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 8, Number 12, December 2016, pages 878-887

The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial

**Table 1.** Baseline Characteristics
Data are expressed as the mean ± SD or number (%). BMI: body mass index.
Age (years)	68.9 ± 8.1
Gender (male/female)	17/15
Height (cm)	162.3 ± 9.3
Body weight (kg)	68.1 ± 14.5
BMI (kg/m²)	25.7 ± 4.3
Diabetes duration (years)	9.8 ± 3.5
HbA1c (%)	6.7 ± 0.4
Medications
Anti-diabetes (%)	28 (88)
Sulfonylureas (%)	11 (34)
Biguanides (%)	16 (50)
Thiazolidines (%)	5 (16)
Incretin-based drugs (%)	16 (50)
Insulin (%)	3 (9)
Anti-hypertension (%)	18 (56)
Angiotensin II receptor blockers (%)	15 (47)
Calcium channel blockers (%)	13 (41)
β-blockers (%)	5 (16)
Anti-dyslipidemia (%)	20 (63)
Statins (%)	18 (56)
Fibrates (%)	2 (6)
Ethyl icosapentate (%)	3 (9)

Table 1. Baseline Characteristics

Data are expressed as the mean ± SD or number (%). BMI: body mass index.

Age (years)

68.9 ± 8.1

Gender (male/female)

17/15

Height (cm)

162.3 ± 9.3

Body weight (kg)

68.1 ± 14.5

BMI (kg/m²)

25.7 ± 4.3

Diabetes duration (years)

9.8 ± 3.5

HbA1c (%)

6.7 ± 0.4

Medications

Anti-diabetes (%)

28 (88)

Sulfonylureas (%)

11 (34)

Biguanides (%)

16 (50)

Thiazolidines (%)

5 (16)

Incretin-based drugs (%)

16 (50)

Insulin (%)

3 (9)

Anti-hypertension (%)

18 (56)

Angiotensin II receptor blockers (%)

15 (47)

Calcium channel blockers (%)

13 (41)

β-blockers (%)

5 (16)

Anti-dyslipidemia (%)

20 (63)

Statins (%)

18 (56)

Fibrates (%)

2 (6)

Ethyl icosapentate (%)

3 (9)

**Table 2.** Effects of Ramelteon in the First Period
	Baseline	3 months	P value
Data are expressed as the mean ± SD or number (%). BMI: body mass index; GA: glycated albumin; FPG: fasting plasma glucose; IRI: immunoreactive insulin; s-CPR: serum C-peptide immunoreactivity; HOMA-IR: homeostatic model of assessment of insulin resistance; QUICKI: quantitative insulin sensitivity check index; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; eGFR: estimated glomerular filtration rate; UAE: urinary albumin excretion; hs-CRP: high-sensitivity C-reactive protein; PSQI: Pittsburgh sleep questionnaire index; SF-36: short form 36; PCS: physical component summary; MCS: mental component summary; RCS: role/social component summary.
Gender (male/female)	17/15
Body weight (kg)	68.1 ± 14.5	68.4 ± 14.4
BMI (kg/m²)	25.7 ± 4.3	25.8 ± 4.3
Systolic blood pressure (mm Hg)	138 ± 21	135 ± 20
Diastolic blood pressure (mm Hg)	79 ± 11	81 ± 11
HbA1c (%)	6.7 ± 0.4	6.7 ± 0.5
GA (%)	17.1 ± 2.6	17.2 ± 2.4
FPG (mg/dL)	120 ± 18	125 ± 23
IRI (μU/mL)	8.01 ± 6.80	8.01 ± 7.30
s-CPR (ng/mL)	2.19 ± 1.23	2.12 ± 1.16
HOMA-IR	2.08 ± 1.59	1.92 ± 1.40
QUICKI	0.35 ± 0.04	0.35 ± 0.04
CPR index	1.84 ± 1.01	1.72 ± 0.96
Total cholesterol (mg/dL)	177 ± 33	171 ± 29
LDL-C (mg/dL)	105 ± 27	100 ± 24	0.048
HDL-C (mg/dL)	60 ± 17	58 ± 15
LDL-C/HDL-C	1.9 ± 0.6	1.8 ± 0.6
Triglyceride (mg/dL)	131 ± 76	117 ± 63
Non-HDL-C (mg/dL)	117 ± 29	112 ± 27
Cre (mg/dL)	0.82 ± 0.22	0.83 ± 0.23
eGFR (mL/min)	65.4 ± 13.4	65.6 ± 14.0
UAE (mg/g.Cre)	28.6 ± 49.6	42.8 ± 87.3
AST (U/L)	24 ± 8	25 ± 9
ALT (U/L)	25 ± 13	25 ± 9
γGTP (U/L)	30 ± 16	30 ± 16
Ferritin (ng/mL)	140 ± 149	127 ± 102
hs-CRP (ng/mL)	1,060 ± 2,358	1,383 ± 2,569
PSQI (0 - 18)	8.1 ± 4.1	7.2 ± 2.8	0.030
C1 (0 - 3)	1.6 ± 0.8	1.3 ± 0.7	0.010
C2 (0 - 3)	1.7 ± 2.1	1.2 ± 1.8	0.040
C3 (0 - 3)	1.8 ± 1.0	1.6 ± 0.9
C4 (0 - 3)	0.8 ± 1.0	0.8 ± 1.0
C5 (0 - 3)	1.0 ± 0.4	0.9 ± 0.3
C7 (0 - 3)	1.5 ± 1.1	1.5 ± 0.8
Sleep latency (min)	23.6 ± 25.7	18.8 ± 17.6	0.039
Total sleep time (h)	6.1 ± 2.4	6.2 ± 2.1
SF-36
PCS (0 - 100)	47.3 ± 13.5	50.1 ± 12.3
MCS (0 - 100)	54.1 ± 9.7	53.3 ± 8.7
RCS (0 - 100)	36.7 ± 10.5	38.5 ± 8.6

Table 2. Effects of Ramelteon in the First Period

Baseline

3 months

P value

Data are expressed as the mean ± SD or number (%). BMI: body mass index; GA: glycated albumin; FPG: fasting plasma glucose; IRI: immunoreactive insulin; s-CPR: serum C-peptide immunoreactivity; HOMA-IR: homeostatic model of assessment of insulin resistance; QUICKI: quantitative insulin sensitivity check index; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; eGFR: estimated glomerular filtration rate; UAE: urinary albumin excretion; hs-CRP: high-sensitivity C-reactive protein; PSQI: Pittsburgh sleep questionnaire index; SF-36: short form 36; PCS: physical component summary; MCS: mental component summary; RCS: role/social component summary.

Gender (male/female)

17/15

Body weight (kg)

68.1 ± 14.5

68.4 ± 14.4

BMI (kg/m²)

25.7 ± 4.3

25.8 ± 4.3

Systolic blood pressure (mm Hg)

138 ± 21

135 ± 20

Diastolic blood pressure (mm Hg)

79 ± 11

81 ± 11

HbA1c (%)

6.7 ± 0.4

6.7 ± 0.5

GA (%)

17.1 ± 2.6

17.2 ± 2.4

FPG (mg/dL)

120 ± 18

125 ± 23

IRI (μU/mL)

8.01 ± 6.80

8.01 ± 7.30

s-CPR (ng/mL)

2.19 ± 1.23

2.12 ± 1.16

HOMA-IR

2.08 ± 1.59

1.92 ± 1.40

QUICKI

0.35 ± 0.04

CPR index

1.84 ± 1.01

1.72 ± 0.96

Total cholesterol (mg/dL)

177 ± 33

171 ± 29

LDL-C (mg/dL)

105 ± 27

100 ± 24

0.048

HDL-C (mg/dL)

60 ± 17

58 ± 15

LDL-C/HDL-C

1.9 ± 0.6

1.8 ± 0.6

Triglyceride (mg/dL)

131 ± 76

117 ± 63

Non-HDL-C (mg/dL)

117 ± 29

112 ± 27

Cre (mg/dL)

0.82 ± 0.22

0.83 ± 0.23

eGFR (mL/min)

65.4 ± 13.4

65.6 ± 14.0

UAE (mg/g.Cre)

28.6 ± 49.6

42.8 ± 87.3

AST (U/L)

24 ± 8

25 ± 9

ALT (U/L)

25 ± 13

25 ± 9

γGTP (U/L)

30 ± 16

Ferritin (ng/mL)

140 ± 149

127 ± 102

hs-CRP (ng/mL)

1,060 ± 2,358

1,383 ± 2,569

PSQI (0 - 18)

8.1 ± 4.1

7.2 ± 2.8

0.030

C1 (0 - 3)

1.6 ± 0.8

1.3 ± 0.7

0.010

C2 (0 - 3)

1.7 ± 2.1

1.2 ± 1.8

0.040

C3 (0 - 3)

1.8 ± 1.0

1.6 ± 0.9

C4 (0 - 3)

0.8 ± 1.0

C5 (0 - 3)

1.0 ± 0.4

0.9 ± 0.3

C7 (0 - 3)

1.5 ± 1.1

1.5 ± 0.8

Sleep latency (min)

23.6 ± 25.7

18.8 ± 17.6

0.039

Total sleep time (h)

6.1 ± 2.4

6.2 ± 2.1

SF-36

PCS (0 - 100)

47.3 ± 13.5

50.1 ± 12.3

MCS (0 - 100)

54.1 ± 9.7

53.3 ± 8.7

RCS (0 - 100)

36.7 ± 10.5

38.5 ± 8.6

**Table 3.** Effects of Continuating or Discontinuating Ramelteon in the Second Period
	Continuation group	Discontinuation group
Data are expressed as the mean ± SD or number (%). BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; GA: glycated albumin; FPG: fasting plasma glucose; IRI: immunoreactive insulin; s-CPR: serum C-peptide immunoreactivity; HOMA-IR: homeostatic model of assessment of insulin resistance; QUICKI: quantitative insulin sensitivity check index; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglyceride; eGFR: estimated glomerular filtration rate; UAE: urinary albumin excretion; hs-CRP: high-sensitivity C-reactive protein; PSQI: Pittsburgh sleep questionnaire index; SF-36: short form 36; PCS: physical component summary; MCS: mental component summary; RCS: role/social component summary.
Age	68.7 ± 8.2		68.8 ± 8.3
Gender (M/F)	7/8		9/7
Body weight (kg)	69.1 ± 14.6	69.5 ± 14.6	67.9 ± 15.0	67.9 ± 15.0
BMI (kg/m²)	26.1 ± 4.7	26.3 ± 4.8	25.6 ± 4.1	25.6 ± 4.2
SBP (mm Hg)	132 ± 19	131 ± 15	138 ± 22	135 ± 24
DBP (mm Hg)	80 ± 11	77 ± 14	82 ± 12	79 ± 16
HbA1c (%)	6.8 ± 0.6	6.8 ± 0.5	6.7 ± 0.5	6.9 ± 0.6	0.003	0.047
GA (%)	17.1 ± 2.3	17.3 ± 2.9	17.1 ± 2.7	17.6 ± 2.7	0.027
FPG (mg/dL)	126 ± 21	124 ± 16	125 ± 25	128 ± 26
IRI (μU/mL)	9.43 ± 9.52	11.30 ± 12.30	6.9 ± 4.61	6.07 ± 3.06
sCPR (ng/dL)	2.41 ± 1.37	2.78 ± 1.91	1.88 ± 0.93	1.62 ± 0.56
HOMA-IR	1.77 ± 1.23	2.29 ± 2.41	2.14 ± 1.80	1.87 ± 0.76
QUICKI	0.35 ± 0.05	0.34 ± 0.04	0.35 ± 0.03	0.36 ± 0.03
CPR index	1.85 ± 0.84	2.19 ± 1.35	1.63 ± 1.10	1.31 ± 0.5
TC (mg/dL)	171 ± 30	175 ± 35	173 ± 28	177 ± 30
LDL-C (mg/dL)	105 ± 26	106 ± 31	98 ± 20	104 ± 23
HDL-C (mg/dL)	55 ± 15	58 ± 17	61 ± 14	61 ± 14
LDL-C/HDL-C	2.0 ± 0.6	1.9 ± 0.7	1.7 ± 0.5	1.8 ± 0.4
TG (mg/dL)	129 ± 65	127 ± 59	109 ± 62	121 ± 63
Non-HDL-C (mg/dL)	116 ± 28	117 ± 31	112 ± 23	116 ± 20
Cre (mg/dL)	0.89 ± 0.29	0.87 ± 0.25	0.77 ± 0.14	0.75 ± 0.16
eGFR (mL/min)	61.3 ± 18.1	61.8 ± 17.5	68.7 ± 7.6	71.3 ± 9.7
UAE (mg/g.Cre)	39.6 ± 70.1	32.7 ± 41.4	47.6 ± 107.6	35.8 ± 51.7
AST (U/L)	26 ± 11	24 ± 7	23 ± 7	24 ± 5
ALT (U/L)	26 ± 8	25 ± 9	24 ± 10	25 ± 9
γGTP (U/L)	32 ± 14	32 ± 17	28 ± 17	28 ± 17
Ferritin (ng/mL)	161 ± 111	175 ± 121	107 ± 87	105 ± 96
hs-CRP (ng/mL)	2,071 ± 3,628	1,641 ± 3,957	766 ± 733	627 ± 648
PSQI (0 - 18)	7.5 ± 3.4	7.2 ± 4.0	7.2 ± 2.3	6.5 ± 3.2
C1 (0 - 3)	1.1 ± 0.5	1.1 ± 0.7	1.4 ± 0.8	1.3 ± 1.0
C2 (0 - 3)	1.4 ± 1.8	1.8 ± 2.0	1.0 ± 1.8	0.8 ± 1.5
Sleep latency	20.9 ± 20.0	27.6 ± 27.4	15.9 ± 15.6	15.3 ± 12.7
C3 (0 - 3)	1.6 ± 0.7	1.5 ± 1.1	1.7 ± 1.0	1.6 ± 1.0
C4 (0 - 3)	1.0 ± 0.9	0.7 ± 0.8	0.8 ± 1.1	0.7 ± 0.9
C5 (0 - 3)	1.0 ± 0.4	0.9 ± 0.5	0.9 ± 0.3	0.9 ± 0.3
C7 (0 - 3)	1.5 ± 1.0	1.4 ± 0.9	1.4 ± 0.6	1.4 ± 0.7
SF-36
PCS (0 - 100)	52.9 ± 9.7	54.0 ± 9.8	49.6 ± 13.3	48.6 ± 13.3
MCS (0 - 100)	52.4 ± 9.0	53.2 ± 7.7	53.5 ± 9.7	53.8 ± 10.8
RCS (0 - 100)	38.3 ± 7.2	39.5 ± 8.6	37.6 ± 10.1	38.5 ± 10.5

Table 3. Effects of Continuating or Discontinuating Ramelteon in the Second Period

Continuation group

Discontinuation group

Inter group in 6 months (P value)

3 months

6 months

3 months

6 months

Data are expressed as the mean ± SD or number (%). BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; GA: glycated albumin; FPG: fasting plasma glucose; IRI: immunoreactive insulin; s-CPR: serum C-peptide immunoreactivity; HOMA-IR: homeostatic model of assessment of insulin resistance; QUICKI: quantitative insulin sensitivity check index; TC: total cholesterol; LDL-C: low-density lipoprotein cholesterol; HDL-C: high-density lipoprotein cholesterol; TG: triglyceride; eGFR: estimated glomerular filtration rate; UAE: urinary albumin excretion; hs-CRP: high-sensitivity C-reactive protein; PSQI: Pittsburgh sleep questionnaire index; SF-36: short form 36; PCS: physical component summary; MCS: mental component summary; RCS: role/social component summary.

Age

68.7 ± 8.2

68.8 ± 8.3

Gender (M/F)

7/8

9/7

Body weight (kg)

69.1 ± 14.6

69.5 ± 14.6

67.9 ± 15.0

BMI (kg/m²)

26.1 ± 4.7

26.3 ± 4.8

25.6 ± 4.1

25.6 ± 4.2

SBP (mm Hg)

132 ± 19

131 ± 15

138 ± 22

135 ± 24

DBP (mm Hg)

80 ± 11

77 ± 14

82 ± 12

79 ± 16

HbA1c (%)

6.8 ± 0.6

6.8 ± 0.5

6.7 ± 0.5

6.9 ± 0.6

0.003

0.047

GA (%)

17.1 ± 2.3

17.3 ± 2.9

17.1 ± 2.7

17.6 ± 2.7

0.027

FPG (mg/dL)

126 ± 21

124 ± 16

125 ± 25

128 ± 26

IRI (μU/mL)

9.43 ± 9.52

11.30 ± 12.30

6.9 ± 4.61

6.07 ± 3.06

sCPR (ng/dL)

2.41 ± 1.37

2.78 ± 1.91

1.88 ± 0.93

1.62 ± 0.56

HOMA-IR

1.77 ± 1.23

2.29 ± 2.41

2.14 ± 1.80

1.87 ± 0.76

QUICKI

0.35 ± 0.05

0.34 ± 0.04

0.35 ± 0.03

0.36 ± 0.03

CPR index

1.85 ± 0.84

2.19 ± 1.35

1.63 ± 1.10

1.31 ± 0.5

TC (mg/dL)

171 ± 30

175 ± 35

173 ± 28

177 ± 30

LDL-C (mg/dL)

105 ± 26

106 ± 31

98 ± 20

104 ± 23

HDL-C (mg/dL)

55 ± 15

58 ± 17

61 ± 14

LDL-C/HDL-C

2.0 ± 0.6

1.9 ± 0.7

1.7 ± 0.5

1.8 ± 0.4

TG (mg/dL)

129 ± 65

127 ± 59

109 ± 62

121 ± 63

Non-HDL-C (mg/dL)

116 ± 28

117 ± 31

112 ± 23

116 ± 20

Cre (mg/dL)

0.89 ± 0.29

0.87 ± 0.25

0.77 ± 0.14

0.75 ± 0.16

eGFR (mL/min)

61.3 ± 18.1

61.8 ± 17.5

68.7 ± 7.6

71.3 ± 9.7

UAE (mg/g.Cre)

39.6 ± 70.1

32.7 ± 41.4

47.6 ± 107.6

35.8 ± 51.7

AST (U/L)

26 ± 11

24 ± 7

23 ± 7

24 ± 5

ALT (U/L)

26 ± 8

25 ± 9

24 ± 10

25 ± 9

γGTP (U/L)

32 ± 14

32 ± 17

28 ± 17

Ferritin (ng/mL)

161 ± 111

175 ± 121

107 ± 87

105 ± 96

hs-CRP (ng/mL)

2,071 ± 3,628

1,641 ± 3,957

766 ± 733

627 ± 648

PSQI (0 - 18)

7.5 ± 3.4

7.2 ± 4.0

7.2 ± 2.3

6.5 ± 3.2

C1 (0 - 3)

1.1 ± 0.5

1.1 ± 0.7

1.4 ± 0.8

1.3 ± 1.0

C2 (0 - 3)

1.4 ± 1.8

1.8 ± 2.0

1.0 ± 1.8

0.8 ± 1.5

Sleep latency

20.9 ± 20.0

27.6 ± 27.4

15.9 ± 15.6

15.3 ± 12.7

C3 (0 - 3)

1.6 ± 0.7

1.5 ± 1.1

1.7 ± 1.0

1.6 ± 1.0

C4 (0 - 3)

1.0 ± 0.9

0.7 ± 0.8

0.8 ± 1.1

0.7 ± 0.9

C5 (0 - 3)

1.0 ± 0.4

0.9 ± 0.5

0.9 ± 0.3

C7 (0 - 3)

1.5 ± 1.0

1.4 ± 0.9

1.4 ± 0.6

1.4 ± 0.7

SF-36

PCS (0 - 100)

52.9 ± 9.7

54.0 ± 9.8

49.6 ± 13.3

48.6 ± 13.3

MCS (0 - 100)

52.4 ± 9.0

53.2 ± 7.7

53.5 ± 9.7

53.8 ± 10.8

RCS (0 - 100)

38.3 ± 7.2

39.5 ± 8.6

37.6 ± 10.1

38.5 ± 10.5