A Potential Pitfall in Detection of Diabetes Mellitus Non-invasively Using the Second-Derivative of Photoplethysmography: Coexisting Hypertension May Blunt the Distinctive Difference in Early Negative to Initial Positive Wave Ratio (b/a) Between People With and Without Diabetes

Background Digital biomarkers have attracted increasing attention as possible non-invasive diagnostic tools for frequent cardiovascular pathologies. Alterations of features extracted from the derivatives and raw signal of photoplethysmography have been found in the presence of cardiovascular risk factors including but not limited to diabetes, hypertension, arterial stiffness, and endothelial dysfunction. In parallel, recent studies have shown promising results regarding the utilization of PPG as a non-invasive diagnostic tool for diabetes. Whether the presence of hypertension impedes the classification due to mutual endothelial insult resulting in peripheral hemodynamic perturbations remains unknown. Methods The previously described ratio between the amplitudes of early-negative(b) and initial-positive(a) waves (b/a) was derived from the second derivative of the PPG signal. Patients were classified according to diabetes mellitus type 2 and hypertension. Standard statistical tests were used to compare the means between unpaired subgroups. Results Final analysis included 132 patients. Compared to healthy control group DM2(-)HT(-) (-0.263 {+/-} 0.115), both DM2(+)HT(-) (-0.361 {+/-} 0.122, p<0.001, d= 0.83) and HT(+)DM2(-) (-0.319 {+/-} 0.127, p:0.033, d= 0.48) groups had significantly lower b/a values. However, subgroups with one of two conditions had statistically indifferent mean b/a values (DM2(+)HT(-) (-0.361 {+/-} 0.122) vs HT(+)DM2(-) (-0.319 {+/-} 0.127, p:0.212, d:0.32). Moreover, significant difference in b/a between DM2 and non-DM2 subgroups of non-HT group (p<0.001) disappeared in subgroups with HT(p:0.665, d:0.16). Conclusion The utilization of the second-derivative of PPG for the detection of diabetes non-invasively may be impeded in patients with cardiovascular comorbidities, especially in the hypertensive population since both HT and DM2 induce parallel b/a ratio alterations due to the mutual undesired perturbations in the cardiovascular system, affecting peripheral flow dynamics.