Total Synthesis of Miuraenamides A and D.

Miuraenamides A and D, cyclodepsipeptides with antimicrobial and antitumor activity, were synthesized. The synthesis of an unsaturated hydroxycarboxylic acid moiety, starting from a chiral epoxide, was achieved by Suzuki-Miyaura coupling as a key step. As a result, the overall yield for miuraenamide A over the longest linear sequence is 3.2%, while the yield of the previously reported procedure is 1.9%. In addition, the cell growth-inhibitory activity and anti-Phytophthora activity of the synthesized compounds were evaluated.

Development of a hyperosmolar-hyperglycemic state and possible fulminant type 1 diabetes mellitus during the treatment of a case of adenocarcinoma of the lung and interstitial pneumonia.

An 85-year-old man was being treated with anti-cancer drugs for adenocarcinoma of the lung and was on a tapering dose of prednisolone for interstitial pneumonia. He attended our hospital complaining of fatigue, thirst, and polyuria in September 2020. His postprandial plasma glucose concentration was 976 mg/dL, his glycated hemoglobin was 8.0%, his plasma osmolality was 342 mOsm/kg H2O, his urine ketone body content was 1 +, and his blood pH was 7.356. Therefore, we diagnosed a hyperosmolar-hyperglycemic state and he was admitted to the hospital for treatment. He had had no previous upper respiratory symptoms, and his postprandial plasma glucose and glycated hemoglobin were normal 13 days before he was first assessed (90 mg/dL and 5.9%, respectively). On admission, his serum pancreatic exocrine enzyme activities were high and he was negative for islet-specific autoantibodies. His serum C-peptide concentration was 0.60 ng/mL, suggesting that his endogenous insulin secretion was partially intact at that time. Although he did not meet the diagnostic criteria, we suspected him of having fulminant type 1 diabetes mellitus, because of the abrupt onset of hyperosmolar-hyperglycemic state. His general condition was improved by fluid and insulin administration. His human leukocyte antigen genotype was DRB1*04:05 DQB1*04:01:01, which is a disease susceptibility haplotype for fulminant type 1 diabetes mellitus. In addition, his prednisolone treatment may have caused an autoimmune abnormality, further predisposing toward the development of fulminant type 1 diabetes mellitus.

Switching from Insulin Degludec plus Dipeptidyl Peptidase-4 Inhibitor to Insulin Degludec/Liraglutide Improves Glycemic Variability in Patients with Type 2 Diabetes: A Preliminary Prospective Observation Study.

Incretins reduce glycemic variability (GV) in patients with type 2 diabetes, but it is unknown whether switching from a combination of basal insulin and a DPP-4 inhibitor to insulin degludec/liraglutide (IDegLira) improves GV. We performed an exploratory prospective observational study to compare the effect of IDegLira and the combination on GV. We recruited hospitalized patients with type 2 diabetes who had stable glycemic control with insulin degludec (≤16 units/day) and taking a DPP-4 inhibitor. GV was analyzed using continuous glucose monitoring (CGM) before and after switching the medication to IDegLira. The principal endpoint was the change in mean amplitude of glycemic excursions (MAGE). Other indices of GV and CGM parameters were analyzed as the secondary endpoints. Fifteen participants were enrolled and 12 completed the study. In these participants, the DPP-4 inhibitor and insulin degludec were discontinued, and the equivalent dose of IDegLira was commenced. Switching to IDegLira significantly improved MAGE from 74.9 (60.3, 97.7) mg/dL to 64.8 (52.0, 78.2) mg/dL (P < 0.05), as well as other indices of GV and 24-hour mean blood glucose concentration. Analysis of the ambulatory glucose profile showed marked reductions in postprandial glucose concentration. Nocturnal glucose concentration was similar under the two treatment regimens. IDegLira improved GV as well as the mean and the postprandial glucose concentration by switching from insulin degludec plus DPP-4 inhibitor combination. IDegLira might be beneficial for patients being treated with low-dose basal insulin.