Maternal diabetes as an early life risk factor for chronic obstructive pulmonary disease
Bibliographic record
Abstract
Introduction: Chronic obstructive pulmonary disease (COPD) is Canada’s fifth leading cause of death and is primarily caused by smoking. However, only <20% of smokers develop COPD, suggesting that other factors are important. Early-life exposures may also increase COPD risk by impairing lung development and altering response to cigarette smoke (CS). Maternal diabetes (MD) increases the risk for premature birth and childhood asthma, which are risk factors for COPD. However, the direct impact of MD on offspring susceptibility towards CS and COPD remains unexplored. I hypothesize that exposure to MD worsens CS induced lung damage in offspring. Methods: Six-week-old C57BL/6NJ female mice were fed with a high-fat diet (HFD-45% kcal) to induce diabetes-like features or low-fat (LFD-10% kcal) control-diet for 6-weeks, and throughout pregnancy and weaning. Weaned offspring were fed standard research chow-diet until 8-weeks of age, at which point they were exposed to CS/Room air for 50 mins, twice/day, for four days. Lung function and inflammation were assessed on day five. Lung tissues were collected for DNA methylation and gene expression analysis. Data were analyzed in Prism GraphPad using two-way ANOVA, significance set at p<0.05. Results: Offspring from diabetic pregnancy were significantly heavier at 3-weeks than controls. At 8-weeks the body weight difference maintained only in males. CS exposure significantly increased total lung resistance (14%) and airway resistance (18%) in HFD male offspring compared to control. HFD influenced CS induced immune cell infiltration in a sex-specific manner. Female HFD-CS offspring had significantly decreased neutrophils, CD4+ T-cells and NK cells compared to control-smokers. Male HFD-CS offspring had significantly elevated B-cells and NKT cells compared to HFD-control. At baseline, HFD female offspring had elevated Eotaxin and MIG but reduced IL-1α. CS induced cytokine changes in control animals, which were sex specific, were blunted in HFD exposed offspring. Additionally, I observed changes in gene abundance (Igf, Igfbp3 and Ephx1), but without specific changes in DNA methylation in smoking individuals from diabetic pregnancy. Conclusion: MD alters offspring susceptibility towards CS-induced lung dysfunction and inflammation, in a sex-specific manner. MD may modulate response to cigarettes in early adulthood, suggesting a propensity to future COPD.
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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 | 0.000 |
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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 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".