J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website http://www.jocmr.org

Original Article

Volume 12, Number 8, August 2020, pages 530-538

Gender Differences in Cardiac Function Following Three-Month Administration of Tofogliflozin in Patients With Diabetes Mellitus

Figure 3. Interaction plot in E/e' between time and gender. E/e': change in inflow E and mitral e' annular velocities.

**Table 1.** Characteristics of the Patients
Variable	Men (N = 24)	Women (N = 32)
BMI: body mass index; NYHA: New York Heart Association; DPP-4: dipeptidyl peptidase-4; BG: biguanide; SU: sulphonylurea; ARB: angiotensin II receptor blocker; CCB: calcium channel blocker.
Age (years)	80.2 ± 6.4	83.1 ± 6.4
BMI	23.1 ± 3.3	23.0 ± 3.5
NYHA I/II (III, IV: none)	22/2	28/2
Co-administered drug
DPP-4	14	23
BG	7	11
SU	5	3
Insulin	0	0
ARB	6	6
β-blocker	5	4
CCB	10	17
Diuretics	4	13

Table 1. Characteristics of the Patients

Variable

Men (N = 24)

Women (N = 32)

BMI: body mass index; NYHA: New York Heart Association; DPP-4: dipeptidyl peptidase-4; BG: biguanide; SU: sulphonylurea; ARB: angiotensin II receptor blocker; CCB: calcium channel blocker.

Age (years)

80.2 ± 6.4

83.1 ± 6.4

BMI

23.1 ± 3.3

23.0 ± 3.5

NYHA I/II (III, IV: none)

22/2

28/2

Co-administered drug

DPP-4

Insulin

ARB

β-blocker

CCB

Diuretics

**Table 2.** Characteristics of Laboratory Test Results
Variable	Baseline	1 month	3 months	P-value*
*Paired t-test compared to baseline with 3 months after administration. HbA1c: glycated hemoglobin; BNP: brain natriuretic peptide; eGFR: estimated glomerular filtration rate; BUN: blood urea nitrogen.
HbA1c (%)	7.4 ± 1.3	7.0 ± 1.0	6.7 ± 0.8	< 0.01
Body weight (kg)	54.6 ± 10.9	52.5 ± 10.5	51.8 ± 10.1	< 0.01
Systolic blood pressure (mm Hg)	138.4 ± 24.5	125.3 ± 16.9	128.0 ± 20.1	< 0.01
Diastolic blood pressure (mm Hg)	72.0 ± 13.8	70.5 ± 11.5	72.5 ± 12.6	0.81
Hematocrit	37.9 ± 6.9	38.4 ± 5.9	38.4 ± 5.9	0.3
BNP (pg/mL)	222.8 ± 378.5	149.6 ± 240.2	186.8 ± 270.6	0.11
eGFR	60.5 ± 23.2	58.2 ± 24.3	59.3 ± 28.4	0.54
BUN (mg/dL)	19.9 ± 9.9	19.7 ± 7.2	19.5 ± 7.8	0.74
Na⁺ (mEq/L)	138.8 ± 3.5	139.5 ± 3.0	140.5 ± 3.3	< 0.01
K⁺ (mEq/L)	4.2 ± 0.6	4.2 ± 0.5	4.2 ± 0.5	0.78
Cl^- (mEq/L)	102.5 ± 12.2	104.4 ± 5.0	106.0 ± 3.3	< 0.05
Blood osmotic pressure (mOsm/L)	292.8 ± 7.2	292.6 ± 7.3	295.1 ± 7.1	< 0.05

Table 2. Characteristics of Laboratory Test Results

Variable

Baseline

1 month

3 months

P-value*

*Paired t-test compared to baseline with 3 months after administration. HbA1c: glycated hemoglobin; BNP: brain natriuretic peptide; eGFR: estimated glomerular filtration rate; BUN: blood urea nitrogen.

HbA1c (%)

7.4 ± 1.3

7.0 ± 1.0

6.7 ± 0.8

< 0.01

Body weight (kg)

54.6 ± 10.9

52.5 ± 10.5

51.8 ± 10.1

< 0.01

Systolic blood pressure (mm Hg)

138.4 ± 24.5

125.3 ± 16.9

128.0 ± 20.1

< 0.01

Diastolic blood pressure (mm Hg)

72.0 ± 13.8

70.5 ± 11.5

72.5 ± 12.6

0.81

Hematocrit

37.9 ± 6.9

38.4 ± 5.9

0.3

BNP (pg/mL)

222.8 ± 378.5

149.6 ± 240.2

186.8 ± 270.6

0.11

eGFR

60.5 ± 23.2

58.2 ± 24.3

59.3 ± 28.4

0.54

BUN (mg/dL)

19.9 ± 9.9

19.7 ± 7.2

19.5 ± 7.8

0.74

Na⁺ (mEq/L)

138.8 ± 3.5

139.5 ± 3.0

140.5 ± 3.3

< 0.01

K⁺ (mEq/L)

4.2 ± 0.6

4.2 ± 0.5

0.78

Cl^- (mEq/L)

102.5 ± 12.2

104.4 ± 5.0

106.0 ± 3.3

< 0.05

Blood osmotic pressure (mOsm/L)

292.8 ± 7.2

292.6 ± 7.3

295.1 ± 7.1

< 0.05

**Table 3.** Characteristics of Laboratory Test Results
Variable	Baseline	1 month	3 months	P-value*
*Paired t-test compared to baseline with 3 months after administration. EF: ejection fraction; E/A: early filling/atrial filling; E/e': change in inflow E and mitral e' annular velocities; LAD: left atrial dimension; IVCmax: maximal diameter of inferior vena cava.
EF	64.5 ± 8.9	62.3 ± 10.6	63.3 ± 9.3	0.25
E/A	0.69 ± 0.32	0.60 ± 0.18	0.62 ± 0.17	0.31
E/e'	11.7 ± 3.9	9.9 ± 2.9	10.1 ± 3.9	< 0.05
LAD (mm)	38.8 ± 6.8	37.4 ± 6.7	37.6 ± 6.4	0.19
IVCmax (mm)	13.7 ± 3.5	13.5 ± 3.7	13.7 ± 3.6	0.61

Table 3. Characteristics of Laboratory Test Results

Variable

Baseline

1 month

3 months

P-value*

*Paired t-test compared to baseline with 3 months after administration. EF: ejection fraction; E/A: early filling/atrial filling; E/e': change in inflow E and mitral e' annular velocities; LAD: left atrial dimension; IVCmax: maximal diameter of inferior vena cava.

64.5 ± 8.9

62.3 ± 10.6

63.3 ± 9.3

0.25

E/A

0.69 ± 0.32

0.60 ± 0.18

0.62 ± 0.17

0.31

E/e'

11.7 ± 3.9

9.9 ± 2.9

10.1 ± 3.9

< 0.05

LAD (mm)

38.8 ± 6.8

37.4 ± 6.7

37.6 ± 6.4

0.19

IVCmax (mm)

13.7 ± 3.5

13.5 ± 3.7

13.7 ± 3.6

0.61

**Table 4.** Results of Two-Factor Mixed Effect Model to Evaluate Effects and Interaction of EF
SOV	df	Sum sq.	Mean sq.	F	P-value
Analysis of variance table for the mixed effects model. EF: ejection fraction; SOV: source of variance; df: degree of freedom; Sum sq.: sum of squares; Mean sq.: mean squares; F: F statistic.
Time	2	125.1	62.5	2.4	0.10
Subjects	52	10,305.0	198.2	7.5	< 0.01
Gender	1	1,796.5	1,796.5	9.1	< 0.01
Time × gender	2	81.1	40.5	1.5	0.22
Error	105	2,760.2	26.3
Total	162	15,067.8

Table 4. Results of Two-Factor Mixed Effect Model to Evaluate Effects and Interaction of EF

SOV

Sum sq.

Mean sq.

P-value

Analysis of variance table for the mixed effects model. EF: ejection fraction; SOV: source of variance; df: degree of freedom; Sum sq.: sum of squares; Mean sq.: mean squares; F: F statistic.

Time

125.1

62.5

2.4

0.10

Subjects

10,305.0

198.2

7.5

< 0.01

Gender

1,796.5

9.1

< 0.01

Time × gender

81.1

40.5

1.5

0.22

Error

105

2,760.2

26.3

Total

162

15,067.8

**Table 5.** Results of Two-Factor Mixed Effect Model to Evaluate Effects and Interaction of E/A
SOV	df	Sum sq.	Mean sq.	F	P-value
Analysis of variance table for the mixed effects model. E/A: early filling/atrial filling; SOV: source of variance; Sum sq.: sum of squares; df: degree of freedom; Mean sq.: mean squares; F: F statistic.
Time	2	0.04	0.02	2.7	0.07
Subjects	35	2.6	0.1	8.9	< 0.01
Gender	1	0.05	0.05	0.7	0.40
Time × gender	2	0.12	0.06	7.2	< 0.01
Error	105	0.87	0.01
Total	162	3.7

Table 5. Results of Two-Factor Mixed Effect Model to Evaluate Effects and Interaction of E/A

SOV

Sum sq.

Mean sq.

P-value

Analysis of variance table for the mixed effects model. E/A: early filling/atrial filling; SOV: source of variance; Sum sq.: sum of squares; df: degree of freedom; Mean sq.: mean squares; F: F statistic.

Time

0.04

0.02

2.7

0.07

Subjects

2.6

0.1

8.9

< 0.01

Gender

0.05

0.7

0.40

Time × gender

0.12

0.06

7.2

< 0.01

Error

105

0.87

0.01

Total

162

3.7

**Table 6.** Results of two-factor mixed effect model to evaluate effects and interaction of E/e'
SOV	df	Sum sq.	Mean sq.	F	P-value
Analysis of variance table for the mixed effects model. E/e': change in inflow E and mitral e' annular velocities; SOV: source of variance; Sum sq.: sum of squares; df: degree of freedom; Mean sq.: mean squares; F: F statistic.
Time	2	60.9	30.5	11.5	< 0.01
Subjects	52	1012.9	19.5	7.4	< 0.01
Gender	1	36.9	36.9	1.9	0.17
Time × gender	2	11.1	5.6	2.1	0.13
Error	105	277.3	2.6
Total	162	1,399.1

Table 6. Results of two-factor mixed effect model to evaluate effects and interaction of E/e'

SOV

Sum sq.

Mean sq.

P-value

Analysis of variance table for the mixed effects model. E/e': change in inflow E and mitral e' annular velocities; SOV: source of variance; Sum sq.: sum of squares; df: degree of freedom; Mean sq.: mean squares; F: F statistic.

Time

60.9

30.5

11.5

< 0.01

Subjects

1012.9

19.5

7.4

< 0.01

Gender

36.9

1.9

0.17

Time × gender

11.1

5.6

2.1

0.13

Error

105

277.3

2.6

Total

162

1,399.1