New insights into the mechanisms of diabetic complications: role of lipids and lipid metabolism

Abstract

Diabetes adversely affects multiple organs, including the kidney, eye and nerve, leading to diabetic kidney disease, diabetic retinopathy and diabetic neuropathy, respectively. In both type 1 and type 2 diabetes, tissue damage is organ specific and is secondary to a combination of multiple metabolic insults. Hyperglycaemia, dyslipidaemia and hypertension combine with the duration and type of diabetes to define the distinct pathophysiology underlying diabetic kidney disease, diabetic retinopathy and diabetic neuropathy. Only recently have the commonalities and differences in the metabolic basis of these tissue-specific complications, particularly those involving local and systemic lipids, been systematically examined. This review focuses on recent progress made using preclinical models and human-based approaches towards understanding how bioenergetics and metabolomic profiles contribute to diabetic kidney disease, diabetic retinopathy and diabetic neuropathy. This new understanding of the biology of complication-prone tissues highlights the need for organ-specific interventions in the treatment of diabetic complications.

Keywords: Diabetes; Diabetic complications; Lipid metabolism; Omics; Review; Specific mechanisms.

Fig. 1

Systemic and tissue-specific alterations in lipid metabolism specifically associated with the microvascular complications: diabetic kidney disease, diabetic retinopathy and diabetic neuropathy. FA, fatty acid; LDL-c, LDL-cholesterol. This figure is available as part of a downloadable slideset

Fig. 2

Diabetes is associated with tissue-specific lipid alterations. The Venn diagram represents significantly altered lipid features observed in the BKS db/db mouse model of diabetes compared with control. Only 15 lipid features were significantly altered across complication-prone tissues, including diacylglycerol, phospholipids and cardiolipins. The direction of change in these shared features varied across different tissues with only four of the 15 common to all three tissues changing in the same direction (number of features with common direction is shown in parentheses), further demonstrating the tissue-specific nature of the lipid alterations associated with diabetes. Data derived from [30]. This figure is available as part of a downloadable slideset