An adverse lipoprotein phenotype—hypertriglyceridaemic hyperapolipoprotein B—and the long-term risk of type 2 diabetes: a prospective, longitudinal, observational cohort study
Bibliographic record
Abstract
BACKGROUND: This study examines the risk of new-onset diabetes in patients with hypertriglyceridaemic hyperapolipoprotein B (high triglycerides, high apolipoprotein B [apoB], low LDL cholesterol to apoB ratio, and low HDL cholesterol). The aim was to establish whether this lipoprotein phenotype identified a substantial group at high risk of developing diabetes over the next 20 years. METHODS: In this prospective, longitudinal, observational cohort study, we used data from the Framingham Offspring cohort (recruited in Framingham, MA, USA). Participants were aged 40-69 years and free of diabetes and cardiovascular disease at a baseline examination done between April, 1987, and November, 1991, and were followed up until March, 2014. Cox proportional hazards regression with hierarchical adjustment for age and sex, waist circumference, and fasting blood glucose were used to model the relationship between each lipid marker and incident diabetes, as well as the relationship between hypertriglyceridaemic hyperapoB (defined as values greater than sample medians of triglycerides and apoB, and less than medians of HDL cholesterol and LDL cholesterol to apoB ratio) and incident diabetes. FINDINGS: Of 3446 individuals aged 40-69 years who completed baseline examination, 2515 participants were eligible and included in all analyses. During median 21·1 years (IQR 11·1-23·1) of follow-up, 402 (16·0%) individuals developed diabetes. Age (p=0·032), waist circumference (p<0·0001), fasting blood glucose (p<0·0001), and natural logarithm-transformed triglycerides (p<0·0001) were associated with new-onset diabetes, as were apoB (p=0·0016), LDL cholesterol to apoB ratio (p=0·0018), and HDL cholesterol (p=0·0016) when added to this model. The age and sex-adjusted incidence of diabetes in the hypertriglyceridaemic hyperapoB group was 32·4% (95% CI 27·8-37·7) versus 5·5% (3·5-8·6) in the optimal lipid phenotype group and 15·5% (13·5-17·7) in the mixed lipid phenotype group. The fully adjusted hazard ratio, including glucose and waist circumference, for individuals with hypertriglyceridaemic hyperapoB was 3·30 (95% CI 2·06-5·30; p=0·0008) and for mixed lipid phenotype was 2·17 (1·38-3·40; p<0·0001) compared with those with the optimal lipid phenotype. INTERPRETATION: Our findings suggest that individuals with hypertriglyceridaemic hyperapoB are at high risk of new-onset diabetes and might benefit from intensive measures to prevent diabetes. The association between this phenotype and incident diabetes is consistent with a pro-diabetic effect due to increased clearance of apoB particles from plasma, which could injure pancreatic islet cells. This mechanism might explain the increased risk of diabetes with statin therapy. FUNDING: Doggone Foundation.
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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 | 0.007 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 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".