Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects
Bibliographic record
Abstract
Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P < 0.05), hypercortisolemia resulted in higher glucose (P < 0.05) and free fatty acid concentrations (P < 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P < 0.01), indicating the presence of steroid-induced insulin resistance. Postabsorptive glucose production (P = 0.64) and the fractional contribution of gluconeogenesis to EGR (P = 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P < 0.05), implying a decrease in net glucose effectiveness (4.42 +/- 0.52 vs. 6.65 +/- 0.83 ml.kg-1.min-1; P < 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P < 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P < 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3H]glucose during hydrocortisone than during saline infusion (P < 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal beta-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess impairs glucose tolerance by decreasing both insulin action and glucose effectiveness.
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How this classification was reachedexpand
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 | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".