Purpose: Metformin (Met) is widely used in the treatment of type 2 diabetes (T2DM). Because of its short half-life, it is usually prescribed not once but two or three times daily in Japan. To assess the efficacy and safety of Met 500 mg once daily on glucose profiles, a study switching from 250 mg twice daily was conducted in T2DM patients, with evaluations by continuous glucose monitoring (CGM). Methods: Thirty hospitalized patients treated with Met 250 mg twice daily were switched to Met 500 mg once daily at breakfast for 2 days, followed by 2 days consecutive at dinner. We then investigated the changes in the values of fasting plasma glucose, 24-h mean glucose and mean amplitude of glucose excursion over 6 days. Results: The mean fasting plasma glucose and 24-h mean glucose levels were not significantly different after switching to Met 500 mg once daily at breakfast or at dinner; however, the mean amplitude of glucose excursion decreased slightly while taking Met 500 mg once daily at breakfast. Of note, the prevalence of hypoglycemia and gastrointestinal symptoms was not increased. Conclusions: The efficacy and safety of Met 500 mg once daily were almost the same as with Met 250 mg twice daily.

We investigated the potential effect of SGLT2 inhibitor dapagliflozin on renal protection using tubulointerstitial injury marker, urinary liver-type fatty acid-binding protein (L-FABP), and glomerular injury marker, urinary albumin (ACR), in Japanese patients with type 2 diabetes. Dapagliflozin was administered to 90 outpatients for 24 weeks. In all 90 patients, urinary L-FABP decreased, but the ACR and estimated glomerular filtration rate (eGFR) were unchanged. In the 63 patients with normoalbuminuria, urinary L-FABP decreased, whereas the ACR and eGFR remained constant. In the 14 patients with microalbuminuria, urinary L-FABP and ACR decreased, but there was no marked change in the eGFR. In the 13 patients with macroalbuminuria, the eGFR decreased, but urinary L-FABP and ACR were unchanged. The association among urinary L-FABP, ACR, and the eGFR during dapagliflozin intervention showed no statistical significance. We propose that the renal protective potential of this SGLT2 inhibitor was associated with improvements in glomerular hyperfiltration and tubulointerstitial injury from the early stage.

A 67-year-old Japanese man had been diagnosed with type 2 diabetes mellitus at 50 years of age. He was receiving insulin therapy with a DPP-4 inhibitor, and his HbA1c was in the 7 % range. He underwent decompression surgery for lumbar spinal canal stenosis. The surgery improved his intermittent claudication. However, two days after surgery, pain in the bilateral shoulder, elbow, wrist, finger and right knee joints and edema in both hands and feet appeared, although no muscle pain was noted. His laboratory tests revealed an increased C-reactive protein level. Antinuclear antibodies and rheumatoid factor were all negative. X-ray revealed no bone destruction. He was suspected of having RS3PE syndrome and treated with prednisolone 15 mg. After a few days, his edema had markedly improved, and the joint pain and inflammatory response were relieved. The dose of prednisolone was tapered gradually, and the DPP-4 inhibitor was discontinued. A high serum VEGF level may carry a risk of causing RS3PE syndrome. During insulin therapy with the oral administration of a DPP-4 inhibitor that increases the basal level of VEGF, patients may develop RS3PE syndrome following surgical invasion.

A 62-year-old woman with a history of early-onset ovarian insufficiency had been diagnosed with type 1 diabetes because of an insulin secretory defect 4 years earlier. However, she was negative for several islet-specific autoantibodies, including anti-GAD, anti-IA-2, anti-ZnT8 and anti-insulin. In addition, she was weakly positive for anti-TPO antibody, which suggested the existence of autoimmune thyroid disease. Notably, she was considered to have Addison's disease, based on her physical findings, such as pigmentation of the skin, lip and nail bed, and laboratory findings, including a high serum ACTH level and positivity for anti-adrenal cortex antibody. Autoimmune polyglandular syndrome (APS) type 2 is defined as the occurrence of Addison's disease concomitantly with autoimmune thyroid disease and/or type 1 diabetes. Interestingly, she possessed HLA haplotype DRB1*15:01-DQB1*06:02, which was considered to protect against the development of type 1 diabetes. Since cases of APS type 2 are rare in the Japanese population, this was an instructive case for discussing the effects of both the HLA DR-DQ haplotype and islet-specific autoantibodies on the pathogenesis of APS.

We herein report a 57-year-old taxi driver with type 2 diabetes on canagliflozin, a sodium glucose cotransporter 2 inhibitor, who presented to our outpatient clinic with a positive alcohol breath test over the previous 3 days. Two weeks earlier, he had been admitted to our hospital for the improvement of glycemic control. On admission, his body mass index was 33 kg/m², hemoglobin A1c was 9.1 %, and anti-glutamic acid decarboxylase antibody was negative. His dietary energy intake was restricted to 22 kcal/kg of ideal body weight, and canagliflozin was continued. One day after his discharge, an alcohol breath test registered as positive before driving, and he was not allowed to work despite not having drunk any alcohol. Laboratory tests revealed normoglycemia (113 mg/dL) and ketonuria without metabolic acidosis, indicating a diagnosis of euglycemic ketosis due to canagliflozin combined with dietary energy restriction. Alcohol was not detected in his blood. We instructed him to stop taking canagliflozin and increase his dietary carbohydrate intake. Three days later, the alcohol breath test became negative, and we confirmed negative ketonuria. In patients with diabetes, a positive alcohol breath test may allow for the early detection of ketosis, but false-positive results can cause social problems, especially for drivers. Physicians should bear in mind that simple alcohol breath tests detect acetone.