RESUMO
OBJECTIVES: The goals of this study were to develop (1) a safe and effective protocol for the clinical control of type 1 diabetes using conventional self-monitoring blood glucose (SMBG) measurements and multiple daily injections with insulin analogues, and (2) an in silico simulation tool of type 1 diabetes to predict long-term glycemic control outcomes of clinical interventions. METHODS: The virtual patient method was used to develop a simulation tool for type 1 diabetes using data from a type 1 diabetes patient cohort (n = 40). The tool was used to test the adaptive protocol (AC) and a conventional intensive insulin therapy (CC) against results from a representative control cohort. Optimal and suboptimal basal insulin replacements were evaluated as a function of SMBG frequency in conjunction with the (AC and CC) prandial control protocols. RESULTS: In long-term glycemic control, the AC protocol significantly decreased hemoglobin A1c in conditions of suboptimal basal insulin replacement for SMBG frequencies > or = 6/day, and reduced the occurrence of mild and severe hypoglycemia by 86-100% over controls, over all SMBG frequencies in conditions of optimal basal insulin. CONCLUSIONS: A simulation tool to predict long-term glycemic control outcomes from clinical interventions has been developed to test a novel, adaptive control protocol for type 1 diabetes. The protocol is effective and safe compared to conventional intensive insulin therapy and controls. As fear of hypoglycemia is a large psychological barrier to glycemic control, the AC protocol may represent the next evolution of intensive insulin therapy to deliver increased glycemic control with increased safety. Further clinical or experimental validation is needed to fully prove the concept.
RESUMO
BACKGROUND: Timely diagnosis and treatment of sepsis in critical care require significant clinical effort, experience, and resources. Insulin sensitivity is known to decrease with worsening condition and could thus be used to aid diagnosis. Some glycemic control protocols are able to identify insulin sensitivity in real time. METHODS: Receiver operating characteristic curves and cutoff insulin sensitivity values for diagnosing sepsis were calculated for model-based insulin sensitivity (S(I)) and a simpler metric (SS(I)) that was estimated from glycemic control data of 30 patients with sepsis and can be calculated in real time without use of a computer. Results were compared to the insulin sensitivity profiles of a general intensive care unit population of 113 patients without sepsis and 30 patients with sepsis, comprising a total of 26,453 patient hours. Patients with sepsis were identified as having sepsis based on a sepsis score (ss) of 3 or higher (ss = 0 - 4 for increasing severity). Patients with type I or type II diabetes were excluded. Ethics approval for this study was granted by the South Island Regional Ethics Committee. RESULTS: Receiver operating characteristic cutoff values of S(I) = 8 x 10-5 liter mU(-1) min(-1) and SS(I) = 2.8 x 10-4 liter mU(-1) min(-1) were determined for ss > or = 3. The model-based S(I) fell below this value in 15% of all patient hours. The S(I) test had a negative predictive value of 99.8%. The test sensitivity was 78% and specificity was 82%. However, the positive predictor value was 2.8%. Slightly lower sensitivity (68.8%) and specificity (81.7%), but equally good negative prediction (99.7%), were obtained for the estimated SS(I). CONCLUSIONS: Insulin sensitivity provides a negative predictive diagnostic for sepsis. High insulin sensitivity rules out sepsis for the majority of patient hours and may be determined noninvasively in real time from glycemic control protocol data. Low insulin sensitivity is not an effective diagnostic, as it can equally mark the presence of sepsis or other conditions.