The S troke H yperglycemia I nsulin N etwork E ffort ( SHINE ) trial protocol: a randomized, blinded, efficacy trial of standard vs. intensive hyperglycemia management in acute stroke

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102726/1/ijs12045.pd

Expanding the horizon of research into the pathogenesis of the white matter diseases: Proceedings of the 2021 Annual Workshop of the Albert Research Institute for White Matter and Cognition

White matter pathologies are critically involved in the etiology of vascular cognitive impairment–dementia (VCID), Alzheimer’s disease (AD), and Alzheimer’s disease and related diseases (ADRD), and therefore need to be considered a treatable target (Roseborough A, Hachinski V, Whitehead S. White matter degeneration - a treatable target? Roseborough et al. JAMA Neurol [Internet]. 2020 Apr 27;77(7):793–4, [1]. To help address this often-missed area of research, several workshops have been sponsored by the Leo and Anne Albert Charitable Trust since 2015, resulting in the incorporation of “The Albert Research Institute for White Matter and Cognition” in 2020. The first annual “Institute” meeting was held virtually on March 3–4, 2021. The Institute provides a forum and workspace for communication and support of the advancement of white matter science and research to better understand the evolution and prevention of dementia. It serves as a platform for young investigator development, to introduce new data and debate biology mechanisms and new ideas, and to encourage and support new research collaborations and directions to clarify how white matter changes, with other genetic and health risk factors, contribute to cognitive impairment. Similar to previous Albert Trust–sponsored workshops (Barone et al. in J Transl Med 14:1–14, [2]; Sorond et al. in GeroScience 42:81–96, [3]), established expert investigators were identified and invited to present. Opportunities to attend and present were also extended by invitation to talented research fellows and younger scientists. Also, updates on institute-funded research collaborations were provided and discussed. The summary that follows is a synopsis of topics and discussion covered in the workshop

Diabetes Mellitus, Acute Hyperglycemia, and Ischemic Stroke

Acute brain ischemia is a dynamic process susceptible to multiple modulating factors, such as blood glucose level. During acute ischemic brain injury, hyperglycemia exacerbates multiple deleterious derangements. Timely and sufficient correction of hyperglycemia during acute brain ischemia may limit the brain injury and improve clinical outcomes. The clinical efficacy of such intervention remains to be proven. Although results from animal and clinical observational studies suggest that hyperglycemia during acute brain ischemia may exacerbate the brain injury, there is no evidence from randomized treatment trials that rapid correction of the hyperglycemia improves outcomes. Given the excess effort, cost, and risk involved in rapid and safe correction of hyperglycemia during acute stroke, less aggressive treatments with subcutaneous insulin seem appropriate at this time. Subcutaneous insulin protocols can maintain blood glucose levels below 200 mg/dL a majority of the time in most patients, especially if basal insulin is added. When available, an endocrinology consultant can optimize the acute treatment and help the transition to long-term care. Given the multiple reports linking admission hyperglycemia with symptomatic hemorrhagic conversion of ischemic stroke treated with thrombolytic drugs, it may be best to rapidly lower severe hyperglycemia in such patients. For example, if the admission blood glucose is approximately 300 mg/dL and the patient is a candidate for thrombolytic therapy, consider giving an intravenous bolus of regular insulin 8 units. Somewhat lower or higher insulin doses may be best for lesser or greater hyperglycemia. Such a bolus will start lowering the blood glucose in about 5 min. A temporary continuous intravenous insulin infusion may then be used in most patients to maintain the glucose closer to normal levels (eg, below 180 or 140 mg/dL)

Diabetes Mellitus, Acute Hyperglycemia, and Ischemic Stroke

Acute brain ischemia is a dynamic process susceptible to multiple modulating factors, such as blood glucose level. During acute ischemic brain injury, hyperglycemia exacerbates multiple deleterious derangements. Timely and sufficient correction of hyperglycemia during acute brain ischemia may limit the brain injury and improve clinical outcomes. The clinical efficacy of such intervention remains to be proven. Although results from animal and clinical observational studies suggest that hyperglycemia during acute brain ischemia may exacerbate the brain injury, there is no evidence from randomized treatment trials that rapid correction of the hyperglycemia improves outcomes. Given the excess effort, cost, and risk involved in rapid and safe correction of hyperglycemia during acute stroke, less aggressive treatments with subcutaneous insulin seem appropriate at this time. Subcutaneous insulin protocols can maintain blood glucose levels below 200 mg/dL a majority of the time in most patients, especially if basal insulin is added. When available, an endocrinology consultant can optimize the acute treatment and help the transition to long-term care. Given the multiple reports linking admission hyperglycemia with symptomatic hemorrhagic conversion of ischemic stroke treated with thrombolytic drugs, it may be best to rapidly lower severe hyperglycemia in such patients. For example, if the admission blood glucose is approximately 300 mg/dL and the patient is a candidate for thrombolytic therapy, consider giving an intravenous bolus of regular insulin 8 units. Somewhat lower or higher insulin doses may be best for lesser or greater hyperglycemia. Such a bolus will start lowering the blood glucose in about 5 min. A temporary continuous intravenous insulin infusion may then be used in most patients to maintain the glucose closer to normal levels (eg, below 180 or 140 mg/dL)