Ratio of low molecular weight serum adiponectin to the total adiponectin value is associated with type 2 diabetes through its relation to increasing insulin resistance

Aim Among the three adiponectin isoforms, a lower ratio of high molecular weight (HMW) adiponectin to total adiponectin (TA) is well known to cause insulin resistance and type 2 diabetes (T2D). However, how the levels of other adiponectin isoforms, such as the middle molecular weight (MMW) and low molecular weight (LMW) isoforms, and their relative ratio to TA change in T2D subjects has not been determined. Therefore, we investigated the association of these adiponectin-related parameters with T2D. Methods We examined the associations between adiponectin-related parameters and diabetes in a group of 394 T2D subjects and 374 controls (1^st group) randomly selected from among the participants in our previous study. The associations between these parameters and the HOMA- IR in a 2^nd group, consisting of the subjects remaining in the 1^st group after the exclusion of subjects receiving diabetic medication, were also examined. Result In the 1^st group, after adjusting for confounding factor, the levels of all the adiponectin isoforms and the HMW/TA ratio were significantly lower among the diabetic subjects than among the controls (all P values < 0.01). On the contrary, the LMW/TA ratio was significantly higher among the diabetic subjects (P < 0.01) and was positively associated with T2D (odds ratio = 8.64, P < 0.01). In the 2^nd group, the HMW/TA ratio was inversely associated with the HOMA- IR; however, the LMW/TA ratio was positively associated with the HOMA- IR (β for LMW/TA ratio = 0.89, SE = 0.24, P < 0.001), similar to the association with T2D. The MMW/ TA ratio was not associated with T2D or the HOMA- IR. Conclusion The current investigation demonstrated that, unlike the reduction in the levels of all the adiponectin isoforms and the HMW/TA ratio, an increased LMW/TA ratio was associated with T2D through its relation to insulin resistance.