Cerebral Infarction After Switching From Roxadustat to Daprodustat in a Patient With Renal Anemia.

Renal anemia is generally caused by a decrease in the production of erythropoietin in kidney due to renal dysfunction, and this may be associated with the increase in mortality and cardiovascular events in addition to subjective symptoms such as fatigue and wobbliness. We report a case of an 87-year-old man with type 2 diabetes, hypertension, and dyslipidemia who had received roxadustat (a hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) inhibitor) for renal anemia due to diabetic nephropathy and in whom roxadustat was switched to daprodustat (another HIF-PH inhibitor) due to the onset of central hypothyroidism. About three weeks after this change, the patient developed acute asymptomatic cerebral infarction with an elevation of hemoglobin (Hb). It is unclear if the change to daprodustat was involved in the onset of cerebral infarction. However, this case suggests that particular caution should be paid to unexpected acute elevation of Hb after a change from one HIF-PH inhibitor to another, especially in a patient at high risk for cardiovascular events.

Analysis of serum levels and DNA methylation of fibroblast growth factor 21 using peripheral blood-derived genomes in patients with obesity.

Fibroblast growth factor (FGF) 21, a hormone produced by the liver, improves glucose and lipid metabolism. We recently demonstrated that the FGF21 gene (Fgf21) underwent DNA demethylation in the mouse liver via peroxisome proliferator-activated receptor (PPAR) α during the fetal to lactation periods. Furthermore, we found that the DNA methylation state of Fgf21 was involved in obesity in adult animals. In the present study, we analyzed the DNA methylation state of the FGF21 gene (FGF21) in obese patients using genomic DNA extracted from human monocytes and macrophages and investigated the pathophysiological significance of the FGF21 expression response to pemafibrate (PM), a PPARα ligand. We examined 67 patients with obesity stratified into in- and outpatient cohorts. A positive correlation was observed between serum FGF21 levels and triglyceride (TG) levels before PM administration. However, changes in serum FGF21 levels following PM administration did not correlate with the FGF21 DNA methylation rate, except at one CpG site. The body mass index (BMI) and serum TG levels positively correlated with the FGF21 DNA methylation rate, particularly at different CpG positions. A negative correlation was observed between absolute changes in serum FGF21 levels and the ratio of change in serum TG levels after PM administration. Collectively, these results indicate the potential of FGF21 DNA methylation as a surrogate indicator of BMI and serum TG levels, while absolute changes in serum FGF21 levels after PM administration may offer prognostic insights into the efficacy of reducing serum TG levels through PM administration.

Analysis of five cases showing false-high Hemoglobin A1c due to reduced catalase activity.

We encountered five cases that exhibited false-high Hemoglobin A1c (HbA1c) levels when samples were examined using the enzyme-based NORUDIA N HbA1c kit. HbA1c levels were higher than those obtained using other methods, such as HPLC, immune-based methods, and other enzyme-based kits. This kit produced inaccurate results for HbA1c when residual peroxides were present in samples. The addition of peroxidase solution restored false-high HbA1c levels in the five cases, indicating that reduced catalase activity was responsible for these values because catalase eliminates peroxide. Catalase activity and gene mutations were examined in the five cases and an immunohistological analysis was performed to assess the expression of catalase. Cases #1 and 2 were diagnosed as acatalasemia and cases #3, 4, and 5 as hypocatalasemia based on compound heterozygous SNP and heterozygous splicing mutations in the catalase gene. Therefore, impaired catalase activity was responsible for false-high HbA1c levels measured by the NORUDIA N HbA1c kit.

Seasonal variations and the influence of COVID-19 pandemic on hemoglobin A1c, glycoalbumin, and low-density lipoprotein cholesterol.

Aim: The purpose of the study was to investigate seasonal variations in HbA1c, GA and LDL-C and to examine the effects of the COVID-19 pandemic on these variations and on glycemic and lipid control themselves in patients with type 2 diabetes. Patients and methods: The subjects were outpatients with type 2 diabetes who had received standard treatment for glycemic control for more than 3 years. Data for patients who visited our hospital from January 2021 to March 2021 were retrospectively investigated based on electronic medical records. Results: HbA1c showed seasonal variation (high in winter-spring and low in summer-autumn), and this was similar during the COVID-19 pandemic. However, the mean HbA1c over 1 year was significantly elevated during the COVID-19 pandemic (7.53 ± 1.02% in 2020) compared with the previous 2 years: (7.34 ± 0.91 in 2018, 7.39 ± 0.93 in 2019; 2020 vs. 2018; 0.19%, P < 0.001; 2020 vs. 2019; 0.14%, P = 0.0013) and the difference was larger in winter. GA showed no apparent seasonal variation, but mean GA during the COVID-19 pandemic was elevated compared with earlier years (2020 vs. 2018, P < 0.001; 2020 vs. 2019, P < 0.001). LDL-C did not show apparent seasonal variation and was unaffected by COVID-19 pandemic. Conclusion: The COVID-19 pandemic influenced mean HbA1c and GA levels over 1 year, but did not affect seasonal variations, while LDL-C was not affected by COVID-19. Observation of these levels over a longer period is warranted to determine the longer-term influence of the COVID-19 pandemic.

Effects of short-term calorie restriction on circulating DPP-4/sCD26 concentrations and body composition in patients with type 2 diabetes.

Previous studies have shown that dipeptidyl peptidase (DPP)-4, is released from adipocytes in a differentiation-dependent manner and a marker for insulin resistance in obese individuals who have particularly high circulating DPP-4/soluble CD26 (sCD26) concentrations. In this study, we have evaluated the effects of short-term hospitalization with calorie restriction on body composition and circulating DPP-4/sCD26 concentrations in patients with type 2 diabetes. A total of 47 Japanese adults with type 2 diabetes were recruited to the study (age; 56.6 ± 13.0 years, body mass index (BMI); 27.3 ± 5.6 kg/m2). Body composition, circulating DPP-4/sCD26 concentrations and metabolic parameters were assessed upon admission and at discharge from hospital (average of the period: 13.0 ± 2.5 days). Visceral fat area (VFA) was also assessed by dual impedance method. During hospitalization, there was a significant reduction in body weight, BMI, lean body mass, VFA and circulating DPP-4/sCD26 concentrations, but not in body fat mass. Fasting circulating DPP-4/sCD26 concentrations were significantly correlated with fasting insulin, aspartate aminotransferase, γ-glutamyltransferase (γ-GTP) levels, and HOMA-IR (r = 0.477, 0.423, 0.415, 0.548, respectively), but not with VFA (r = - 0.056) by liner regression analyses at base line. It was also observed a positive correlation between changes in circulating DPP-4/sCD26 concentrations and γ-GTP level, HOMA-IR, and a negative correlation between the changes in circulating DPP-4/sCD26 concentrations and VFA significantly (r = 0.300, 0.633, - 0.343, respectively). In conclusion, our observations suggest that liver enzymes as well as VFA might be associated with the response of DPP-4/sCD26 concentrations.

Association of circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 with inflammatory markers and urinary albumin excretion in patients with type 2 diabetes.

OBJECTIVES: The main purpose of the study was to study the association between circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 levels and various markers, including inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen, serum lipids, and renal function, in patients with poorly controlled type 2 diabetes. METHODS: The subjects were 70 patients (men 45, women 25) who were hospitalized for treatment of poor glycemic control. Plasma soluble lectin-like oxidized low-density lipoprotein receptor-1 levels were assayed using a sandwich chemiluminescence enzyme immunoassay. RESULTS: Circulating soluble lectin-like oxidized low-density lipoprotein receptor-1 was significantly positively correlated with lectin-like oxidized low-density lipoprotein-1 ligands containing apolipoprotein B, reflecting modified low-density lipoprotein, and with inflammatory markers such as high-sensitivity C-reactive protein and fibrinogen. In addition, there was a significant positive correlation between soluble lectin-like oxidized low-density lipoprotein receptor-1 and urinary albumin excretion. CONCLUSIONS: Soluble lectin-like oxidized low-density lipoprotein receptor-1 may serve as a marker reflecting the degrees of inflammation and albuminuria in patients with poorly controlled type 2 diabetes.

Severe Non-Islet Cell Hypoglycemia From Ileum-Origin Gastrointestinal Stromal Tumor Producing Insulin-Like Growth Factor-2 in a Patient With Liver Cirrhosis Due to Chronic Hepatitis B.

Non-islet cell tumor hypoglycemia (NICTH) is a rare paraneoplastic syndrome, and NICTH associated with gastrointestinal stromal tumor (GIST) is even more rare. Herein, we describe a patient with severe NICTH due to GIST who had developed liver cirrhosis as a consequence of chronic hepatitis B. Although circulating insulin, C-peptide, and insulin-like growth factor-1 (IGF-1) levels were significantly decreased, in contrast to our expectations, the growth hormone (GH) level was slightly elevated. Steroid therapy with prednisolone appeared to be effective for the prevention of severe and continuous hypoglycemia.

Hb Phnom Penh Showing Falsely High or Reasonable HbA1c Values Depending on the Type of High-performance Liquid Chromatography System.

We herein report a 50-year-old Chinese woman with Hb Phnom Penh (α117Phe-Ile-α118Thr) showing high or reasonable HbA1c values depending on the type of high-performance liquid chromatography (HPLC) system. A high HbA1c value of 7.5% (HPLC assay: G9) and a reasonable HbA1c value of 5.2% (assay unknown) were observed. Therefore, the patient was refereed to our hospital; the oral glucose tolerance test showed normal glucose tolerance. The HbA1c values measured by an enzymatic assay, immunoassay, and affinity assay, as well as most HPLC assays were within the reference range, whereas those measured by the Tosoh HPLC systems were high.

Isolated Adrenocorticotropic Hormone Deficiency and Severe Hypercalcemia After Destructive Thyroiditis in a Patient on Nivolumab Therapy With a Malignant Melanoma.

We describe a 58-year-old man with a malignant melanoma metastasis to the liver. After initiation of nivolumab therapy, he developed destructive thyroiditis and subsequently simultaneous isolated adrenocorticotropic hormone (ACTH) deficiency and severe hypercalcemia. Although isolated ACTH deficiency and hypercalcemia due to nivolumab therapy are both rare occurrences, these conditions can often cause a severe clinical course accompanied by a disturbance of consciousness. Therefore, clinicians should pay attention to these possible side effects of nivolumab if the patients have clinical symptoms, such as fatigue and a disturbance of consciousness.