Endocrinology Section, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy
Copyright © 2024 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: all authors.
Acquisition, analysis, or interpretation of data: I.D., M.M., C.D., V.S.
Drafting the work or revising: V.S.
Final approval of the manuscript: all authors.
FUNDING
None
Variable | T1DM (n=79) | T2DM (n=140) | P value |
---|---|---|---|
Sex, males:females | 30:49 | 93:47 | <0.0001a |
Age, yr | 42.0 (33.0–49.8) | 64.0 (57.0–69.0) | <0.0001a |
Disease duration, yr | 24.0 (16.0–43.0) | 10.0 (5.0–18.5) | <0.0001a |
BMI, kg/m2 | 24.3 (22.3–26.7) | 28.9 (25.7–32.4) | <0.0001a |
HbA1c, % | 7.5 (6.8–8.3) | 6.8 (6.2–7.6) | 0.0001a |
HbA1c, mmol/mol | 58.0 (50.7–67.0) | 51.0 (45.0–59.7) | 0.0001a |
Total cholesterol, mg/dL | 176.0 (157.0–201.5) | 169.0 (138.5–132.0) | 0.095 |
LDL cholesterol, mg/dL | 96.1 (77.0–117.0) | 89.4 (67.0–114.0) | 0.365 |
HDL cholesterol, mg/dL | 60.0 (48.5–70.0) | 44.5 (37.0–55.0) | <0.0001a |
Triglycerides, mg/dL | 82.0 (59.5–98.5) | 117.0 (92.00–162.5) | <0.0001a |
With retinopathy, %b | 33 (46.7) | 32 (24.2) | 0.009a |
With microalbuminuria, %c | 10 (14.1) | 23 (19.0) | 0.433 |
eGFR, mL/min/1.73 m2 | 96.0 (80.8–111.7) | 84.6 (71.0–99.0) | <0.0001a |
With chronic kidney disease, %d | 10 (14.7) | 33 (27.2) | 0.070 |
Casual systolic BP, mm Hg | 121.7±16.9 | 133.1±19.1 | <0.0001a |
Casual diastolic BP, mm Hg | 71.4±10.8 | 76.8±10.2 | <0.001a |
With hypertension, % | 31 (39.2) | 107 (76.4) | <0.0001a |
With cardiovascular disease, % | 9 (11.4) | 34 (24.3) | 0.022a |
With peripheral vascular disease, %e | 10 (13.2) | 29 (21.2) | 0.195 |
Alcohol consumption, %f | 15 (19.2) | 30 (21.7) | 0.729 |
Current smokers, %g | 21 (26.9) | 26 (18.6) | 0.171 |
Regular physical activity, %h | 26 (33.8) | 52 (37.9) | 0.558 |
With CAN (early and confirmed) | 29 (36.7) | 31 (22.1) | 0.027a |
With confirmed CAN | 16 (20.3) | 15 (10.7) | 0.068 |
With DPN | 38 (48.1) | 81 (57.9) | 0.204 |
Values are presented as median (interquartile range), number (%), or mean±standard deviation. Unpaired Student’s t-test (parametric) and Mann-Whitney U test (non-parametric) as tests of significance for means and the chi-square test for categorical variables were used.
T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; BMI, body mass index; HbA1c, glycosylated hemoglobin; LDL, low-density lipoprotein; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; BP, blood pressure; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy.
a Significant P value, Missing data for
b T2DM patients (n=8),
c T1DM (n=8) and T2DM (n=18) patients,
d T1DM (n=11) and T2DM (n=18) patients,
e T1DM (n=3) and T2DM (n=3) patients,
f T1DM (n=1) and T2DM (n=2) patients,
g T1DM (n=1) patient,
h T1DM (n=2) and T2DM (n=3) patients.
COMPASS 31 | With CAN | Without CAN | With confirmed CAN | Without confirmed CAN | With DPN | Without DPN | P valuea | P valueb | P valuec |
---|---|---|---|---|---|---|---|---|---|
T1DM | |||||||||
Orthostatic intolerance WS | 12.0 (0–24.0) | 0.0 (0–16.0) | 16.0 (4.0–28.0) | 0.0 (0–16.0) | 16.0 (0–24.0) | 0.0 (0–6.0) | 0.123 | 0.020d | <0.001d |
Vasomotor WS | 0.0 (0–2.5) | 0.0 (0–1.8) | 0.0 (0–2.5) | 0.0 (0–0) | 0.0 (0–2.5) | 0.0 (0–0) | 0.864 | 0.257 | 0.166 |
Secretomotor WS | 2.1 (0–8.6) | 2.1 (0–4.3) | 3.2 (1.1–8.6) | 2.1 (0–6.4) | 4.3 (0–8.6) | 0 (0–4.3) | 0.246 | 0.246 | 0.009d |
Gastrointestinal symptoms WS | 8.0 (4.0–13.4) | 4.5 (1.8–8.0) | 10.3 (5.8–14.3) | 4.5 (1.8–8.4) | 8.5 (2.7–13.3) | 4.5 (1.8–6.5) | 0.010d | 0.009d | <0.001d |
Bladder WS | 1.1 (0–3.6) | 0 (0–1.1) | 2.2 (0–4.4) | 0.0 (0–1.1) | 1.1 (0–3.3) | 0.0 (0–1.1) | 0.029d | 0.029d | <0.001d |
Pupillomotor WS | 2.0 (1.0–3.7) | 1.6 (1.0–2.7) | 2.5 (1.0–4.0) | 1.6 (1.0–2.7) | 2.6 (1.3–3.7) | 1.3 (0.7–2.3) | 0.180 | 0.180 | 0.001d |
Total WS | 25.3 (10.0–50.7) | 12.1 (5.2–34.0) | 35.1 (22.7–56.7) | 13.0 (5.2–34.2) | 34.1 (17.0–50.6) | 8.8 (4.5–42.0) | 0.006d | 0.006d | <0.0001d |
T2DM | |||||||||
Orthostatic intolerance WS | 8.0 (0–24.0) | 0.0 (0–16.0) | 0.0 (0–24.0) | 0.0 (0–16.0) | 0.0 (0–20.0) | 0.0 (0–12.0) | 0.084 | 0.819 | 0.159 |
Vasomotor WS | 0.0 (0–2.3) | 0.0 (0–1.7) | 0.0 (0–3.1) | 0.0 (0–0.4) | 0.0 (0–2.5) | 0.0 (0–0) | 0.661 | 0.307 | 0.005d |
Secretomotor WS | 4.3 (2.1–6.4) | 4.3 (2.1–6.4) | 4.3 (2.1–6.4) | 4.3 (0–6.4) | 4.3 (2.1–6.4) | 2.1 (0–4.3) | 0.120 | 0.358 | <0.0001d |
Gastrointestinal symptoms WS | 7.1 (5.3–11.6) | 5.4 (2.4–8.0) | 8.0 (4.0–11.6) | 5.4 (2.7–8.0) | 6.2 (4.5–10.0) | 4.5 (0.9–7.1) | 0.013d | 0.089 | <0.0001d |
Bladder WS | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 0.0 (0–1.1) | 0.370 | 0.455 | 0.023d |
Pupillomotor WS | 2.0 (1.0–2.7) | 1.3 (0.6–2.3) | 2.0 (1.3–2.7) | 1.6 (0.7–2.3) | 2.0 (1.0–3.0) | 1.3 (0.1–2.0) | 0.132 | 0.223 | 0.001d |
Total WS | 27.7 (11.0–41.6) | 15.4 (8.2–32.3) | 24.1 (11.0–39.7) | 16.7 (8.8–34.0) | 22.8 (10.9–40.0) | 12.0 (4.3–25.9) | 0.018d | 0.177 | <0.001d |
Values are presented as median (interquartile range). Mann-Whitney U test as test of significance was used.
COMPASS, Composite Autonomic Symptom Score; WS, weighted score; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy.
a With vs. without CAN,
b With vs. without confirmed CAN,
c With vs. without DPN,
d Significant P value.
CAN |
DPN |
||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
CARTs score | Expiration: inspiration ratio | 30:15 ratio | Valsalva ratio | Orthostatic hypotension | MNSI-Q | MDNS | DN4 | VPT | WTT | CTT | |
T1DM | |||||||||||
Rho | 0.356a,b | –0.282b | –0.283b | –0.228 | 0.246b | 0.631b | 0.286b | 0.707b | 0.353b,c | 0.329b | –0.351b |
P value | 0.0016b | 0.013b | 0.012b | 0.075 | 0.030b | <0.0001b | 0.011b | <0.0001b | 0.002b | 0.006b | 0.003b |
T2DM | |||||||||||
Rho | 0.084 | –0.107 | –0.087 | –0.225b | 0.089 | 0.570b | 0.335b | 0.595b | 0.132 | 0.169 | –0.183 |
P value | 0.322 | 0.210 | 0.303 | 0.017b | 0.298 | <0.0001b | <0.0001b | <0.0001b | 0.151 | 0.073 | 0.052 |
Spearman’s rank correlations coefficients (rho) are presented with P value.
COMPASS, Composite Autonomic Symptom Score; TWS, total weighted score; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; CART, cardiovascular autonomic reflex test; MNSI-Q, Michigan Neuropathy Screening Instrument Questionnaire; MDNS, Michigan Diabetic Neuropathy Score; DN4, Douleur Neuropathique en 4 questions; VPT, vibration perception threshold; WTT, warm thermal perception threshold; CTT, cold thermal perception threshold.
a P=0.016 between T1DM and T2DM rho,
b Significant P value,
c P=0.038 between T1DM and T2DM rho.
T1DM |
T2DM |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|
AUC | Sensitivity, % | Specificity, % | PPV, % | NPV, % | AUC | Sensitivity, % | Specificity, % | PPV, % | NPV, % | |
CAN | 0.651±0.066 | 65.5 (48.2–82.8) | 62.0 (48.5–75.4) | 50.0 (34.1–65.9) | 75.6a (62.5–88.8) | 0.639±0.056 | 67.7 (51.3–84.2) | 52.3 (42.9–61.7) | 28.8 (18.4–39.1) | 85.1a (76.5–93.6) |
Confirmed CAN | 0.725a ±0.073 | 81.2a (62.1–100) | 60.3 (48.2–72.4) | 34.2 (19.1–49.3) | 92.7a (84.7–100) | 0.607±0.077 | 66.7 (42.8–90.5) | 49.6 (40.8–58.4) | 13.7 (5.8–21.6) | 92.5a (86.2–98.8) |
DPN | 0.753a ±0.059 | 76.3a (62.8–89.8) | 78.0a (65.4–90.7) | 76.3a (62.8–89.8) | 78.0a (65.4–90.7) | 0.682±0.045 | 61.7 (51.1–72.3) | 61.0 (48.6–73.5) | 68.5 (57.8–79.1) | 53.7 (41.8–65.7) |
Non-parametric receiver operating characteristic (ROC) analysis and chi-square test were used to obtain AUCs (±standard error) and sensitivity, specificity, PPV, and NPV (95% confidence intervals) of COMPASS 31 TWS for the presence of CAN, confirmed CAN, and DPN.
COMPASS, Composite Autonomic Symptom Score; TWS, total weighted score; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; AUC, area under the receiver operating characteristic curve; PPV, positive predictive value; NPV, negative predictive value.
a ≥0.7% and ≥70%.
Variable | T1DM (n=79) | T2DM (n=140) | P value |
---|---|---|---|
Sex, males:females | 30:49 | 93:47 | <0.0001 |
Age, yr | 42.0 (33.0–49.8) | 64.0 (57.0–69.0) | <0.0001 |
Disease duration, yr | 24.0 (16.0–43.0) | 10.0 (5.0–18.5) | <0.0001 |
BMI, kg/m2 | 24.3 (22.3–26.7) | 28.9 (25.7–32.4) | <0.0001 |
HbA1c, % | 7.5 (6.8–8.3) | 6.8 (6.2–7.6) | 0.0001 |
HbA1c, mmol/mol | 58.0 (50.7–67.0) | 51.0 (45.0–59.7) | 0.0001 |
Total cholesterol, mg/dL | 176.0 (157.0–201.5) | 169.0 (138.5–132.0) | 0.095 |
LDL cholesterol, mg/dL | 96.1 (77.0–117.0) | 89.4 (67.0–114.0) | 0.365 |
HDL cholesterol, mg/dL | 60.0 (48.5–70.0) | 44.5 (37.0–55.0) | <0.0001 |
Triglycerides, mg/dL | 82.0 (59.5–98.5) | 117.0 (92.00–162.5) | <0.0001 |
With retinopathy, % |
33 (46.7) | 32 (24.2) | 0.009 |
With microalbuminuria, % |
10 (14.1) | 23 (19.0) | 0.433 |
eGFR, mL/min/1.73 m2 | 96.0 (80.8–111.7) | 84.6 (71.0–99.0) | <0.0001 |
With chronic kidney disease, % |
10 (14.7) | 33 (27.2) | 0.070 |
Casual systolic BP, mm Hg | 121.7±16.9 | 133.1±19.1 | <0.0001 |
Casual diastolic BP, mm Hg | 71.4±10.8 | 76.8±10.2 | <0.001 |
With hypertension, % | 31 (39.2) | 107 (76.4) | <0.0001 |
With cardiovascular disease, % | 9 (11.4) | 34 (24.3) | 0.022 |
With peripheral vascular disease, % |
10 (13.2) | 29 (21.2) | 0.195 |
Alcohol consumption, % |
15 (19.2) | 30 (21.7) | 0.729 |
Current smokers, % |
21 (26.9) | 26 (18.6) | 0.171 |
Regular physical activity, % |
26 (33.8) | 52 (37.9) | 0.558 |
With CAN (early and confirmed) | 29 (36.7) | 31 (22.1) | 0.027 |
With confirmed CAN | 16 (20.3) | 15 (10.7) | 0.068 |
With DPN | 38 (48.1) | 81 (57.9) | 0.204 |
COMPASS 31 | With CAN | Without CAN | With confirmed CAN | Without confirmed CAN | With DPN | Without DPN | P value |
P value |
P value |
---|---|---|---|---|---|---|---|---|---|
T1DM | |||||||||
Orthostatic intolerance WS | 12.0 (0–24.0) | 0.0 (0–16.0) | 16.0 (4.0–28.0) | 0.0 (0–16.0) | 16.0 (0–24.0) | 0.0 (0–6.0) | 0.123 | 0.020d | <0.001 |
Vasomotor WS | 0.0 (0–2.5) | 0.0 (0–1.8) | 0.0 (0–2.5) | 0.0 (0–0) | 0.0 (0–2.5) | 0.0 (0–0) | 0.864 | 0.257 | 0.166 |
Secretomotor WS | 2.1 (0–8.6) | 2.1 (0–4.3) | 3.2 (1.1–8.6) | 2.1 (0–6.4) | 4.3 (0–8.6) | 0 (0–4.3) | 0.246 | 0.246 | 0.009 |
Gastrointestinal symptoms WS | 8.0 (4.0–13.4) | 4.5 (1.8–8.0) | 10.3 (5.8–14.3) | 4.5 (1.8–8.4) | 8.5 (2.7–13.3) | 4.5 (1.8–6.5) | 0.010d | 0.009d | <0.001 |
Bladder WS | 1.1 (0–3.6) | 0 (0–1.1) | 2.2 (0–4.4) | 0.0 (0–1.1) | 1.1 (0–3.3) | 0.0 (0–1.1) | 0.029d | 0.029d | <0.001 |
Pupillomotor WS | 2.0 (1.0–3.7) | 1.6 (1.0–2.7) | 2.5 (1.0–4.0) | 1.6 (1.0–2.7) | 2.6 (1.3–3.7) | 1.3 (0.7–2.3) | 0.180 | 0.180 | 0.001 |
Total WS | 25.3 (10.0–50.7) | 12.1 (5.2–34.0) | 35.1 (22.7–56.7) | 13.0 (5.2–34.2) | 34.1 (17.0–50.6) | 8.8 (4.5–42.0) | 0.006d | 0.006d | <0.0001 |
T2DM | |||||||||
Orthostatic intolerance WS | 8.0 (0–24.0) | 0.0 (0–16.0) | 0.0 (0–24.0) | 0.0 (0–16.0) | 0.0 (0–20.0) | 0.0 (0–12.0) | 0.084 | 0.819 | 0.159 |
Vasomotor WS | 0.0 (0–2.3) | 0.0 (0–1.7) | 0.0 (0–3.1) | 0.0 (0–0.4) | 0.0 (0–2.5) | 0.0 (0–0) | 0.661 | 0.307 | 0.005 |
Secretomotor WS | 4.3 (2.1–6.4) | 4.3 (2.1–6.4) | 4.3 (2.1–6.4) | 4.3 (0–6.4) | 4.3 (2.1–6.4) | 2.1 (0–4.3) | 0.120 | 0.358 | <0.0001 |
Gastrointestinal symptoms WS | 7.1 (5.3–11.6) | 5.4 (2.4–8.0) | 8.0 (4.0–11.6) | 5.4 (2.7–8.0) | 6.2 (4.5–10.0) | 4.5 (0.9–7.1) | 0.013d | 0.089 | <0.0001 |
Bladder WS | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 1.1 (0–2.2) | 0.0 (0–1.1) | 0.370 | 0.455 | 0.023 |
Pupillomotor WS | 2.0 (1.0–2.7) | 1.3 (0.6–2.3) | 2.0 (1.3–2.7) | 1.6 (0.7–2.3) | 2.0 (1.0–3.0) | 1.3 (0.1–2.0) | 0.132 | 0.223 | 0.001 |
Total WS | 27.7 (11.0–41.6) | 15.4 (8.2–32.3) | 24.1 (11.0–39.7) | 16.7 (8.8–34.0) | 22.8 (10.9–40.0) | 12.0 (4.3–25.9) | 0.018d | 0.177 | <0.001 |
CAN |
DPN |
||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
CARTs score | Expiration: inspiration ratio | 30:15 ratio | Valsalva ratio | Orthostatic hypotension | MNSI-Q | MDNS | DN4 | VPT | WTT | CTT | |
T1DM | |||||||||||
Rho | 0.356 |
–0.282 |
–0.283 |
–0.228 | 0.246 |
0.631 |
0.286 |
0.707 |
0.353 |
0.329 |
–0.351 |
P value | 0.0016 |
0.013 |
0.012 |
0.075 | 0.030 |
<0.0001 |
0.011 |
<0.0001 |
0.002 |
0.006 |
0.003 |
T2DM | |||||||||||
Rho | 0.084 | –0.107 | –0.087 | –0.225 |
0.089 | 0.570 |
0.335 |
0.595 |
0.132 | 0.169 | –0.183 |
P value | 0.322 | 0.210 | 0.303 | 0.017 |
0.298 | <0.0001 |
<0.0001 |
<0.0001 |
0.151 | 0.073 | 0.052 |
T1DM |
T2DM |
|||||||||
---|---|---|---|---|---|---|---|---|---|---|
AUC | Sensitivity, % | Specificity, % | PPV, % | NPV, % | AUC | Sensitivity, % | Specificity, % | PPV, % | NPV, % | |
CAN | 0.651±0.066 | 65.5 (48.2–82.8) | 62.0 (48.5–75.4) | 50.0 (34.1–65.9) | 75.6 |
0.639±0.056 | 67.7 (51.3–84.2) | 52.3 (42.9–61.7) | 28.8 (18.4–39.1) | 85.1 |
Confirmed CAN | 0.725 |
81.2 |
60.3 (48.2–72.4) | 34.2 (19.1–49.3) | 92.7 |
0.607±0.077 | 66.7 (42.8–90.5) | 49.6 (40.8–58.4) | 13.7 (5.8–21.6) | 92.5 |
DPN | 0.753 |
76.3 |
78.0 |
76.3 |
78.0 |
0.682±0.045 | 61.7 (51.1–72.3) | 61.0 (48.6–73.5) | 68.5 (57.8–79.1) | 53.7 (41.8–65.7) |
Values are presented as median (interquartile range), number (%), or mean±standard deviation. Unpaired Student’s T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; BMI, body mass index; HbA1c, glycosylated hemoglobin; LDL, low-density lipoprotein; HDL, high-density lipoprotein; eGFR, estimated glomerular filtration rate; BP, blood pressure; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy. Significant T2DM patients ( T1DM ( T1DM ( T1DM ( T1DM ( T1DM ( T1DM (
Values are presented as median (interquartile range). Mann-Whitney COMPASS, Composite Autonomic Symptom Score; WS, weighted score; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy. With vs. without CAN, With vs. without confirmed CAN, With vs. without DPN, Significant
Spearman’s rank correlations coefficients (rho) are presented with COMPASS, Composite Autonomic Symptom Score; TWS, total weighted score; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; CART, cardiovascular autonomic reflex test; MNSI-Q, Michigan Neuropathy Screening Instrument Questionnaire; MDNS, Michigan Diabetic Neuropathy Score; DN4, Douleur Neuropathique en 4 questions; VPT, vibration perception threshold; WTT, warm thermal perception threshold; CTT, cold thermal perception threshold. Significant
Non-parametric receiver operating characteristic (ROC) analysis and chi-square test were used to obtain AUCs (±standard error) and sensitivity, specificity, PPV, and NPV (95% confidence intervals) of COMPASS 31 TWS for the presence of CAN, confirmed CAN, and DPN. COMPASS, Composite Autonomic Symptom Score; TWS, total weighted score; CAN, cardiovascular autonomic neuropathy; DPN, diabetic polyneuropathy; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; AUC, area under the receiver operating characteristic curve; PPV, positive predictive value; NPV, negative predictive value. ≥0.7% and ≥70%.