Background
Methods
Study participants
Assessment of visit-to-visit glycemic variability
Assessment of baroreflex sensitivity
Statistical analyses
Results
Baseline characteristics of study participants
Variables | |
---|---|
No. patients | 57 |
Sex, male/female | 39/18 |
Age (years) | 67.2 ± 7.7 |
BMI (kg/m2) | 25.4 ± 4.2 |
Duration of diabetes (years) | 11.5 ± 9.6 |
Fasting plasma glucose (mg/dL) | 134.7 ± 30.7 |
HbA1c (%) | 7.3 ± 1.0 |
Long-term data | |
No. HbA1c measurements in 2 years (times/2 years) | 14.8 ± 4.7 |
Two-year mean HbA1c (%) | 7.2 ± 1.0 |
HbA1c CV (%) | 0.049 (0.029–0.080) |
HbA1c SD (%) | 0.33 (0.18–0.62) |
Adjusted HbA1c SD (%) | 0.32 (0.18–0.59) |
Short-term data | |
CGM mean glucose (mg/dL) | 154.5 ± 28.8 |
CGM CV (mg/dL) | 23.6 ± 7.1 |
CGM SD (mg/dL) | 36.7 ± 13.2 |
Hypertension, n (%) | 42 (74) |
Blood pressure (mmHg) | |
Systolic | 124.6 ± 17.0 |
Diastolic | 77.1 ± 9.4 |
Heart rate (beats/min) | 69.3 ± 11.8 |
Dyslipidemia, n (%) | 51 (89) |
Lipid profile (mg/dL) | |
Triglycerides | 115 (100–175) |
LDL-cholesterol | 111.0 ± 30.2 |
HDL-cholesterol | 52.8 ± 15.5 |
BRS (msec/mmHg) | 7.6 ± 2.7 |
Univariate correlates of baroreflex sensitivity
Variables |
r
|
p
|
---|---|---|
Fasting plasma glucose (mg/dL) | − 0.173 | 0.199 |
HbA1c (%) | − 0.337 | 0.010 |
Long-term data | ||
Two-year mean HbA1c (%) | − 0.384 | 0.003 |
HbA1c CV (%) | − 0.354 | 0.007 |
HbA1c SD (%) | − 0.384 | 0.003 |
Adjusted HbA1c SD (%) | − 0.391 | 0.003 |
Short-term data | ||
CGM mean glucose (mg/dL) | − 0.238 | 0.074 |
CGM CV (mg/dL) | − 0.325 | 0.014 |
CGM SD (mg/dL) | − 0.366 | 0.005 |
Heart rate (beats/min) | − 0.446 | 0.001 |
SBP (mmHg) | 0.154 | 0.252 |
DBP (mmHg) | 0.092 | 0.498 |
Age (years) | − 0.358 | 0.006 |
BMI (kg/m2) | 0.006 | 0.965 |
Triglycerides (mg/dL) | 0.085 | 0.527 |
LDL-cholesterol (mg/dL) | 0.074 | 0.586 |
HDL-cholesterol (mg/dL) | − 0.088 | 0.514 |
Multiple regression analysis of baroreflex sensitivity
Independent variables | Univariate | Multivariate | ||||||
---|---|---|---|---|---|---|---|---|
r
|
p
| Model 1 | Model 2 | Model 3 | ||||
β
|
p
|
β
|
P
|
β
|
p
| |||
(a) | ||||||||
HbA1c CV (%) | − 0.354 | 0.007 | − 0.341 | 0.020 | − 0.359 | 0.014 | − 0.339 | 0.014 |
Two-year mean HbA1c (%) | − 0.384 | 0.003 | − 0.073 | 0.641 | − 0.052 | 0.741 | − 0.006 | 0.969 |
CGM CV (mg/dL) | − 0.325 | 0.014 | − 0.288 | 0.035 | − 0.308 | 0.025 | − 0.229 | 0.072 |
Age (years) | − 0.358 | 0.006 | − 0.323 | 0.008 | − 0.330 | 0.006 | − 0.302 | 0.008 |
Sex (male/female) | – | 0.550 | − 0.129 | 0.283 | − 0.161 | 0.180 | − 0.149 | 0.182 |
BMI (kg/m2) | 0.006 | 0.965 | − 0.221 | 0.120 | − 0.205 | 0.127 | − 0.159 | 0.212 |
SBP (mmHg) | 0.154 | 0.252 | 0.067 | 0.585 | – | – | – | – |
LDL-cholesterol (mg/dL) | 0.074 | 0.586 | – | – | 0.122 | 0.297 | – | – |
Heart rate (beats/min) | − 0.446 | 0.001 | – | – | – | – | − 0.300 | 0.011 |
(b) | ||||||||
HbA1c SD (%) | − 0.384 | 0.003 | − 0.373 | 0.021 | − 0.395 | 0.014 | − 0.371 | 0.014 |
Two-year mean HbA1c (%) | − 0.384 | 0.003 | − 0.020 | 0.906 | 0.006 | 0.971 | 0.048 | 0.769 |
CGM CV (mg/dL) | − 0.325 | 0.014 | − 0.288 | 0.035 | − 0.309 | 0.025 | − 0.230 | 0.071 |
Age (years) | − 0.358 | 0.006 | − 0.322 | 0.008 | − 0.328 | 0.006 | − 0.301 | 0.008 |
Sex (male/female) | – | 0.550 | − 0.130 | 0.278 | − 0.163 | 0.176 | − 0.150 | 0.179 |
BMI (kg/m2) | 0.006 | 0.965 | − 0.228 | 0.111 | − 0.215 | 0.113 | − 0.167 | 0.192 |
SBP (mmHg) | 0.154 | 0.252 | 0.064 | 0.606 | – | – | – | – |
LDL-cholesterol (mg/dL) | 0.074 | 0.586 | – | – | 0.123 | 0.290 | – | – |
Heart rate (beats/min) | − 0.446 | 0.001 | – | – | – | – | − 0.299 | 0.011 |
(c) | ||||||||
Adjusted HbA1c SD (%) | − 0.391 | 0.003 | − 0.376 | 0.020 | − 0.397 | 0.014 | − 0.376 | 0.013 |
Two-year mean HbA1c (%) | − 0.384 | 0.003 | − 0.017 | 0.919 | 0.007 | 0.967 | 0.051 | 0.752 |
CGM CV (mg/dL) | − 0.325 | 0.014 | − 0.290 | 0.034 | − 0.309 | 0.025 | − 0.231 | 0.070 |
Age (years) | − 0.358 | 0.006 | − 0.318 | 0.009 | − 0.325 | 0.007 | − 0.297 | 0.009 |
Sex (male/female) | – | 0.550 | − 0.131 | 0.273 | − 0.163 | 0.173 | − 0.152 | 0.174 |
BMI (kg/m2) | 0.006 | 0.965 | − 0.227 | 0.111 | − 0.213 | 0.115 | − 0.166 | 0.193 |
SBP (mmHg) | 0.154 | 0.252 | 0.065 | 0.596 | – | – | – | – |
LDL-cholesterol (mg/dL) | 0.074 | 0.586 | – | – | 0.122 | 0.297 | – | – |
Heart rate (beats/min) | − 0.446 | 0.001 | – | – | – | – | − 0.301 | 0.010 |
Respective and combined effects of short-term and long-term glycemic variability on baroreflex sensitivity
Variables | Group 1 (n = 16) | Group 2 (n = 13) | Group 3 (n = 13) | Group 4 (n = 15) | p value§ | Test for trend p value |
---|---|---|---|---|---|---|
BRS (msec/mmHg) | ||||||
Mean ± SD | 9.58 ± 3.0 | 7.10 ± 1.9* | 6.64 ± 2.2* | 6.66 ± 2.4* | 0.004 | 0.002 |
p value | 0.045 | 0.012 | 0.009 | |||
Age (years) | 66.9 ± 5.6 | 67.2 ± 7.5 | 65.9 ± 8.4 | 68.6 ± 9.6 | 0.840 | |
Diabetes duration (years) | 8.3 ± 8.2 | 14.3 ± 12.4 | 8.2 ± 4.2 | 15.4 ± 10.4 | 0.069 | |
CGM CV (mg/dL) | 18.3 ± 2.5 | 29.5 ± 5.5* | 18.1 ± 3.5† | 29.1 ± 5.9*‡ | 0.000 | |
Two-year mean HbA1c (%) | 6.6 ± 0.4 | 6.8 ± 0.8 | 7.6 ± 0.8* | 7.8 ± 1.1*† | 0.000 | |
HbA1c CV (%) | 0.030 (0.024–0.044) | 0.027 (0.021–0.033) | 0.065 (0.060–0.114)*† | 0.082 (0.064–0.107)*† | 0.000 |
Comparison of baroreflex sensitivity in subgroups
Subgroup | No (%) | HbA1c CV (%) | p value | HbA1c SD (%) | p value | Adjusted HbA1c SD (%) | p value | BRS (msec/mmHg) | p value |
---|---|---|---|---|---|---|---|---|---|
Sex | 0.140 | 0.186 | 0.181 | 0.550 | |||||
Male | 39 (68) | 0.053 (0.032–0.082) | 0.37 (0.23–0.66) | 0.36 (0.23–0.64) | 7.7 ± 2.7 | ||||
Female | 18 (32) | 0.040 (0.021–0.070) | 0.29 (0.13–0.59) | 0.27 (0.13–0.57) | 7.3 ± 2.8 | ||||
Hypertension | 0.088 | 0.107 | 0.095 | 0.011 | |||||
Yes | 42 (74) | 0.055 (0.032–0.090) | 0.40 (0.24–0.67) | 0.39 (0.23–0.64) | 7.0 ± 2.5* | ||||
No | 15 (26) | 0.032 (0.026–0.059) | 0.21 (0.17–0.62) | 0.20 (0.16–0.59) | 9.1 ± 2.9 | ||||
Dyslipidemia | 0.585 | 0.694 | 0.713 | 0.903 | |||||
Yes | 51 (89) | 0.049 (0.029–0.089) | 0.33 (0.18–0.66) | 0.31 (0.18–0.64) | 7.6 ± 2.6 | ||||
No | 6 (11) | 0.051 (0.024–0.060) | 0.33 (0.15–0.51) | 0.32 (0.14–0.49) | 7.7 ± 3.7 | ||||
Insulin use | 0.422 | 0.233 | 0.223 | 0.655 | |||||
Yes | 6 (11) | 0.061 (0.042–0.091) | 0.54 (0.32–0.83) | 0.52 (0.31–0.80) | 7.1 ± 3.8 | ||||
No | 51 (89) | 0.048 (0.028–0.082) | 0.32 (0.18–0.63) | 0.31 (0.17–0.59) | 7.6 ± 2.6 | ||||
Sulfonylurea use | 0.043 | 0.018 | 0.015 | 0.028 | |||||
Yes | 17 (30) | 0.065 (0.035–0.103)* | 0.60 (0.26–0.88)* | 0.59 (0.25–0.85)* | 6.4 ± 2.1* | ||||
No | 40 (70) | 0.047 (0.025–0.065) | 0.32 (0.16–0.47) | 0.30 (0.16–0.46) | 8.1 ± 2.8 | ||||
Statin use | 0.108 | 0.132 | 0.124 | 0.035 | |||||
Yes | 20 (35) | 0.062 (0.041–0.105) | 0.45 (0.27–0.80) | 0.44 (0.26–0.76) | 6.6 ± 2.6* | ||||
No | 37 (65) | 0.047 (0.027–0.065) | 0.32 (0.17–0.51) | 0.30 (0.16–0.49) | 8.1 ± 2.6 | ||||
RAAS inhibitor use | 0.635 | 0.600 | 0.544 | 0.526 | |||||
Yes | 22 (39) | 0.049 (0.032–0.069) | 0.35 (0.24–0.52) | 0.34 (0.23–0.50) | 7.3 ± 2.6 | ||||
No | 35 (61) | 0.049 (0.027–0.089) | 0.32 (0.17–0.63) | 0.30 (0.17–0.60) | 7.8 ± 2.8 | ||||
CCB use | 0.272 | 0.349 | 0.324 | 0.241 | |||||
Yes | 24 (42) | 0.062 (0.030–0.087) | 0.44 (0.24–0.65) | 0.43 (0.23–0.63) | 7.1 ± 2.4 | ||||
No | 33 (58) | 0.045 (0.028–0.080) | 0.31 (0.18–0.63) | 0.30 (0.17–0.59) | 7.9 ± 2.9 | ||||
Beta-blocker use | 0.902 | 1.000 | 0.989 | 0.462 | |||||
Yes | 5 (9) | 0.048 (0.027–0.085) | 0.33 (0.20–0.71) | 0.32 (0.19–0.69) | 8.4 ± 3.7 | ||||
No | 52 (91) | 0.050 (0.028–0.081) | 0.33 (0.18–0.63) | 0.31 (0.17–0.60) | 7.5 ± 2.6 |