P0894OBESITY IMPAIRS THE ACUTE RESPONSE TO AN ORAL PHOSPHATE CHALLENGE
Bibliographic record
Abstract
Abstract Background and Aims T Obesity is an increasing health problem world-wide. People who are overweight or obese are at greater risk of developing chronic diseases including cardiovascular disease (CVD). Factors associated with dysregulated phosphate metabolism have been linked to the presence of vascular calcification in people with type 2 diabetes (T2D) with normal kidney function. Insulin resistance and abdominal obesity are associated with increased circulating levels of phosphaturic hormones including fibroblast growth factor 23 (FGF-23) and parathyroid hormone (PTH). Abnormalities in phosphate regulation may not be reflected in single circulating measurements of serum phosphate, but can be revealed by the acute circulating and mineral response to an oral challenge of phosphate. The aim of this study was to determine if obesity and insulin resistance impact the acute capacity to excrete an oral phosphate challenge. Method Community-dwelling people (N=78) free of T2D and symptomatic CVD (∼10 males and ∼10 females from each decade between 40 and 80 years) with normal kidney function were recruited from Kingston, Ontario, Canada. Following a 12-hour fast, participants consumed a 1250 mg phosphate drink (sodium phosphate) where blood and urine were collected at baseline, 1, 2 and 3 hours following the oral challenge. Participants with a high-risk metabolic profile characterized by an elevated waist-to-height ratio (WHtR) (> 0.58) were matched by age and sex to participants with a low risk WHtR (<0.5). Results The results reveal a significant impact of obesity on phosphate excretion in response to an oral phosphate challenge. There was an association between WHtR ratio and the level of iFGF-23 (R=-0.34 p<0.01) but not PTH. After adjustment for age and sex, WHtR ratio was inversely correlated with urinary phosphate excretion in response to the phosphate challenge (R=-0.29, p=0.02) and the change in fractional excretion of phosphate (r=-0.34, p=0.007). From the larger cohort, an age- and sex- matched subset was selected for 12 high risk and 12 low risk metabolic profiles with WHtR of 0.66±0.02 and 0.46±0.01, respectively. Kidney function was the same between the two groups (eGFR 92.3±13.1 versus 95.8±13.6 ml/min/1.73m2 respectively) but high risk participants had significantly higher homeostatic model assessment of insulin resistance (HOMA-IR) (1.61±0.81 versus 0.68±0.3, p<0.01). Participants with a high risk metabolic profile had a greater increase in serum phosphate from baseline (29% increase in the area under the curve, p=0.04) and a significantly blunted increase in the fractional excretion of phosphate in response to the oral phosphate challenge (35% reduction in area under the curve [AUC], p=0.03) compared to the matched low risk profile participants. Conclusion Overweight/obese individuals demonstrate impaired response to an oral phosphate challenge, whereby phosphate excretion was impaired and there was increased exposure to new circulating phosphate. An impaired acute phosphate response may contribute to the initiation or propagation of vascular calcification. Dysregulated phosphate homeostasis may be an under-recognized cardiovascular risk factor in obese people that could be modified by diet and weight loss. Whether insulin enhances renal phosphate reabsorption requires further study.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".