J Endocrinol Metab

Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access

Article copyright, the authors; Journal compilation copyright, J Endocrinol Metab and Elmer Press Inc

Journal website http://www.jofem.org

Original Article

Volume 1, Number 2, June 2011, pages 64-72

Reduced Glucose Variability Is Associated With Improved Quality of Glycemic Control in Patients With Type 2 Diabetes: A 12-Month Observational Study

Figure 1. Proportions of various classes of antihyperglycemic medication used for glycemic control in outpatients with type 2 diabetes by quartiles of the baseline mean amplitude of glycemic excursions (MAGE). (A) Treatment at baseline. (B) Treatment at 12 month. Indication of treatments: diet (black solid columns), OHA (light grey columns), OHA + insulin (dark grey columns), and insulin alone (white columns). Number of patients in quartiles 1 to 4: n = 94, 105, 100, and 106, respectively.

Figure 2. Relationship between the mean amplitude of glycemic excursions and mean sensor glucose levels at the endpoint of the 12-month observation period (r = 0.452, P < 0.001), showing different values for glucose variability at the same mean sensor glucose concentration.

**Table 1.** Baseline Measures of Glucose Variability and Glycemic Control Categorized by Quartiles of the Mean Amplitude of Glycemic Excursions (MAGE)
Parameter	Quartiles of MAGE
Data are presented as means ± SD or medians (25th - 75th percentile).Hyperglycemia: > 8.9 mmol/l; target range: 3.9 - 8.9 mmol/l; hypoglycemia: < 3.9 mmol/l.
Glucose variability
MAGE (mmol/l)	2.4 ± 0.5	3.7 ± 0.4	5.0 ± 0.4	7.7 ± 1.9
SD (mmol/l)	0.9 ± 0.1	1.4 ± 0.2	1.9 ± 0.3	2.8 ± 0.7
MODD (mmol/l)	1.0 ± 0.3	1.5 ± 0.4	1.9 ± 0.6	2.7 ± 0.9
Glycemic control
A1C (%)	6.6 ± 0.7	6.9 ± 0.9	7.1 ± 0.9	7.5 ± 1.1
(mmol/L)	49.1 ± 8.1	51.4 ± 9.8	54.3 ± 10.2	58.4 ± 11.9
Fasting glucose (mmol/l)	6.6 ± 1.1	6.8 ± 1.8	7.0 ± 1.7	7.2 ± 2.3
Mean glucose (mmol/l)	6.9 ± 1.0	7.4 ± 1.7	8.0 ± 1.7	8.7 ± 1.8
Hyperglycemia (h/day)	0.9 (0.1 - 2.4)	3.3 (1.4 - 6.3)	6.3 (3.8 - 9.7)	8.7 (5.4 - 14.1)
Target range (h/day)	22.9 (21.2 - 23.5)	19.8 (17.2 - 21.7)	17.3 (14.3 - 19.6)	13.2 (9.7 - 16.8)
Hypoglycemia (min/day)	0.0 (0.0 - 11.4)	2.4 (0.0 - 36.0)	5.7 (9.9 - 51.6)	39.3 (0.0 - 140.3)
GRADE score	2.9 (2.3 - 4.4)	4.2 (3.0 - 6.3)	5.9 (4.6 - 7.6)	8.1 (6.1 - 11.1)
HBGI	0.4 (0.2 - 0.9)	1.0 (0.5 - 1.8)	1.8 (1.1 - 2.8)	3.1 (1.9 - 5.5)
LBGI	0.1 (0.0 - 0.3)	0.2 (0.0 - 0.6)	0.2 (0.0 - 0.7)	0.5 (0.1 - 1.4)

Table 1. Baseline Measures of Glucose Variability and Glycemic Control Categorized by Quartiles of the Mean Amplitude of Glycemic Excursions (MAGE)

Parameter

Quartiles of MAGE

1st (n = 94)

2nd (n = 105)

3rd (n = 100)

4th (n = 106)

Data are presented as means ± SD or medians (25th - 75th percentile).Hyperglycemia: > 8.9 mmol/l; target range: 3.9 - 8.9 mmol/l; hypoglycemia: < 3.9 mmol/l.

Glucose variability

MAGE (mmol/l)

2.4 ± 0.5

3.7 ± 0.4

5.0 ± 0.4

7.7 ± 1.9

SD (mmol/l)

0.9 ± 0.1

1.4 ± 0.2

1.9 ± 0.3

2.8 ± 0.7

MODD (mmol/l)

1.0 ± 0.3

1.5 ± 0.4

1.9 ± 0.6

2.7 ± 0.9

Glycemic control

A1C (%)

6.6 ± 0.7

6.9 ± 0.9

7.1 ± 0.9

7.5 ± 1.1

(mmol/L)

49.1 ± 8.1

51.4 ± 9.8

54.3 ± 10.2

58.4 ± 11.9

Fasting glucose (mmol/l)

6.6 ± 1.1

6.8 ± 1.8

7.0 ± 1.7

7.2 ± 2.3

Mean glucose (mmol/l)

6.9 ± 1.0

7.4 ± 1.7

8.0 ± 1.7

8.7 ± 1.8

Hyperglycemia (h/day)

0.9 (0.1 - 2.4)

3.3 (1.4 - 6.3)

6.3 (3.8 - 9.7)

8.7 (5.4 - 14.1)

Target range (h/day)

22.9 (21.2 - 23.5)

19.8 (17.2 - 21.7)

17.3 (14.3 - 19.6)

13.2 (9.7 - 16.8)

Hypoglycemia (min/day)

0.0 (0.0 - 11.4)

2.4 (0.0 - 36.0)

5.7 (9.9 - 51.6)

39.3 (0.0 - 140.3)

GRADE score

2.9 (2.3 - 4.4)

4.2 (3.0 - 6.3)

5.9 (4.6 - 7.6)

8.1 (6.1 - 11.1)

HBGI

0.4 (0.2 - 0.9)

1.0 (0.5 - 1.8)

1.8 (1.1 - 2.8)

3.1 (1.9 - 5.5)

LBGI

0.1 (0.0 - 0.3)

0.2 (0.0 - 0.6)

0.2 (0.0 - 0.7)

0.5 (0.1 - 1.4)

**Table 2.** Changes From Baseline in Measures of Glucose Variability and Glycemic Control by Quartiles of the Mean Amplitude of Glycemic Excursions (MAGE)
Parameter	Quartiles of MAGE
Data are presented as means ± SD or medians (25th - 75th percentile) of differences (Δ) from baseline. Negative values correspond to a reduction in parameters. P values for paired t test or Wilcoxon signed-rank test within individual patients are shown: *P < 0.05; †P < 0.01; ‡P < 0.001. Hyperglycemia: > 8.9 mmol/l; target range: 3.9 - 8.9 mmol/l; hypoglycemia: < 3.9 mmol/l. Significance level P < 0.05.
Glucose variability
ΔMAGE (mmol/l)	0.75 ± 1.37‡	0.31 ± 1.45*	-0.21 ± 1.77	-1.78 ± 2.29‡
ΔSD (mmol/l)	0.25 ± 0.48‡	0.10 ± 0.54	-0.05 ± 0.59	-0.61 ± 0.83‡
ΔMODD (mmol/l)	0.23 ± 0.54‡	0.13 ± 0.70	-0.02 ± 0.76	-0.42 ± 1.10‡
Glycemic control
ΔA1C (%)	-0.15 ± 0.57*	-0.02 ± 0.86	-0.10 ± 0.86	-0.32 ± 0.82‡
(mmol/L)	-1.65 ± 6.27	-0.25 ± 9.35	-1.14 ± 9.35	-3.49 ± 9.00
ΔFasting glucose (mmol/l)	0.14 ± 1.18	-0.05 ± 1.81	0.02 ± 1.81	-0.30 ± 2.50
ΔMean glucose (mmol/l)	0.14 ± 1.00	-0.02 ± 1.54	-0.17 ± 1.79	-0.58 ± 1.81†
ΔHyperglycemia (h/day)	0.4 (-0.7 - 2.3)*	-0.2 (-2.0 - 1.4)	-0.6 (-3.0 - 2.5)	-1.4 (-4.2 - 1.3)†
ΔTarget range (h/day)	-0.5 (-2.5 - 0.7)*	0.6 (-1.7 - 2.7)	0.2 (-2.5 - 3.2)	2.2 (-0.2 - 5.5)‡
ΔHypoglycemia (min/day)	0.0 (-7.1 - 5.3)	0.0 (-30.3 - 25.8)	0.0 (-26.1 - 15.0)	-5.1 (-94.4 - 21.9)†
ΔGRADE score	0.54 ± 2.18*	-0.11 ± 3.44	-0.47 ± 3.99	-1.80 ± 3.73‡
ΔHBGI	0.1 (-0.1 - 0.7)†	-0.0 (-0.6 - 0.7)	-0.2 (-0.9 - 0.8)	-0.8 (-2.4 - 0.3)‡
ΔLBGI	0.0 (-0.2 - 0.2)	0.0 (-0.3 - 0.2)	-0.0 (-0.2 - 0.3)	-0.1 (-0.8 - 0.2)*

Table 2. Changes From Baseline in Measures of Glucose Variability and Glycemic Control by Quartiles of the Mean Amplitude of Glycemic Excursions (MAGE)

Parameter

Quartiles of MAGE

1st (n = 94)

2nd (n = 105)

3rd (n = 100)

4th (n = 106)

Change

Data are presented as means ± SD or medians (25th - 75th percentile) of differences (Δ) from baseline. Negative values correspond to a reduction in parameters. P values for paired t test or Wilcoxon signed-rank test within individual patients are shown: *P < 0.05; †P < 0.01; ‡P < 0.001. Hyperglycemia: > 8.9 mmol/l; target range: 3.9 - 8.9 mmol/l; hypoglycemia: < 3.9 mmol/l. Significance level P < 0.05.

Glucose variability

ΔMAGE (mmol/l)

0.75 ± 1.37‡

0.31 ± 1.45*

-0.21 ± 1.77

-1.78 ± 2.29‡

ΔSD (mmol/l)

0.25 ± 0.48‡

0.10 ± 0.54

-0.05 ± 0.59

-0.61 ± 0.83‡

ΔMODD (mmol/l)

0.23 ± 0.54‡

0.13 ± 0.70

-0.02 ± 0.76

-0.42 ± 1.10‡

Glycemic control

ΔA1C (%)

-0.15 ± 0.57*

-0.02 ± 0.86

-0.10 ± 0.86

-0.32 ± 0.82‡

(mmol/L)

-1.65 ± 6.27

-0.25 ± 9.35

-1.14 ± 9.35

-3.49 ± 9.00

ΔFasting glucose (mmol/l)

0.14 ± 1.18

-0.05 ± 1.81

0.02 ± 1.81

-0.30 ± 2.50

ΔMean glucose (mmol/l)

0.14 ± 1.00

-0.02 ± 1.54

-0.17 ± 1.79

-0.58 ± 1.81†

ΔHyperglycemia (h/day)

0.4 (-0.7 - 2.3)*

-0.2 (-2.0 - 1.4)

-0.6 (-3.0 - 2.5)

-1.4 (-4.2 - 1.3)†

ΔTarget range (h/day)

-0.5 (-2.5 - 0.7)*

0.6 (-1.7 - 2.7)

0.2 (-2.5 - 3.2)

2.2 (-0.2 - 5.5)‡

ΔHypoglycemia (min/day)

0.0 (-7.1 - 5.3)

0.0 (-30.3 - 25.8)

0.0 (-26.1 - 15.0)

-5.1 (-94.4 - 21.9)†

ΔGRADE score

0.54 ± 2.18*

-0.11 ± 3.44

-0.47 ± 3.99

-1.80 ± 3.73‡

ΔHBGI

0.1 (-0.1 - 0.7)†

-0.0 (-0.6 - 0.7)

-0.2 (-0.9 - 0.8)

-0.8 (-2.4 - 0.3)‡

ΔLBGI

0.0 (-0.2 - 0.2)

0.0 (-0.3 - 0.2)

-0.0 (-0.2 - 0.3)

-0.1 (-0.8 - 0.2)*

**Table 3.** Correlation Matrix for the Mean Amplitude of Glycemic Excursions (MAGE) and Measures of Glycemic Control: GRADE Score and A1C
	MAGE_BL	ΔMAGE_BL-EP	GRADE_BL	ΔGRADE_BL-EP	A1C_BL
Data represent Pearson correlation coefficients. The area above the diagonal is not shown because the table is symmetrical. *P < 0.05 (two-sided); ‡P < 0.001 (two-sided). GRADE: Glycemic Risk Association Diabetes Equation; BL: baseline; EP: endpoint. Δ_BL-EP: difference between baseline and endpoint of the 12-month observation period.
ΔMAGE_BL-EP	-0.540‡
GRADE_BL	0.530‡	-0.167‡
ΔGRADE_BL-EP	-0.256‡	0.371‡	-0.619‡
A1C_BL	0.328‡	-0.076	0.531‡	-0.203‡
ΔA1C_BL-EP	-0.081	0.103*	-0.247‡	0.321‡	-0.579‡

Table 3. Correlation Matrix for the Mean Amplitude of Glycemic Excursions (MAGE) and Measures of Glycemic Control: GRADE Score and A1C

MAGE_BL

ΔMAGE_BL-EP

GRADE_BL

ΔGRADE_BL-EP

A1C_BL

Data represent Pearson correlation coefficients. The area above the diagonal is not shown because the table is symmetrical. *P < 0.05 (two-sided); ‡P < 0.001 (two-sided). GRADE: Glycemic Risk Association Diabetes Equation; BL: baseline; EP: endpoint. Δ_BL-EP: difference between baseline and endpoint of the 12-month observation period.

ΔMAGE_BL-EP

-0.540‡

GRADE_BL

0.530‡

-0.167‡

ΔGRADE_BL-EP

-0.256‡

0.371‡

-0.619‡

A1C_BL

0.328‡

-0.076

0.531‡

-0.203‡

ΔA1C_BL-EP

-0.081

0.103*

-0.247‡

0.321‡

-0.579‡

**Table 4.** Results of Stepwise Forward Multiple Regression Analysis
Dependent variable	Explanatory variable	Regression coefficient (ß)	SE	Pvalue	Coefficient of determination (R²)
Significance level P < 0.05.
Time spent at < 3.9 mmol/l	Mean glucose	-0.558	2.057	< 0.001	0.121
	MAGE	0.544	1.604	< 0.001	0.374
Time spent at > 8.9 mmol/l	Mean glucose	0.868	0.061	< 0.001	0.857
	MAGE	0.154	0.048	< 0.001	0.877

Table 4. Results of Stepwise Forward Multiple Regression Analysis

Dependent variable

Explanatory variable

Regression coefficient (ß)

Pvalue

Coefficient of determination (R²)

Significance level P < 0.05.

Time spent at < 3.9 mmol/l

Mean glucose

-0.558

2.057

< 0.001

0.121

MAGE

0.544

1.604

< 0.001

0.374

Time spent at > 8.9 mmol/l

Mean glucose

0.868

0.061

< 0.001

0.857

MAGE

0.154

0.048

< 0.001

0.877