Association of triglycerides to high-density lipoprotein cholesterol ratio with incident cardiovascular disease but not end-stage kidney disease among patients with biopsy-proven diabetic nephropathy

Uemura, Takayuki; Nishimoto, Masatoshi; Eriguchi, Masahiro; Tamaki, Hiroyuki; Tasaki, Hikari; Furuyama, Riri; Fukata, Fumihiro; Kosugi, Takaaki; Morimoto, Katsuhiko; Matsui, Masaru; Samejima, Ken-ichi; Tsuruya, Kazuhiko

doi:10.1038/s41440-023-01197-y

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…In a study of patients with biopsy-confirmed diabetes nephropathy, the ratio of TG to HDL-C levels was associated with the incidence of cardiovascular disease but not with end-stage renal disease. 25 Yadegar et al 26 found that the average level of TG decreased with the progression of renal failure in patients with T2DM. A study on 15 836 participants showed a linear correlation between AIP and eGFR, with each increase in SD of AIP reducing the risk of eGFR.…”

Section: Discussionmentioning

confidence: 99%

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

Li,

Miao,

Zhong

et al. 2024

Clin Med Insights Endocrinol Diabetes

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Background: Diabetic kidney disease (DKD) is the main cause of end-stage renal disease and has a high mortality rate. Currently, no effective treatments are available to reduce the progression of kidney damage associated with diabetes. Objectives: To explore the influence and predictive value of the atherogenic index of plasma (AIP) on early chronic kidney disease and liver injury in patients with type 2 diabetes mellitus (T2DM). Methods: Medical records of 1057 hospitalized adult patients with T2DM between January 2021 and December 2022 were collected. The predictive value of AIP, renal function, and liver injury in patients with T2DM were analyzed using Pearson’s correlation, multiple logistic regression, and receiver operating characteristic (ROC) curve analyses. Results: AIP was a sensitive indicator of early liver and kidney injury in patients with T2DM. Patients in the DKD group showed increased AIP that positively correlated with serum creatinine, uric acid, and β2-microglobulin levels. Increased AIP negatively correlated with estimated glomerular filtration rate (eGFR). AIP significantly correlated with alanine aminotransferase and aspartate aminotransferase levels and glutamyl transpeptidase-to-platelet ratio (GPR). An eGFR of 60-100 mL/min/1.73 m2 significantly increased the risk of DKD as the AIP increased. At lower GPR levels, the risk of DKD significantly increased with increasing AIP. However, no significant difference was found between the 2 groups when the GPR was >0.1407. The ROC curve analysis showed that AIP could predict early liver injury. Conclusions: AIP is directly involved in early liver and kidney injury in T2DM and may be a sensitive indicator for early detection.

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Section: Discussionmentioning

confidence: 99%

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

Li,

Miao,

Zhong

et al. 2024

Clin Med Insights Endocrinol Diabetes

View full text Add to dashboard Cite

show abstract

“…Serum creatinine is used to evaluate renal function [24]. An increase in the level of triglycerides and a decrease in the level of HDL cholesterol are the characteristics of dyslipidemias in patients with diabetes [25]. Low levels of HDL cholesterol and high levels of triglycerides are independent risk factors for DKD [26].…”

Section: Discussionmentioning

confidence: 99%

Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy

Zhang,

Fu,

Zhou

et al. 2024

Journal of Diabetes Research

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Background. Better therapeutic drugs are required for treating hypertensive diabetic nephropathy. In our previous study, the Huaju Xiaoji (HJXJ) formula promoted the renal function of patients with diabetes and hypertensive nephropathy. In this study, we investigated the therapeutic effect and regulation mechanism of HJXJ in hypertensive diabetic mice with nephropathy. Methods. We constructed a mouse hypertensive diabetic nephropathy (HDN) model by treating mice with streptozotocin (STZ) and nomega-nitro-L-arginine methyl ester (LNAME). We also constructed a human glomerular mesangial cell (HGMC) model that was induced by high doses of sugar (30 mmol/mL) and TGFβ1 (5 ng/mL). Pathological changes were evaluated by hematoxylin and eosin (H&E) staining, periodic acid Schiff (PAS) staining, and Masson staining. The fibrosis-related molecules (TGFβ1, fibronectin, laminin, COL I, COL IV, α-SMA, and p-smad2/3) were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA levels and protein expression of endoplasmic reticulum stress, fibrosis molecules, and their downstream molecules were assessed using qPCR and Western blotting assays. Results. Administering HJXJ promoted the renal function of HDN mice. HJXJ reduced the expression of ER stress makers (CHOP and GRP78) and lncMGC, miR379, miR494, miR495, miR377, CUGBP2, CPEB4, EDEM3, and ATF3 in HDN mice and model HGMCs. The positive control drugs (dapagliflozin and valsartan) also showed similar effects after treatment with HJXJ. Additionally, in model HGMCs, the overexpression of CHOP or lncMGC decreased the effects of HJXJ-M on the level of fibrosis molecules and downstream target molecules. Conclusion. In this study, we showed that the HJXJ formula may regulate ERS-lncMGC/miRNA to enhance renal function in hypertensive diabetic mice with nephropathy. This study may act as a reference for further investigating whether combining HJXJ with other drugs can enhance its therapeutic effect. The findings of this study might provide new insights into the clinical treatment of hypertensive diabetic nephropathy with HJXJ.

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“…Cholesterol, a vital component of cell membranes, also serves as a precursor for several bioactive molecules. Its biosynthesis, involving intermediates such as desmosterol, appears to be more than just a metabolic pathway; it seems to be intricately linked to immune modulation [ 14 ]. Desmosterol, an intermediate in cholesterol synthesis [ 15 ], has been highlighted of its potential role as an endogenous modulator of macrophage function [ 16 ] and of its elevation during diabetes [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Desmosterol-driven atypical macrophage polarization regulates podocyte dynamics in diabetic nephropathy

2024

Mol Biol Rep

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Background Diabetic nephropathy (DN) stands as a leading diabetes complication, with macrophages intricately involved in its evolution. While glucose metabolism’s impact on macrophage activity is well-established, cholesterol metabolism’s contributions remain less explored. Our study seeks to elucidate this association. Methods and results Methods and Results: Gene expression analysis of monocytes from the blood of both normal and diabetic patients was conducted using public databases, showing that cholesterol metabolism pathways, especially Bloch and Kandutsch-Russell, were more altered in diabetic monocytes/macrophages than glucose-responsive pathways. When bone marrow-derived macrophages (BMDMs) were subjected to desmosterol, they exhibited an unconventional polarization. These BMDMs displayed heightened levels of both M1-related pro-inflammatory cytokines and M2-linked anti-inflammatory factors. Further, in co-culture, desmosterol-conditioned BMDMs paralleled M2 macrophages in augmenting Ki-67 + podocyte populations while mimicking M1 macrophages in elevating TUNEL + apoptotic podocytes. Comparable outcomes on podocytes were obtained using conditioned media from the respective BMDMs. Conclusions Our data underscores the pivotal role of cholesterol metabolism, particularly via desmosterol, in steering macrophages toward an unconventional polarization marked by both inflammatory and regulatory traits. Such unique macrophage behavior concurrently impacts podocyte proliferation and apoptosis, shedding fresh light on DN pathogenesis and hinting at potential therapeutic interventions.

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Association of triglycerides to high-density lipoprotein cholesterol ratio with incident cardiovascular disease but not end-stage kidney disease among patients with biopsy-proven diabetic nephropathy

Cited by 4 publications

References 38 publications

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

Atherogenic Index of Plasma as an Early Marker of Chronic Kidney Disease and Liver Injury in Type 2 Diabetes

Huaju Xiaoji Formula Regulates ERS-lncMGC/miRNA to Enhance the Renal Function of Hypertensive Diabetic Mice with Nephropathy

Desmosterol-driven atypical macrophage polarization regulates podocyte dynamics in diabetic nephropathy

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