Klotho And Ngal Responses To Exercise-heat Stress In Older Men With And Without Type-2 Diabetes
Bibliographic record
Abstract
Klotho is a protein expressed by the kidneys and is vital in protecting cellular function during acute physiological stressors (e.g., inflammation, oxidative stress), as occurs during exercise-heat stress. We previously showed that serum klotho concentrations are blunted in healthy older men, with further impairments in older men with type 2 diabetes (T2D) during prolonged exercise in the heat. These altered klotho responses may increase vulnerability to heat-induced cellular injury and consequently increase the risk of acute kidney injury (AKI). However, biomarkers of AKI, such as neutrophil gelatinase-associated lipocalin (NGAL), have yet to be evaluated in the context of blunted klotho production during an exercise-heat stress in older adults with T2D. PURPOSE: We evaluated serum concentrations of klotho and NGAL during exercise-heat stress in older men with and without T2D. METHODS: 28 habitually active older (60 ± 6 years) men with (n = 14, T2D) and without (n = 14, Control) controlled T2D performed 3 successive 30-min cycling bouts in a whole-body air calorimeter in the heat (40 °C, ~15% relative humidity) at fixed rates of metabolic heat production of 150, 200, and 250 W·m2 (to maintain a fixed thermal drive for heat loss), each separated by 15-min rest. Concentrations of klotho and NGAL were assessed via an ELISA at baseline and following the final exercise bout (end-exercise). Statistical significance was determined via a two-way ANOVA with fisher LSD (α = 0.05). RESULTS: Serum NGAL concentrations increased similarly at end-exercise in T2D and controls (+704 pg/mL [SD: 1326] and + 964 pg/mL [1399], respectively, both p < 0.05). Despite this, serum klotho concentrations did not differ in response to exercise in the heat, yet concentrations were higher in the controls at baseline (1593 pg/mL [1318] vs 743 [431] pg/mL; p = 0.038) and at end-exercise (1614 pg/mL [1407] vs 761 pg/mL [465]; p = 0.017) compared to T2D. CONCLUSION: A similar increase in circulating NGAL concentrations between men with and without T2D may indicate a greater vulnerability to AKI during exercise-heat stress. Paired with reduced circulating klotho concentrations in older men with T2D, this may further predispose these individuals to heat-related cellular injury. FUNDING SUPPORT: Canadian Institutes of Population Health (399434)
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| 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 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".