Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance but the large clinical phase 3 trial (Pemafibrate to Reduce Cardiovascular OutcoMes by Reducing Triglycerides IN patiENts With diabe- Tes [PROMINENT]) was recently stopped due to the underperformance from interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

We aimed to investigate the association of iron and polyunsaturated fatty acid (PUFA) intake with diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes. This cross-sectional study included 147 individuals with type 2 diabetes. Dietary intake was assessed using three-day food records. DPN was diagnosed on the basis of a Michigan Neuropathy Screening Instrument—Physical Examination score ≥2.5. Adjusted for total energy intake, iron intake was significantly higher in individuals with DPN than in those without DPN (10.9 ± 4.0 mg vs. 9.9 ± 3.6 mg, p = 0.041). In addition, the iron/PUFA ratio was significantly higher in individuals with DPN (1.4 ± 0.8 vs. 1.1 ± 0.4, p = 0.005). Logistic regression analyses showed that iron intake (odds ratio (OR): 1.152; 95% confidence interval (CI): 1.012, 1.311) and iron/PUFA ratio (OR: 2.283; 95% CI: 1.066, 4.887) were associated with DPN after adjustment for total energy intake, sex, age, body mass index, systolic blood pressure, diabetes duration, estimated glomerular filtration rate, glycated hemoglobin, low-density lipoprotein cholesterol, and smoking. In conclusion, high dietary iron intake and an elevated iron/PUFA ratio were associated with the presence of DPN. The present study suggests the importance of the dietary pattern of iron and PUFA intake in individuals with type 2 diabetes.

High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

The association between nonalcoholic fatty liver (NAFL) or liver fibrosis and diabetic peripheral neuropathy (DPN) has not been well studied. We aimed to investigate the association of NAFL or liver fibrosis indices and DPN in individuals with type 2 diabetes. In this observational study, we included 264 individuals with type 2 diabetes, and calculated non-alcoholic fatty liver disease (NAFLD) liver fat score, NAFLD fibrosis score, and Fibrosis-4 (FIB-4) index to evaluate the status of NAFLD or liver fibrosis. DPN was diagnosed when the Michigan Neuropathy Screening Instrument—Physical Examination score was ≥ 2.5. The NAFLD fibrosis score and FIB-4 index were significantly higher in individuals with DPN than in those without DPN. Logistic analyses showed that the NAFLD fibrosis score and FIB-4 index were associated with DPN after adjustment for covariates (adjusted odds ratio 1.474 and 1.961, respectively). In the subgroup analysis, this association was only significant in the group with a high NAFLD liver fat score (> − 0.640). Serum levels of fetuin-A, a hepatokine, were decreased in individuals with abnormal vibration perception or 10-g monofilament tests compared with their counterparts. The present study suggests that liver fibrosis might be associated with DPN in individuals with type 2 diabetes.

Ultrasonography (US) is the primary diagnostic tool for thyroid nodules, while the accuracy is operator-dependent. It is widely used not only by radiologists but also by physicians with different levels of experience. The aim of this study was to investigate whether US with computer-aided diagnosis (CAD) has assisting roles to physicians in the diagnosis of thyroid nodules. 451 thyroid nodules evaluated by fine-needle aspiration cytology following surgery were included. 300 (66.5%) of them were diagnosed as malignancy. Physicians with US experience less than 1 year (inexperienced, n = 10), or more than 5 years (experienced, n = 3) reviewed the US images of thyroid nodules with or without CAD assistance. The diagnostic performance of CAD was comparable to that of the experienced group, and better than those of the inexperienced group. The AUC of the CAD for conventional PTC was higher than that for FTC and follicular variant PTC (0.925 vs. 0.499), independent of tumor size. CAD assistance significantly improved diagnostic performance in the inexperienced group, but not in the experienced groups. In conclusion, the CAD system showed good performance in the diagnosis of conventional PTC. CAD assistance improved the diagnostic performance of less experienced physicians in US, especially in diagnosis of conventional PTC.