The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide was administered at 0.9 mg/day to 34 Japanese patients with type 2 diabetes mellitus receiving insulin, oral hypoglycemic agents, or combination therapy, and the endogenous insulin secretory capacity in response to intravenous glucagon administration (change in C-peptide immunoreactivity ΔCPR and C-peptide index (CPI; a measure of fasting C-peptide secretion) were measured before and after the administration. The relationship between liraglutide administration and glycemic control indicators for up to 24 months was also investigated. Hemoglobin A1c (HbA1c) levels decreased significantly after three months and did not change greatly thereafter. A negative correlation was observed between the ΔCPR before treatment initiation and the change in HbA1c after 24 months. The CPI improved significantly at 12 months after treatment initiation, and the ΔCPR decreased significantly compared to before treatment initiation. These findings indicate that performing a glucagon loading test to determine the endogenous insulin secretory capacity prior to the initiation of GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes mellitus may be effective for predicting the efficacy of liraglutide. These findings also suggest that liraglutide administration increases the fasting endogenous insulin secretion.

When combining sodium-glucose co-transporter 2 (SGLT2) inhibitors with insulin therapy, it is recommended that the insulin dose be reduced while paying careful attention to the occurrence of hypoglycemia. We previously conducted a retrospective investigation in patients treated with this combination, and our findings revealed that a mean decrease of 15 % in the total insulin dose is effective and safe, and that reducing long-acting insulin results in a greater decrease of hemoglobin (Hb) A1c. In order to verify these results, we conducted a prospective study where 27 patients with ≥7 %HbA1c were randomly assigned to two groups: including one receiving a 15 % reduction in rapid-acting insulin alone with subsequent additions (the rapid reduction group); and another receiving a 15 % reduction in long-acting insulin alone (the long reduction group). HbA1c was thus observed to significantly decrease in both groups after 2 months (-0.3 % in rapid reduction group; -0.5 % in long reduction group). However, these decreases did not differ significantly between the groups and the impacts of such dose reduction on the treatment effects were similar between the groups. In addition, no serious side effects were observed. Our results demonstrated that a 15 % reduction in the total insulin dose, when combined with SGLT2 inhibitors, is therefore considered to be safe and effective, while indicating that specific adjustments depending on the type of insulin are not necessary.

A 67-year-old man with type 1 diabetes had no residual endogenous insulin secretion and had been treated with basal-bolus insulin therapy. He was diagnosed with adrenaline-producing pheochromocytoma and underwent laparoscopic left adrenalectomy. His glycemic variability for 24 h was evaluated using continuous glucose monitoring (CGM) before and 7 days after the operation. The mean glucose level was 177.1 mg/dL, the M value was 36.6, MAGE was 167 mg/dL, and J-index was 55.8 on preoperative CGM. Seven days after the operation, the mean glucose level had decreased to 131.5 mg/dL with an M value of 22.9, MAGE of 116 mg/dL, and J-index of 37.0, indicating that the glycemic variability had decreased markedly after surgery. In addition, the total daily insulin dose was immediately decreased from 21 to 16 units by excision of the pheochromocytoma. This clinical course suggested that a decrease in excessive catecholamine resulted in the improvement of the glucose levels through the improvement of insulin resistance in a patient with type 1 diabetes.

Introduction: This report describes a 53-year-old female with slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) and rheumatoid arthritis (RA) in whom treatment for RA reduced her insulin requirement. Case Description: A routine laboratory examination in March 2004 showed hyperglycemia, which had worsened 5 months later. At this initial examination, her fasting blood glucose and HbA1c levels were 238 mg/dL and 13.1 %, respectively, and she was positive for anti-GAD and anti-IA-2 antibodies. She was diagnosed with SPIDDM and started on insulin therapy, which improved her glycemic control. Following a diagnosis of RA in February 2006, she was started on the immunomodulator leflunomide, which gradually reduced her insulin requirement from 23 U/day to 19 U/day. After starting administration of the tumor necrosis factor (TNF)-alpha inhibitor infliximab in June 2007, she experienced frequent episodes of hypoglycemia. Infliximab was discontinued, and, in December 2008, she started treatment with a combination of methotrexate and leflunomide. She began treatment with adalimumab in April 2015. Her insulin requirement has gradually but progressively decreased to 11 U/day. Her glycemic control remains excellent, with an HbA1c concentration of 5.8 % in August 2015. Conclusion: TNF-alpha inhibitors and/or immunomodulators for RA may preserve the beta cell function, reducing the insulin requirement in patients with SPIDDM.

A 68-year-old woman was admitted for the examination of fasting hypoglycemia (42 mg/dL) and a tumorous lesion incidentally found by abdominal ultrasonography. A 75-g oral glucose tolerance test revealed that she had diabetes according to the Japan Diabetes Society criteria, with impaired first-phase insulin secretion. She also had postprandial hyperglycemia, as shown by a continuous glucose monitoring system. A dynamic computed tomography scan of the abdomen located a 4-cm-diameter mass lesion densely but inhomogeneously stained in the arterial phase in the pancreatic body. A prolonged 18-h fast reduced her plasma glucose without suppressing insulin secretion, while her serum glucagon (1030 pg/mL) and total ketone body (908 μmol/L) levels were not suppressed. After the prolonged fast, the administration of glucagon resulted in a 29-mg/dL increase in her plasma glucose levels, a finding compatible with insulinoma. Angiography and a selective arterial calcium injection test determined the localization of the insulinoma. Concomitant development of glucagonoma was also suggested in light of the elevated serum glucagon levels before surgery. The patient underwent distal pancreatectomy, and the pancreatic mass was histologically diagnosed as neuroendocrine tumor grade 2. Immunohistochemically, the tumor cells were positively stained for insulin, glucagon and somatostatin. After surgery, her glucose tolerance, the first-phase insulin secretion and postprandial hyperglycemia were totally improved. A case of comorbid insulinoma and glucagonoma, in which the patient's glucose tolerance was atypically modified by two hormone-secreting tumors, was reported.

A 44-year-old-man was diagnosed with diabetes in a medical examination and was admitted to our hospital due to hyperglycemia (FPG 285 mg/dL, HbA1c 10.8 %). He had experienced acute pancreatitis on 3 occasions. The laboratory data on admission revealed that the patient's CEA and DUPAN-2 levels were elevated. Abdominal enhanced CT and MRI demonstrated a tumor of 3 cm in diameter in the pancreatic head. Although pancreatic cancer was strongly suspected, a PET scan was negative. A percutaneous biopsy of the pancreas and a cytological analysis of the pancreatic juice were performed and the pathological diagnosis was tumor-forming pancreatitis. The acute onset of diabetes is considered to be a predictive marker of pancreatic cancer. It is very difficult to differentiate tumor-forming pancreatitis from pancreatic cancer. We should therefore make a comprehensive diagnosis using imaging, an analysis of the tumor marker levels, and a pathological examination.