Machine learning-based detection of diabetes mellitus from single-lead electrocardiography: A phenotype-stratified approach

Table 1 Patient inclusion and exclusion criteria for the study

Criterion type	Description
Inclusion	Patient age over 18 years; agreement to participate in the study
Exclusion	Significant QRS complex morphology changes (such as bundle branch block and ventricular extrasystole); poor quality electrocardiography recorded from the fingers (Parkinson’s disease, tremor of any origin, mental disorders). Unsatisfactory quality of electrocardiography and/or photoplethysmography; withdrawal of consent for further participation in the study

Table 2 Comparative statistics of the groups, n (%)/mean ± SD

Factor	Index	Without DM	With DM	Р value
Age (years)		56.1 ± 17.1	63.7 ± 10.6	0.000
Sex	Female	177 (38.6)	83 (48.5)	0.032
Left ventricle diastolic dysfunction	No	333 (72.7)	74 (43.3)	0.000
	Yes	125 (27.3)	97 (56.7)
Left ventricle diastolic dysfunction_1 stage	No	340 (74.2)	84 (49.1)	0.000
	Yes	118 (25.8)	87 (50.9)
Left ventricle diastolic dysfunction 2_3 stage	No	418 (91.3)	132 (77.2)	0.000
	Yes	40 (8.7)	39 (22.8)
Hypertension degree	No	190 (41.5)	40 (23.4)	0.000
	1st degree	39 (8.5)	25 (14.6)
	2nd degree	140 (30.6)	50 (29.2)
	3rd degree	89 (19.4)	56 (32.7)
Aterial fibrillation at the registration moment (from the single lead ECG)	No	435 (95.0)	162 (94.7)	1.000
	Yes	23 (5.0)	9 (5.3)
Ischemic heart disease	No	361 (78.8)	113 (66.1)	0.001
	1st functional class	68 (14.8)	48 (28.1)
	2nd functional class	29 (6.3)	10 (5.8)
Disturbance of cardiac rhythm and conduction	No	443 (96.7)	162 (94.7)	0.092
	1	11 (2.4)	3 (1.8)
	2	3 (0.7)	5 (2.9)
	3	1 (0.2)	1 (0.6)
Chronic heart failure	No	407 (89.6)	150 (88.2)	0.324
	1st stage	7 (1.5)	0 (0.0)
	2nd stage	22 (4.8)	10 (5.9)
	3rd stage	17 (3.7)	9 (5.3)
	4th stage	1 (0.2)	1 (0.6)
Aortic valve insufficiency	No	351 (76.6)	147 (86.0)	0.022
	1st stage	95 (20.7)	23 (13.5)
	2nd stage	12 (2.6)	1 (0.6)
Aortic valve stenosis	No	443 (96.7)	163 (95.9)	0.753
	1st stage	9 (2.0)	5 (2.9)
	2nd stage	4 (0.9)	2 (1.2)
	3rd stage	2 (0.4)	0 (0.0)
Mitral valve insufficiency	No	134 (29.5)	105 (61.4)	0.000
	1st stage	274 (60.4)	60 (35.1)
	2nd stage	39 (8.6)	6 (3.5)
	3rd stage	7 (1.5)	0 (0.0)
Mitral valve stenosis	No	454 (99.1)	166 (97.1)	0.053
	1st stage	3 (0.7)	5 (2.9)
	2nd stage	1 (0.2)	0 (0.0)
Ejection fraction		59.5 ± 8.6	58.1 ± 8.0	0.005
Ejection fraction > 55	No	73 (15.9)	42 (24.6)	0.018
	Yes	385 (84.1)	129 (75.4)
Ejection fraction < 40	No	436 (95.2)	164 (95.9)	0.870
	Yes	22 (4.8)	7 (4.1)
Ejection fraction < 30	No	453 (98.9)	169 (98.8)	1.000
	Yes	5 (1.1)	2 (1.2)
End diastolic volume (mL)		93.8 ± 36.2	99.9 ± 46.7	0.632
Left atrial volume index		34.9 ± 11.1	36.7 ± 8.1	0.000
Smoking	No	371 (81.0)	154 (90.1)	0.009
	Yes	87 (19.0)	17 (9.9)
SDLA		11.0 ± 5.2	10.4 ± 2.7	0.176
HFNoise		60.7 ± 28.3	66.0 ± 25.5	0.003
RR		822.0 ± 156.2	811.2 ± 141.7	0.533
TpTe		89.4 ± 20.3	94.3 ± 29.7	0.487
VAT		38.8 ± 11.1	41.6 ± 13.4	0.020
QTc		425.8 ± 44.4	447.0 ± 52.4	0.000
QT_TQ		1.0 ± 0.4	1.0 ± 0.4	0.001
HFQRS		15919.9 ± 199679.8	10.3 ± 8.5	0.989
HFSNR		2.5 ± 2.3	2.1 ± 1.8	0.149
JA		-24.9 ± 57.7	-35.9 ± 81.8	0.054
J80A		1504.0 ± 31942.7	-3.8 ± 92.9	0.025
TA		185.0 ± 153.9	151.2 ± 162.2	0.006
QRSenergy		616.1 ± 557.9	728.6 ± 870.9	0.117
Tenergy		108.4 ± 101.3	111.7 ± 113.7	0.926
Tpenergy		77.0 ± 86.1	73.6 ± 89.1	0.218
Sbeta		0.9 ± 0.5	1.0 ± 0.9	0.003
Beta		0.8 ± 0.4	0.9 ± 0.5	0.000
QRS11energy		539.0 ± 692.3	713.6 ± 1339.7	0.075
QRS12energy		809.2 ± 1129.4	1074.5 ± 1901.7	0.077
QRS2energy		226.5 ± 301.4	305.8 ± 551.4	0.042
QRSE1		4730.9 ± 94779.9	2707.4 ± 34733.0	0.004
QRSE2		1303.9 ± 25310.4	164.5 ± 290.3	0.040
QRSE3		224.6 ± 202.5	266.1 ± 323.5	0.177
QRSE4		230.8 ± 189.8	238.7 ± 194.6	0.454
TE1		45.2 ± 57.1	54.0 ± 72.5	0.263
TE2		2548.4 ± 53784.0	31.7 ± 27.2	0.186
TE3		3621.5 ± 77261.8	9.5 ± 9.2	0.019
TE4		10275.1 ± 134000.1	5.2 ± 5.1	0.031
QRSw		88.7 ± 23.5	92.3 ± 25.9	0.078
PAn		67.3 ± 37.6	60.5 ± 40.1	0.081
Pan_1		-1.4 ± 17.6	-1.6 ± 10.3	0.981
RA		903.0 ± 414.2	916.9 ± 432.6	0.794
SA		180.0 ± 155.1	198.7 ± 209.0	0.632
Pst		217.6 ± 121.4	144.2 ± 123.3	0.000
Pfi		77.3 ± 77.0	101.5 ± 79.9	0.000
QRSst		165.6 ± 85.6	190.7 ± 88.4	0.000
QRSfi		436.2 ± 117.0	371.1 ± 169.8	0.000
Tfi		5.5 ± 170.3	293.1 ± 301.6	0.000
PpeakP		-67.5 ± 55.2	-7.2 ± 71.5	0.000
PpeakP		107.9 ± 81.7	80.7 ± 106.0	0.000
Rpeak		138.4 ± 92.7	197.8 ± 94.6	0.000
Speak		176.0 ± 109.5	223.3 ± 102.9	0.000
Tpeak		375.6 ± 106.9	453.2 ± 123.7	0.000
Tons		329.7 ± 105.4	403.1 ± 118.7	0.000
Toffs		416.8 ± 113.5	493.4 ± 126.5	0.000
RonsF		34.1 ± 4.7	33.0 ± 5.8	0.030
RoffsF		33.2 ± 6.0	32.1 ± 6.8	0.078
SDNN		2776.7 ± 58807.6	25.9 ± 19.1	0.030

The used statistical tests include Mann-Whitney U test, χ² test, and Fisher’s exact test as per demand. Starting from the standard deviation of all normal-to-normal intervals to the standard deviation of normal-to-normal intervals, this part of the table represents the parameters obtained from the Qardio-Qvark^® device based on some mathematical formulas. ECG: Electrocardiography; SDLA: Standard deviation of all normal-to-normal intervals; HFNoise: High frequency noise; RR: RR interval; TpTe: Tpeak-tend; VAT: Ventricular activation time; QTc: Corrected QT; HFQRS: High-frequency QRS; HFSNR: High frequency signal-to-noise ratio; JA: J-point amplitude; J80A: J-point + 80 milliseconds, amplitude; TA: T-wave amplitude; QRSE: QRS energy/spectral integral; TE: T-wave energy; QRSw: QRS width; PAn: P-wave amplitude negative; RA: R-wave amplitude; SA: S-wave amplitude; Pst: P-wave start; Pfi: P-wave finish; QRSst: QRS start; QRSfi: QRS finish/end; Tfi: T-wave flatness index; PpeakP: P-peak amplitude; Rpeak: R-wave amplitude; Speak: S-peak amplitude; Tpeak: T-peak amplitude; RonsF: R onset; RoffsF: R offset; SDNN: Standard deviation of normal-to-normal intervals.

Table 3 Comparative descriptive statistics of the clusters, n (%)/mean ± SD

Factor	Statistic	Cluster 1	Cluster 2	Cluster 3	Cluster 4	P value
Age (years)		43.1 ± 16.2	62.1 ± 12.6	64.8 ± 12.2	64.8 ± 10.3	0.000
Sex	Female	72 (44.2)	112 (48.3)	53 (37.3)	23 (25.0)	0.001
	Male	91 (55.8)	120 (51.7)	89 (62.7)	69 (75.0)
Left ventricle diastolic dysfunction	No	146 (89.6)	166 (71.6)	51 (35.9)	44 (47.8)	0.000
	Yes	17 (10.4)	66 (28.4)	91 (64.1)	48 (52.2)
Atrial fibrillation at the time of single lead ECG registration	No	163 (100.0)	226 (97.4)	119 (83.8)	89 (96.7)	0.000
	Yes	0 (0.0)	6 (2.6)	23 (16.2)	3 (3.3)
Ejection fraction (%)		61.4 ± 5.7	61.5 ± 5.1	52.9 ± 12.1	58.7 ± 7.7	0.000
End diastolic volume (mL)		81.7 ± 24.4	87.7 ± 24.0	113.1 ± 51.4	101.0 ± 42.3	0.000
Left atrial volume index		30.3 ± 5.6	34.4 ± 7.8	42.3 ± 15.3	36.1 ± 6.9	0.000
Diabetes mellitus	No	131 (80.4)	163 (70.3)	108 (76.1)	56 (60.9)	0.005
	Yes	32 (19.6)	69 (29.7)	34 (23.9)	36 (39.1)
Smoking	No	137 (84.0)	200 (86.2)	114 (80.3)	74 (80.4)	0.398
	Yes	26 (16.0)	32 (13.8)	28 (19.7)	18 (19.6)
Pulmonary artery systolic pressure		10.0 ± 0.0	10.0 ± 0.0	13.6 ± 9.3	10.0 ± 0.0	0.000
Hypertension_0	No	0 (0.0)	211 (90.9)	113 (79.6)	75 (81.5)	0.000
	Yes	163 (100.0)	21 (9.1)	29 (20.4)	17 (18.5)
Hypertension_1	No	163 (100.0)	178 (76.7)	138 (97.2)	86 (93.5)	0.000
	Yes	0 (0.0)	54 (23.3)	4 (2.8)	6 (6.5)
Hypertension_2	No	163 (100.0)	100 (43.1)	102 (71.8)	74 (80.4)	0.000
	Yes	0 (0.0)	132 (56.9)	40 (28.2)	18 (19.6)
Hypertension_3	No	163 (100.0)	207 (89.2)	73 (51.4)	41 (44.6)	0.000
	Yes	0 (0.0)	25 (10.8)	69 (48.6)	51 (55.4)
Ischemic heart disease_0	No	0 (0.0)	1 (0.4)	63 (44.4)	91 (98.9)	0.000
	Yes	163 (100.0)	231 (99.6)	79 (55.6)	1 (1.1)
Ischemic heart disease_1	No	163 (100.0)	231 (99.6)	93 (65.5)	26 (28.3)	0.000
	Yes	0 (0.0)	1 (0.4)	49 (34.5)	66 (71.7)
Ischemic heart disease_2	No	163 (100.0)	232 (100.0)	128 (90.1)	67 (72.8)	0.000
	Yes	0 (0.0)	0 (0.0)	14 (9.9)	25 (27.2)
Disturbance of cardiac rhythm and conduction_0	No	0 (0.0)	0 (0.0)	24 (16.9)	0 (0.0)	0.000
	Yes	163 (100.0)	232 (100.0)	118 (83.1)	92 (100.0)
Disturbance of cardiac rhythm and conduction_1	No	163 (100.0)	232 (100.0)	128 (90.1)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	14 (9.9)	0 (0.0)
Disturbance of cardiac rhythm and conduction_2	No	163 (100.0)	232 (100.0)	134 (94.4)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	8 (5.6)	0 (0.0)
Disturbance of cardiac rhythm and conduction_3	No	163 (100.0)	232 (100.0)	140 (98.6)	92 (100.0)	0.069
	Yes	0 (0.0)	0 (0.0)	2 (1.4)	0 (0.0)
Chronic heart failure_0	No	0 (0.0)	0 (0.0)	67 (48.6)	0 (0.0)	0.000
	Yes	163 (100.0)	231 (100.0)	71 (51.4)	92 (100.0)
Chronic heart failure_1	No	163 (100.0)	231 (100.0)	131 (94.9)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	7 (5.1)	0 (0.0)
Chronic heart failure_2	No	163 (100.0)	231 (100.0)	106 (76.8)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	32 (23.2)	0 (0.0)
Chronic heart failure_3	No	163 (100.0)	231 (100.0)	112 (81.2)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	26 (18.8)	0 (0.0)
Chronic heart failure_4	No	163 (100.0)	231 (100.0)	136 (98.6)	92 (100.0)	0.063
	Yes	0 (0.0)	0 (0.0)	2 (1.4)	0 (0.0)
Aortic valve stenosis_0	No	0 (0.0)	55 (23.7)	59 (41.5)	17 (18.5)	0.000
	Yes	163 (100.0)	177 (76.3)	83 (58.5)	75 (81.5)
Aortic valve insufficiency_1	No	163 (100.0)	177 (76.3)	96 (67.6)	75 (81.5)	0.000
	Yes	0 (0.0)	55 (23.7)	46 (32.4)	17 (18.5)
Aortic valve insufficiency_2	No	163 (100.0)	232 (100.0)	129 (90.8)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	13 (9.2)	0 (0.0)
Aortic valve stenosis_0	No	0 (0.0)	0 (0.0)	22 (15.6)	0 (0.0)	0.000
	Yes	163 (100.0)	232 (100.0)	119 (84.4)	92 (100.0)
Aortic valve stenosis_1	No	163 (100.0)	232 (100.0)	127 (90.1)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	14 (9.9)	0 (0.0)
Aortic valve stenosis_2	No	163 (100.0)	232 (100.0)	135 (95.7)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	6 (4.3)	0 (0.0)
Aortic valve stenosis_3	No	163 (100.0)	232 (100.0)	139 (98.6)	92 (100.0)	0.078
	Yes	0 (0.0)	0 (0.0)	2 (1.4)	0 (0.0)
Mitral valve insufficiency_0	No	59 (36.2)	145 (62.5)	121 (87.7)	61 (66.3)	0.000
	Yes	104 (63.8)	87 (37.5)	17 (12.3)	31 (33.7)
Mitral valve insufficiency_1	No	104 (63.8)	102 (44.0)	52 (37.7)	33 (35.9)	0.000
	Yes	59 (36.2)	130 (56.0)	86 (62.3)	59 (64.1)
Mitral valve insufficiency_2	No	163 (100.0)	217 (93.5)	110 (79.7)	90 (97.8)	0.000
	Yes	0 (0.0)	15 (6.5)	28 (20.3)	2 (2.2)
Mitral valve insufficiency_3	No	163 (100.0)	232 (100.0)	131 (94.9)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	7 (5.1)	0 (0.0)
Mitral valve stenosis_0	No	0 (0.0)	0 (0.0)	9 (6.3)	0 (0.0)	0.000
	Yes	163 (100.0)	232 (100.0)	133 (93.7)	92 (100.0)
Mitral valve stenosis_1	No	163 (100.0)	232 (100.0)	134 (94.4)	92 (100.0)	0.000
	Yes	0 (0.0)	0 (0.0)	8 (5.6)	0 (0.0)
Mitral valve stenosis_2	No	163 (100.0)	232 (100.0)	141 (99.3)	92 (100.0)	0.356
	Yes	0 (0.0)	0 (0.0)	1 (0.7)	0 (0.0)

The numbers associated with the name of the diseases represent the stage of the disease. 0: Absent, 1: 1^st stage, 2: 2^nd stage, 3: 3^rd stage, 4: 4^th stage. ECG: Electrocardiography.

Table 4 The models performance metrics

Validation cluster	Area under the receiver operating characteristic curve	Sensitivity	Specificity	Positive predictive value	Negative predictive value	Threshold
Cluster 1	0.947	0.969	0.781	0.948	0.862	0.350
Cluster 2	0.835	0.816	0.725	0.875	0.625	0.221
Cluster 3	0.589	0.398	0.941	0.956	0.330	0.131
Cluster 4	0.880	0.750	0.833	0.875	0.682	0.164

Table 5 The top 5 important features for each cluster with the importance coefficient

Cluster 1; feature (importance coefficient)	Cluster 2; feature (importance coefficient)	Cluster 3; feature (importance coefficient)	Cluster 4; feature (importance coefficient)
Tfi (0.203)	QRSfi (0.206)	Tfi (0.593)	Tfi (0.235)
HFQRS (0.043)	Age (0.120)	QTc (0.053)	Age (0.076)
RR (0.041)	Toffs (0.106)	Age (0.049)	PpeakN (0.051)
Beta (0.033)	QRSE1 (0.053)	Sbeta (0.020)	Rpeak (0.043)
QRSE4 (0.032)	QTc (0.040)	QRSE4 (0.019)	Pst (0.035)

Tfi: T-wave flatness index; QRSfi: QRS complex morphology; HFQRS: High-frequency QRS; QTc: Corrected QT; RR: RR interval; PpeakN: Negative P-wave peak amplitude; QRSE: QRS energy/spectral integral; Rpeak: R-wave amplitude; Pst: P-wave start time.