Decreased High Molecular Weight Adiponectin in Sera Is Associated With White Matter Lesions in Japanese Men With Type 2 Diabetes

The presence of white matter lesions (WML) is an important prognostic factor for the development of stroke in patients with type 2 diabetes (1). Adiponectin, especially high molecular weight (HMW) adiponectin, an adipocyte-derived peptide with antidiabetic and antiatherogenic effects, is known to protect against the initiation and progression of diabetes, atherosclerosis, and insulin resistance (2). However, the relationship between HMW adiponectin and WML in type 2 diabetes has not been fully elucidated. The current study was therefore designed to test the hypothesis that the presences of WML correlates with HMW adiponectin in patients with type 2 diabetes. The 112 Japanese men seen in the Oita Red Cross Hospital between January 2009 and June 2010 for the treatment of type 2 diabetes were included in the current study. Patients aged 49–66 years (mean 6 SD, 59 6 6 years) fulfilled the inclusion criteria. Seventy-four patients met the criteria in the WML-negative group and 38 patients met the criteria in the WML-positive group. All subjects gave their written informed consent to participate in the study. The study protocol was approved by the ethics committee of the Oita Red Cross Hospital. All patients underwent laboratory tests, including total and HMW adiponectin concentration measured by enzyme-linked immunosorbent assay (ELISA) (Otsuka Pharmaceutical, Tokyo, Japan). All magnetic resonance imaging studies were performed using 1.5 T units, Magnetom Vision and Symphony (Siemens Medical Systems, Erlangen, Germany) using the previous study (3). The Student t test was used for continuous variables, and a logistic regression and stepwise multiple logistic backward regression analysis was performed by a standard statistical package (JMP 6.0; SAS Institute, Cary, NJ). The mean ages of the WML-positive and WML-negative groups were similar, and there were no significant differences between the groups with respect to duration of diabetes, hypertension, dyslipidemia, renal function, and administered medications. Univariate logistic regression analysis showed that the risk of WML was associated with BMI (odds ratio 1.17 [95% CI 1.00–1.38], P5 0.0456), waist circumferences (1.10 [1.05–1.16], P 5 0.0030), F-IRI (2.27 [1.74–3.78], P 5 0.0021), homeostasis model assessment index (2.67 [1.47–5.88],P50.0008), total adiponectin (0.76 [0.34–0.89], P 5 0.0031) and HMW adiponectin (0.45 [0.13–0.87], P , 0.0001). And finally, multivariate logistic analysis identified only HMW adiponectin in type 2 diabetic patients as the independent and significant risk factors for WML (P , 0.0001). A previous study suggested that the presence of WML is associated with type 2 diabetes (4). The novel and important findings of the current study revealed the relationship between HMW adiponectin and WML in patients with type 2 diabetes. Although the specific mechanism of the potential pathological link between HMW adiponectin and the presence of WML remains to be elucidated, it is possible that interactions between the presence of WML and adiponectin may be associated with atherosclerosis, inflammation, and endothelial dysfunction (5). In conclusion, our findings suggest that the presence of WML is associated with HMW adiponectin. HMW adiponectin might be a therapeutic target for WML in type 2 diabetes. In the future, large cohort studies including other hormones and other populations may be beneficial.