Relation between diabetes and WMLs
| Study (ref.) | Study population | Subjects (total/diabetic) (n) | Mean age (years) | Diabetes type | Imaging | Rating scale | Outcome and results | P value | Adjustments/matching |
|---|---|---|---|---|---|---|---|---|---|
| General cohorts | |||||||||
| Dejgaard et al. (16) | Case/control | 60/20 | 40 | 1 | MRI | Dich | OR 15.4 (3.8–63.2)† | <0.05 | Age |
| Yousem et al. (37) | Case/ control | 35/25 | 31 | 1 | MRI | Dich | No WML in either group | NS | Age, sex |
| Longstreth et al. (7) | Population based | 3,301/369 | >65 | 2 | MRI | Ord (0–9) | NS | Age, sex | |
| den Heijer et al. (12) | Population based | 506/41 | >60 | 2 | MRI | Ord (0–9) PVH | PVH: diff +0.4 (−0.2 to 1.1), d = 0.4† | NS | Age, sex |
| Int WML | WML: diff +0.01 ml (−1.0 to 1.0), d = 0.2† | NS | |||||||
| Schmidt et al. (13) | Population based | 1,252/114 | 69 | 2 | MRI | Int | PVH: median diff 0 | 0.1 | Sex, age, edu, BP, smoking, BMI, HL, PVD |
| WML: median diff +0.2 | 0.2 | ||||||||
| Jerekathil et al. (9) | Population based | 1814/91 | 54 | ND | MRI | Volumetry | WML: β = 0.02 | 0.8 | Age, sex |
| Jorm et al. (15) | Population based | 475/? | >60 | 2 | MRI | Volumetry | WML: r = 0.03 | NS | No |
| Vascular cohorts | |||||||||
| Hijdra et al. (19) | Stroke | 376/59 | >65 | 2 | CT | Ord (0–4)* | OR 2.0 (1.1–3.5)†‡ | 0.02 | No |
| Schmidt et al. (17) | Stroke/vascular risk factors and control | 234/38 | 55 | ND | MRI | Ord (0–3) | β = 0.2 (SE 0.1) | <0.001 | Age, BP, sex, ICD, PVD |
| Manolio et al. (10) | Stroke and control | 303/76 | >65 | 2 | MRI | Ord (0–8) | Diabetes: mean diff 0.4 | 0.1 | No |
| Fukuda and Kitani (63) | Hypertension | 238/52 | >40 | ND | MRI | Ord (0–5) | Diabetes: mean diff 0.1, d = 0.2† | 0.3 | No |
| Jorgensen et al. (64) | Stroke or TIA | 1,084/203 | >70 | 2 | CT | Dich | OR 0.8 (0.5–2.3)†‡ | 0.3 | No |
| Awada and Omojola (39) | Stroke | 398/131 | >60 | 2 | CT | Dich | OR 0.9 (0.6–1.5)†‡ | No | |
| Henon et al. (65) | Stroke | 610/83 | 64 | 2 | CT | Ord (0–3) | Estimated coefficient 1.2 (SE 0.8) | 0.1 | Age, sex, BP, alcohol, HL, ICD, cerebral atrophy |
| Padovani et al. (34) | Stroke and control | 100/20 | >60 | 2 | MRI | Ord (0–3) | β = 0.02 (SE 0.1) | 0.9 | Age, sex, BP, PVD, ICD, ventricular index |
| Coskun et al. (38) | Stroke | 288/57 | >65 | 2 | CT | Ord (0–4)* | OR 0.6 (0.06–0.3)†‡ | NS | No |
| Streifler et al. (18) | Stroke | 596/110 | >60 | 2 | CT | Ord* | OR 1.6 (1.0–2.6)†‡ | 0.04 | No |
| Kario et al. (47) | Hypertension | 20/20 | 69 | 2 | MRI | Ord* | OR 2.2 (0.5–9.0) | NS | Age, sex, BP |
| Outpatient cohorts | |||||||||
| Raiha et al. (41) | Geriatric department | 204/55 | 74 | 2 | CT | Dich | OR 0.9 (0.5–1.7)† | NS | No |
| Araki et al. (21) | MRI for any indication | 2,725/159 | 60 | 2 | MRI | Dich | OR 1.4 (0.7–2.8)†‡ | NS | No |
| Fukuda and Kitani (66) | Neurologically normal | 253/50 | 66 | 2 | MRI | Ord (0-4) | d = 0.1† | 0.6 | Age, sex, BP, smoking, HL, ICD |
| Kobayashi et al. (22) | Neurologically normal | 933/66 | 58 | ND | MRI | Ord (PVH: 0–4)* | PVH: OR 2.0 (0.8–4.8)†‡ | 0.2 | No |
| Dich (WML) | DWML: OR 0.8 (0.3–2.8)†‡ | 0.6 | |||||||
| Hogervorst et al. (24) | Alzheimer’s disease and control subjects | 414/29 | 74 | 2 | CT | Ord (0–3)* | OR 1.4 (0.5–4.3) | 0.5 | Age, sex, diagnosis, smoking, diabetes, BP, apoE4 |
| Masana and Motozaki (23) | Mild headache and vertigo | 1,674/87 | 51 | ND | MRI | Ord (0–3) | OR 1.6 (0.8–3.0)‡ | 0.2 | Age, sex, BP, HL, family history, smoking, alcohol, ICD |
| Biessels et al. (11) | Memory clinic | 347/29 | 73 | 2 | MRI | Ord (0–6) | PVH: mean diff 0 (−0.5 to 0.5) | NS | Age, sex |
| Ord (0–24) | DWML: mean diff −0.5 (−2.0 to 1.5) | NS | |||||||
| Lazarus et al. (20) | Memory clinic | 177/20 | >65 | 2 | MRI | Ord (0–4)* | PVH: OR 1.6 (0.6–5.2)‡ | NS | Age, BP, AF, ICD |
| DWML: OR 2.9 (1.0–7.8) | ? | ||||||||
| Taylor et al. (14) | Depressive disorder and control subjects | 399/34 | 70 | 2 | MRI | Volumetry | WML: t = −1.3 | 0.2 | Age, sex, BP |
| GML in BG: t = −1.08 | 0.3 |
Studies are listed in chronological order. Study populations: general cohorts, population-based or case-control studies; vascular cohorts, cohort with stroke or other cardiovascular risk factors; outpatient cohorts, neurological, or psychiatric outpatients. Diabetes type: 2 (except for the Study by Kario et al. [47]), population type classified as predominantly type 2 diabetes (see research design and methods). ND, not determined. Rating scale: Dich, dichotomous scale; Int, interval scale; Ord, ordinal scale.
↵* Dichotomization was performed for analysis. Outcome and results (diabetic patients vs. control subjects): BG, basal ganglia; DWML, deep WMLs; GML, gray matter lesions; PVH, periventricular hyperintensities. ORs are presented with 95% CIs in parentheses.
↵† Where possible, we calculated OR or effect sizes (d) if they were not provided in the original article. Mean differences (diff; with 95% CIs in parentheses), d, β, and t values >0 reflect more severe WMLs in the diabetic group relative to control subjects. Studies marked with
↵‡ were included in the meta-analysis presented in Table 4. P value: NS, not significant; ?, not specified. Adjustments/matching: apo, apolipoprotein; AF, atrial fibrillation; BP, blood pressure (including hypertension, mean arterial pressure, systolic blood pressure, use of antihypertensive drugs, left ventricular hypertrophy, and ankle-to-arm index); edu, education; HL, hyperlipidemia; ICD, ischemic cerebrovascular disease (including transient ischemic attack [TIA], stroke, leukoaraiosis, WMLs, and ultrasound examination of carotid or intracranial arteries); PVD, peripheral vascular disease (including peripheral artery disease, coronary artery disease, cardiac disease, congestive heart failure, and electrocardiogram changes).