Baseline characteristics of the study population
Five hundred and thirty-five T1D patients using a CGM were followed in the Endocrinology Department of CHUSJ during the study period. Of these, we excluded 61 due to lack on available data and 232 due to having a percentage of active CGM time < 70%. The final number of individuals analyzed was 242 (Supplemental Fig. 1).
The baseline characteristics of the study population are shown in Tables 1A and 1B. Among the cohort of 242 patients, 51.7% were men, the mean age (± standard deviation) was 36.6 ± 12.6 years and 56.7% had higher education. Concerning the T1D related parameters (Table 1A), the mean duration of this disease was 16.8 ± 10.3 years and 35.1% of the patients had an insulin pump. The mean baseline TIR was 56.7 ± 18.2% and the mean baseline CV was 38.5 ± 7.7%. Regarding the dyslipidemia related parameters (Table 1B), 69.8% of the patients were not treated with a statin and, of those who were, 5.5%, 45.2% and 49.3%, were treated, respectively, with a low, moderate, and high potency statin. None of these patients was under fibrates. The mean baseline HDL cholesterol level was 57.3 ± 14.5 mg/dL, and the mean triglyceride level was 84.1 ± 78.1 mg/dL.
Cross-sectional evaluation
In the cross-sectional evaluation (n = 242), higher TIR levels were associated with lower triglyceride levels (Table 2A). The mean triglyceride levels were 75.5 [57.0, 109.0] mg/dL in patients with TIR < 50%, 65.5 [51.0, 90.0] mg/dL in patients with TIR between 50 and 70% and 64.0 [51.0, 80.0] mg/dL in patients with TIR ≥ 70% (p = 0.006). TIR levels were not significantly associated with total cholesterol, HDL cholesterol, LDL cholesterol or non-HDL cholesterol levels.
Regarding the association of CV with lipid profile in the cross-sectional analysis, lower CV levels were associated with higher HDL cholesterol levels. As CV decreases, HDL levels are higher: 58.4 ± 14.6 mg/dL in patients with CV ≤ 36%, 58.8 ± 15.2 mg/dL in patients with CV between 36 and 45% and 51.8 ± 11.6 mg/dL in patients with CV > 45% (p = 0.035). Total cholesterol, LDL cholesterol, triglycerides and non-HDL cholesterol are not significantly associated with CV levels (Table 2B).
In Table 3, we present the unadjusted and adjusted results of the linear regressions of the association of HbA1c and CGM parameters with lipid profile. Higher TIR levels were associated with lower triglycerides levels in the unadjusted and adjusted analysis. Higher HbA1C, GMI, TAR and TA250 were also associated with higher triglycerides levels in both analyses. The only glycemic parameter associated with HDL cholesterol was CV (-0.30 mg/dL, 95%CI -0.54 to -0.06, per 1% increase in CV in the adjusted analysis, p = 0.015). Neither HbA1c nor CGM parameters were significantly associated with total cholesterol, LDL cholesterol and non-HDL cholesterol.
Table 1 Baseline characteristics of the study population (n=242).
Table 1a: Baseline characteristics of the study population such as demographic and social features and T1D monitoring values. Missing data for each variable shown in the supplemental table 1A.
Male sex, n (%)
|
124 (51.7%)
|
Age, years
|
36.6 ± 12.6
|
Educational level, n (%)
|
|
Less than 9th grade
|
24 (11.2%)
|
9th to 12th grade
|
69 (32.1%)
|
Higher Education
|
122 (56.7%)
|
Duration of diabetes, years
|
16.8 ± 10.3
|
With insulin pump, n (%)
|
85 (35.1%)
|
Body Mass Index, kg/m2
|
24.8 ± 3.9
|
Physical activity, n (%)
|
92 (46.2%)
|
With smoking habits, n (%)
|
43 (23.8%)
|
With drinking habits, n (%)
|
22 (12.4%)
|
Hypertension, n (%)
|
32 (13.2%)
|
ASCVD, n (%)
|
12 (5.0%)
|
Nephropathy, n (%)
|
21 (8.7%)
|
Retinopathy, n (%)
|
53 (22.2%)
|
Neuropathy, n (%)
|
10 (4.1%)
|
Heart failure, n (%)
|
5 (2.1%)
|
HbA1C, %
|
7.6 ± 1.3
|
GMI, %
|
7.4 ± 0.9
|
Time in range, %
|
56.7 ± 18.2
|
Time below range, %
|
6.6 ± 8.2
|
Time below 54mg/dL, %
|
2.3 ± 4.2
|
Time above range, %
|
42.9 ± 26.7
|
Time above 250mg/dL, %
|
15.4 ± 15.0
|
CV, %
|
38.5 ± 7.7
|
Table 1b: Baseline characteristics of the study population such as statin treatment and lipid profile analysis. Missing data for each variable shown in the supplemental table 1B.
Without statin, n (%)
|
169 (69.8%)
|
With statin, n (%)
|
73 (30.2%)
|
Atorvastatin, n (%)
|
50 (20.7%)
|
Rosuvastatin, n (%)
|
19 (7.9%)
|
Simvastatin, n (%)
|
4 (1.7%)
|
Statin Potency
|
|
Low, n (%)
|
4 (5.5%)
|
Moderate, n (%)
|
33 (45.2%)
|
High, n (%)
|
36 (49.3%)
|
With Ezetimibe
|
12 (5.0%)
|
Total cholesterol, mg/dL
|
166.5 ± 37.2
|
HDL cholesterol, mg/dL
|
57.3 ± 14.5
|
LDL cholesterol, mg/dL
|
95.0 ± 29.2
|
Triglycerides, mg/dL
|
84.1 ± 78.1
|
Non-HDL cholesterol, mg/dL
|
109.5 ± 31.6
|
ASCVD: Atherosclerotic Cardiovascular Disease; HbA1C: Hemoglobin A1C; GMI: Glucose management indicator; CV: Coefficient of variability; LDL: Low-density lipoprotein; HDL: High-density lipoprotein.
Table 2 caption:
Cross-sectional associations of categories of TIR (table 1A) and CV (table 1B) with lipid profile.
Table 2a: Cross-sectional associations of categories of TIR (<50%, ≥50 to <70% and ≥70%) with total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and non-HDL cholesterol.
Table 2b: Cross-sectional associations of categories of CV (≤36%, >36 to <45% and ≥45%) with total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides and non-HDL cholesterol.
Parameters with a significant difference (p<0.05) are highlighted.
TIR: Time in range, LDL: Low-density lipoprotein; HDL: High-density lipoprotein; CV: Coefficient of Variability.
Table 3 caption:
Cross-sectional evaluation (n=242). Cross-sectional evaluation of the association of CGM data with lipid profile. Triglycerides, TBR, TB54, TAR and TA250 values were log-transformed for the regression. Statistically significant differences (p<0.05) are highlighted.
Adjusted model: adjusted for age and sex; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; HbA1C: Hemoglobin A1C; GMI: Glucose management indicator; TIR: time in range; TBR: time below range (<70mg/dL); TB54: time below 54 mg/dL; TAR: time above range (≥181 mg/dL); TA250: time above 250mg/dL); CV: Coefficient of variability; CGM: Continuous Glucose Monitoring.
|
HbA1c (%)
|
|
GMI (%)
|
|
TIR (%)
|
|
TBR (%)
|
|
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
Total Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
1.62 (-2.25 to 5.49)
|
0.41
|
1.14 (-4.26 to 6.54)
|
0.68
|
-0.08 (-0.35 to 0.20)
|
0.58
|
-0.37 (-5.80 to 5.05)
|
0.89
|
Adjusted
|
2.35 (-1.48 to 6.17)
|
0.23
|
2.12 (-3.24 to 7.48)
|
0.44
|
-0.14 (-0.41 to 0.13)
|
0.31
|
-0.33 (-5.72 to 5.06)
|
0.90
|
HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-0.35 (-1.84 to 1.14)
|
0.64
|
-0.44 (-2.53 to 1.65)
|
0.68
|
0.04 (-0.06 to 0.15)
|
0.42
|
0.16 (-1.93 to 2.24)
|
0.88
|
Adjusted
|
-0.48 (-1.95 to 0.98)
|
0.52
|
-0.47 (-2.52 to 1.57)
|
0.65
|
0.03 (-0.07 to 0.14)
|
0.53
|
0.15 (-1.91 to 2.20)
|
0.89
|
LDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
0.50 (-2.66 to 3.65)
|
0.76
|
0.91 (-3.61 to 5.43)
|
0.70
|
-0.04 (-0.26 to 0.17)
|
0.70
|
-0.53 (-4.88 to 3.82)
|
0.81
|
Adjusted
|
1.15 (-1.95 to 4.26)
|
0.47
|
1.75 (-2.71 to 6.20)
|
0.44
|
-0.08 (-0.30 to 0.13)
|
0.45
|
-0.40 (-4.69 to 3.88)
|
0.85
|
Triglycerides (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
0.12 (0.07 to 0.16)
|
0.000
|
0.10 (0.03 to 0.16)
|
0.004
|
-0.01 (-0.01 to -0.00)
|
0.003
|
-0.02 (-0.09 to 0.05)
|
0.64
|
Adjusted
|
0.12 (0.07 to 0.17)
|
0.000
|
0.09 (0.03 to 0.16)
|
0.006
|
-0.00 (-0.01 to -0.00)
|
0.005
|
-0.01 (-0.08 to 0.06)
|
0.69
|
Non HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
2.03 (-1.24 to 5.31)
|
0.22
|
1.68 (-2.90 to 6.26)
|
0.47
|
-0.12 (-0.35 to 0.11)
|
0.31
|
-0.77 (-5.44 to 3.90)
|
0.75
|
Adjusted
|
2.85 (-0.39 to 6.09)
|
0.085
|
2.63 (-1.91 to 7.17)
|
0.26
|
-0.17 (-0.40 to 0.06)
|
0.15
|
-0.68 (-5.29 to 3.94)
|
0.77
|
|
TB54 (%)
|
|
TAR (%)
|
|
TA250 (%)
|
|
CV (%)
|
|
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
Total Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-7.75 (-14.89 to -0.62)
|
0.033
|
-0.06 (-6.81 to 6.69)
|
0.99
|
0.09 (-4.77 to 4.96)
|
0.97
|
-0.46 (-1.10 to 0.19)
|
0.17
|
Adjusted
|
-6.78 (-13.93 to 0.36)
|
0.063
|
1.74 (-5.00 to 8.49)
|
0.61
|
1.17 (-3.67 to 6.01)
|
0.63
|
-0.35 (-0.99 to 0.30)
|
0.29
|
HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-2.42 (-5.39 to 0.55)
|
0.11
|
-1.78 (-4.38 to 0.81)
|
0.18
|
-0.19 (-2.02 to 1.64)
|
0.84
|
-0.33 (-0.58 to -0.09)
|
0.008
|
Adjusted
|
-1.69 (-4.65 to 1.28)
|
0.26
|
-1.42 (-3.97 to 1.14)
|
0.28
|
0.06 (-1.73 to 1.84)
|
0.95
|
-0.30 (-0.54 to -0.06)
|
0.015
|
LDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-5.25 (-10.70 to 0.19)
|
0.058
|
1.12 (-4.31 to 6.55)
|
0.68
|
0.09 (-3.75 to 3.94)
|
0.96
|
-0.25 (-0.77 to 0.26)
|
0.33
|
Adjusted
|
-4.59 (-10.04 to 0.86)
|
0.098
|
2.46 (-2.91 to 7.84)
|
0.37
|
0.85 (-2.95 to 4.65)
|
0.66
|
-0.19 (-0.70 to 0.31)
|
0.46
|
Triglycerides (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-0.02 (-0.10 to 0.07)
|
0.71
|
0.12 (0.03 to 0.20)
|
0.006
|
0.09 (0.03 to 0.14)
|
0.005
|
0.01 (-0.00 to 0.02)
|
0.084
|
Adjusted
|
-0.02 (-0.11 to 0.07)
|
0.68
|
0.11 (0.02 to 0.19)
|
0.013
|
0.08 (0.02 to 0.14)
|
0.008
|
0.01 (-0.00 to 0.01)
|
0.12
|
Non HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-5.33 (-11.30 to 0.63)
|
0.079
|
1.88 (-3.84 to 7.60)
|
0.52
|
0.38 (-3.73 to 4.49)
|
0.86
|
-0.17 (-0.72 to 0.38)
|
0.54
|
Adjusted
|
-5.10 (-11.06 to 0.87)
|
0.093
|
3.28 (-2.42 to 8.99)
|
0.26
|
1.19 (-2.89 to 5.28)
|
0.57
|
-0.09 (-0.64 to 0.45)
|
0.74
|
Longitudinal evaluation
In the longitudinal evaluation, we included the 90 participants with two different moments of analysis (6 to 18 months apart) (characteristics of these participants are shown in supplemental table 2A and 2B). Of these participants, 23 were treated with statins and 17 maintained the same statin treatment between periods. The time between evaluations was 10.5 ± 3.0 months. The mean variation of TIR was 0.1 ± 13.4%, of CV was − 1.0 ± 6.8% and of HbA1c was − 0.1 ± 0.7%. As shown in Table 4, there was a significant association between the variation of CV and the variation of HDL cholesterol levels, both in the unadjusted and adjusted models (-0.54 mg/dL, 95%CI (-0.95 to -0.13), per 1% increase in CV in the adjusted analysis, p = 0.010). The variation of TBR was significantly associated with the variation of HDL cholesterol in both models (-0.46 mg/dL, 95%CI (-0.91 to -0.00), per 1% increase in TBR in the adjusted analysis, p = 0.048). Similarly to the previous analysis, neither HbA1c nor CGM parameters were significantly associated with total cholesterol, LDL cholesterol and non-HDL cholesterol. Differently from the cross-sectional analysis, variation of TIR, HbA1C, GMI, TAR and TA250 were not significantly associated with the variation of triglycerides values.
Table 4 caption:
Longitudinal evaluation (n=90). Longitudinal evaluation of the association of variations of CGM data with variations of lipid profile (6 to 18 months of interval between evaluations). Statistically significant differences (p<0.05) are highlighted.
Adjusted model: adjusted for age and sex; LDL: Low-density lipoprotein; HDL: High-density lipoprotein; HbA1C: Hemoglobin A1C; GMI: Glucose management indicator; TIR: time in range; TBR: time below range (<70mg/dL); TB54: time below 54 mg/dL; TAR: time above range (≥181 mg/dL); TA250: time above 250mg/dL); CV: Coefficient of variability; CGM: Continuous Glucose Monitoring.
|
HbA1c (%)
|
|
GMI (%)
|
|
TIR (%)
|
|
TBR (%)
|
|
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
Total Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-3.61 (-13.82 to 6.60)
|
0.48
|
-3.44 (-11.89 to 5.02)
|
0.42
|
0.29 (-0.14 to 0.72)
|
0.17
|
-0.28 (-1.21 to 0.65)
|
0.56
|
Adjusted
|
-4.05 (-14.65 to 6.56)
|
0.45
|
-3.67 (-12.31 to 4.96)
|
0.40
|
0.30 (-0.13 to 0.74)
|
0.17
|
-0.27 (-1.22 to 0.67)
|
0.57
|
HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
1.46 (-3.55 to 6.47)
|
0.56
|
1.84 (-2.34 to 6.02)
|
0.38
|
-0.04 (-0.25 to 0.18)
|
0.73
|
-0.45 (-0.90 to -0.00)
|
0.049
|
Adjusted
|
1.94 (-3.21 to 7.09)
|
0.45
|
1.96 (-2.28 to 6.21)
|
0.36
|
-0.04 (-0.26 to 0.18)
|
0.71
|
-0.46 (-0.91 to -0.00)
|
0.048
|
LDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-2.96 (-11.65 to 5.73)
|
0.50
|
-5.22 (-13.07 to 2.63)
|
0.19
|
0.30 (-0.10 to 0.70)
|
0.14
|
0.20 (-0.77 to 1.16)
|
0.69
|
Adjusted
|
-2.74 (-11.72 to 6.25)
|
0.55
|
-5.10 (-13.10 to 2.91)
|
0.21
|
0.29 (-0.12 to 0.70)
|
0.16
|
0.19 (-0.79 to 1.17)
|
0.70
|
Triglycerides (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
4.50 (-7.08 to 16.07)
|
0.44
|
0.62 (-9.39 to 10.63)
|
0.90
|
0.04 (-0.47 to 0.55)
|
0.88
|
-0.25 (-1.35 to 0.85)
|
0.65
|
Adjusted
|
3.99 (-7.93 to 15.91)
|
0.51
|
0.18 (-9.94 to 10.29)
|
0.97
|
0.06 (-0.46 to 0.58)
|
0.82
|
-0.23 (-1.33 to 0.88)
|
0.68
|
Non-HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-5.25 (-14.29 to 3.80)
|
0.25
|
-5.37 (-12.80 to 2.06)
|
0.15
|
0.33 (-0.05 to 0.71)
|
0.09
|
0.17 (-0.65 to 1.00)
|
0.68
|
Adjusted
|
-6.20 (-15.53 to 3.12)
|
0.19
|
-5.74 (-13.31 to 1.82)
|
0.13
|
0.35 (-0.04 to 0.73)
|
0.08
|
0.19 (-0.65 to 1.02)
|
0.66
|
|
TB54 (%)
|
|
TAR (%)
|
|
TA25 (%)
|
|
VC (%)
|
|
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
β (95% CI)
|
P Value
|
Total Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-0.37 (-2.04 to 1.29)
|
0.66
|
-0.18 (-0.47 to 0.11)
|
0.22
|
-0.09 (-0.50 to 0.32)
|
0.67
|
-0.66 (-1.50 to 0.19)
|
0.13
|
Adjusted
|
-0.36 (-2.06 to 1.33)
|
0.67
|
-0.19 (-0.49 to 0.10)
|
0.20
|
-0.10 (-0.53 to 0.32)
|
0.63
|
-0.66 (-1.51 to 0.20)
|
0.13
|
HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-0.54 (-1.36 to 0.28)
|
0.19
|
0.00 (-0.14 to 0.15)
|
0.95
|
0.01 (-0.20 to 0.21)
|
0.94
|
-0.55 (-0.96 to -0.15)
|
0.008
|
Adjusted
|
-0.55 (-1.37 to 0.28)
|
0.19
|
0.00 (-0.14 to 0.15)
|
0.97
|
0.01 (-0.20 to 0.22)
|
0.91
|
-0.54 (-0.95 to -0.13)
|
0.010
|
LDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
0.17 (-1.70 to 2.04)
|
0.86
|
-0.14 (-0.41 to 0.13)
|
0.30
|
-0.00 (-0.39 to 0.39)
|
0.99
|
-0.08 (-0.92 to 0.75)
|
0.84
|
Adjusted
|
0.16 (-1.76 to 2.07)
|
0.87
|
-0.14 (-0.41 to 0.14)
|
0.33
|
0.01 (-0.39 to 0.41)
|
0.96
|
-0.09 (-0.94 to 0.76)
|
0.84
|
Triglycerides (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
-0.20 (-2.17 to 1.77)
|
0.84
|
-0.02 (-0.36 to 0.33)
|
0.92
|
-0.06 (-0.55 to 0.42)
|
0.80
|
-0.64 (-1.64 to 0.36)
|
0.21
|
Adjusted
|
-0.17 (-2.15 to 1.80)
|
0.86
|
-0.02 (-0.37 to 0.33)
|
0.91
|
-0.09 (-0.58 to 0.41)
|
0.72
|
-0.70 (-1.70 to 0.31)
|
0.17
|
Non-HDL Cholesterol (mg/dL)
|
|
|
|
|
|
|
|
|
Unadjusted
|
0.15 (-1.33 to 1.63)
|
0.84
|
-0.18 (-0.44 to 0.07)
|
0.15
|
-0.09 (-0.46 to 0.27)
|
0.61
|
-0.10 (-0.86 to 0.66)
|
0.79
|
Adjusted
|
0.17 (-1.33 to 1.67)
|
0.82
|
-0.20 (-0.46 to 0.06)
|
0.13
|
-0.11 (-0.49 to 0.26)
|
0.55
|
-0.11 (-0.88 to 0.66)
|
0.78
|