We investigated the emergency outpatients with diabetes due to drug-related severe hypoglycemia (requiring external assistance for recovery) who visited our hospital over a 10-year period (between April 2009 and March 2019) and found 329 cases (0.66 % of emergency outpatients). Elderly and lean patients accounted for the largest group. Patients with type 1 diabetes accounted for at least 11.2 % of patients. The mode of treatment was insulin in 42.2 %, combined usage of insulin and an oral hypoglycemic agent (OHA) in 16.4 %, and an OHA in 41.3 %. Most (86 %) patients treated with an OHA were administered sulfonylureas (SU). Among the patients treated with SU, 25.9 % had a reduced renal function, and 29.9 % were co-treated with a dipeptidyl-peptidase-4 inhibitor. Both the annual number of patients and their annual ratio to emergency outpatients peaked in 2009 and then decreased gradually. These decreases were largely due to a decrease in patients treated with SU.

Case 1 was a 78-year-old woman receiving treatment for type 2 diabetes. Upon admission to our hospital with dehydration, during HbA1c measurement using high-performance liquid chromatography (HPLC), an abnormal chromatogram was revealed, and HbA1c could not be measured. HbA1c was therefore instead measured by an enzymatic assay and immunoassay, both showing a level of 7.7 %, and glycated albumin (GA) level of 27.7 %. A globin gene analysis revealed a heterozygous mutation in β-chain codon 56 [GCC (Gly) →GAC (Asp) ]; the patient was therefore diagnosed with Hb J-Bangkok. Case 2 was an 81-year-old man who was the husband of Case 1. He was receiving treatment for type 2 diabetes and chronic kidney disease. He had been admitted to our hospital with heart failure. During HbA1c measurement, an abnormal HPLC chromatogram was revealed, and the HbA1c was therefore unmeasurable. HbA1c measured by an enzymatic assay was 9.2 %, and GA was 32.6 %. A globin gene analysis revealed a mutation identical to that in Case 1, and he was also diagnosed with Hb J-Bangkok. We encountered an unrelated married couple with the same hemoglobinopathy. Although the couple did not have a blood relationship, both were from Yakushima, Kagoshima, Japan. A further analysis of this hemoglobinopathy in the family line and the region will be necessary.

A 71-year-old man was referred by the Department of Urology to our department due to the development of hyperglycemia approximately 7 months after the initiation of programmed cell death protein-1 (PD-1) inhibitor therapy using nivolumab for the treatment of multiple metastatic lesions after renal cell carcinoma resection. Endogenous insulin secretion was not depleted and was comparatively maintained at the first visit; however, marked hyperglycemia (blood glucose level: 736 mg/dL) and mild ketoacidosis were observed. His HbA1c level was found to be relatively low (7.6 %), and the patient tested negative for all islet-related autoantibodies. Based on these findings, the patient was diagnosed with fulminant type 1 diabetes. The human leukocyte antigen (HLA) gene was homozygous for DRB1*09:01-DQB1 *03:03. After injecting insulin subcutaneously multiple times per day, the control of the glycemic levels improved. Several cases of fulminant type 1 diabetes due to anti-PD1 antibody treatment have been reported globally. Based on a systematic review of the relevant literature, we ascertained a few characteristics that were specific to this type of diabetes by comparing them to those in our previous cases of typical fulminant type 1 diabetes.

Late dumping syndrome may cause severe hypoglycemia. However, effective treatments of severe hypoglycemia due to dumping syndrome are limited. A 75-year-old man who underwent total gastrectomy at 51 years old presented with dizziness and unconsciousness 4 h after a meal. We diagnosed him with late dumping syndrome based on his clinical course and proposed dietary modification, but continuous glucose monitoring exhibited oxyhyperglycemia and subsequent hypoglycemia. The administration of voglibose, an alpha-glucosidase inhibitor (α-GI) was effective; however, it was not tolerated because of liver dysfunction. After the hospital interruption, he lost consciousness 2.5 h after eating, and his plasma glucose level was 20 mg/dL. We administered 50 mg of diazoxide, and his insulin secretion pattern and postprandial hypoglycemia improved. He has not lost consciousness for over six months with no side effects. These data suggest that diazoxide may be a good option for treating postprandial hypoglycemia in a patient with dumping syndrome when α-GI does not work.

Several methods are available for measuring HbA1c in Japan, including high-performance liquid chromatography (HPLC), immunoassays and enzymatic assays. HPLC is commonly used in many facilities in Japan, but recently, the numbers of enzymatic assays and immunoassays have been increasing. We herein report a case of hemoglobin C (HbC) considered to involve diabetic mellitus because of falsely high levels of HbA1c on an immunoassay. A 74-year-old woman visited our hospital for the re-examination of HbA1c, as she was recommended to take medicine for diabetes mellitus by her local doctor. An HbA1c analysis using HPLC in our hospital showed an abnormally low value that was within the reference value using the enzymatic assay. Glycated albumin levels were in the normal range. A genetic analysis showed the presence of a heterozygous miss-sense mutation of the β-globin chain, which we diagnosed as HbC. HbC is frequently recognized in African populations as hemoglobinopathy, but it is rare in Japan. However, its frequency might increase in the future with internationalization. We should carefully evaluate the HbA1c level when we detect a discrepancy between HbA1c and the expected glucose level using a glucose tolerance evaluation.