1Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
2Research Institute for Skin Image, Korea University College of Medicine, Seoul, Korea
3Core Research & Development Center, Korea University Ansan Hospital, Ansan, Korea
4Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
5Department of Statistics and Actuarial Science, Soongsil University, Seoul, Korea
6BK21 FOUR R&E Center for Learning Health Systems, Korea University, Seoul, Korea
Copyright © 2022 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
Ji A Seo has been associate editors of the Diabetes & Metabolism Journal since 2021. Hye Jin Yoo was been associate editors of the Diabetes & Metabolism Journal from 2020 to 2021. They were not involved in the review process of this article. Otherwise, there was no conflict of interest.
AUTHOR CONTRIBUTIONS
Conception or design: D.Y.L., J.K., S.Y.P., K.H., N.H.K.
Acquisition, analysis, or interpretation of data: D.Y.L., J.K., S.P., J.A.S., N.H.K., H.J.Y., K.H., N.H.K.
Drafting the work or revising: D.Y.L., J.K., S.Y.P., J.H.Y.
Final approval of the manuscript: S.G.K., K.M.C., S.H.B., K.H., N.H.K.
FUNDING
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2019M3E5D3073102 and NRF-2019R1H1A2039682), a Korea University Grant (K1810951), the Basic Science Research Program through NRF funded by the Ministry of Education (NRF-2020R1I1A1A01071665), and a Korea University Ansan Hospital grant (O2000291). However, the funders did not participate in study design or reporting
Characteristic | VIM Q1 (n=192,387) | VIM Q2 (n=192,390) | VIM Q3 (n=192,389) | VIM Q4 (n=192,388) | P value | |
---|---|---|---|---|---|---|
Age, yr | 61.1±9.8 | 60.1±9.9 | 59.6±10.1 | 59.2±10.4 | <0.001 | |
Male sex | 108,883 (56.6) | 115,446 (60) | 119,618 (62.2) | 124,812 (64.9) | <0.001 | |
Body mass index, kg/m2 | 24.8±3.0 | 24.9±3.1 | 24.9±3.1 | 24.8±3.2 | <0.001 | |
Systolic BP, mm Hg | 128.3±15.2 | 128.7±15.2 | 128.8±15.3 | 128.5±15.3 | <0.001 | |
FG, mg/dL | 125.1±34.0 | 130.2±35.5 | 135.8±39.0 | 146±53.4 | <0.001 | |
TC, mg/dL | 193.6±39.1 | 194.9±39.9 | 195.6±40.7 | 194.4±41.5 | <0.001 | |
Triglyceride, mg/dL | 132.9 (132.6–133.2) | 138.51 (138.2–138.9) | 143.1 (142.7–143.5) | 146.4 (146.1–146.8) | <0.001 | |
HDL-C, mg/dL | 52.6±22.7 | 52.3±21.6 | 52±21.8 | 51.5±21.2 | <0.001 | |
FG_VIM, % | 8.2±3.0 | 16.6±2.3 | 25.5±3.0 | 43.6±11.1 | <0.001 | |
FG_SD, mg/dL | 8.1±5.3 | 16.8±8.5 | 26.7±13.1 | 49±25.2 | <0.001 | |
FG_CV, % | 6.2±2.6 | 12.8±2.8 | 19.9±4.3 | 35±11.2 | <0.001 | |
FG_ARV, mg/dL | 10±7.2 | 20.3±11.9 | 31.7±18.3 | 56.5±34.3 | <0.001 | |
Current smoker | 31,515 (16.4) | 36,711 (19.1) | 42,474 (22.1) | 49,993 (26.0) | <0.001 | |
Heavy drinking | 12,345 (6.4) | 13,803 (7.2) | 14,628 (7.6) | 14,245 (7.4) | <0.001 | |
Regular exercise | 49,632 (25.8) | 48,136 (25) | 46,054 (23.9) | 43,129 (22.4) | <0.001 | |
Comorbidities | ||||||
Hypertension | 118,250 (61.5) | 116,410 (60.5) | 114,378 (59.5) | 111,527 (58.0) | <0.001 | |
Dyslipidemia | 101,550 (52.8) | 97,619 (50.7) | 94,080 (48.9) | 89,773 (46.7) | <0.001 | |
CKDb | 22,748 (11.8) | 22,675 (11.8) | 23,351 (12.1) | 25,858 (13.4) | <0.001 | |
IHD | 28,227 (14.7) | 26,090 (13.6) | 24,489 (12.7) | 23,436 (12.2) | <0.001 | |
Stroke | 10,356 (5.4) | 9,681 (5.0) | 9,347 (4.9) | 9,239 (4.8) | <0.001 | |
Depressive disorder | 13,266 (6.9) | 12,147 (6.3) | 11,513 (6.0) | 10,802 (5.6) | <0.001 | |
Income (lower 20%) | 34,619 (18.0) | 36,476 (19.0) | 38,776 (20.2) | 43,129 (22.4) | <0.001 | |
Oral GLM | ||||||
Metformin | 71,746 (37.3) | 74,741 (38.9) | 78,666 (40.9) | 84,539 (43.9) | <0.001 | |
Sulfonylurea | 69,720 (36.2) | 76,044 (39.5) | 83,883 (43.6) | 91,683 (47.7) | <0.001 | |
Meglitinide | 3,926 (2.0) | 4,258 (2.2) | 4,767 (2.5) | 5,895 (3.1) | <0.001 | |
Thiazolidinedione | 11,549 (6.0) | 12,336 (6.4) | 13,279 (6.9) | 14,556 (7.6) | <0.001 | |
DPP-4 inhibitor | 7,517 (3.9) | 7,775 (4.0) | 8,205 (4.3) | 8,425 (4.4) | <0.001 | |
α-Glucosidase inhibitor | 18,679 (9.7) | 20,872 (10.9) | 23,989 (12.5) | 28,594 (14.9) | <0.001 | |
Number of oral GLM | <0.001 | |||||
0 | 96,069 (49.9) | 92,826 (48.3) | 88,128 (45.8) | 82,178 (42.7) | ||
1 | 34,001 (17.7) | 31,634 (16.4) | 29,259 (15.2) | 26,576 (13.8) | ||
2 | 41,699 (21.7) | 44,149 (23.0) | 47,255 (24. 6) | 50,910 (26.5) | ||
3 | 17,080 (8.9) | 19,466 (10.12) | 22,559 (11.7) | 26,347 (13.7) | ||
≥4 | 3,538 (1.8) | 4,315 (2.24) | 5,188 (2.7) | 6,377 (3.3) | ||
Insulin | 8,029 (4.2) | 9,406 (4.9) | 11,803 (6.1) | 19,440 (10.1) | <0.001 | |
Duration of diabetes (≥5 years) | 56,320 (29.3) | 58,809 (30.6) | 62,606 (32.5) | 67,659 (35.2) | <0.001 | |
E10 | 2,921 (1.52) | 3,325 (1.73) | 4,079 (2.1) | 6,139 (3.2) | <0.001 | |
Number of exams | <0.001 | |||||
3 | 165,083 (85.8) | 150,451 (78.2) | 144,273 (75.0) | 140,434 (73.0) | ||
4 | 13,841 (7.2) | 19,425 (10.1) | 22,308 (11.6) | 24,602 (12.8) | ||
5 | 13,463 (7.0) | 22,514 (11.7) | 25,808 (13.4) | 27,352 (14.2) | ||
Time interval between adjacent exams, yr | 1.9 (1.3–2.1) | 1.8 (1.11–2.1) | 1.76 (1.1–2.1) | 1.7 (1–2.1) | <0.001 |
Values are presented as mean±standard deviation, number (%), or median (interquartile range). One-way analysis of variance and the chi-square test were used to compare the characteristics of the study participants at baseline. Post hoc multiple comparison analysis was performed using Bonferroni correction, and triglyceride levels were log-transformed for analysis.
VIM, variability independent of mean; BP, blood pressure; FG, fasting glucose; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; SD, standard deviation; CV, coefficient of variation; ARV, average real variability; CKD, chronic kidney disease; IHD, ischemic heart disease; GLM, glucose-lowering medication; DPP-4, dipeptidyl peptidase 4.
a Q1: 0–12.7; Q2: 12.8–20.5; Q3: 20.6–31.2; Q4: ≥31.3,
b Presence of chronic kidney disease represents estimated glomerular filtration rate <60 mL/min/1.73 m2.
Model 1 was adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, and hemoglobin levels. Model 2 is the same as model 1, with additional adjustment for the duration of diabetes for at least 5 years, the prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder.
a Q1, 0–12.7; Q2, 12.8–20.5; Q3, 20.6–31.2; Q4, ≥31.3.
Adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, hemoglobin levels, duration of diabetes for at least 5 years, prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder.
IR, incidence rate; HR, hazard ratio; CI, confidence interval; CKD, chronic kidney disease.
Adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, hemoglobin levels, duration of diabetes for at least 5 years, prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder.
IR, incidence rate; HR, hazard ratio; CI, confidence interval; DPP-4, dipeptidyl peptidase 4.
Characteristic | VIM Q1 (n=192,387) | VIM Q2 (n=192,390) | VIM Q3 (n=192,389) | VIM Q4 (n=192,388) | P value | |
---|---|---|---|---|---|---|
Age, yr | 61.1±9.8 | 60.1±9.9 | 59.6±10.1 | 59.2±10.4 | <0.001 | |
Male sex | 108,883 (56.6) | 115,446 (60) | 119,618 (62.2) | 124,812 (64.9) | <0.001 | |
Body mass index, kg/m2 | 24.8±3.0 | 24.9±3.1 | 24.9±3.1 | 24.8±3.2 | <0.001 | |
Systolic BP, mm Hg | 128.3±15.2 | 128.7±15.2 | 128.8±15.3 | 128.5±15.3 | <0.001 | |
FG, mg/dL | 125.1±34.0 | 130.2±35.5 | 135.8±39.0 | 146±53.4 | <0.001 | |
TC, mg/dL | 193.6±39.1 | 194.9±39.9 | 195.6±40.7 | 194.4±41.5 | <0.001 | |
Triglyceride, mg/dL | 132.9 (132.6–133.2) | 138.51 (138.2–138.9) | 143.1 (142.7–143.5) | 146.4 (146.1–146.8) | <0.001 | |
HDL-C, mg/dL | 52.6±22.7 | 52.3±21.6 | 52±21.8 | 51.5±21.2 | <0.001 | |
FG_VIM, % | 8.2±3.0 | 16.6±2.3 | 25.5±3.0 | 43.6±11.1 | <0.001 | |
FG_SD, mg/dL | 8.1±5.3 | 16.8±8.5 | 26.7±13.1 | 49±25.2 | <0.001 | |
FG_CV, % | 6.2±2.6 | 12.8±2.8 | 19.9±4.3 | 35±11.2 | <0.001 | |
FG_ARV, mg/dL | 10±7.2 | 20.3±11.9 | 31.7±18.3 | 56.5±34.3 | <0.001 | |
Current smoker | 31,515 (16.4) | 36,711 (19.1) | 42,474 (22.1) | 49,993 (26.0) | <0.001 | |
Heavy drinking | 12,345 (6.4) | 13,803 (7.2) | 14,628 (7.6) | 14,245 (7.4) | <0.001 | |
Regular exercise | 49,632 (25.8) | 48,136 (25) | 46,054 (23.9) | 43,129 (22.4) | <0.001 | |
Comorbidities | ||||||
Hypertension | 118,250 (61.5) | 116,410 (60.5) | 114,378 (59.5) | 111,527 (58.0) | <0.001 | |
Dyslipidemia | 101,550 (52.8) | 97,619 (50.7) | 94,080 (48.9) | 89,773 (46.7) | <0.001 | |
CKD |
22,748 (11.8) | 22,675 (11.8) | 23,351 (12.1) | 25,858 (13.4) | <0.001 | |
IHD | 28,227 (14.7) | 26,090 (13.6) | 24,489 (12.7) | 23,436 (12.2) | <0.001 | |
Stroke | 10,356 (5.4) | 9,681 (5.0) | 9,347 (4.9) | 9,239 (4.8) | <0.001 | |
Depressive disorder | 13,266 (6.9) | 12,147 (6.3) | 11,513 (6.0) | 10,802 (5.6) | <0.001 | |
Income (lower 20%) | 34,619 (18.0) | 36,476 (19.0) | 38,776 (20.2) | 43,129 (22.4) | <0.001 | |
Oral GLM | ||||||
Metformin | 71,746 (37.3) | 74,741 (38.9) | 78,666 (40.9) | 84,539 (43.9) | <0.001 | |
Sulfonylurea | 69,720 (36.2) | 76,044 (39.5) | 83,883 (43.6) | 91,683 (47.7) | <0.001 | |
Meglitinide | 3,926 (2.0) | 4,258 (2.2) | 4,767 (2.5) | 5,895 (3.1) | <0.001 | |
Thiazolidinedione | 11,549 (6.0) | 12,336 (6.4) | 13,279 (6.9) | 14,556 (7.6) | <0.001 | |
DPP-4 inhibitor | 7,517 (3.9) | 7,775 (4.0) | 8,205 (4.3) | 8,425 (4.4) | <0.001 | |
α-Glucosidase inhibitor | 18,679 (9.7) | 20,872 (10.9) | 23,989 (12.5) | 28,594 (14.9) | <0.001 | |
Number of oral GLM | <0.001 | |||||
0 | 96,069 (49.9) | 92,826 (48.3) | 88,128 (45.8) | 82,178 (42.7) | ||
1 | 34,001 (17.7) | 31,634 (16.4) | 29,259 (15.2) | 26,576 (13.8) | ||
2 | 41,699 (21.7) | 44,149 (23.0) | 47,255 (24. 6) | 50,910 (26.5) | ||
3 | 17,080 (8.9) | 19,466 (10.12) | 22,559 (11.7) | 26,347 (13.7) | ||
≥4 | 3,538 (1.8) | 4,315 (2.24) | 5,188 (2.7) | 6,377 (3.3) | ||
Insulin | 8,029 (4.2) | 9,406 (4.9) | 11,803 (6.1) | 19,440 (10.1) | <0.001 | |
Duration of diabetes (≥5 years) | 56,320 (29.3) | 58,809 (30.6) | 62,606 (32.5) | 67,659 (35.2) | <0.001 | |
E10 | 2,921 (1.52) | 3,325 (1.73) | 4,079 (2.1) | 6,139 (3.2) | <0.001 | |
Number of exams | <0.001 | |||||
3 | 165,083 (85.8) | 150,451 (78.2) | 144,273 (75.0) | 140,434 (73.0) | ||
4 | 13,841 (7.2) | 19,425 (10.1) | 22,308 (11.6) | 24,602 (12.8) | ||
5 | 13,463 (7.0) | 22,514 (11.7) | 25,808 (13.4) | 27,352 (14.2) | ||
Time interval between adjacent exams, yr | 1.9 (1.3–2.1) | 1.8 (1.11–2.1) | 1.76 (1.1–2.1) | 1.7 (1–2.1) | <0.001 |
Variable | No. of events | Follow-up duration, person-yr | Incidence rate, /1,000 person-yr | Age- and sex-adjusted HR (95% CI) | Multivariate adjusted HR (95% CI) |
||
---|---|---|---|---|---|---|---|
Model 1 | Model 2 | ||||||
All-cause dementia | |||||||
Q1 (n=192,387) | 13,842 | 1,255,840.2 | 11.02 | 1 (Ref) | 1 (Ref) | 1 (Ref) | |
Q2 (n=192,390) | 12,800 | 1,265,367.2 | 10.12 | 1.02 (0.99–1.04) | 1.01 (0.99–1.04) | 1 (0.98–1.03) | |
Q3 (n=192,389) | 13,291 | 1,264,308.9 | 10.51 | 1.11 (1.08–1.14) | 1.10 (1.08–1.13) | 1.07 (1.04–1.09) | |
Q4 (n=192,388) | 14,904 | 1,253,722.4 | 11.89 | 1.29 (1.26–1.32) | 1.26 (1.23–1.29) | 1.18 (1.15–1.21) | |
P for trend | <0.001 | <0.001 | <0.001 | ||||
Alzheimer’s disease | |||||||
Q1 (n=192,387) | 10,336 | 1,255,840.2 | 8.23 | 1 (Ref) | 1 (Ref) | 1 (Ref) | |
Q2 (n=192,390) | 9,610 | 1,265,367.2 | 7.59 | 1.02 (0.99–1.05) | 1.02 (0.99–1.05) | 1.01 (0.98–1.04) | |
Q3 (n=192,389) | 9,964 | 1,264,308.9 | 7.88 | 1.12 (1.09–1.15) | 1.11 (1.08–1.14) | 1.08 (1.05–1.11) | |
Q4 (n=192,388) | 11,122 | 1,253,722.4 | 8.87 | 1.29 (1.26–1.33) | 1.26 (1.23–1.30) | 1.19 (1.15–1.22) | |
P for trend | <0.001 | <0.001 | <0.001 | ||||
Vascular dementia | |||||||
Q1 (n=192,387) | 1,730 | 1,255,840.2 | 1.38 | 1 (Ref) | 1 (Ref) | 1 (Ref) | |
Q2 (n=192,390) | 1,582 | 1,265,367.2 | 1.25 | 0.99 (0.93–1.07) | 0.99 (0.93–1.06) | 0.98 (0.91–1.04) | |
Q3 (n=192,389) | 1,681 | 1,264,308.9 | 1.33 | 1.11 (1.04–1.18) | 1.09 (1.02–1.17) | 1.06 (0.99–1.13) | |
Q4 (n=192,388) | 1,899 | 1,253,722.4 | 1.51 | 1.30 (1.22–1.38) | 1.26 (1.18–1.35) | 1.17 (1.09–1.25) | |
P for trend | <0.001 | <0.001 | <0.001 |
Variable | All-cause dementia |
Alzheimer’s disease |
Vascular dementia |
||||
---|---|---|---|---|---|---|---|
IR per 1,000 | HR (95% CI) | IR per 1,000 | HR (95% CI) | IR per 1,000 | HR (95% CI) | ||
Age, yr | |||||||
40–64 (n=522,120) | 2.81 | 1.17 (1.12–1.22) | 1.91 | 1.15 (1.09–1.22) | 0.51 | 1.21 (1.09–1.35) | |
≥65 (n=247,434) | 36.48 | 1.15 (1.13–1.18) | 27.74 | 1.16 (1.13–1.18) | 4.23 | 1.14 (1.07–1.21) | |
P for interaction | 0.620 | 0.861 | 0.314 | ||||
Sex | |||||||
Men (n=468,759) | 8.18 | 1.17 (1.13–1.20) | 5.91 | 1.18 (1.14–1.22) | 1.18 | 1.13 (1.05–1.22) | |
Women (n=300,795) | 18.86 | 1.14 (1.11–1.17) | 14.43 | 1.14 (1.1–1.17) | 2.15 | 1.18 (1.09–1.27) | |
P for interaction | 0.263 | 0.127 | 0.417 | ||||
BMI, kg/m2 | |||||||
<25 (n=420,549) | 13.85 | 1.17 (1.14–1.20) | 10.32 | 1.16 (1.13–1.20) | 1.70 | 1.15 (1.08–1.24) | |
≥25 (n=349,005) | 9.60 | 1.12 (1.09–1.16) | 7.19 | 1.13 (1.09–1.18) | 1.30 | 1.15 (1.06–1.25) | |
P for interaction | 0.034 | 0.263 | 0.984 | ||||
Current smoking | |||||||
No (n=608,861) | 13.94 | 1.16 (1.14–1.18) | 10.49 | 1.16 (1.13–1.19) | 1.70 | 1.16 (1.09–1.23) | |
Yes (n=160,693) | 6.15 | 1.11 (1.05–1.17) | 4.35 | 1.11 (1.04–1.18) | 0.99 | 1.12 (0.98–1.28) | |
P for interaction | 0.114 | 0.189 | 0.624 | ||||
Income lower 20% | |||||||
No (n=653,030) | 12.05 | 1.16 (1.13–1.18) | 9.01 | 1.16 (1.13–1.19) | 1.52 | 1.17 (1.10–1.24) | |
Yes (n=116,524) | 11.33 | 1.13 (1.08–1.18) | 8.40 | 1.13 (1.08–1.18) | 1.48 | 1.11 (0.99–1.24) | |
P for interaction | 0.264 | 0.320 | 0.417 | ||||
Hypertension | |||||||
No (n=308,989) | 7.56 | 1.14 (1.1–1.18) | 5.68 | 1.13 (1.09–1.18) | 0.94 | 1.21 (1.09–1.34) | |
Yes (n=460,565) | 15.16 | 1.16 (1.13–1.18) | 11.29 | 1.16 (1.13–1.19) | 1.95 | 1.14 (1.07–1.21) | |
P for interaction | 0.479 | 0.312 | 0.325 | ||||
Dyslipidemia | |||||||
No (n=386,532) | 11.06 | 1.13 (1.1–1.16) | 8.25 | 1.13 (1.09–1.17) | 1.46 | 1.18 (1.10–1.28) | |
Yes (n=383,022) | 12.84 | 1.17 (1.14–1.21) | 9.58 | 1.18 (1.14–1.21) | 1.58 | 1.12 (1.04–1.21) | |
P for interaction | 0.047 | 0.070 | 0.323 | ||||
Depressive disorder | |||||||
No (n=733,973) | 10.94 | 1.16 (1.13–1.18) | 8.16 | 1.16 (1.13–1.19) | 1.41 | 1.15 (1.09–1.22) | |
Yes (n=35,581) | 29.31 | 1.12 (1.07–1.183) | 21.97 | 1.12 (1.05–1.18) | 3.44 | 1.17 (1.00–1.37) | |
P for interaction | 0.300 | 0.252 | 0.829 | ||||
CKD | |||||||
No (n=674,922) | 10.03 | 1.15 (1.13–1.18) | 7.47 | 1.15 (1.12–1.18) | 1.29 | 1.16 (1.09–1.23) | |
Yes (n=94,632) | 24.91 | 1.15 (1.11–1.19) | 18.69 | 1.16 (1.11–1.21) | 3.09 | 1.15 (1.03–1.28) | |
P for interaction | 0.801 | 0.802 | 0.935 |
Variable | All-cause dementia |
Alzheimer’s disease |
Vascular dementia |
||||
---|---|---|---|---|---|---|---|
IR per 1,000 | HR (95% CI) | IR per 1,000 | HR (95% CI) | IR per 1,000 | HR (95% CI) | ||
Duration of diabetes, yr | |||||||
<5 (n=524,160) | 8.57 | 1.10 (1.07–1.12) | 6.45 | 1.11 (1.07–1.14) | 1.07 | 1.07 (0.99–1.15) | |
≥5 (n=245,394) | 18.37 | 1.22 (1.18–1.25) | 13.60 | 1.21 (1.17–1.24) | 2.38 | 1.25 (1.16–1.35) | |
P for interaction | <0.001 | <0.001 | 0.004 | ||||
Baseline fasting glucose, mg/dL | |||||||
<126 (n=345,225) | 15.72 | 1.11 (1.08–1.14) | 11.86 | 1.12 (1.09–1.16) | 1.93 | 1.10 (1.02–1.19) | |
≥126 (n=424,329) | 9.74 | 1.20 (1.17–1.23) | 7.20 | 1.19 (1.15–1.23) | 1.28 | 1.21 (1.12–1.30) | |
P for interaction | <0.001 | 0.016 | 0.11 | ||||
Subtype of diabetes | |||||||
E11–14 (n=753,090) | 11.59 | 1.15 (1.13–1.17) | 8.66 | 1.15 (1.12–1.18) | 1.47 | 1.14 (1.08–1.21) | |
E10 (n=16,464) | 21.72 | 1.22 (1.11–1.33) | 15.68 | 1.19 (1.07–1.32) | 3.07 | 1.37 (1.07–1.76) | |
P for interaction | 0.225 | 0.564 | 0.153 | ||||
Metformin | |||||||
No (n=459,862) | 9.83 | 1.12 (1.09–1.15) | 7.36 | 1.12 (1.09–1.16) | 1.21 | 1.07 (0.99–1.16) | |
Yes (n=309,692) | 14.58 | 1.19 (1.16–1.22) | 10.85 | 1.18 (1.15–1.22) | 1.91 | 1.24 (1.15–1.34) | |
P for interaction | 0.001 | 0.014 | 0.007 | ||||
Sulfonylurea | |||||||
No (n=448,224) | 8.86 | 1.12 (1.08–1.15) | 6.63 | 1.12 (1.09–1.16) | 1.09 | 1.07 (0.98–1.16) | |
Yes (n=321,330) | 15.30 | 1.18 (1.15–1.21) | 11.40 | 1.17 (1.14–1.21) | 1.99 | 1.21 (1.13–1.30) | |
P for interaction | 0.007 | 0.055 | 0.023 | ||||
Meglitinide | |||||||
No (n=750,708) | 11.66 | 1.15 (1.13–1.17) | 8.70 | 1.15 (1.12–1.18) | 1.49 | 1.16 (1.10–1.22) | |
Yes (n=18,846) | 19.39 | 1.20 (1.09–1.32) | 14.45 | 1.24 (1.12–1.38) | 2.36 | 1.04 (0.81–1.35) | |
P for interaction | 0.379 | 0.158 | 0.439 | ||||
Thiazolidinedione | |||||||
No (n=717,834) | 11.84 | 1.15 (1.12–1.17) | 8.83 | 1.14 (1.12–1.17) | 1.51 | 1.15 (1.09–1.22) | |
Yes (n=51,720) | 12.47 | 1.24 (1.15–1.33) | 9.37 | 1.26 (1.16–1.36) | 1.52 | 1.19 (0.97–1.45) | |
P for interaction | 0.036 | 0.031 | 0.754 | ||||
DPP-4 inhibitor | |||||||
No (n=737,632) | 11.91 | 1.15 (1.13–1.17) | 8.89 | 1.15 (1.12–1.18) | 1.53 | 1.15 (1.09–1.22) | |
Yes (n=31,922) | 11.36 | 1.19 (1.08–1.31) | 8.53 | 1.19 (1.07–1.33) | 1.27 | 1.14 (0.86–1.51) | |
P for interaction | 0.524 | 0.556 | 0.935 | ||||
α-Glucosidase inhibitor | |||||||
No (n=677,420) | 10.68 | 1.14 (1.12–1.17) | 7.98 | 1.14 (1.11–1.17) | 1.36 | 1.14 (1.07–1.20) | |
Yes (n=92,134) | 19.10 | 1.20 (1.15–1.25) | 14.21 | 1.19 (1.14–1.25) | 2.42 | 1.21 (1.08–1.36) | |
P for interaction | 0.039 | 0.119 | 0.362 | ||||
Insulin | |||||||
No (n=720,876) | 10.89 | 1.14 (1.11–1.16) | 8.14 | 1.14 (1.11–1.17) | 1.38 | 1.14 (1.07–1.20) | |
Yes (n=48,678) | 21.50 | 1.25 (1.19–1.32) | 15.93 | 1.24 (1.17–1.32) | 2.77 | 1.27 (1.10–1.47) | |
P for interaction | 0.001 | 0.008 | 0.172 |
Values are presented as mean±standard deviation, number (%), or median (interquartile range). One-way analysis of variance and the chi-square test were used to compare the characteristics of the study participants at baseline. VIM, variability independent of mean; BP, blood pressure; FG, fasting glucose; TC, total cholesterol; HDL-C, high-density lipoprotein cholesterol; SD, standard deviation; CV, coefficient of variation; ARV, average real variability; CKD, chronic kidney disease; IHD, ischemic heart disease; GLM, glucose-lowering medication; DPP-4, dipeptidyl peptidase 4. Q1: 0–12.7; Q2: 12.8–20.5; Q3: 20.6–31.2; Q4: ≥31.3, Presence of chronic kidney disease represents estimated glomerular filtration rate <60 mL/min/1.73 m2.
Model 1 was adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, and hemoglobin levels. Model 2 is the same as model 1, with additional adjustment for the duration of diabetes for at least 5 years, the prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder. Q1, 0–12.7; Q2, 12.8–20.5; Q3, 20.6–31.2; Q4, ≥31.3.
Adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, hemoglobin levels, duration of diabetes for at least 5 years, prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder. IR, incidence rate; HR, hazard ratio; CI, confidence interval; CKD, chronic kidney disease.
Adjusted for age, sex, body mass index, alcohol consumption, smoking, regular exercise, presence of hypertension, dyslipidemia, chronic kidney disease, lower 20% income, hemoglobin levels, duration of diabetes for at least 5 years, prescription number of glucose-lowering medications, prescription history of insulin, mean fasting glucose, and presence of depressive disorder. IR, incidence rate; HR, hazard ratio; CI, confidence interval; DPP-4, dipeptidyl peptidase 4.