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 9, Number 4, April 2017, pages 310-316

Visit-to-Visit Low-Density Lipoprotein Cholesterol Variability Is an Independent Determinant of Carotid Intima-Media Thickness in Patients With Type 2 Diabetes

Figure 1. Maximum carotid intima-media thickness (IMT) in type 2 diabetes patients with the highest (black column) compared to the other three quartiles (white column) of SD-LDLC. Mean ± SE after adjustment for age and sex. *P < 0.05.

**Table 1.** Characteristics of 162 Patients With Type 2 Diabetes and Correlation Coefficients of Maximum Carotid IMT (Age- and Sex-Adjusted) and SD-LDLC
	Overall (n = 162)	Correlation coefficients
Mean ± SD or n, %. SD-LDLC: standard deviation of low-density lipoprotein cholesterol; OHA: oral hypoglycemic agents; CCB: calcium channel blockers; RASi: renin-angiotensin system inhibitors; PG: plasma glucose; CV: coefficient of variation; eGFR: estimated glomerular filtration rate; BP: blood pressure; ACR: albumin/creatinine ratio; IMT: intima-media thickness. P < 0.05. P < 0.01. **P < 0.001.
Male sex (n, %)	89 (54.9)	-0.17*	Adjusted	0.159*
Age (years)	62 ± 10	0.29***	Adjusted	-0.14
Smokers (n, %)	53 (32.7)	0.06	-0.01	0.04
BMI (kg/m²)	24.2 ± 3.7	-0.02	0.05	0.06
Waist circumference (cm)	87.0 ± 10.0	0.07	0.12	0.2**
Duration of diabetes (years)	9.7 ± 7.2	0.10	-0.01	0.01
Treatment of diabetes
Diet/OHA/insulin (n, %)	53/81/28 (33/50/17)	-0.01	-0.02	-0.03
Users of CCB/RASi/diuretics (n, %)	56/68/7 (35/42/4)	0.15	0.10	-0.06
Users of hypolipidemic drugs (n, %)	70 (43.2)	0.17*	0.22**	0.26***
HbA1c (%)	7.0 ± 0.8	0.13	0.10	0.01
Fasting PG (mg/dL)	125 ± 23	0.03	0.00	0.02
Post-breakfast PG (mg/dL)	154 ± 48	0.06	0.01	-0.11
CV-HbA1c (%)	6.7 ± 5.7	-0.04	0.01	0.25***
Total cholesterol (mg/dL)	188 ± 21	0.02	0.11	0.27***
LDLC (mg/dL)	112 ± 22	0.12	0.19*	0.28***
SD-LDLC (mg/dL)	15 ± 10	0.10	0.21*	1
HDLC (mg/dL)	55 ± 15	-0.18*	-0.13	-0.07
Fasting TG (mg/dL)	114 ± 51	0.07	0.07	0.21**
Post-breakfast TG (mg/dL)	145 ± 62	0.01	-0.05	0.13
Serum creatinine (mg/dL)	0.8 ± 0.2	0.18*	0.03	-0.16*
eGFR (mL/min/1.73 m²)	76 ± 16	-0.13	0.01	0.18*
Uric acid (mg/dL)	5.2 ± 1.3	0.10	0.03	-0.12
Systolic BP (mm Hg)	128 ± 12	0.13	0.09	0.06
SD-systolic BP (mm Hg)	8.1 ± 2.2	0.20*	0.15	-0.01
Diastolic BP (mm Hg)	72 ± 6	0.00	0.08	0.12
Urinary ACR (mg/g)	86 ± 327	0.01	-0.01	0.06
Log ACR	1.3 ± 0.6	0.23**	0.18*	0.06
Leucocyte count (10³/μL)	5.8 ± 1.5	0.05	0.03	0.14
Maximum IMT (mm)	1.04 ± 0.30	1	1	0.10
Mean IMT (mm)	0.83 ± 0.18	0.93***	0.92***	0.05
ACR ≥ 30 mg/g (n, %)	53 (32.7)	0.20*	0.15	0.034
eGFR < 60 mL/min/1.73 m²)	25 (15.4)	0.11	0.03	-0.12
Chronic kidney disease (n, %)	66 (40.7)	0.18*	0.10	0.00

Table 1. Characteristics of 162 Patients With Type 2 Diabetes and Correlation Coefficients of Maximum Carotid IMT (Age- and Sex-Adjusted) and SD-LDLC

Overall (n = 162)

Correlation coefficients

Maximum IMT

SD-LDLC

Mean ± SD or n, %. SD-LDLC: standard deviation of low-density lipoprotein cholesterol; OHA: oral hypoglycemic agents; CCB: calcium channel blockers; RASi: renin-angiotensin system inhibitors; PG: plasma glucose; CV: coefficient of variation; eGFR: estimated glomerular filtration rate; BP: blood pressure; ACR: albumin/creatinine ratio; IMT: intima-media thickness. *P < 0.05. **P < 0.01. ***P < 0.001.

Male sex (n, %)

89 (54.9)

-0.17*

Adjusted

0.159*

Age (years)

62 ± 10

0.29***

Adjusted

-0.14

Smokers (n, %)

53 (32.7)

0.06

-0.01

0.04

BMI (kg/m²)

24.2 ± 3.7

-0.02

0.05

0.06

Waist circumference (cm)

87.0 ± 10.0

0.07

0.12

0.2**

Duration of diabetes (years)

9.7 ± 7.2

0.10

-0.01

0.01

Treatment of diabetes

Diet/OHA/insulin (n, %)

53/81/28 (33/50/17)

-0.01

-0.02

-0.03

Users of CCB/RASi/diuretics (n, %)

56/68/7 (35/42/4)

0.15

0.10

-0.06

Users of hypolipidemic drugs (n, %)

70 (43.2)

0.17*

0.22**

0.26***

HbA1c (%)

7.0 ± 0.8

0.13

0.10

0.01

Fasting PG (mg/dL)

125 ± 23

0.03

0.00

0.02

Post-breakfast PG (mg/dL)

154 ± 48

0.06

0.01

-0.11

CV-HbA1c (%)

6.7 ± 5.7

-0.04

0.01

0.25***

Total cholesterol (mg/dL)

188 ± 21

0.02

0.11

0.27***

LDLC (mg/dL)

112 ± 22

0.12

0.19*

0.28***

SD-LDLC (mg/dL)

15 ± 10

0.10

0.21*

HDLC (mg/dL)

55 ± 15

-0.18*

-0.13

-0.07

Fasting TG (mg/dL)

114 ± 51

0.07

0.21**

Post-breakfast TG (mg/dL)

145 ± 62

0.01

-0.05

0.13

Serum creatinine (mg/dL)

0.8 ± 0.2

0.18*

0.03

-0.16*

eGFR (mL/min/1.73 m²)

76 ± 16

-0.13

0.01

0.18*

Uric acid (mg/dL)

5.2 ± 1.3

0.10

0.03

-0.12

Systolic BP (mm Hg)

128 ± 12

0.13

0.09

0.06

SD-systolic BP (mm Hg)

8.1 ± 2.2

0.20*

0.15

-0.01

Diastolic BP (mm Hg)

72 ± 6

0.00

0.08

0.12

Urinary ACR (mg/g)

86 ± 327

0.01

-0.01

0.06

Log ACR

1.3 ± 0.6

0.23**

0.18*

0.06

Leucocyte count (10³/μL)

5.8 ± 1.5

0.05

0.03

0.14

Maximum IMT (mm)

1.04 ± 0.30

0.10

Mean IMT (mm)

0.83 ± 0.18

0.93***

0.92***

0.05

ACR ≥ 30 mg/g (n, %)

53 (32.7)

0.20*

0.15

0.034

eGFR < 60 mL/min/1.73 m²)

25 (15.4)

0.11

0.03

-0.12

Chronic kidney disease (n, %)

66 (40.7)

0.18*

0.10

0.00

**Table 2.** Multiple Stepwise Linear Regression Analysis for Maximum Carotid Intima-Media Thickness as a Dependent Variable
Independent variables	Standardized β	Cumulative R²	P values
Other independent variables included mean LDLC, BMI, waist circumference, duration and treatment of diabetes, means and SDs of systolic blood pressure, glycemic and other lipid variables, and uses of hypolipidemic and anti-hypertensive medications.
Sex	0.355	0.083	< 0.001
Age	0.234	0.117	0.002
SD-LDLC	0.201	0.151	0.009

Table 2. Multiple Stepwise Linear Regression Analysis for Maximum Carotid Intima-Media Thickness as a Dependent Variable

Independent variables

Standardized β

Cumulative R²

P values

Other independent variables included mean LDLC, BMI, waist circumference, duration and treatment of diabetes, means and SDs of systolic blood pressure, glycemic and other lipid variables, and uses of hypolipidemic and anti-hypertensive medications.

Sex

0.355

0.083

< 0.001

Age

0.234

0.117

0.002

SD-LDLC

0.201

0.151

0.009

**Table 3.** Characteristics of Type 2 Diabetic Patients With the Highest Compared to Other Three Quartiles of SD-LDLC Combined
	Quartiles of SD-LDLC	P values
Mean ± SD or n, %. SD-LDLC: standard deviation of low-density lipoprotein cholesterol; OHA: oral hypoglycemic agents; CCB: calcium channel blockers; RASi: renin-angiotensin system inhibitors; PG: plasma glucose; CV: coefficient of variation; eGFR: estimated glomerular filtration rate; BP: blood pressure; ACR: albumin/creatinine ratio; IMT: intima-media thickness.
Male sex (n, %)	69 (57)	20 (50)	0.47
Age (years)	63 ± 10	60 ± 11	0.15
Smokers (n, %)	39 (32)	14 (35)	0.75
BMI (kg/m²)	24.1 ± 3.7	24.6 ± 3.8	0.49
Waist circumference (cm)	86.2 ± 8.4	89.4 ± 13.6	0.08
Duration of diabetes (years)	9.4 ± 7.1	10.5 ± 7.8	0.40
Treatment of diabetes
Diet/OHA/insulin (n, %)	41/58/23 (34/48/19)	12/23/5 (30/58/13)	0.49
Users of CCB/RASi/diuretics (n, %)	46/53/6 (38/43/5)	10/15/1 (25/38/3)	0.32
Users of hypolipidemic drugs (n, %)	38 (31)	23 (58)	0.003
HbA1c (%)	7.0 ± 0.9	7.0 ± 0.8	0.94
Fasting PG (mg/dL)	125 ± 22	126 ± 24	0.79
Post-breakfast PG (mg/dL)	157 ± 49	142 ± 46	0.11
CV-HbA1c (%)	5.9 ± 5.2	9.1 ± 6.7	0.002
Total cholesterol (mg/dL)	185 ± 21	197 ± 20	0.003
LDLC (mg/dL)	109 ± 22	121 ± 21	0.002
SD-LDLC (mg/dL)	11 ± 4	30 ± 8	0.000
HDLC (mg/dL)	56 ± 16	54 ± 14	0.47
Fasting TG (mg/dL)	109 ± 49	132 ± 52	0.01
Post-breakfast TG (mg/dL)	140 ± 61	164 ± 65	0.05
Serum creatinine (mg/dL)	0.8 ± 0.2	0.7 ± 0.2	0.34
eGFR (mL/min/1.73 m²)	75 ± 16	79 ± 18	0.10
Uric acid (mg/dL)	5.2 ± 1.4	5.2 ± 1.0	0.85
Systolic BP (mm Hg)	128 ± 12	129 ± 11	0.50
SD-systolic BP (mm Hg)	10.3 ± 3.0	10.2 ± 3.0	0.78
Diastolic BP (mm Hg)	72 ± 7	74 ± 6	0.15
Urinary ACR (mg/g)	47 ± 128	203 ± 608	0.01
Log ACR	1.3 ± 0.5	1.4 ± 0.7	0.10
Leucocyte count (10³/μL)	5.7 ± 1.4	6.2 ± 1.6	0.06
Maximum IMT (mm)	1.03 ± 0.27	1.10 ± 0.39	0.17
Mean IMT (mm)	0.83 ± 0.18	0.85 ± 0.19	0.49
ACR ≥ 30 mg/g (n, %)	37 (30)	16 (40)	0.26

Table 3. Characteristics of Type 2 Diabetic Patients With the Highest Compared to Other Three Quartiles of SD-LDLC Combined

Quartiles of SD-LDLC

P values

Other three (n = 122)

Highest (n = 40)

Male sex (n, %)

69 (57)

20 (50)

0.47

Age (years)

63 ± 10

60 ± 11

0.15

Smokers (n, %)

39 (32)

14 (35)

0.75

BMI (kg/m²)

24.1 ± 3.7

24.6 ± 3.8

0.49

Waist circumference (cm)

86.2 ± 8.4

89.4 ± 13.6

0.08

Duration of diabetes (years)

9.4 ± 7.1

10.5 ± 7.8

0.40

Treatment of diabetes

Diet/OHA/insulin (n, %)

41/58/23 (34/48/19)

12/23/5 (30/58/13)

0.49

Users of CCB/RASi/diuretics (n, %)

46/53/6 (38/43/5)

10/15/1 (25/38/3)

0.32

Users of hypolipidemic drugs (n, %)

38 (31)

23 (58)

0.003

HbA1c (%)

7.0 ± 0.9

7.0 ± 0.8

0.94

Fasting PG (mg/dL)

125 ± 22

126 ± 24

0.79

Post-breakfast PG (mg/dL)

157 ± 49

142 ± 46

0.11

CV-HbA1c (%)

5.9 ± 5.2

9.1 ± 6.7

0.002

Total cholesterol (mg/dL)

185 ± 21

197 ± 20

0.003

LDLC (mg/dL)

109 ± 22

121 ± 21

0.002

SD-LDLC (mg/dL)

11 ± 4

30 ± 8

0.000

HDLC (mg/dL)

56 ± 16

54 ± 14

0.47

Fasting TG (mg/dL)

109 ± 49

132 ± 52

0.01

Post-breakfast TG (mg/dL)

140 ± 61

164 ± 65

0.05

Serum creatinine (mg/dL)

0.8 ± 0.2

0.7 ± 0.2

0.34

eGFR (mL/min/1.73 m²)

75 ± 16

79 ± 18

0.10

Uric acid (mg/dL)

5.2 ± 1.4

5.2 ± 1.0

0.85

Systolic BP (mm Hg)

128 ± 12

129 ± 11

0.50

SD-systolic BP (mm Hg)

10.3 ± 3.0

10.2 ± 3.0

0.78

Diastolic BP (mm Hg)

72 ± 7

74 ± 6

0.15

Urinary ACR (mg/g)

47 ± 128

203 ± 608

0.01

Log ACR

1.3 ± 0.5

1.4 ± 0.7

0.10

Leucocyte count (10³/μL)

5.7 ± 1.4

6.2 ± 1.6

0.06

Maximum IMT (mm)

1.03 ± 0.27

1.10 ± 0.39

0.17

Mean IMT (mm)

0.83 ± 0.18

0.85 ± 0.19

0.49

ACR ≥ 30 mg/g (n, %)

37 (30)

16 (40)

0.26

**Table 4.** Multiple Stepwise Linear Regression Analysis for SD-LDLC as a Dependent Variable
Independent variables	Standardized β	Cumulative R²	P values
Independent variables included waist circumference, users of hypolipidemic drugs, CV-HbA1c, mean LDLC, fasting TG, and eGFR. SD-LDLC: standard deviation of low-density lipoprotein cholesterol; OHA: oral hypoglycemic agents; CCB: calcium channel blockers; RASi: renin-angiotensin system inhibitors; PG: plasma glucose; CV: coefficient of variation; eGFR: estimated glomerular filtration rate; BP: blood pressure; ACR: albumin/creatinine ratio; IMT: intima-media thickness.
LDLC	0.232	0.069	0.001
CV-HbA1c	0.189	0.124	0.011
Users of hypolipidemic drugs	0.247	0.180	0.001
Fasting TG	0.172	0.197	0.018
eGFR	0.151	0.213	0.039

Table 4. Multiple Stepwise Linear Regression Analysis for SD-LDLC as a Dependent Variable

Independent variables

Standardized β

Cumulative R²

P values

Independent variables included waist circumference, users of hypolipidemic drugs, CV-HbA1c, mean LDLC, fasting TG, and eGFR. SD-LDLC: standard deviation of low-density lipoprotein cholesterol; OHA: oral hypoglycemic agents; CCB: calcium channel blockers; RASi: renin-angiotensin system inhibitors; PG: plasma glucose; CV: coefficient of variation; eGFR: estimated glomerular filtration rate; BP: blood pressure; ACR: albumin/creatinine ratio; IMT: intima-media thickness.

LDLC

0.232

0.069

0.001

CV-HbA1c

0.189

0.124

0.011

Users of hypolipidemic drugs

0.247

0.180

0.001

Fasting TG

0.172

0.197

0.018

eGFR

0.151

0.213

0.039