Aim: Evidence has emerged on the cardio-renal protective effect of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors. The mechanisms are multifactorial, but the uric acid (UA) lowering effect of SGLT2 inhibitors may-at least in part-contribute to it. The present study explores whether the same holds true in our daily outpatient practice. Methods: The fluctuation of serum UA was monitored retrospectively in 114 patients who received SGLT2 inhibitors for a period of 24 weeks. Results: HbA1c, body weight, and BMI were significantly decreased (p<0.001). The overall serum UA value was reduced from 5.6±1.3 to 5.2±1.0 mg/dL (p<0.001). When divided into three quartiles based on the basal serum UA values, the UA level was significantly reduced in the high quartile group. On the other hand, the UA levels increased in the low quartile group in which the patients' pre-treatment UA levels were in the neighborhood of the lower normal range. Conclusion: The present study suggests that treatment with SGLT2 inhibitors lowers serum UA levels in type 2 diabetics with hyperuricemia. However, they may act as a UA-increasing agent in individuals with lower normal pre-treatment UA levels.

A 66-year-old woman with type 2 diabetes was admitted to our hospital due to an insulin and GLP-1 overdose. She had self-administered 300 units of insulin (glargineU-100) and 36 mg of liraglutide. She was admitted to hospital due to vomiting. Several hours after her admission, she developed hypoglycemia. She was treated by an intravenous infusion of glucose and meals. She recovered from hypoglycemia 4 days after the insulin overdose. Her eating improvement was delayed as a result of vomiting or nausea due to liraglutide overdose. Additionally, glucagon-like peptide-1 and insulin synergistically interacted and possibly prolonged her hypoglycemia.

A 62-year man diagnosed with type 2 diabetes mellitus at 61 years old was started on an insulin agent due to poor blood glycemic control. When this discontinued insulin therapy was restarted at the time of hospitalization with pneumonia at 62 years old, hypoglycemia appeared frequently in the early morning. His blood insulin antibody titer was found to be elevated. A high binding capacity and low affinity at high-affinity binding sites of the patient's insulin antibodies was detected by a Scatchard analysis with pig insulin. His hypoglycemia was improved with corticosteroid therapy started after the insulin therapy was discontinued. The insulin antibody characteristics were aggravated by discontinuation of the corticosteroid therapy, as confirmed by the Scatchard analysis over 5 years and 9 months. During the course of the corticosteroid therapy, hyperinsulinemia was remarkable. Based on the present findings, the effects of corticosteroid therapy were thought to involve the improvement of the insulin antibody characteristics. However, long-term corticosteroid therapy was not enough to improve the insulin antibody characteristics, and we were ultimately unable to avoid restarting the previously discontinued corticosteroid therapy. Nevertheless, continuous administration of low-dose corticosteroids did help reduce the frequency of hypoglycemia.

A 76-year-old woman underwent left pleural tumor resection at 70 years old and showed no recurrence for 3 years after the operation. However, she had to suspend her visits after this. At 76 years old, she was transported to our facility emergently due to hypoglycemia. Her intrinsic insulin secretion and blood insulin-like growth factor (IGF)-I levels were low during this hypoglycemic episode. However, no hepatic or renal dysfunction was observed, and the blood cortisol level was normal. Computed tomography showed a coarse mass in the left thoracic cavity. A Western blotting analysis of a serum sample demonstrated the presence of large-molecular-weight IGF-II. We therefore considered her hypoglycemia to be due to a large-molecular-weight IGF-II-producing extrapancreatic tumor. She did not wish to undergo surgery, so palliative care was given. We continued central intravenous feeding to avoid hypoglycemia, and the patient ultimately died on the 94th day of illness. At necropsy, immunostaining detected IGF-II and IGF-II receptors. The complex of large-molecular-weight IGF-II and IGF-II receptors may affect tumor development.