Clinical- and omics-based models of subclinical atherosclerosis in healthy Chinese adults: a cross-sectional exploratory study.

BACKGROUND: Classical risk factors, such as fasting cholesterol, blood pressure (BP), and diabetes status are used today to predict the risk of developing cardiovascular disease (CVD). However, accurate prediction remains limited, particularly in low-risk groups such as women and younger individuals. Growing evidence suggests that biomarker concentrations following consumption of a meal challenge are better and earlier predictors of disease development than biomarker concentrations. OBJECTIVE: To test the hypothesis that postprandial responses of circulating biomarkers differ between healthy subjects with and without subclinical atherosclerosis (SA) in an Asian population at low risk of coronary artery disease (CAD). METHODS: One hundred healthy Chinese subjects (46 women, 54 men) completed the study. Subjects consumed a mixed-meal test and 164 blood biomarkers were analyzed over 6 h by using a combination of chemical and NMR techniques. Models were trained using different methodologies (including logistic regression, elastic net, random forest, sparse partial least square) on a random 75% subset of the data, and their performance was evaluated on the remaining 25%. RESULTS: We found that models based on baseline clinical parameters or fasting biomarkers could not reliably predict SA. By contrast, an omics model based on magnitude and timing of postprandial biomarkers achieved high performance [receiving operating characteristic (ROC) AUC: 91%; 95% CI: 77, 100). Investigation of key features of this model enabled derivation of a considerably simpler model, solely based on postprandial BP and age, with excellent performance (AUC: 91%; 95% CI: 78, 100). CONCLUSION: We report a novel model to detect SA based on postprandial BP and age in a population of Asian subjects at low risk of CAD. The use of this model in large-scale CVD prevention programs should be explored. This trial was registered at ClinicalTrials.gov as NCT03531879.

Fibroblast Growth Factor-21, Leptin, and Adiponectin Responses to Acute Cold-Induced Brown Adipose Tissue Activation.

BACKGROUND: Adipocyte-derived hormones play a role in insulin sensitivity and energy homeostasis. However, the relationship between circulating fibroblast growth factor 21 (FGF21), adipocytokines and cold-induced supraclavicular brown adipose tissue (sBAT) activation is underexplored. OBJECTIVE: Our study aimed to investigate the relationships between cold-induced sBAT activity and plasma FGF21 and adipocytokines levels in healthy adults. DESIGN: Nineteen healthy participants underwent energy expenditure (EE) and supraclavicular infrared thermography (IRT) within a whole-body calorimeter at baseline and at 2 hours post-cold exposure. 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging scans were performed post-cold exposure. PET sBAT mean standardized uptake value (SUV mean), MR supraclavicular fat fraction (sFF), anterior supraclavicular maximum temperature (Tscv max) and EE change (%) after cold exposure were used to quantify sBAT activity. MAIN OUTCOME MEASURES: Plasma FGF21, leptin, adiponectin, and tumor necrosis factor alpha (TNFα) at baseline and 2 hours post-cold exposure. Body composition at baseline by dual-energy x-ray absorptiometry (DXA). RESULTS: Plasma FGF21 and adiponectin levels were significantly reduced after cold exposure in BAT-positive subjects but not in BAT-negative subjects. Leptin concentration was significantly reduced in both BAT-positive and BAT-negative participants after cold exposure. Adiponectin concentration at baseline was positively strongly associated with sBAT PET SUV mean (coefficient, 3269; P = 0.01) and IRT Tscv max (coefficient, 6801; P  = 0.03), and inversely correlated with MR sFF (coefficient, -404; P  = 0.02) after cold exposure in BAT-positive subjects but not in BAT-negative subjects. CONCLUSION: Higher adiponectin concentrations at baseline indicate a greater cold-induced sBAT activity, which may be a novel predictor for sBAT activity in healthy BAT-positive adults. HIGHLIGHTS: A higher adiponectin concentration at baseline was associated with higher cold-induced supraclavicular BAT PET SUV mean and IRT Tscv max, and lower MR supraclavicular FF. Adiponectin levels maybe a novel predictor for cold-induced sBAT activity.

Postprandial glucose, insulin and incretin responses differ by test meal macronutrient ingestion sequence (PATTERN study).

BACKGROUND: Previous studies have shown that the sequential order of consuming different food components significantly impacts postprandial glucose and insulin excursions in prediabetes and type 2 diabetes, but the causative mechanisms in healthy humans remain ill-defined. OBJECTIVE: Using a typical Asian meal comprising vegetables, protein (chicken breast), and carbohydrate (white rice), the aim of this study was to examine the effect of food intake sequence on postprandial glucose, insulin and incretin secretions in healthy adults. DESIGN: Sixteen healthy Chinese adults participated in a randomized, controlled, crossover meal trial. Subjects consumed in random order 5 experimental isocaloric meals that differed in the food intake sequence of vegetables, protein and carbohydrate. Glucose, insulin, incretins and satiety markers were measured over 3 h. RESULTS: There were significant food intake sequence × time interaction effects on plasma glucose, insulin, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations (P < 0.001). In comparison with rice consumed first followed by vegetable and meat (R-VM), the overall postprandial glucose response was significantly attenuated after the food intake sequence of vegetable first, followed by meat and rice (V-MR) or meat first, followed by vegetable and rice (M-VR) or vegetable first followed by meat and rice (V-M-R) or vegetable, meat and rice consumed together (VMR). The insulin iAUC (0-60) was significant lower after V-M-R than M-VR, VMR and R-VM. V-M-R food intake sequence stimulated higher GLP-1 release than other meal sequences. However, GIP response was lower after V-MR and V-M-R than M-VR and R-MR food intake sequences. CONCLUSIONS: Food macronutrient intake sequence can considerably influence its glycemic, insulinemic and incretin responses. V-M-R food intake sequence attenuates the glycemic response to a greater degree with accentuated GLP-1 stimulation without any increased demand for insulin. The sequence of food intake has great potential as a novel and simple behavioral strategy to modulate glycemic response in healthy adults. The trial was registered at clinicaltrials.gov as NCT03533738.

Differential Effects of Monounsaturated and Polyunsaturated Fats on Satiety and Gut Hormone Responses in Healthy Subjects.

The difference between fat saturation on postprandial hormone responses and acute appetite control is not well understood. The aim of this study was to compare the postprandial ghrelin, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP1) response and subjective appetite responses after isoenergetic high-fat meals rich in either monounsaturated (MUFAs) or polyunsaturated fatty acids (PUFAs) in healthy Chinese males. A randomized, controlled, single-blinded crossover study was conducted in 13 healthy Chinese men. Two high-fat meals (64% of energy) rich in MUFAs or PUFAs were tested. Total ghrelin, GIP and active GLP1 and visual analog scale (VAS) were measured over 4 h. Ghrelin was reduced greater after MUFA compared to PUFA at the beginning of the meal (at 30 and 60 min) and was significantly negatively correlated with subjective VAS for preoccupation for both MUFA and PUFA meals. No significant difference for ghrelin 240 min incremental area under the curve (iAUCs) were found. MUFA induced higher GIP response than PUFA. GIP was associated with all the VAS measurements except preoccupation for MUFA meal. No difference was found for GLP1 between two meals, nor was GLP1 associated with VAS. In conclusion, the results demonstrate that ghrelin, GIP and VAS respond differently to MUFA and PUFA meals. Ghrelin and GIP, but not GLP1, were associated with acute appetite control, especially after MUFA meal.