Aims: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D).Materials and methods: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater.Results: During the 7-to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( À27.6 vs. À4.4 mg/dL [À1.5 vs. À0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants.Conclusions: When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancer-specific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immune-associated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes.

Total pancreatectomy (TP) and islet cell autotransplantation (IAT) are complex operations that require intensive postoperative monitoring with standardized protocols. There are few studies detailing immediate perioperative management. The purpose of this study was to describe the perioperative management of post-pancreatectomy patients in the first week following surgery to guide clinicians in addressing salient points from different organ systems. This is a retrospective cohort review of prospectively collected data from September 2017 to September 2022 at a single institution, including patients 16 years and older who underwent TP or TPIAT for chronic pancreatitis. Patients were maintained on a heparin drip (TPIAT), insulin drip, and ketamine infusion. Primary outcomes were complications in the first 5 days following surgery and ICU length of stay (LOS). Secondary outcomes included overall LOS and mortality. Of 31 patients, 26 underwent TPIAT, and 5 underwent TP. Median ICU LOS was five days (IQR 4–6). The most common immediate postoperative complications were reintubation [n = 5 (16%)] and bleeding [n = 2 (6%)]. Median insulin drip use was 70 h (IQR 20–124). There was no mortality. Patients were extubated quickly and progressed well on the protocol. Immediate postoperative complications were generally minor and without long-term effects.