Identification of key lipid metabolites during metabolic dysregulation in the diabetic retinopathy disease mouse model and efficacy of Keluoxin capsule using an UHPLC-MS-based non-targeted lipidomics approach

Diabetic retinopathy (DR) is an important complication of diabetes, and is currently the main cause of blindness among young adults in the world. Previous studies have shown that Keluoxin (KLX) capsules have a significant effect on DR in C57BL/KsJ/db^−/− mice (db/db mice), however the unclear mechanism limits its further clinical application and actual value. Further research is urgently needed for the treatment of DR disease. Discovery of key lipid biomarkers and metabolic pathways can reveal and explore the molecular mechanisms related to DR development and discover the effect of Keluoxin (KLX) capsule against DR in db/db mice. Lipidomics has been used for characterizing the pathological conditions via identification of key lipid metabolites and the metabolic pathway. In this study, the high-throughput lipidomics using UHPLC-Q-TOF/MS combined with multivariate statistical analysis, querying multiple network databases and employing ingenuity pathway analysis (IPA) method for molecular target prediction. A total of 30 lipid biomarkers were identified and 7 metabolic pathways including arachidonic acid metabolism and steroid hormone biosynthesis were found. The preventive effect of KLX intervention can regulate 22 biomarkers such as LysoPA(16:0/0:0), prostaglandin D₂, cortisol and γ-linolenic acid, etc. IPA platform has predicted that PI3K/MAPK pathway are closely related to DR development. It also showed that high-throughput lipidomics combined with multivariate statistical analysis could deep excavate of the biological significance of the big data, and can provide molecular targets information about the disease treatment.

Diabetic retinopathy (DR) is an important complication of diabetes, and is currently the main cause of blindness among young adults in the world.     

High-throughput lipidomics reveal mirabilite regulating lipid metabolism as anticancer therapeutics

Altered lipid metabolism is an emerging hallmark of cancers. Mirabilite has a therapeutic effect on colorectal cancer (CRC); however, its metabolic mechanism remains unclear. This study aims to explore the potential therapeutic targets of mirabilite protection against colorectal cancer in APC^min/+ mice model. Oral administration of mirabilite was started from the ninth month, while the same dosage of distilled water was given to both the control group and the model group. Based on lipidomics, we collected serum samples of all mice at the 20^th week and used a non-targeted method to identify the lipid biomarkers of CRC. Compared with C57BL/6J mice, the metabolic profile of CRC model mice was significantly disturbed, and we identified that 25 lipid-related biomarkers, including linoleic acid, 2-hydroxybutyric acid, 6-deoxocastasterone, hypoxanthine, PC(16:1), PC(18:4), and retinyl acetate, were associated with CRC. According to the abovementioned results, there were six lipid molecules with significant differences that can be used as new targets for handling of CRC through six metabolic pathways, namely, linoleic acid metabolism, retinol metabolism, propanoate metabolism, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids and purine metabolism. Compared with the model group, the metabolic profiles of these disorders tend to recover after treatment. These results indicated that the lipid molecules associated with CRC were regulated by mirabilite. In addition, we identified seven key lipid molecules, of which four had statistical significance. After administration of mirabilite, all disordered metabolic pathways showed different degrees of regulation. In conclusion, high-throughput lipidomics approach revealed mirabilite regulating the altered lipid metabolism as anticancer therapeutics.

Altered lipid metabolism is an emerging hallmark of cancers.     

A high-throughput and untargeted lipidomics approach reveals new mechanistic insight and the effects of salvianolic acid B on the metabolic profiles in coronary heart disease rats using ultra-performance liquid chromatography with mass spectrometry

High-throughput lipidomics provides the possibility for the development of new therapeutic drugs. Accordingly, herein, we reveal the protective role of salvianolic acid B (Sal B) in rats with coronary heart disease (CHD) and propose a new mechanism for its action through a high-throughput and non-targeted lipidomics strategy. A CHD animal model was induced by consecutive high-fat diet feeding with vitamin D3 injection. At the end of the 8th week, the serum sample was analyzed to explore the metabolic biomarker and pathway changes using untargeted lipidomics based on ultra-performance liquid chromatography with mass spectrometry (UPLC/MS). In addition, blood and heart tissue samples were collected and processed for the detection of biochemical indicators and liver histological observation. After salvianolic acid B treatment, the levels of LDH, CK, CK-MB, MYO, CTn1, TG, TC, LDL-c, and Apo(b) were significantly lower than that in the model group, while the levels of HDL-c and Apo(a1) were significantly higher than that in the model group. Furthermore, the histological features of fibrosis and steatosis were also evidently relieved in the model group. A total of twenty-six potential biomarkers were identified to express the lipid metabolic turbulence in the CHD animal models, of which twenty-two were regulated by salvianolic acid B trending to the normal state, including TG(20:0/20:4/o-18:0), PC(20:4/18:1(9Z)), PC(18:3/20:2), PA(18:0/18:2), LysoPE(18:2/0:0), SM(d18:0/22:1), PE(22:6/0:0), LysoPE (20:4/0:0), sphinganine, Cer(d18:0/18:0), PS(14:0/14:1), PC (18:0/16:0), LysoPC(17:0), PE(22:2/20:1), PC(20:3/20:4), PE(20:4/P-16:0), PS(20:3/18:0), cholesterol sulfate, TG(15:0/22:6/18:1), prostaglandin E2, arachidonic acid and sphingosine-1-phosphate. According to the metabolite enrichment and pathway analyses, the pharmacological activity of salvianolic acid B on CHD is mainly involved in three vital metabolic pathways including glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism. Thus, based on the lipidomics-guided biochemical analysis of the lipid biomarkers and pathways, Sal B protects against CHD with good therapeutic effect by regulating glycerophospholipid metabolism, sphingolipid metabolism and arachidonic acid metabolism, inhibiting oxidative stress damage and lipid peroxidation.

High-throughput lipidomics provides the possibility for the development of new therapeutic drugs.     

Plasma fatty acid metabolic profiling coupled with clinical research reveals the risk factors for atherosclerosis development in type 2 diabetes mellitus

Many publications have reported that the incidence of atherosclerotic cardiovascular diseases is higher in patients with type 2 diabetes mellitus (T2DM) than in the non-diabetic population; however, until now, the reason has been unclear. In this study, 25 males (25/64, 39.06%) and 19 females (19/54, 35.19%) had complications with atherosclerosis after two years. To reveal the risk factors for developing atherosclerosis in patients with T2DM, plasma fatty acid metabolic profiling based on gas chromatography-mass spectrometry was combined with the analysis of clinical biochemical indices. The results of partial least squares-discriminant and canonical correlation analyses suggested that C20:0, C22:6n-3, glycosylated hemoglobin, waist circumference, and waist-to-hip ratio are likely to be closely related to T2DM complicated with atherosclerosis. Metabolomic information is a beneficial supplement to existing clinical indices and is useful in predicting the development of a patient''s disease and optimizing the treatment.

FFAs metabolic profiling and clinical research were combined to reveal the risk factors for atherosclerosis development in T2DM patients.     

Rapid lipidomics analysis for sepsis-induced liver injury in rats and insights into lipid metabolic pathways using ultra-performance liquid chromatography/mass spectrometry

Lipidomics has been applied in the identification and quantification of molecular lipids within an organism, and to provide insights into mechanisms in clinical medicine. Sepsis is a major systemic inflammatory syndrome and the liver here is a potential target organ for dysfunctional response. However, the study of alterations in global lipid profiles associated with sepsis-induced liver injury is still limited. In this work, we set out to determine alterations of lipidomics profiles in a rat model of sepsis-induced liver injury using an untargeted lipidomics strategy. Liquid chromatography coupled with mass spectrometry in conjunction with multivariate data analysis and pathway analysis were used to acquire a global lipid metabolite profile. Meanwhile, biochemistry index and histopathological examinations of the liver were performed to obtain auxiliary measurements for determining the pathological changes associated with sepsis-induced liver injury. Eleven lipid metabolites and two metabolic pathways were discovered and associated with sepsis-induced liver injury. The results indicated that various biomarkers and pathways may provide evidence for and insight into lipid profile alterations associated with sepsis-induced liver injury, and hence pointed to potential strategic targets for clinical diagnosis and therapy in the future.

Lipidomics has been applied in the identification and quantification of molecular lipids within an organism, and to provide insights into mechanisms in clinical medicine.     

Analysis of serum metabolomics among biopsy-proven diabetic nephropathy,type 2 diabetes mellitus and healthy controls

Type 2 diabetes mellitus (T₂DM) has a rising prevalence and diabetic nephropathy (DN) is a major complication of T₂DM. Metabolomics could provide novel insights into the pathogenesis, so we aimed to explore serum metabolomic profiles from DN to T₂DM. Serum samples were collected from 14 biopsy-proven DNs, 14 age/gender-matched T₂DMs without renal diseases (DM), 14 age/gender-matched healthy controls (CTRL) and household contacts of DM group (HH). Serum metabolomics was analyzed by untargeted liquid chromatography-tandem mass spectrometry (LC/MS) assays. There were a total of 1470 metabolites identified from all serum samples. 45 metabolites with significantly different intensity were found between DN and DM, e.g., biliverdin and taurine were reduced while l-arginine was increased in DN comparing to DM. DN could be distinguished from age/gender matched DM patients by l-arginine (AUC = 0.824) or taurine levels (AUC = 0.789). The metabolic pathways affected by metabolite distinctions between DN and DM also existed, among which taurine and hypotaurine metabolism exhibited the highest pathway impact. l-Methionine, deethylatrazine, l-tryptophan and fumaric acid were reduced in DM comparing with those of CTRL, but had no different intensity in DM and HH groups. The changes were demonstrated in the metabolomic profiles of biopsy-proven DN compared to DM. Biopsy-proven DN patients could be distinguished from age/gender matched DM by l-arginine or taurine levels in serum metabolomic profiles. Taurine and hypotaurine metabolism pathway had the highest impact in pathway set enrichment analysis, which potentially affected the pathogenesis of DN from T₂DM.

Metabolites between healthy controls (CTRL)/type 2 diabetes mellitus without renal diseases (DM), and DM/diabetic nephropathy (DN).     

High-resolution lipidomics reveals dysregulation of lipid metabolism in respiratory syncytial virus pneumonia mice

Respiratory syncytial virus (RSV) is a leading viral pathogen responsible for lower respiratory tract infections, particularly in children under five years worldwide, often resulting in hospitalization. At present, the molecular-level interactions between RSV and its host and the underlying mechanisms of RSV-induced inflammation are poorly understood. Herein, we describe an untargeted high-resolution lipidomics platform based on UHPLC-Q-Exactive-MS to assess the lipid alterations of lung tissues and plasma from a mouse model of RSV pneumonia. Untargeted lipidomics using LC-MS with multivariate analysis was applied to describe the lipidomic profiling of the lung tissues and plasma in RSV pneumonia mice. Lipid identification was conducted via an in silico MS/MS LipidBlast library using the MS-DIAL software. We observed distinct compartmental lipid signatures in the mice lung tissues and plasma and significant lipid profile changes between the systematic and localized host responses to RSV. A total of 87 and 68 differential lipids were captured in the mice lung tissue and plasma, respectively, including phospholipids, sphingolipids, acylcarnitine, and fatty acids. Some of these lipids belong to pulmonary surfactants, illustrating that RSV pneumonia-induced aberrations of the pulmonary surfactant system may play a vital role in the etiology of respiratory inflammation. Our findings reveal that the host responses to RSV and various lipid metabolic pathways were linked to disease pathology. Furthermore, our findings could provide mechanistic insights into RSV pneumonia.

Respiratory syncytial virus (RSV) is a leading viral pathogen responsible for lower respiratory tract infections, particularly in children under five years worldwide, often resulting in hospitalization.     

Lipidomic characterisation discovery for coronary heart disease diagnosis based on high-throughput ultra-performance liquid chromatography and mass spectrometry

Although many diagnostic tools have been developed for coronary heart disease (CHD), its diagnosis is still challenging. Lipids play an important role in diseases and a lipidomics approach could offer a platform to clarify the pathogenesis and pathologic changes of this disease. To the best of our knowledge, no lipidomics studies on serum have been attempted to improve the diagnosis and identify the potential biomarkers of CHD. The aim of this study was to investigate the distinctive lipid changes in serum samples of CHD patients and to identify candidate biomarkers for the reliable diagnosis of CHD using this platform. In this study, the serum lipid profiles of CHD patients were measured via ultra-performance liquid chromatography-G2-Si-high definition mass spectrometry combined with multivariate data analysis. A MetaboAnalyst tool was used for the analysis of the receiver operating-characteristic, while the IPA software was applied for the pathway analysis. The obtained results inferred that 33 lipid molecular species involving 6 fatty acids, 21 glycerophospholipids and 6 sphingolipids have significant differences in the serum of CHD patients. Simultaneously, 4 upstream regulatory proteins related to lipid metabolism disorders of CHD were predicted. Ten lipids have high clinical diagnostic significance according to the receiver operating-characteristic curves. This research shows that the in-depth study of lipids in the serum contributes to the clinical diagnosis of CHD and interprets the occurrence and development of CHD.

Although many diagnostic tools have been developed for coronary heart disease (CHD), its diagnosis is still challenging.     

Non-invasive Raman spectroscopy for time-resolved in-line lipidomics

Oil-producing yeast cells are a valuable alternative source for palm oil production and, hence, may be one important piece of the puzzle for a more sustainable future. To achieve a high-quality product, the lipid composition inside oil-producing yeast cells is a crucial parameter for effective process control. Typically, the lipid composition is determined by off-line gas chromatography. A faster, less cumbersome approach is proposed here, by using non-invasive in-line Raman spectroscopy. A fed-batch fermentation of C. oleaginosus – a well-known oleaginous yeast – is used as model experiment to highlight the potential of Raman spectroscopy for in-line lipidomics. The temporal progression of biomass formation, lipid production and glucose consumption are determined based on PLS-regression models allowing process-relevant information on time to be accessed. Additionally, Gaussian curve fitting was applied to extract increasing and decreasing trends of saturated and unsaturated fatty acids produced by C. oleaginosus throughout the fermentation process.

Oil-producing yeast cells are a valuable alternative source for palm oil production and, hence, may be one important piece of the puzzle for a more sustainable future.     

Ag-exchanged NaY zeolite introduced polyvinyl alcohol/polyacrylic acid mixed matrix membrane for pervaporation separation of water/isopropanol mixture

Ag-exchanged NaY zeolite (Ag-NaZ) particles were prepared by ion exchange and introduced to a polyvinyl alcohol (PVA) membrane cross-linked with polyacrylic acid (PAA) for the pervaporation dehydration of an isopropanol (IPA) aqueous mixture. The Ag-exchanged NaY zeolite particles were characterized by FE-SEM, EDS, BET, and XRD studies. The prepared Ag-NaZ-loaded PVA/PAA composite membrane was characterized by FE-SEM, XRD, a swelling study, and contact angle measurements. Pervaporation characteristics were investigated in terms of Ag-NaZ concentrations within PVA/PAA membranes using diverse feed solution conditions. The preferential sorption of IPA/water mixtures for Ag-NaZ-introduced membranes were also determined by calculating the apparent activation energies of IPA and water permeation, respectively. As a result, flux and selectivity increased with the Ag-NaZ concentration to 5 wt% in the membrane. Optimum pervaporation performance was observed in a 5 wt% Ag-NaZ-incorporated membrane with a flux equal to 0.084 kg m⁻² h⁻¹ and a separation factor of 2717.9 at 40 °C from an 80 wt% IPA aqueous feed solution.

Ag-exchanged NaY zeolite (Ag-NaZ) particles were prepared by ion exchange and introduced to a polyvinyl alcohol (PVA) membrane cross-linked with polyacrylic acid (PAA) for the pervaporation dehydration of an isopropanol (IPA) aqueous mixture.     

Fabrication of fine-pored polydimethylsiloxane using an isopropyl alcohol and water mixture for adjustable mechanical,optical, and thermal properties

Porous polydimethylsiloxane (PDMS) has garnered interest owing to its large inner surface area, high deformability, and lightweight, while possessing inherent properties, such as transparency, flexibility, cost-effectiveness, ease of fabrication, chemical/mechanical stability, and biocompatibility. For producing porous PDMS, gas foaming, sacrificial template, and emulsion template techniques have been used extensively. However, the aforementioned methods have difficulty in achieving submicron-sized inner pores, which is advantageous for improving flexibility and transparency. This study demonstrates a simple fabrication method for obtaining porous PDMS with fine pores partially down to the sub-micron scale. This is possible by the use of cheap, volatile, and easily accessible isopropyl alcohol (IPA) as a co-solvent in water and pre-PDMS emulsion. IPA shows an affinity towards both water and prepolymer, resulting in an increased distribution of small water particles inside PDMS before curing. These water particles evaporate while curing the prepolymer emulsion, thereby generating fine pores. The fine size and number density of pores are controlled by water and the added amount of IPA, resulting in adjustable mechanical, optical, and thermal properties of porous PDMS.

A fabrication method for obtaining fine-pored PDMS is presented. Low-cost, volatile, and easily accessible IPA is used as a co-solvent in water and PDMS emulsions, allowing porous PDMS with adjustable mechanical, optical and thermal properties.     

New players in the sepsis-protective activated protein C pathway

Recombinant activated protein C (aPC) improves the survival of patients with severe sepsis, but the precise molecular and cellular targets through which it mediates this effect remain incompletely understood. In this issue of the JCI, Kerschen et al. show that endothelial cell protein C receptor (EPCR) is specifically expressed by mouse CD8⁺ dendritic cells and that these coordinators of host responses to systemic infection are required for aPC to provide protection against the lethality of sepsis. An additional study, by Cao and colleagues, recently published in the JCI, implicates the leukocyte integrin CD11b in the pathways by which aPC mediates antiinflammatory effects in the context of lethal sepsis in mice, suggesting a common thread of synergistic control of innate immune responses by life-saving aPC therapy. Sepsis affects as many as 500,000 individuals in the United States each year, and in many of these cases it is lethal. Uncontrolled inflammation and coagulation are two hallmarks of severe sepsis. The latter is a result of increased coagulation mediated by tissue factor and impaired anticoagulation following cellular downregulation or depletion of thrombomodulin, endothelial cell protein C receptor (EPCR), and protein C (PC). The fact that sepsis-induced uncontrolled coagulation leads to microvascular thrombosis, which in turn can result in organ failure, provided the rationale for the clinical development of recombinant activated PC (aPC) as a therapy for sepsis. This approach markedly improved overall 28-day mortality in patients, specifically in the subgroup of patients with severe sepsis.After the discovery that aPC could improve the survival of patients with severe sepsis, researchers sought to understand the molecular and cellular mechanisms underlying its effects. Initial observations that aPC attenuated inflammatory NF-κB signaling in endothelial and monocytic cells led to the hypothesis that the effects of aPC were not mediated simply by its ability to promote anticoagulation. Subsequent analysis identified an aPC signaling complex in which aPC binds to EPCR, facilitating the proteolytic cleavage of protease-activated receptor 1 (PAR1) on endothelial cells by aPC (1). Endothelial EPCR/aPC/PAR1 signaling typically counterbalances the detrimental effects of inflammation as well as those of thrombin/PAR1 signaling, which promote apoptosis, barrier disruption, and endothelial activation (2, 3). Although the paradoxical, opposing roles of PAR1 signaling are incompletely understood, several contributing factors have been identified, including the inability of EPCR/aPC-cleaved PAR1 to cross-activate PAR2 (3); coupling of EPCR/aPC signaling to sphingosine-1-phosphate receptor signaling (2); localization of EPCR/aPC signaling to caveolae, resulting in PAR1 desensitization (4); and ligand occupancy of EPCR, leading to EPCR/caveolin dissociation and a broad switch of PAR1 signaling specificity (5). The development of mutants of aPC that were either permissive for signaling but had minimal anticoagulant activity (6) or potent anticoagulants with drastically reduced signaling function (7) provided the decisive tools to investigate whether aPC-mediated signaling, rather than its anticoagulant activity, was crucial for mortality reduction following aPC therapy in mouse models of sepsis, and this was demonstrated to be the case (6, 7). Furthermore, mice with very low levels of EPCR or deficiency of PAR1 did not benefit from aPC administration (6). However, these studies did not provide insight into relevant cellular targets for sepsis-protective aPC signaling (6, 7). Notably, the effects of aPC in other cell types can be independent of EPCR or PAR1 and may involve additional receptors. EPCR also supports PAR2 cleavage by aPC (1), aPC requires PAR3 for neuroprotection in stroke (8), and aPC utilizes the endocytic receptor LDL receptor–related protein 8 (LRP8; also known as ApoER2) to directly trigger disabled 1 (Dab1) and glycogen synthase kinase 3β phosphorylation in myeloid cells (9). Data published recently in the JCI by Cao et al. (10) and in this issue of the JCI by Kerschen et al. (11) elucidate new non-anticoagulant mechanisms by which aPC can protect against lethal sepsis in mice. Specifically, these reports indicate that aPC can control immune responses and are consistent with another recent article showing that aPC suppresses neutrophil migration (12).     

Stability and pervaporation characteristics of PVA and its blend with PVAm membranes in a ternary feed mixture containing highly reactive epichlorohydrin

In order to find an alternative for classical distillation in the recovery of ECH/IPA from azeotropic ECH/IPA/water (50/30/20 w/w, %) mixtures, a pervaporation process has been applied. Membranes from the crosslinking of poly(vinyl alcohol)/poly(vinyl amine) (PVA/PVAm) were prepared, and then the membrane stability and pervaporation efficiency of the crosslinked PVA/PVAm membranes were studied for highly reactive ECH systems containing a ternary feed mixture. From the Fourier-transform infrared (FT-IR) spectroscopy analysis, it was observed that all of the membranes were chemically stable for 15 days of immersion in a 50 : 30 : 20 ECH/IPA/water (w/w, %) feed mixture at 60 °C. The degree of membrane swelling increased with increasing PVAm content in the membrane composition, water content in the feed composition, and feed temperature, which was attributed to the increase in the number of hydrophilic sites in the membrane. The field-emission scanning electron microscopy (FE-SEM) study revealed that higher PVAm content membranes (PVAm1.0 and PVAm1.5) show polymer phase extraction in ECH/IPA/water (50 : 30 : 20) (w/w, %) at 60 °C in long-term stability tests. The pervaporation dehydration characteristics for all of the membranes with the feed comprising an ECH/IPA/water (50 : 30 : 20 by weight) azeotropic mixture at 30 °C were examined and excellent pervaporation dehydration efficiency was found. Quantitatively, the flux increased from 0.025 to 0.32 kg (m² h)⁻¹ and the separation factor decreased from 1908 to 60 with increasing PVAm content in the blended membrane.

In order to find an alternative for classical distillation in the recovery of ECH/IPA from azeotropic ECH/IPA/water (50/30/20 w/w, %) mixtures, a pervaporation process has been applied.     

Real role of growth factor receptor-binding protein 10: Linking lipid metabolism to diabetes cardiovascular complications

Cardiovascular complications of patients with type 2 diabetes mellitus (T2DM) threaten the health and life of numerous individuals. Recently, growth factor receptor-binding protein 10 (GRB10) was found to play a pivotal role in vascular complications of T2DM, which participates in the regulation of lipid metabolism of T2DM patients. The genetic variation of GRB10 rs1800504 is closely related to the risk of coronary heart disease in patients with T2DM. The development of GRB10 as a key mediator in the association of lipid metabolism with cardiovascular complications in T2DM is detailed in and may provide new potential concerns for the study of cardiovascular complications in T2DM patients.     

Two-photon fluorescent probes for detecting the viscosity of lipid droplets and its application in living cells

Lipid droplets (LDs) are storage organelles at the centre of lipid and energy homeostasis, which act as vital hubs of cellular metabolism and the key to maintaining lipid and energy homeostasis. We synthesized a new two-photon fluorescent probe (CIV) that could detect the viscosity of lipid droplets. The probe is constructed via the typical ICT system of D–π–A using carbazole as the donor and imidazole as the acceptor. With the increase in viscosity from PBS to 99% glycerol, the fluorescence intensity of CIV increased by 13-fold, showing sensitivity and specificity towards viscosity. In addition, CIV showed low toxicity and excellent biocompatibility in cytotoxicity tests, and was successfully used for living cell LD imaging. Taken together, the results widen the way for the development of novel fluorescent probe-based the visualization LDs and detection in solutions, physiology and pathology.

A novel two-photon fluorescence probe (CIV) can detect the viscosity and locate lipid droplets in living cells.     

Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD)

OBJECTIVE

Prediabetes and type 2 diabetes mellitus (T2DM) are believed to be common and associated with a worse metabolic profile in patients with nonalcoholic fatty liver disease (NAFLD). However, no previous study has systematically screened this population.

RESEARCH DESIGN AND METHODS

We studied the prevalence and the metabolic impact of prediabetes and T2DM in 118 patients with NAFLD. The control group comprised 20 subjects without NAFLD matched for age, sex, and adiposity. We measured 1) plasma glucose, insulin, and free fatty acid (FFA) concentration during an oral glucose tolerance test; 2) liver fat by magnetic resonance spectroscopy (MRS); 3) liver and muscle insulin sensitivity (euglycemic insulin clamp with 3-[³H]glucose); and 4) indexes of insulin resistance (IR) at the level of the liver (HIR_i= endogenous glucose production × fasting plasma insulin [FPI]) and adipose tissue (Adipo-IR_i= fasting FFA × FPI).

RESULTS

Prediabetes and T2DM was present in 85% versus 30% in controls (P < 0.0001), all unaware of having abnormal glucose metabolism. NAFLD patients were IR at the level of the adipose tissue, liver, and muscle (all P < 0.01–0.001). Muscle and liver insulin sensitivity were impaired in patients with NAFLD to a similar degree, whether they had prediabetes or T2DM. Only adipose tissue IR worsened in T2DM and correlated with the severity of muscle (r = 0.34; P < 0.001) and hepatic (r = 0.57; P < 0.0001) IR and steatosis by MRS (r = 0.35; P < 0.0001).

CONCLUSIONS

Patients with NAFLD may benefit from early screening for T2DM, because the prevalence of abnormal glucose metabolism is much higher than previously appreciated. Regardless of glucose tolerance status, severe IR is common. In patients with T2DM, adipose tissue IR appears to play a major role in the severity of NAFLD.Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease in industrialized countries (1). NAFLD is strongly correlated with insulin-resistant states such as obesity, metabolic syndrome (MetS), and type 2 diabetes mellitus (T2DM). Cross-sectional studies have associated T2DM with worse histology in NAFLD (2) and possibly with a greater risk of progression and more aggressive disease. For instance, patients with diabetes have a higher risk of developing fibrosis and cirrhosis (2–5), although the natural history of the disease in patients with T2DM remains unclear. Compared with nondiabetic subjects, subjects with T2DM are believed to have an increased risk of developing NAFLD (3,6), but the true prevalence of prediabetes and T2DM has never been systematically assessed by means of an oral glucose tolerance test (OGTT) among patients with NAFLD. The magnitude of the problem is large: an estimated 25.8 million people, or 8.3% of the U.S. population, have type 1 and type 2 diabetes (7). Even more worrisome is that 35% of adults and ∼50% of those aged >60 years have prediabetes, a condition that puts them at higher risk for developing T2DM. Whether NAFLD, a condition associated with insulin resistance (IR), increases the risk of developing T2DM remains unclear.The purpose of our study was to determine the prevalence of abnormal glucose metabolism and understand how hyperglycemia and NAFLD impact the metabolic profile of these subjects.     

Monohydrate and anhydrate of nylon 5I monomer 1,5-pentanediamine–isophthalate

Nylon 5I is one of the new bio-based nylon materials. Its raw material 1,5-pentanediamine (PDA) is prepared by biological methods using biomass as the raw material. The high-performance polymer materials require the original high-quality monomers. 1,5-Pentanediamine–isophthalate (PDA–IPA) was taken as the direct monomer for the preparation of nylon 5I, and the crystallization was a valuable and essential approach to preparing the good-performance monomer salt. In this report, we found and obtained two crystal forms of PDA–IPA, monohydrate and an anhydrous form. Their crystal structures were determined and analyzed by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Hirshfeld surface maps were employed to capture the differences in the interactions present in the two forms. The thermal behaviors were characterized by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Moreover, the monohydrate and anhydrous phase can transform to each other through solid–solid transformation or solution-mediated phase transformation, and the critical values of the phase transformation were determined. Finally, the relative stability of the two forms under different thermodynamic conditions was discussed, especially the influence of temperature and water activity on the stability.

Monohydrate and anhydrous phases of PDA–IPA single crystals have been identified by single crystal X-ray diffraction. The monohydrate and anhydrate phases can achieve mutual transformation under certain conditions, and depend strongly on the temperature and water activity.     

初诊2型糖尿病患者胰腺脂质沉积程度与脂代谢紊乱的相关性

目的探讨初诊2型糖尿病(T2DM)患者胰腺脂质沉积与脂代谢紊乱的关系。方法收集T2DM患者64例和对照组60例,均接受上腹部CT平扫,计算脾胰CT差值,评估胰腺脂质沉积程度;设定脾脏CT值-胰腺CT值差值>5 HU为脂肪胰组,≤5 HU为非脂肪胰组。将T2DM患者再分为单纯T2DM组(20例),合并脂肪胰组(44例)。测定各组血浆三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)含量评估脂代谢状况。结果脾胰CT差值T2DM组为(11.7±8.9)Hu较对照组的(8.9±6.9)Hu有所增加;两组TG、HDL差异有统计学意义(P<0.05)。偏相关分析表明,脾胰CT差值与TG正相关(r=0.525),与HDL负相关(r=-0.575)。结论胰腺脂质沉积程度与脂代谢密切相关,可能参与T2DM患者代谢紊乱的发生、发展。