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Review
. 2020 Apr;27(2):115-123.
doi: 10.1097/MED.0000000000000533.

The emerging role of dyslipidemia in diabetic microvascular complications

Masha G Savelieff  1 , Brian C Callaghan, Eva L Feldman
Affiliations
Review

The emerging role of dyslipidemia in diabetic microvascular complications

Masha G Savelieff et al. Curr Opin Endocrinol Diabetes Obes. 2020 Apr.

Abstract

Purpose of review: To summarize recent advancements in our understanding of the impact of dyslipidemia on microvascular complications in type 2 diabetes (T2D), with an emphasis on peripheral neuropathy and nephropathy.

Recent findings: Mounting evidence suggests that rigorous glycemic control only mitigates certain microvascular complications in T2D patients. Particularly, well regulated blood glucose levels only marginally improve peripheral neuropathy in the T2D setting. Dyslipidemia, an abnormal lipid profile, is emerging as a key factor in peripheral neuropathy. Furthermore, although glycemic control may prevent or slow nephropathy, recent developments demonstrate that dyslipidemia can also affect kidney outcomes in normoglycemic patients. Transcriptomic, epigenomic, and lipidomic investigations, as well as integrative approaches, are shedding light on potential pathomechanisms. These molecular studies are identifying possible targets for therapeutic intervention. Complementing molecular research, lifestyle interventions are on-going to assess whether dietary choices and/or exercise, weight-loss, or surgical interventions, such as bariatric surgery, can ameliorate peripheral neuropathy and nephropathy in T2D patients.

Summary: Dyslipidemia is an emerging mechanism in microvascular complications in T2D. Elucidating the molecular pathomechanisms may pinpoint potential lipid-centric treatments. Interventional studies of dietary changes, exercise, or weight-loss surgery may also positively impact these highly prevalent and morbid complications.

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Figures

Figure 1.
Figure 1.
Illustration of microvascular complications in T2D patients. Retinopathy affects the eyes, nephropathy affect the kidneys, and peripheral neuropathy (PN) affects the sensory peripheral nerves.
Figure 2.
Figure 2.
Lipid-dependent effects on sensory neurons. TGs accumulate in nerves upon a HFD enriched in SFAs (28). Long-chain SFAs impair mitochondrial trafficking, increase mitochondrial circularity, and decrease mitochondrial size (excessive fission) and MMP (14). MUFAs “trap” SFAs within lipid droplets and protects neurons from SFA-induced defects (17). Vital mitochondria are red; lipid droplets are yellow. Damaged mitochondria are brown. HFD, high-fat diet; MMP, mitochondrial membrane potential; MUFAs, mono-saturated fatty acids; SFAs; saturated fatty-acids; TGs, triglycerides.
Figure 3.
Figure 3.
Lipid-dependent effects in renal tissue. SFAs increase ROS production and decrease peroxidases, increasing oxidative stress (–42). Lipids accumulate in renal tissue upon a HFD, leading to lipotoxicity. Blocking FA uptake, by inhibiting VEGF-B or VEGFR-3, slows progressive kidney disease (45, 46). SFAs also stimulate inflammation (47, 48). Damaged mitochondria are brown. FA, fatty acid; MMP, mitochondrial membrane potential; MUFAs, mono-saturated fatty acids; ROS, reactive oxygen species; SFAs; saturated fatty-acids.
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References

    1. O’Neill S, O’Driscoll L. Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev. 2015;16(1):1–12. - PubMed
    1. Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract. 2019;157:107843. - PubMed
    1. Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, et al. Diabetic neuropathy. Nat Rev Dis Primers. 2019;5(1):41. - PubMed
    1. Winocour PH. Diabetes and chronic kidney disease: an increasingly common multi-morbid disease in need of a paradigm shift in care. Diabet Med. 2018;35(3):300–5. - PubMed
    1. Ting DS, Cheung GC, Wong TY. Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2016;44(4):260–77. - PubMed

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