Abstract 605: Association of Apolipoprotein B with Impaired Insulin Sensitivity and Secretion Is Mediated by Reduced Fat Clearance in Obese Subjects
Bibliographic record
Abstract
OBJECTIVE: Human data from our lab and others have demonstrated that elevated concentrations of apoB-lipoproteins, measured as plasma apoB, are associated with insulin resistance (IR), hyperinsulinemia and the development of type 2 diabetes. However, the underlying mechanism to date remains unknown. We recently reported that LDL, the major form of apoB-lipoproteins, directly impairs the hydrolysis and storage of triglyceride-rich lipoproteins ex vivo in human white adipose tissue. Therefore, we hypothesized that the association between apoB and IR and compensatory increase in insulin secretion (IS) is mediated by delayed postprandial TG clearance in vivo in obese subjects. METHODS: We performed a Botnia clamp on normoglycemic obese men (N=14) and postmenopausal women (N=16) (BMI ≥ 27 kg/m2, age ≥ 45 years). First phase, 2 nd phase and total IS were measured during a 1-hour intravenous-glucose tolerance test (IVGTT) while insulin sensitivity was measured during a 3-hours hyperinsulinemic euglycemic clamp that followed. On a separate date, postprandial plasma clearance of TG was measured over 6 hours following the ingestion of a 13 C-triolein-labeled high-fat meal. RESULTS: Plasma apoB correlated positively with IR (r=0.15, p=0.037), 2 nd phase IS (r=0.15, p=0.039) and delayed TG clearance (AUC 6hrs of total plasma TG: r=0.64, p<0.001; AUC 6hrs of 13 C-plasma TG: r=0.77, p<0.001). Moreover, AUC 6hr of total plasma TG was associated with higher IR (r=0.16, p=0.042), 1 st phase IS (r=0.20, p=0.023), 2 nd phase IS (r=0.16, p=0.044) and total IS (r=0.16, p=0.046). Similarly, a positive association existed between delayed 13 C-labeled plasma TG clearance (AUC 6hrs ) and IR (r=0.41, p=0.046). A gender difference existed as TG clearance was mainly associated with IR in women (r=0.41, p=0.046) whereas it was mainly associated with 2 nd phase IS in men (r=0.41, p=0.046). As hypothesized, correcting for TG clearance eliminated the association of plasma apoB with IR and IS. CONCLUSION: The association of apoB with insulin resistance and secretion may be secondary to LDL-mediated delayed TG clearance by adipose tissue in humans.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.003 | 0.001 |
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 source (direct Gemma or distilled Codex), 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".