Fig. 1Flow chart of the sample selection. DM, diabetes mellitus.
Fig. 2Kaplan-Meier plots for (A) all-cause dementia, (B) Alzheimer disease, and (C) vascular dementia in patients with or without underlying hypoglycemia.
Table 1Baseline characteristics of propensity score matched patients
Characteristic |
Patients without underlying hypoglycemia |
Patients with underlying hypoglycemia |
SMD |
P value |
Number |
5,966 |
5,966 |
|
|
Age, yr |
75.82±5.34 |
75.82±5.41 |
<0.001 |
0.947 |
Male sex, % |
37.81 |
38.50 |
0.014 |
0.778 |
Socio-economic status |
|
|
0.042 |
0.427 |
1st to 4th of 11 quantiles |
1,628 (27.29) |
1,627 (27.27) |
5th to 8th of 11 quantiles |
1,822 (30.54) |
1,860 (31.18) |
9th to 11th of 11 quantiles |
2,516 (42.17) |
2,479 (41.55) |
Hypertension |
86.24 |
85.82 |
0.012 |
0.401 |
Dyslipidemia |
58.85 |
59.65 |
0.016 |
0.394 |
Chronic kidney disease |
7.58 |
7.71 |
0.005 |
0.945 |
End-stage renal disease |
3.62 |
4.22 |
0.031 |
0.473 |
Any malignancy |
11.33 |
11.26 |
0.002 |
0.439 |
Migraine |
4.53 |
4.51 |
0.001 |
0.654 |
Asthma |
19.18 |
19.01 |
0.004 |
0.971 |
Chronic obstructive pulmonary disease |
14.28 |
13.88 |
0.012 |
0.685 |
Connective tissue disease |
5.88 |
6.22 |
0.014 |
0.828 |
Atrial fibrillation |
4.51 |
4.64 |
0.006 |
0.172 |
Heart failure |
8.3 |
8.41 |
0.004 |
0.945 |
Osteoporosis |
25.96 |
26.22 |
0.006 |
0.699 |
Cerebrovascular disease |
|
|
|
|
Ischemic stroke |
15.37 |
15.39 |
<0.001 |
0.533 |
Hemorrhagic stroke |
0.62 |
0.85 |
0.027 |
0.914 |
Transient ischemic attack |
4.24 |
3.97 |
0.014 |
0.608 |
Acute myocardial infarction |
4.61 |
4.27 |
0.016 |
0.587 |
Other ischemic heart disease |
28.43 |
28.03 |
0.009 |
0.768 |
Other heart disease |
22.18 |
21.77 |
0.01 |
0.826 |
Peripheral artery disease |
2.77 |
2.63 |
0.008 |
0.476 |
Microvascular complications of diabetes |
|
|
|
|
Neuropathy |
22.95 |
23.21 |
0.006 |
0.533 |
Nephropathy |
8.95 |
9.34 |
0.013 |
0.271 |
Retinopathy |
20.62 |
20.62 |
<0.001 |
0.254 |
Alcohol usea
|
2.83 |
2.65 |
0.011 |
0.736 |
Obesitya
|
0.02 |
0.03 |
0.011 |
0.465 |
Medication use |
|
|
|
|
Anti-diabetic medicine |
|
|
|
|
Metformin |
67.83 |
67.77 |
0.001 |
0.583 |
Sulfonylurea |
73.57 |
72.93 |
0.014 |
0.254 |
Thiazolidinedione |
9.1 |
9.52 |
0.014 |
0.105 |
DPP-4i |
9.29 |
8.73 |
0.019 |
0.722 |
α-Glucosidase inhibitor |
23.33 |
22.9 |
0.01 |
0.662 |
Meglitinide |
4.76 |
5.43 |
0.03 |
0.777 |
Insulin |
15.35 |
16.46 |
0.03 |
0.878 |
Anti-hypertensive agent |
|
|
|
|
Calcium channel blocker |
35.89 |
35.97 |
0.002 |
0.446 |
ACEI |
10.46 |
10.81 |
0.011 |
0.463 |
ARB |
52.46 |
52.03 |
0.009 |
0.728 |
β-Blocker |
18.67 |
18.54 |
0.003 |
0.573 |
α-Blocker |
3.1 |
3.07 |
0.002 |
0.532 |
Diuretics |
33.44 |
33.02 |
0.009 |
0.473 |
Aspirin |
45.31 |
45.31 |
<0.001 |
0.956 |
P2Y12 inhibitor |
14.08 |
13.68 |
0.012 |
0.438 |
Warfarin |
1.91 |
2.15 |
0.017 |
0.949 |
Other antiplatelet |
9.45 |
9.35 |
0.003 |
0.925 |
NOAC |
0.08 |
0.05 |
0.013 |
0.705 |
Lipid-lowering agent |
|
|
|
|
Statin |
35.77 |
35.97 |
0.004 |
0.789 |
Fibrate |
3.4 |
3.3 |
0.006 |
0.757 |
Ezetimibe |
1.42 |
1.51 |
0.007 |
0.819 |
Table 2The risk of dementia in patients with hypoglycemia compared to patients without hypoglycemia
Variable |
Number |
Events |
HR |
95% CI |
P value |
All-cause dementia |
11,932 |
2,934 |
1.254 |
1.166–1.349 |
<0.001 |
Alzheimer's disease |
11,932 |
2,186 |
1.264 |
1.162–1.375 |
<0.001 |
Vascular dementia |
11,932 |
721 |
1.286 |
1.110–1.490 |
<0.001 |
Table 3The risk of dementia according to number of hypoglycemic episodes in patients with and without previous hypoglycemic episode
No. of previous hypoglycemic episodes |
Number |
Events |
HR |
95% CI |
P value |
1 |
4,622 |
1,159 |
1.170 |
1.043–1.313 |
0.008 |
2–3 |
2,946 |
550 |
1.201 |
1.016–1.421 |
0.032 |
>3 |
4,354 |
256 |
1.358 |
1.060–1.740 |
0.016 |
Table 4Subgroup analyses according to sex, age, and the presence of diabetic microvascular or macrovascular complications
Variable |
Number |
Events |
HR |
95% CI |
P value |
Male sex |
4,553 |
921 |
1.180 |
1.037–1.344 |
<0.05 |
Female sex |
7,379 |
2,013 |
1.297 |
1.188–1.416 |
<0.001 |
Patients aged ≥75 years |
6,210 |
1,893 |
1.197 |
1.093–1.310 |
<0.001 |
Patients aged <75 years |
5,722 |
1,041 |
1.376 |
1.217–1.556 |
<0.001 |
Patients with DM microvascular complications |
5,039 |
1,330 |
1.312 |
1.177–1.462 |
<0.001 |
Patients without DM microvascular complications |
6,893 |
1,604 |
1.208 |
1.095–1.332 |
<0.001 |
Patients with DM macrovascular complications |
5,089 |
1,354 |
1.226 |
1.102–1.365 |
<0.001 |
Patients without DM macrovascular complications |
6,843 |
1,580 |
1.276 |
1.155–1.409 |
<0.001 |