The present study is the first to demonstrate that despite similar levels of red blood cell 2, 3-DPG, PO2, PCO2, pH and body temperature, type 2 diabetic patients with HbA1c > 7% had higher SaO2 (the mean difference was 1.1%) and bias (1.83 ±0.55%) compared with those with HbA1c ≤ 7%, suggesting that elevated blood HbAlc levels led to an overestimation of SaO2 by pulse oximetry.
Hypoxemia denotes a condition that is characterized by low oxygen content or percent saturation of hemoglobin with oxygen. Arterial blood gases have been traditionally used to assess the status of oxygenation and to adjust fractional inspired oxygen in patients receiving mechanical ventilation or oxygen therapy. Currently, noninvasive continuous monitoring of SaO2 with SpO2 has become the standard care for patients with critical conditions[13, 21], to decrease the likelihood of hypoxemia[22–25] and to wean mechanical ventilation[10, 11, 26]. In the present study, when comparisons were performed at identical PO2, SaO2 was higher in type 2 diabetic patients with HbA1c > 7%, which is likely due to an increased hemoglobin-oxygen affinity. Our results are in line with previous findings that higher blood concentrations of HbA1c significantly reduce oxygen dissociation velocity. Although the exact mechanism remains not fully understood, it may be, at least partly, explained by glycation of multiple ß-chain sites of hemoglobin A molecule, accompanied by increasing -chain glycation at high glycohemoglobin concentrations[28, 29].
The major finding of this study is that in type 2 diabetic patients with poor glycemic control, pulse oximetry overestimated arterial blood gases-determined SaO2 by a mean of 2.7% when compared with those with HbA1c ≤ 7%. Previous studies showed that older women have higher HbA1c than men, even after controlling for body mass index, and accumulation of AGE in human skin collagen is age-dependent. However, both gender distribution and age did not significantly differ between the two groups in the present study, suggesting that the difference between SpO2 and SaO2 may be mainly related to HbA1c levels as higher HbA1c levels were associated with great differences (Pearson’s r = 0.307, p < 0.01).
Our findings may be of important clinical relevance. First, falsely high SpO2 could cause under-diagnosis of hypoxemia in type 2 diabetic patients. Second, because a greater SpO2 was required to achieve the same arterial blood gases-determined PO2 for diabetic patients with HbA1c >7% compared with those with HbA1c ≤ 7%, care should be taken in adjusting oxygen supply during mechanical ventilation or oxygen therapy. The reason for a higher SpO2 than SaO2 may be partly explained by an extensive accumulation of AGE in the skin collagen in patients with poor glycemic control, interfering with transdermal absorption of the specific wavelength light by hemoglobin with finger probes[12, 32]. These observations support a notion that the causes of high bias does include skin effect[33, 34], and when SaO2 needs to be determined with a high degree of accuracy, arterial blood gases are recommended in type 2 diabetic patients with poor glycemic control.
Due to relatively small sample size, potential for selection bias may raise some concerns on the statistical precision of the estimates. A large-scale study is warranted to confirm our findings. The other major limitation is that most of the data are at high SaO2 because of a specially selected study population as all patients were receiving mechanical ventilation and/or oxygen therapy. The oxyhemoglobin dissociation curves could actually be fitted with non-linear regression, and a partial pressure of oxygen in blood associated to a hemoglobin oxygen saturation of 50% (P50) could also be calculated. Most oximetry testing intentionally gathers data below 90% by performing desaturation experiments in volunteers. Gather multiple data points on volunteers increase the data set substantially, and allow one to test over a wide range of SaO2, and control for other effects. By creating a gas pocket with CO2 and O2/N2 mixtures, one can create a much more detailed oxyhemoglobin dissociation curve. The US FDA requires testing balanced by gender and ethnicity. Repeated measures statistics would then be necessary, and P50 is not determined quite as precisely unless the sample is near a SaO2 of 50%. Certainly, it remains unclear whether the issue with diabetic patients would be safe given the possibility of cardiovascular disease, although younger subjects could be reasonable.