensional surface state by optical doping. The control of MIT is carried out by regulating the Fermi level in the surface state around the half-filled position, depending on the carrier density introduced at the interface. We successfully achieved the reversible and active control of MIT via the charge doping by regulating the intensity of photoexcitation. This method is widely applicable to other low-dimensional systems and makes MIT more controllable and suitable for use in nanowires as an active element in future architectures of nanosized functional devices as well as nanoscale interdevice wiring.

Development of bellows and gate valves with a comb-type rf shield for high-current accelerators: four-year beam test at KEK B-Factory.

Since a comb-type rf shield was proposed in 2003 as a rf shield for future high-intensity accelerators, various types of bellow chambers and gate valves with this rf shield have been installed in the KEK B-Factory rings in series and tested with beams. Through beam tests to check the performance, a structural simplification has been tried in parallel. The temperatures of the bellow corrugations decreased by a factor of 3-6 compared to those with a conventional finger-type rf shield in most cases. The temperatures of the body of the gate valves also decreased by a factor of 2-5. These results demonstrated the availability of the comb-type rf shield. Although a discharge was observed in one simplified model, the latest model has shown no problem up to a stored beam current of 1.8 A (1.3 mA/bunch, 6 mm bunch length). Experiences with the comb-type rf shield in these four-year beam tests are reviewed here.

What orchestrates the self-assembly of glycine molecules on Cu(100)?

The structures of two competing phases and their interrelationship in the self-organization of glycine molecules on a Cu(100) surface were clarified. Despite their similar structural energies predicted using first-principles calculation, completely different mechanisms were found to stabilize the two phases. The balance and coordination of the two mechanisms that induce a variety of self-assembled structures in this attractive system were revealed. Furthermore, the importance of the microscopic arrangement of the molecules in designing the macroscopic electronic structures was directly demonstrated.