The association between plasma lipidome and diabetic microangiopathy: a mendelian randomization study.

Background: Current studies have identified severe lipid metabolism diseases in diabetic microangiopathy patients, especially in diabetic kidney disease (DKD), diabetic retinopathy (DR) and diabetic neuropathy (DN), with unclear causal relationships.

Methods: We employed a large-scale dataset containing 179 lipid species as the exposure and large-scale public summary-level datasets of DKD, DR and DN as the outcome. We applied Mendelian randomization (MR) approach to explore causal associations between circulating liposomes and diabetic microangiopathy. A sequence of sensitivity tests was conducted to verify the stability of the MR analysis.

Results: We manifest that diacylglycerol (18:1_18:3) (OR = 0.716, 95%CI = 0.559-0.917, P = 0.008), triacylglycerol (OR:0.741-0.763, P < 0.05) and phosphatidylcholine (OR:0.620-1.247, P < 0.05) have a potential association with DKD. And there is a nominal causal effect of phosphatidylinositol (16:0_18:2) (OR = 0.617, 95%CI = 0.401-0.948, P = 0.028), phosphatidylcholine (OR:0.499-0.672, P < 0.05) and sphingomyelin (OR:0.652-1.850, P < 0.05) to DR. In addition, phosphatidylethanolamine (18:1_0:0) (OR = 0.616, 95%CI = 0.405-0.935, P = 0.023), diacylglycerol (16:0_18:1) (OR = 0.675, 95%CI = 0.463-0.984, P = 0.041) and phosphatidylcholine (OR = 0.720-1.619, P < 0.05) nominally associate with DN. It is noteworthy that plasma lipidome of different structures show different effects.

Conclusion: We establish a possible causal connection between certain plasma lipidome and major diabetic microangiopathies. Implementing intervention strategies targeting different lipid molecules may provide novel approaches for preventing and treating diabetic microangiopathies.