Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy

Objective: Adiponectin is secreted specifically from adipocytes, and improves insulin sensitivity. Of its isoforms, the high molecular weight (HMW) complex is thought to be the most active. The aim of this study was to determine the relationship between serum total or HMW adiponectin and diabetic microangiopathy. Design, patients and measurements: We analysed 198 Japanese patients with type 2 diabetes mellitus (T2DM) whose fasting serum samples were available. Serum total adiponectin and HMW adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA). Results: Serum total adiponectin was found to have increased in the advanced stages of diabetic retinopathy (mean ± SE, none, 6.9 ± 0.3; simple, 8.3 ± 1.0; preproliferative, 8.4 ± 0.8; proliferative, 12 ± 1.1 mg/l; anovaP = 0.0004) and nephropathy (stage I, 7.0 ± 0.3; II, 7.7 ± 0.5; III, 9.5 ± 0.9; IV, 16 ± 4.5 mg/l, P < 0.0001). Similarly, serum HMW adiponectin had increased in the advanced stages of retinopathy (3.7 ± 0.2, 4..6 ± 0.5, 4.6 ± 0.6 and 6.9 ± 0.8 mg/l, respectively, P = 0.0005) and nephropathy (3.7 ± 0.2, 4.3 ± 0.4, 5.3 ± 0.7 and 7.9 ± 2.2 mg/l, respectively, P = 0.0007). Neither serum total nor HMW adiponectin was correlated with neuropathy. The HMW/total adiponectin ratio was not correlated with microangiopathy. Multiple regression analysis revealed that serum total and HMW adiponectin were independent factors for retinopathy stage (P = 0.0055 and P = 0.0027, respectively) and nephropathy stage (P = 0.0003 and P = 0.0018, respectively), when adjusted for age, gender, body mass index (BMI) and the duration of T2DM. This correlation remained significant when serum creatinine (or estimated glomerular filtration rate) and hypertension were added as independent variables. Treatment with thiazolidinediones (TZDs) did not affect these findings. Conclusions: Serum total adiponectin and HMW adiponectin were found to be positively correlated with the severity of retinopathy and nephropathy but not with neuropathy in T2DM.