In April 2010, the "Committee on proper usage of incretin and sulfonylurea drugs" advocated the recommended dosage of SUs, and the attached document on sitagliptin was also revised. We studied cases of severe hypoglycemia associated with the combined use of sitagliptin plus a SU drug, and examined the changes in the daily dosage of SUs after implementation of the new safety measures using case reports of side effects and receipt data reported to the Pharmaceuticals and Medical Devices Agency. The number of hypoglycemia cases decreased from 70 before the implementation (for five months) to 47 cases after implementation of the measures (for 20 months). Among the cases of hypoglycemia, the percentage of cases receiving the recommended daily dose (2 mg/day or less) of glimepiride had increased after implementation of the measures. An analysis of the receipt data revealed that the percentage of cases receiving the recommended daily dose of glimepiride for combined use increased to 68.2 % (p=0.0015) and 81.1 % (p<0.0001) with time after the measures were implemented (compared to 52.2 % before the measures were implemented). Consequently, severe hypoglycemia developing in association with combined sitagliptin plus glimepiride use is expected to decrease in incidence with the reduction of the glimepiride dose.

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The use of pancreatic transplantation from heart-beating donors began in Japan in 2000; however, the long-term prognoses of patients undergoing this procedure have not been fully investigated. We evaluated the survival rates, complications and quality of life (QOL) in 65 patients with indications for pancreatic transplantation. No deaths occurred in the 25 transplanted patients (median follow-up period: 8.0 years), whereas the 5-year survival rate was 85 % in the 40 patients waiting for transplantation (p=0.0004). The cause of death was sudden death in half of the patients who died. The 5-year withdrawal rate of insulin was 73 %, while that of dialysis in 23 simultaneous pancreas-kidney transplantation recipients was 92 %. The event-free rates in the patients with macrovascular diseases tended to be higher among the transplanted patients (p=0.091), while those in the patients with cancer or bone fractures did not differ between the two groups. In contrast, infectious diseases requiring hospitalization developed more often in the transplanted patients than in the patients waiting for transplantation (5-year rate: 53 %, p=0.0008). The QOL in the transplanted patients with functioning grafts remained to be improved, while the patients with non-functioning grafts exhibited a worsening QOL. The present study demonstrated that pancreatic transplantation markedly improves the survival rate in patients with type 1 diabetes mellitus.

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Dipeptidyl peptidase-4 inhibitors, first approved in Japan in 2009, are rapidly expanding as one of the useful therapeutic options for patients with type 2 diabetes mellitus. However, the fact that DPP-4 is identical to CD26, a cell surface glycoprotein expressed by a variety of cells, including T cells, B cells, NK cells and macrophages, had long been suggested to influence the immune system by DPP-4 inhibition. We recently experienced the case of a patient with type 2 diabetes who developed a fever, which was possibly attributable to sitagliptin administration. The rise and fall of the blood inflammatory markers, such as IL-1β, IL-6 and TNF-α, coincided with the progression and improvement of the fever, suggesting that the administration of sitagliptin might lead to the development of a drug-induced fever through the production of inflammatory cytokines.

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A 59-year-old man developed a disturbance of consciousness, and was in a state of shock when transported to the hospital. About two weeks earlier, he had been diagnosed to have rheumatoid arthritis and thus started taking oral prednisolone. As hyperglycemia (1815 mg/dl), metabolic acidosis and a high ketone level were observed, diabetic ketoacidosis (DKA) was diagnosed, and he was admitted to the hospital on the same day. Although the consciousness disturbance improved after undergoing a transfusion and insulin administration, his circulatory condition did not stabilize, thus raising the possibility of concurrent septic shock. The patient had mild abdominal pain and showed edematous wall thickening of the ascending colon on computed tomography (CT). However, the causes of these findings were unknown. A gradual improvement was observed with intensive care, but his abdominal pain became severe the night of the first hospital day 11; peritonitis resulting from intestinal perforation was then diagnosed by CT, and he therefore underwent emergency surgery. Discontinuous necrosis was detected from the ileum to the appendix, consistent with localized peritonitis resulting from ileal perforation. There was no obstruction of the mesenteric artery. Based on these observations, the patient was considered to have non-obstructive mesenteric ischemia (NOMI) associated with gradually progressive DKA, which had resulted in a delayed perforation. While NOMI generally has a very poor prognosis, the reported survival rate was high in DKA patients with concurrent NOMI. Although dehydration in DKA patients can trigger NOMI, the circulatory failure can generally be ameliorated by transfusion, which is considered to be the reason for the high survival rate in these cases.

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A 28-year-old male with an 8-year history of type 2 diabetes mellitus was admitted for consciousness disturbance. He had been receiving treatment with metformin and pioglitazone. His blood glucose control was worsening due to binge drinking of soft drinks. On admission, the laboratory data showed a blood glucose level of 1,620 mg/dl, an HbA1c level of 15.0 %, a Cr level of 2.89 mg/dl and an amylase level of 548 IU/l in addition to elevation of the serum level of ketone bodies and metabolic acidosis. A CT scan of the abdomen revealed swelling of the pancreas and inflammatory changes over the left prerenal cleft. A diagnosis of diabetic ketoacidosis (DKA) and acute pancreatitis was made. Because the patient did not have gallstones or dyslipidemia and did not report excessive alcohol consumption, we considered the etiology of the acute pancreatitis to be DKA. After admission, the patient went into respiratory failure. Continuous hemodiafiltration (CHDF) was performed to treat the severe acute pancreatitis, and the patient fully recovered. Dysfunction of autophagy, a protein degradation system, has been implicated in the pathogenesis of acute pancreatitis. In this case, hyperglycemia may have caused autophagy dysfunction via ER stress. The fructose contained in soft drinks promotes lipogenesis, hyperuricemia and chronic inflammation in fat tissue. These characteristics are suspected to have caused the onset and exacerbation of acute pancreatitis in this patient via endothelial dysfunction and lipotoxicity, respectively.

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A 36-year-old woman had been aware of changes in her facial features since approximately 2006 (at 33 years of age). A sense of excessive thirst manifested in 2008 (at 35 years of age); however, it was left untreated. The patient developed a fever of 37.3 °C, nausea and epigastric pain in January 2009 (at 36 years of age) and presented to our hospital the following day. Her blood glucose level was 645 mg/dl. Metabolic acidosis (pH: 7.144, HCO₃^-: 3.8 mmol/l, PCO₂: 11.4 mmHg) with a high anion gap (31.2 mEq/l) was detected and the urinary ketone body concentration was 3+. Diabetic ketoacidosis was diagnosed. The patient had acromegalic facial features and high levels of growth hormone (260 ng/ml) and insulin-like growth factor-1 (1,047 ng/ml). A head computed tomography scan revealed a well-defined mass with a maximum diameter of 4 cm and a high density in the sella turcica. These findings led to a diagnosis of acromegaly. The patient experienced sudden onset of visual disturbance and headaches on hospital day 6 and underwent emergency surgery under a diagnosis of pituitary apoplexy. There are few reports of patients with diabetic ketoacidosis that are diagnosed with acromegaly. We herein describe this rare case of acromegaly complicated by pituitary apoplexy.

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