ABSTRACT
BACKGROUND: The primary objective of this study was to measure the prevalence, incidence, and resolution of insulin resistance (IR) in critically ill patients. A secondary objective was to explore the relationship between IR and inflammatory cytokines, coagulation abnormalities, and clinical outcomes. DESIGN: Prospective observational study. METHODS: The setting was the medical/surgical intensive care unit (ICU). We enrolled consecutive patients within 24 hours of admission to the ICU. Blood samples were collected daily until discharge, death, or a maximum of 10 days, then sent for measurement of markers of IR, inflammation, and coagulation. Charts were reviewed retrospectively to determine clinical outcomes. The homeostasis model assessment method (HOMA) was used to determine IR; a score of > or = 4 represents insulin resistance. RESULTS: A total of 96 patients were enrolled. Upon admission, 64 (67%) patients had overt IR (glucose > 7 mmol/L or insulin use), 9 (9.4%) had non-overt IR (normal glucose but HOMA > 4), and 23 (24%) were insulin sensitive (IS; normal glucose and HOMA < 4). During the course of ICU stay, an additional 16 patients developed overt IR, while 10 (10%) remained IS. There were no significant differences in inflammatory markers, coagulation tests, and clinical outcomes between IR and IS patients. There was no significant correlation between HOMA and inflammatory markers and coagulation markers. In a multivariable regression model, only interleukin-6 levels were significantly associated with mortality. CONCLUSIONS: A high proportion of critically ill patients have IR. There may not be any significant relationship between IR and measures of inflammation, coagulation, and clinical outcomes in a heterogeneous population of critically ill patients.
Subject(s)
Blood Coagulation Disorders/epidemiology , Critical Illness/mortality , Critical Illness/therapy , Cytokines/biosynthesis , Insulin Resistance , Aged , Blood Glucose/metabolism , Cytokines/blood , Female , Homeostasis/physiology , Humans , Incidence , Insulin/metabolism , Insulin/therapeutic use , Intensive Care Units , Interleukin-6/blood , Length of Stay , Male , Middle Aged , Multivariate Analysis , Outcome Assessment, Health Care , Prevalence , Prospective Studies , Treatment OutcomeABSTRACT
In order to evaluate the changes within the VWF gene that might contribute to the pathogenesis of type 1 von Willebrand disease (VWD), a large multicenter Canadian study was undertaken. We present data from the sequence analysis of the VWF gene in 123 type 1 VWD index cases and their families. We have identified putative mutations within the VWF gene in 63% (n = 78) of index cases, leaving 37% (n = 45) with no identified changes. These changes comprise 50 different putative mutations: 31 (62%) missense mutations, 8 (16%) changes involving the VWF transcriptional regulatory region, 5 (10%) small deletions/insertions, 5 (10%) splicing consensus sequence mutations, and 1 nonsense mutation. Twenty-one of the index cases had more than one putative VWF mutation identified. We were somewhat more likely to identify putative mutations in cases with lower VWF levels, and the contribution of other factors, such as ABO blood group, seems more important in milder cases. Taken as a whole, our data support a complex spectrum of molecular pathology resulting in type 1 VWD. In more severe cases, genetic changes are common within the VWF gene and are highly penetrant. In milder cases, the genetic determinants are more complex and involve factors outside of the VWF gene.
