Survey of glucocorticoid dose escalation in patients with adrenal insufficiency during the peri-COVID-19 vaccination period.There is uncertainty regarding the need for COVID-19 peri-vaccination glucocorticoid coverage in patients with adrenal insufficiency. In this survey conducted in a single tertiary medical institution, 167 consecutive outpatients taking physiological glucocorticoids because of adrenal insufficiency were included. The patients declared if they developed an adrenal crisis after vaccination, and the amount and duration of an increase in their glucocorticoid dosage, if any. None of the patients without preventive glucocorticoid increase suffered an adrenal crisis after COVID-19 vaccination. Only 8.3% (14 cases) and 27.5% (46 cases) of the patients needed to escalate the dose of glucocorticoids when systemic symptoms appeared after the first and second injections, respectively. Glucocorticoids were increased in patients
Effects of imeglimin on mitochondrial function, AMPK activity, and gene expression in hepatocytes.Imeglimin is a recently launched antidiabetic drug structurally related to metformin. To provide insight into the pharmacological properties of imeglimin, we investigated its effects on hepatocytes and compared them with those of metformin. The effects of imeglimin on mitochondrial function in HepG2 cells or mouse primary hepatocytes were examined with an extracellular flux analyzer and on gene expression in HepG2 cells by comprehensive RNA-sequencing analysis. The effects of the drug on AMPK activity in HepG2 cells, mouse primary hepatocytes, and mouse liver were also examined. Treatment of HepG2 cells or mouse primary hepatocytes with imeglimin reduced the oxygen consumption rate coupled to ATP production. Imeglimin activated AMPK in these cells whereas the potency was smaller than metformin. Bolus administration of imeglimin in mice also activated AMPK in the liver. Whereas the effects of imeglimin and metformin on gene expression in HepG2 cells were similar overall, the expression of genes encoding proteins of mitochondrial respiratory complex III and complex I was upregulated by imeglimin but not by metformin. Our results suggest that imeglimin and metformin exert similar pharmacological effects on mitochondrial respiration, AMPK activity, and gene expression in cultured hepatocytes, whereas the two drugs differ in their effects on the expression of certain genes related to mitochondrial function.
Observational Study of the Impact of Infusion Set Replacement in Insulin Pump Users on Glycemic Management.BACKGROUND: Although several studies have evaluated the impact of prolonged infusion set use in insulin pump users on glycemic management with the use of continuous glucose monitoring (CGM), real-world assessments without intervention have been unavailable. METHODS: This retrospective observational study recruited individuals with type 1 diabetes who received insulin pump therapy with real-time CGM. Insulin pump and CGM logs were extracted from the Medtronic CareLink system, and a dataset was constructed programmatically, counting tracking days from infusion set replacement every 24 hours up to day 4. The primary outcome was mean sensor glucose (SG) level, and the impact of infusion set usage duration on glycemic management was assessed. RESULTS: The study enrolled 45 individuals with a median age of 40 (interquartile range = 32-51) years and median body mass index of 22.5 (21.2-23.8) kg/m². Mean SG was significantly higher on day 4 (median of 151.9 [136.5-173.7] mg/dL) than on day 2 (144.4 [124.0-162.9] mg/dL, P = .024). Similarly, time above range (TAR), time in range (TIR), and time in tight range (TITR) had worsened on day 4 compared with day 2. The TAR increased from a median of 22.0% (7.3%-35.8%) on day 2 to 27.6% (17.7%-44.9%) on day 4, whereas TIR decreased from 74.2% (59.9%-87.1%) to 66.5% (52.0%-79.8%) and TITR decreased from 47.6% (37.1%-67.5%) to 42.2% (34.6%-54.1%). CONCLUSIONS: Our evaluation of the real-world impact of prolonged infusion set use revealed an association between longer use and worsening of glycemic management.
Acromegaly caused by a somatotroph adenoma in patient with neurofibromatosis type 1.Although acromegaly has been reported in patients with Neurofibromatosis type 1 (NF1), these cases have not been associated with growth hormone (GH)-producing somatotroph adenoma, but with optic pathway glioma. A 68 year-old Japanese woman, who had been clinically diagnosed with NF1, was referred to our hospital due to a thyroid tumor and hypercalcemia. Acromegaly was suspected due to her facial features, and subsequent examinations revealed the presence of GH excess with a pituitary tumor, leading to the diagnosis of acromegaly. Histological and immunohistochemical analysis demonstrated an eosinophilic pituitary adenoma with diffuse positivity for GH, indicating typical somatotroph adenoma. In addition, her thyroid tumor was diagnosed histologically as follicular thyroid carcinoma (FTC) with primary hyperparathyroidism (PHPT). To investigate the pathogenesis of this untypical multiple endocrine tumor case of NF1, genetic analysis was performed using peripheral leukocytes and tissue of resected tumors. A heterozygous novel germline nonsense mutation (p.Arg1534*) in exon 35 of the NF1 gene was detected from peripheral leukocytes, which results in a truncated protein lacking the critical domain for GTPase activity, strongly suggesting its causal role in NF1. The loss of heterozygosity (LOH) in exon 35 of the NF1 gene was not detected in the somatotroph adenoma, parathyroid adenoma, and FTC. Although any mutations of the following genes; MEN1, CDKN1B, and PAX8-PPARγ were not detected, a heterozygous GNAS R201C mutation was detected in the somatotroph adenoma. To our knowledge, this is the first rare MEN1-like case of genetically diagnosed NF1 complicated with acromegaly caused by a somatotroph adenoma.
