WHITE PAPER:
Prediabetes quality-improvement study using an oxygen-centric adjunct as intervention: XenaGen™ clinical QI observational analysis.
Authors
Alan P. Xenakis, MD, ScD, MPH, MS
Audra Renee Smith Xenakis, RN, BSN, DNP
1. What was the main purpose of this quality-improvement evaluation?
This evaluation observed longitudinal physiologic and metabolic patterns during adjunct exposure to an oxygen-centric enzymatic formulation over 60 days. It was designed as a quality-improvement trial. The focus was on documenting directionality, stability, and internal coherence of multiple physiologic signals.
2. Who participated in this evaluation?
Participants were adults with laboratory-defined prediabetes, reflecting real-world metabolic risk profiles. Both men and women were included across a broad adult age range. Common features included mild obesity, sedentary behavior, and early cardiometabolic risk. All participants completed the full observation period.
3. Why is prediabetes clinically important even before diabetes develops?
Prediabetes is associated with early metabolic inflexibility, vascular stress, and increased long-term cardiometabolic risk. Many physiologic changes occur before diabetes thresholds are crossed. These upstream changes often progress silently. Addressing them early aligns with a reduction in downstream risk.
4. What does an microvascular oxygen-centric adjunct framework mean in this context?
An oxygen-centric framework focuses on microvascular tissue-level oxygen delivery, release, and utilization rather than oxygen saturation alone. It emphasizes microcirculatory function and aerobic metabolism. Impaired oxygen delivery and release aligns with limiting metabolic efficiency even when SpO₂ is normal. This perspective complements glucose-centered models.
5. How was microvascular tissue oxygen delivery and release assessed?
Microvascular tissue oxygen delivery and release was assessed using transcutaneous oxygen tension (TcPO₂). TcPO₂ reflects microvascular oxygen availability at the tissue level. It is measured non-invasively and provides information beyond arterial oxygen saturation. TcPO₂ is a science-based valid tool for evaluating microcirculatory physiology.
6. What changes were observed in glycemic measures?
Fasting glucose, post-prandial glucose, and HbA1c declined over the observation period. Participants demonstrated favorable coherent glycemic stability rather than isolated reductions. Variability narrowed alongside average values. These changes followed a favorable coherent and directional longitudinal pattern.
7. Why is glucose variability important?
Daily FBG and PPG Glucose variability reflects how much blood sugar fluctuates throughout the day/week. Continual large swings align with stressing vascular and metabolic systems. Reduced variability is associated with improved metabolic regulation. In this evaluation, favorable declines in FBG and PPG Glucose variability and alignment with improved averages were observed.
8. What happened to microvascular tissue oxygen measurements over time?
TcPO₂ values were associated with a progressive increase stabilized by approximately six weeks. This suggested improved microvascular oxygen availability. The timing aligned with changes in metabolic and glycemic measures. These patterns were internally coherent. TcPO2 at the thigh, a valid non-invasive proxy for microcirculatory oxygen delivery and aerobic metabolic capacity, increased from 52.5 ± 1.4 mmHg at baseline to 64.4 ± 4.1 mmHg at Day 60, representing an absolute gain of +11.9 mmHg (22.7% increase, Cohen’s dz = 2.49). This large positive effect size demonstrates a marked increase in measured tissue oxygenation.
9. Why were lactate levels measured?
Lactate reflects reliance on anaerobic metabolism. Elevated lactate can indicate reduced aerobic efficiency. Declining lactate suggests improved oxidative metabolism. In this evaluation, lactate reductions aligned with improved oxygen-centric measures. In the context of concurrent fasting glucose normalization, this lactate reduction is consistent with improved aerobic metabolic handling.
10. What does a reduction in ESR indicate?
ESR is a nonspecific marker of systemic inflammation. Reductions suggest lower inflammatory burden. Inflammation can impair microvascular flow and metabolic efficiency. ESR declines aligned with other physiologic improvements. Systemic inflammation, assessed by ESR, declined from 40.0 ± 3.9 mm/hr at baseline to 26.4 ± 5.7 mm/hr at Day 60 (−13.6 mm/hr; −34.1%, Cohen’s dz = −2.14). This decline represents a large within-person reduction in systemic inflammatory burden.
11. Were changes in fatigue or energy observed?
Participants reported alignment with favorable reductions in cognitive fatigue and daytime tiredness. These changes were secondary observations. They followed similar directionality to metabolic and glycemic measures. These perceptions share directionality with improved energy (microvascular O2 availability and release at the tissue level).
12. Did arterial oxygen saturation change significantly?
As expected, arterial oxygen saturation remained within normal ranges throughout the evaluation. Only small numerical shifts were observed. This highlights that normal SpO₂ does not guarantee optimal tissue oxygen delivery. Increased TcPO2 tissue-level measures provided additional insight that aligned with favorable metabolic and glycemic results.
13. Why did participants serve as their own longitudinal comparators?
Using within-participant comparisons reduces variability from genetic and lifestyle differences. Each individual’s baseline served as their reference. This approach is common in quality-improvement work. It demonstrated pattern detection, direction, and coherence.
14. What does internal coherence mean in this evaluation?
Internal coherence refers to multiple physiologic signals moving in aligned, biologically plausible directions. Glycemic, oxygen-centric, metabolic, and inflammatory measures changed favorably together in directionality. This strengthens physiologic plausibility.
15. How do microcirculation and metabolism relate?
Microcirculation governs oxygen and nutrient delivery and release to tissues. Impaired flow, delivery, and release can limit aerobic metabolism. Reduced efficiency can contribute to glucose dysregulation. Examining microcirculation provides upstream metabolic context. Flow alone (i.e. increased by vasodilators) is not a dependable clinical marker for effective microvascular oxygenation. O2 must be released at the tissue level not just presented by increased flow.
16. Were there safety or tolerability concerns?
Tolerability was favorable across the observation period. Only mild (mild headaches secondary to non-compliant hydration), self-limited events were reported. No serious safety signals were identified. Findings support acceptable short-term tolerability in this context.
17. What does this evaluation suggest for clinicians?
The findings encourage clinicians to consider microvascular oxygen centric adjuncts in aligning with improved metabolic efficiency and glucose metrics. The findings highlight physiologic dimensions, coherence, and directionality often overlooked. These observations complement, rather than replace, existing guidelines.
18. What should wellness consumers take away?
Metabolic health involves more than weight or sugar intake alone. Oxygen delivery, inflammation, and energy efficiency matter. Improvements often occur together rather than in isolation. Findings in this study are presented as educational when wellness planning is considered and discussed.
19. Why is microvascular tissue oxygenation different from oxygen saturation?
Oxygen saturation reflects how much oxygen is carried in the blood. Microvascular tissue oxygenation reflects how much oxygen actually reaches and is released to cells. Under normal conditions there is a gap in these values with further separation occurring under inflammatory or rheologic stress. Comparing SpO2 blood level and TcPO2 microvascular tissue-level measures reveals this gap.
20. What is the logical next step following this evaluation?
An additional question may be presented: What role could microvascular oxygen centric adjuncts have on favorably affecting metabolic and glycemic measures in patients who progress from prediabetes to diabetes?
Source: Xenakis, A. R-S. X., & Xenakis, A. X. (2025). Prediabetes quality-improvement study using an oxygen-centric adjunct as intervention: XenaGen™ clinical QI observational analysis. XenaDigm. https://xenadigm.com/qi-white-papers-for-xenagen/