Hyperglycemia enhances coagulation and reduces neutrophil degranulation, whereas hyperinsulinemia inhibits fibrinolysis during human endotoxemia
Why this work is in the frame
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Bibliographic record
Abstract
Type 2 diabetes is associated with altered immune and hemostatic responses. We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune, coagulation, and fibrinolytic responses during systemic inflammation. Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose, insulin, both, or none was increased, depending on randomization. Target plasma concentrations were 5 versus 12 mM for glucose, and 100 versus 400 pmol/L for insulin. After 3 hours, 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response. Endotoxin administration induced cytokine release, activation of neutrophils, endothelium and coagulation, and inhibition of fibrinolysis. Hyperglycemia reduced neutrophil degranulation (plasma elastase levels, P < .001) and exaggerated coagulation (plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor, both P < .001). Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels (P < .001). Endothelial cell activation markers and cytokine concentrations did not differ between clamps. We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation, whereas hyperinsulinemia inhibits fibrinolysis. These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it