Figure 1: Schematic representation of the study protocol

Figure 2: Comparison between Treatment Group (blue columns) and Placebo Group (red columns) with respect to Waist Circumference (cm), Truncal Fat (%), and Visceral Fat (%) at 12 (T12-w) and 24 (T24-w) treatment-week: * p<0.05 vs baseline; **p<0.01 vs baseline: the horizontal bars indicate the significance of the differences between groups at the single time points

Figure 3: Comparison between Treatment Group (blue columns) and Placebo Group (red columns) with respect to BMI (M±DS; kg/m2) during a 24-week treatment period (**<0.01 vs baseline; * p<0.05 vs baseline)

 

Treatment Group

Placebo
Group

p

Subjects (n.)

50

50

-

Male (n.)

25

27

.315

Age (year)

53.03±7.11

54.16±6.14

.287

Waist circumference (cm)

115.00±9.12

113.41±13.22

.671

BMI (kg/m2)

34.46±4.24

35.34±2.07

.512

Trunk fat level (%)

44.34±5.17

44.04±6.23

.214

Visceral fat level (%)

24.05±6.41

22.18±8.60

.338

Systolic BP (mmHg)

148.42±12.68

146.39±11.07

.619.

Diastolic BP (mmHg)

98.32±5.75

97.48±5.67

.227

Heart rate (beats/min)

73.04±7.61

72.82±9.37

.189

Fasting plasma glucose (mg/dl) IFG subjects [n 7]
 IGT subjects [n 47]

114.73±2.81
95.60±3.13

115.06±2.84
93.40±3.53

.214
.324

2h after a 75-g OGTT (mg/dl) IFG subjects [n 7]
 IGT subjects [n 47]

130.51±3.36
179.6±8.6

128.62±2.82
181.6±3.2

 .314
.226

Fasting plasma glucose overall (mg/dl)

97.31±2.03

96.43±1.81

.307

HbA1c (%)

5.26±0.37

5.19±0.48

.229

HOMA-R

4.80±0.82

4.54±0.75

.313

eGFR (ml/min/1,73 m2)

86.07±9.15

89.21±12.35

.417

Total cholesterol (mg/dl)

230.18±18.34

237.43±15.53

.289

HDL cholesterol (mg/dl)

41.65±3.49

41.37±4.19

.216

LDL cholesterol (mg/dl)

151.09±18.75

153.67±14.48

.331

Triglycerides (mg/dl)

198.37±23.62

199.28±18.32

.724

AST (IU/L)

29.16±9.02

29.24±8.20

.338

ALT (IU/L)

29.33±8.06

27.65±9.09

.187

γGT (IU/L)

21.32±7.23

24.33±5.27

.219

Uric Acid (mg/dl)

7.52±1.34

7.47±1.56

.611

Cardiovascular risk factors

Elevated waist-hip ratio (%)

65

61

.229

Recent or current smokers (%)

15

16

.174

Low concentration of HDL cholesterol (%)

60

62

.310

Family history of premature heart disease (%)

10

11

.243

Hypertension (%)

58

55

.267

> 2 Risk Factors (%)

79

80

.335

Table 1: Clinically relevant parameters at baseline: no significant differences were found between groups. Absolute, percent or M ± SD values were reported depending on individual parameters. (Treatment Group = on Kirocomplex; P Group = Placebo Group)

Comparison of lipid parameters between treatment groups

 

Total Cholesterol
(mg/dl)

HDL Cholesterol Cholesterol
(mg/dl)

Triglycerides
(mg/dl)

LDL Cholesterol
(mg/dl)

 

T Group

P Group

T Group

P Group

T Group

P Group

T Group

P Group

Baseline
T0

 

230.18±18.34

 

237.43±15.53

 

41.65±3.49

 

41.37±4.19

 

198.37±23.62

 

199.28±18.32

 

151.09±18.75

 

153.67±14.48

12 weeks
% ∆ vs T0

 

201.44±14.43*
-13**

217.76±18.97
-8

 

43.65±4.67
+5

42.41±4,34
+3

176.69±16.74*
-11*

187.41±16.65
-6

123.35±12.43*
-18*

138.68±15.74
-10

24 weeks
% ∆ vs T0

 

178.43±16.19**#
-22**

198.58±17.81*
-16*

48.95±3.76*#
+18*

42.49±4.33
+3

148.35±13.45**#
-25**

185.57±15.68
-7

100.48±14.39**#
-33**

139.49±12.70
-9

**p<0.01, *p<0.05 vs baseline; # p<0.01, § p<0.05 vs Placebo group

Comparison of HOMA-R and bioimpedance parameters between treatment groups

 

HOMA-R

WC (cm)

TF (%)

VF (%)

 

T Group

P Group

T Group

P Group

T Group

P Group

T Group

P Group

Baseline
T0

4.81±0.82

4.55±0.74

115.00±9.12

113.41±13.22

44.34±5.17

44.04±6.23

24.05±6.41

22.18±8.60

12 weeks
% ∆ vs T0

3.3±0.8*
-31*

4.43±0.62
- 2

96.22±4.17*
-17

111.43±11.30
-2

36.14±4.02*
-17*

40.06±6
-9

19.06±6.24*
-21*

20.41±8.25
-8

24 weeks
% ∆ vs T0

 

2.63±0.51**#
- 46**

4.34±0.61
-4

88.24±5.31*#
- 23*

100.57±!4.34
-11

31.46±3.24**#
-29**

39.98±5.89
-9

14.43±4.24** #
-40**

19.97±9.97
-10

**p<0.01, *p<0.05 vs baseline; # p<0.01, § p<0.05 vs Placebo group

 

Uric Acid
(mg/dl)

SBP
(mmHg)

DBP
(mmHg)

HbA1c
(%)

 

T Group

P Group

T Group

P Group

T Group

P Group

T Group

P Group

Baseline
T0

7.52±1.34

 

7.47±1.56

 

148.42±12.68

 

146.39±11.07

 

98.32±5.75

 

97.48±5.67

 

5.26±0.37

 

5.19±0.48

12 weeks
% ∆ vs T0

 

5.45±0.63**#
-28**

7.28±0.98
-3

126.67±18.86*§
-15

141.87±11.92
-3

81.57±4.91*
-17

96.58±6.76
-1

5.26±0.44
0

5.19±0.46
0

24 weeks
% ∆ vs T0

 

4.29±0.58**#
-43**

7.09±0.57*
-5

123.86±15.57**#
-17

138.76±14.86**#
-5

78.57±8.44**#
-18

95.38±9.86
-2

5.45±0.37
+4

5.47±0.28
+5

**p<0.01, *p<0.05 vs baseline; # p<0.01, § p<0.05 vs Placebo group

Table 2: Effects of a 24-week treatment on biochemical, clinical and bioimpedance parameters (M±SD); (T Group and P Group as reported in Table 1)

FASTING PLASMA GLUCOSE
(mg/dl)

 

T Group

P Group

p between Groups

IFG patients (n = 7) (mg/dl)
 Baseline

 

114.72±2.80

 

115.81±2.83

 

.6281

 24 weeks
% ∆ vs T0

81.16±3.21*
(-29%)

104.13±3.41
(-10%)

.0365

IGT patients (n = 47) (mg/dl)
 Baseline

 

95.62±3.13

 

93.42±3.53

 

.5837

 24 weeks
% ∆ vs T0

80.25±3.36 *
(-16%)

84.07±4.16
(-10%)

.8292

Overall (n = 50) (mg/dl)
 Baseline

 

97.31±2.03

 

96.43±1.81

 

.6374

 24 weeks
% ∆ vs T0

80.33±4.31
(-19%)

87.24±4.25
(-10%)

.559

* p vs baseline

Table 3: Fasting plasma glucose levels observed in IGF and IGT patients