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We report the first case of intraoperatively detected euglycemic diabetic ketoacidosis (DKA) associated with sodium–glucose cotransporter 2 inhibitors during thoracic surgery. A 59‐year‐old man had a 12‐year history of type 2 diabetes mellitus treated with insulin and empagliflozin. The patient developed bacterial empyema and was initiated with antibiotics at a local hospital. Owing to the persistence of his symptoms, he was transferred to our hospital after the medication of empagliflozin the day before surgery. After overnight fasting, the patient underwent thoracoscopic debridement and intrathoracic lavage surgery. During this surgery, he was noted to have euglycemic ketosis and acidosis, and diagnosed as euglycemic DKA. Immediately after the consultation in our department, the patient underwent treatment for DKA. He awoke from anesthesia normally and showed no symptoms of DKA. DKA gradually resolved over the next 24 h. Early identification and management are critical for rapid recovery from perioperative euglycemic DKA associated with sodium–glucose cotransporter 2 inhibitors, especially during thoracic surgery. [ABSTRACT FROM AUTHOR]

Introduction Autosomal dominant hypocalcemia (ADH) is caused by gain-of-function mutations of the calcium sensing receptor (CaSR). It is characterized by hypercalciuria in spite of hypocalcemia. Vitamin D deficiency increases calcium reabsorption in the distal tubules of the kidneys, resulting in hypocalciuria. Materials and methods A 38-year-old female proband had hypocalcemia, hypocalciuria, and vitamin D deficiency. Her father and brother also had hypocalcemia, but her mother was normocalcemic. We analyzed the CaSR gene abnormality in this family. Polymerase chain reaction (PCR) and sequence analysis were performed to explore the CaSR gene mutation. Mutagenesis, transfection, and functional analysis were performed on the discovered genetic abnormalities. Result PCR and sequence analysis revealed that the proband, her father, and brother had a novel heterozygous mutation of the CaSR genes that causes threonine to asparagine substitution at codon 186 (T186N). Using HEK293 cells transfected with wild-type or T186N CaSR complementary DNA, we assessed the intracellular Ca2+ concentration in response to changes in the extracellular Ca2+ concentration. The cells transfected mutant CaSR gene had higher activity than that of wild-type. Therefore, we determined our patient had ADH with a novel mutation of the CaSR gene and hypocalciuria resulting from a vitamin D deficiency. We administered vitamin D to the proband, which caused elevation of her urinary calcium level, a typical finding of ADH. Conclusion Vitamin D deficiency was suggested to potentially mask hypercalciuria in ADH. Hypocalcemia with vitamin D deficiency should be diagnosed with care. [ABSTRACT FROM AUTHOR]

Activating mutations in the ABCC8 gene cause diabetes and inactivating mutations usually cause hyperinsulinemic hypoglycemia in infancy. Patients with hypoglycemia in infancy due to a heterozygous inactivating mutation have been reported to occasionally progress to diabetes later in life. We explored the gene responsible for diabetes in two brothers, who were suspected to have diabetes at 15 and 18 years‐of‐age, respectively, with whole exome sequencing, and identified a compound heterozygous ABCC8 gene mutation (p.Arg168Cys and p.Arg1421Cys). Although their father and mother were heterozygous carriers of the p.Arg168Cys and the p.Arg1421Cys mutation, respectively, neither parent had diabetes. These mutations have been reported to be responsible for hypoglycemia in infancy and function as an inactivating mutation. Our results suggest that the inactivating ABCC8 gene mutation is also important in the etiology of diabetes. [ABSTRACT FROM AUTHOR]

Neonatal diabetes is a rare disease, often caused by a monogenic abnormality. A male infant patient developed diabetic ketoacidosis at 2 months‐of‐age due to the heterozygous ABCC8 gene mutation (p.Pro1198Leu). After genetic diagnosis, insulin therapy was successfully transitioned to oral sulfonylurea therapy. For >6 years, oral sulfonylurea therapy has been safe and effective, and the required amount of sulfonylureas has progressively decreased. The mutation was transmitted in an autosomal‐dominant fashion across three generations of his family, but the severity of diabetes varied among members from neonatal diabetes to mild diabetes. One family member had normal glucose tolerance despite having the mutation. This case presentation could help in the understanding of neonatal diabetes caused by the ABCC8 gene mutation. [ABSTRACT FROM AUTHOR]

HighlightsInactivating mutations of the ABCC8 gene usually cause hyperinsulinemic hypoglycemia.We report a family in which people with the inactivating mutation have progressed hyperinsulinemic hypoglycemia to hyperglycemia.Treatment with incretin‐related drugs might be a useful therapeutic approach to hyperglycemia in people with the inactivating mutation. [ABSTRACT FROM AUTHOR]

Background: Adult‐onset idiopathic isolated adrenocorticotropic hormone deficiency (id‐IAD) is a rare disease with unknown aetiology. Recently, numerous cases of anti‐PD‐1 antibody‐induced IAD (PD1‐IAD) have been reported, but the clinical course, predictive factors and relationship to id‐IAD have not been clarified. Moreover, associations of id‐IAD and PD1‐IAD with human leucocyte antigen (HLA) require elucidation. Methods: Clinical characteristics of 13 Japanese patients with id‐IAD and eight Japanese patients with PD1‐IAD were analysed, and HLA‐typing test was performed for each patient. Allele and haplotype frequencies of the patients were compared to those of healthy Japanese controls. Results: In the HLA allele and haplotype analyses of id‐IAD, the frequencies of HLA‐C*14:02, HLA‐DPB1*05:01, HLA‐DRB1*04:05‐DQB1*04:01‐DPB1*05:01 and HLA‐DRB1*09:01‐DQB1*03:03‐DPB1*05:01 were significantly increased. On the other hand, HLA alleles account for PD1‐IAD susceptibility as follows: HLA‐DQB1*06:01, HLA‐DPB1*09:01 and HLA‐DRB5*01:02. Moreover, protective effect for HLA‐C*03:03 was suggested in combined id‐IAD and PD1‐IAD patients. Comparison of the effects of HLA on id‐IAD and PD1‐IAD revealed some differences. Alleles or haplotypes frequencies increased in id‐IAD group were as follows: HLA‐DPB1*05:01, HLA‐DRB1*09:01, HLA‐DRB4*01:03:02, HLA‐DQB1*03:03 and HLA‐DRB1*09:01‐DQB1*03:03. In clinical settings, hyponatremia, disturbance of consciousness and hypoglycaemia were less frequently seen in patients with PD1‐IAD than in patients with id‐IAD. Conclusions: Distinct clinical characteristics and predisposing HLA allele contributions were proposed between id‐IAD and PD1‐IAD. Further investigations with greater number of cases are warranted to clarify the detailed mechanisms of id‐IAD and PD1‐IAD. [ABSTRACT FROM AUTHOR]

Whole‐exome sequencing is a new technology. We used it to explore the gene responsible for early‐onset diabetes as a result of impaired insulin secretion in a family. In the INS gene, we identified the heterozygous c.188‐31G>A mutation in the proband – a 43‐year‐old woman. The mutation was also identified in her two daughters with diabetes, but not in her son or her parents, all of whom did not have diabetes. The substitution was located 31 bp proximal to exon 3 in intron 2. It was predicted to create an ectopic splice site leading to inserting 29 nucleotides of intron 2 as an exonic sequence in the transcript. The mutation has been reported in White families, and the present case is the first report in an Asian person. The present results would help in understanding the role of the mutation in developing diabetes. [ABSTRACT FROM AUTHOR]