ABSTRACT
Background: Reducing hyperglycemia while avoiding hypoglycemia is the key clinical goal in managing people with type 1 diabetes. Insulin delivery techniques and regimens are constantly evolving to achieve these goals. At present, use of multiple daily injections (MDI) is the standard of care, but there is increasing interest in continuous subcutaneous insulin infusion (CSII). There is a deficit of studies comparing long-term glycemic control and hypoglycemia outcomes between these therapeutic options. Methods: This was a single-center, retrospective cohort study of adults with type 1 diabetes. Data were derived from electronic medical records and included demographic and clinical factors. Participants had all undergone intensive diabetes education, followed by CSII or continued MDI. The primary outcome was difference in hypoglycemia, defined as the percentage of self-monitoring blood glucose levels less than 3.9 mmol/L. Up to 10 years of follow-up data were available, between 2000 and 2016. Results: There were 69 participants using CSII and 78 using MDI. Self-monitoring blood glucose data showed significantly less hypoglycemia with CSII by over 30%, occurring as early as the first year and sustained throughout the follow-up period (P < 0.001). This benefit of CSII on reducing hypoglycemia was independent of more frequent hypoglycemia and higher body weight at baseline, factors that were also independently associated with reduced hypoglycemia. Conclusions: In selected adults with type 1 diabetes, long-term CSII can provide long-term clinically relevant and sustained reductions in hypoglycemia, particularly in those with greater initial risk of hypoglycemia and higher body weight, and improved glycemic control compared with MDI.
Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Adult , Blood Glucose/drug effects , Blood Glucose Self-Monitoring , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Drug Administration Schedule , Female , Humans , Hypoglycemia/etiology , Infusions, Subcutaneous , Insulin Infusion Systems , Male , Retrospective Studies , Time Factors , Treatment OutcomeABSTRACT
Use of continuous subcutaneous insulin infusion (CSII) in adults with type 1 diabetes has become increasingly popular in recent years, with recent studies examining the efficacy of CSII use in pregnancy and in type 2 diabetes. However, there is very limited information on the benefit of CSII in older patients with type 1 diabetes. Electronic medical records were retrospectively analyzed for patients with type 1 diabetes undertaking structured patient education and initiated on CSII or multiple daily injections (MDI) between 2000 and 2016. Outcomes examined related to changes in glycemic parameters and weight and utilization of healthcare resources. Data relating to 293 patients fulfilled the inclusion criteria, with up to 10 years of follow-up data available. For patients commencing CSII, glycemic and weight outcomes and utilization of healthcare resources were similar in older compared with younger patients. For older patients, use of CSII was associated with better glycemic outcomes at the cost of a small increase in healthcare resources compared with MDI. CSII can be used effectively and safely in the longer term in carefully selected older patients with type 1 diabetes, with similar outcomes as observed in younger patients using CSII, and potentially better glycemic outcomes than MDI in older patients.
Subject(s)
Blood Glucose Self-Monitoring/methods , Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Adult , Aged , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Infusions, Subcutaneous , Injections, Subcutaneous , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Treatment OutcomeABSTRACT
Cell death is an important target for imaging the early response of tumors to treatment. We describe here the validation of a phosphatidylserine-binding agent for detecting tumor cell death in vivo based on the C2A domain of synaptotagmin-I. Methods: The capability of near-infrared fluorophore-labeled and 99mTc- and 111In-labeled derivatives of C2Am for imaging tumor cell death, using planar near-infrared fluorescence imaging and SPECT, respectively, was evaluated in implanted and genetically engineered mouse models of lymphoma and in a human colorectal xenograft. Results: The fluorophore-labeled C2Am derivative showed predominantly renal clearance and high specificity and sensitivity for detecting low levels of tumor cell death (2%-5%). There was a significant correlation (R > 0.9, P < 0.05) between fluorescently labeled C2Am binding and histologic markers of cell death, including cleaved caspase-3, whereas there was no such correlation with a site-directed mutant of C2Am (iC2Am) that does not bind phosphatidylserine. 99mTc-C2Am and 111In-C2Am also showed favorable biodistribution profiles, with predominantly renal clearance and low nonspecific retention in the liver and spleen at 24 h after probe administration. 99mTc-C2Am and 111In-C2Am generated tumor-to-muscle ratios in drug-treated tumors of 4.3× and 2.2×, respectively, at 2 h and 7.3× and 4.1×, respectively, at 24 h after administration. Conclusion: Given the favorable biodistribution profile of 99mTc- and 111In-labeled C2Am, and their ability to produce rapid and cell death-specific image contrast, these agents have potential for clinical translation.