Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent of obesity in humans
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Bibliographic record
Abstract
BACKGROUND/OBJECTIVE: Plasma apoB predicts the incidence of type 2 diabetes (T2D); however, the link between apoB-linpoproteins and risks for T2D remain unclear. Insulin resistance (IR) and compensatory hyperinsulinemia characterize prediabetes, and the involvement of an activated interleukin-1 (IL-1) family, mainly IL-1β and its receptor antagonist (IL-Ra), is well documented. ApoB-lipoproteins were reported to promote IL-1β secretion in immune cells; however, in vivo evidence is lacking. We hypothesized that obese subjects with hyperapoB have an activated IL-1 system that explains hyperinsulinemia and IR in these subjects. SUBJECTS/METHODS: We examined 81 well-characterized normoglycemic men and postmenopausal women (⩾27 kg m(-2), 45-74 years, non-smokers, sedentary, free of chronic disease). Insulin secretion and sensitivity were measured by the gold-standard Botnia clamp, which is a combination of a 1-h intravenous glucose tolerance test (IVGTT) followed by 3-h hyperinsulinemic euglycemic clamp. RESULTS: Plasma IL-1β was near detection limit (0.071-0.216 pg ml(-1)), while IL-1Ra accumulated at 1000-folds higher (77-1068 pg ml(-1)). Plasma apoB (0.34-1.80 g l(-1)) associated significantly with hypersinsulinemia (totalIVGTT: C-peptide r=0.27, insulin r=0.22), IR (M/I=-0.29) and plasma IL-1Ra (r=0.26) but not with IL-1β. Plasma IL-1Ra associated with plasma IL-1β (r=0.40), and more strongly with hyperinsulinemia and IR than apoB, while the association of plasma IL-1β was limited to second phase and total insulin secretion (r=0.23). Adjusting the association of plasma apoB to hyperinsulinemia and IR for IL-1Ra eliminated these associations. Furthermore, despite equivalent body composition, subjects with hyperapoB (⩾80th percentile, 1.14 g l(-1)) had higher C-peptide secretion and lower insulin sensitivity than those with low plasma apoB (⩽20th percentile, 0.78 g l(-1)). Adjustment for plasma IL-1 Ra eliminated all group differences. CONCLUSION: Plasma apoB is associated with hyperinsulinemia and IR in normoglycemic obese subjects, which is eliminated upon adjustment for plasma IL-1Ra. This may implicate the IL-1 family in elevated risks for T2D in obese subjects with hyperapoB.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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