Diet-Related Lipidomic Signatures and Changed Type 2 Diabetes Risk in a Randomized Controlled Feeding Study With Mediterranean Diet and Traditional Chinese or Transitional Diets.

OBJECTIVE: Few trials studied the links of food components in different diets with their induced lipidomic changes and related metabolic outcomes. Thus, we investigated specific lipidomic signatures with habitual diets and modified diabetes risk by using a trial and a cohort. RESEARCH DESIGN AND METHODS: We included 231 Chinese with overweight and prediabetes in a randomized feeding trial with Mediterranean, traditional, or transitional diets (control diet) from February to September 2019. Plasma lipidomic profiles were measured at baseline, third month, and sixth month by high-throughput targeted liquid chromatography-mass spectrometry. Associations of the identified lipids with habitual dietary intakes were examined in another lipidomic database of a Chinese cohort (n = 1,117). The relationships between diet-induced changes of lipidomic species and diabetes risk factors were further investigated through both individual lipids and relevant modules in the trial. RESULTS: Out of 364 lipidomic species, 26 altered across groups, including 12 triglyceride (TAG) fractions, nine plasmalogens, four phosphatidylcholines (PCs), and one phosphatidylethanolamine. TAG fractions and PCs were associated with habitual fish intake while plasmalogens were associated with red meat intake in the cohort. Of the diet-related lipidomic metabolites, 10 TAG fractions and PC(16:0/22:6) were associated with improved Matsuda index (ß = 0.12 to 0.42; PFDR < 0.030). Two plasmalogens were associated with deteriorated fasting glucose (ß = 0.29 to 0.31; PFDR < 0.014). Similar results were observed for TAG and plasmalogen related modules. CONCLUSIONS: These fish- and red meat-related lipidomic signatures sensitively reflected different diets and modified type 2 diabetes risk factors, critical for optimizing dietary patterns.

Isocaloric-restricted Mediterranean Diet and Chinese Diets High or Low in Plants in Adults With Prediabetes.

CONTEXT: Calorie restriction plus dietary advice is suggested as a preventive strategy for individuals with obesity and prediabetes; however, optimal diet is still debatable. We aimed to compare the effects of Mediterranean diet (MD) and Chinese diets high or low in plants on body weight and glucose homeostasis among high-risk Chinese. SUBJECTS AND METHODS: In this parallel-arm randomized controlled trial, 253 Chinese adults aged 25 to 60 years with a body mass index ≥ 24.0 kg/m2 and fasting blood glucose ≥ 5.6 mmol/L were randomly assigned to 3 isocaloric-restricted diets: MD (n = 84), a traditional Jiangnan diet high in plants (TJD, n = 85), or a control diet low in plants (CD, n = 84). During the 6-month trial, a 5-weekday full-feeding regimen was followed, along with mobile app-based monitoring. Abdominal fat measurement (magnetic resonance imaging), oral glucose tolerance test (OGTT), and continuous glucose monitoring (CGM) were conducted at baseline and 3 and 6 months. RESULTS: With a 25% calorie restriction for 6 months, weight deduction was 5.72 kg (95% confidence interval, 5.03-6.40) for MD, 5.05 kg (4.38-5.73) for TJD, and 5.38 kg (4.70-6.06) for CD (Ptime < 0.0001). No between-group differences were found for fasting glucose, insulin, and the Matsuda index from OGTT. Notably, CD had significantly longer time below range (glucose < 3.9 mmol/L) than MD (0.81% [0.21-1.40], P = 0.024) and marginally longer time than TJD (0.56% [-0.03 to 1.15], P = 0.065), as measured by CGM. CONCLUSIONS: With the 6-month isocaloric-restricted feeding, TJD and MD achieved comparable weight deduction and improved glucose homeostasis, whereas CD showed a higher risk for hypoglycemia.

Plasma Lipidomic Subclasses and Risk of Hypertension in Middle-Aged and Elderly Chinese.

While disrupted lipid metabolism is a well-established risk factor for hypertension in animal models, the links between various lipidomic signatures and hypertension in human studies remain unclear. We aimed to examine associations between plasma lipidomic profiles and prevalence of hypertension among 2248 community-living Chinese aged 50-70 years. Hypertension was defined according to 2020 International Society of Hypertension global hypertension practice guidelines and 2018 Chinese guidelines. In total, 728 plasma lipidomic species were profiled using high-coverage targeted lipidomics. After multivariate adjustment, including lifestyle, body mass index, blood lipids, and sodium intake, 110 metabolites from nine lipidomic subclasses showed significant associations with hypertension, among which phosphatidylethanolamines (PEs) had the strongest association. Eleven lipidomic signals for hypertension risk were further identified from the nine subclasses, including PE(18:0/18:2) (OR per SD, 1.49; 95% confidence intervals, 1.30-1.69), phosphatidylcholine (PC) (18:0/18:2) (1.27; 1.13-1.43), phosphatidylserine (18:0/18:0) (1.24; 1.09-1.41), lysophosphatidylinositol (18:1) (1.17; 1.06-1.29), triacylglycerol (52:5) (1.38; 1.18-1.61), diacylglycerol (16:0/18:2) (1.42; 1.19-1.69), dihydroceramide (24:0) (1.25; 1.09-1.43), hydroxyl-sphingomyelins (SM[2OH])C34:1 (1.19; 1.07-1.33), lysophosphatidylcholine (20:1) (0.86; 0.78-0.95), SM(OH)C38:1 (0.87; 0.79-0.96), and PC (18:2/20:1) (0.84; 0.75-0.94). Principal component analysis also showed that a factor mainly containing specific PEs was positively associated with hypertension (1.20; 1.09-1.33). Collectively, our study revealed that disturbances in multiple circulating lipidomic subclasses and signatures, especially PEs, were significantly associated with the prevalence of hypertension in middle-aged and elderly Chinese. Future studies are warranted to confirm our findings and determine the mechanisms underlying these associations. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-022-00057-y.

N-Butyl-2-cyanoacrylate-based injectable and in situ-forming implants for efficient intratumoral chemotherapy.

The local delivery of chemotherapeutic drugs to tumor sites is an effective approach for achieving therapeutic drug concentrations in solid tumors. Injectable implants with the ability to form in situ represent one of the most promising technologies for intratumoral chemotherapy. However, many issues must be resolved before these implants can be applied in clinical practice. Herein, we report a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA) and ethyl oleate, and the sol-gel phase transition is activated by anions in body fluids or blood. This newly developed injectable NBCA ethyl oleate implant (INEI) is biodegradable, biocompatible, and non-toxic. INEI solidifies in several seconds after exposure to body fluids or blood, and the implant's in vivo degradation time can be controlled. In addition, the pore sizes formed by the polymerization of NBCA can be decreased by increasing the NBCA concentration in the implants. Therefore, the drug retention/release time can be adjusted from a few weeks to several months by changing the concentration of NBCA in the implant formulation. Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human breast cancer cells by the paclitaxel-loaded INEI (40% NBCA) was 80%, and they also indicated that tumors in some of the mice were completely eliminated by just a single dosage injection. For the epirubicin-loaded INEI (50% NBCA), the average growth inhibition rate of xenografted human liver cancer cells was 58%. Thus, the chemotherapeutic drug-loaded INEIs exhibited excellent therapeutic efficacy for local chemotherapy.