Joblin-Mills Aidan, Wu Zhanxuan, Fraser Karl, Jones Beatrix, Yip Wilson, Lim Jia Jiet, Lu Louise, Sequeira Ivana, Poppitt Sally
Food Chemistry and Structure Team, Agresearch, Palmerston North, New Zealand.
High-Value Nutrition, National Science Challenge, Auckland, New Zealand.
Front Clin Diabetes Healthc. 2022 Oct 14;3:980856. doi: 10.3389/fcdhc.2022.980856. eCollection 2022.
The "Thin on the Outside Fat on the Inside" TOFI_Asia study found Asian Chinese to be more susceptible to Type 2 Diabetes (T2D) compared to European Caucasians matched for gender and body mass index (BMI). This was influenced by degree of visceral adipose deposition and ectopic fat accumulation in key organs, including liver and pancreas, leading to altered fasting plasma glucose, insulin resistance, and differences in plasma lipid and metabolite profiles. It remains unclear how intra-pancreatic fat deposition (IPFD) impacts TOFI phenotype-related T2D risk factors associated with Asian Chinese. Cow's milk whey protein isolate (WPI) is an insulin secretagogue which can suppress hyperglycemia in prediabetes. In this dietary intervention, we used untargeted metabolomics to characterize the postprandial WPI response in 24 overweight women with prediabetes. Participants were classified by ethnicity (Asian Chinese, n=12; European Caucasian, n=12) and IPFD (low IPFD < 4.66%, n=10; high IPFD ≥ 4.66%, n=10). Using a cross-over design participants were randomized to consume three WPI beverages on separate occasions; 0 g (water control), 12.5 g (low protein, LP) and 50 g (high protein, HP), consumed when fasted. An exclusion pipeline for isolating metabolites with temporal (T) WPI responses was implemented, and a support vector machine-recursive feature elimination (SVM-RFE) algorithm was used to model relevant metabolites by ethnicity and IPFD classes. Metabolic network analysis identified glycine as a central hub in both ethnicity and IPFD WPI response networks. A depletion of glycine relative to WPI concentration was detected in Chinese and high IPFD participants independent of BMI. Urea cycle metabolites were highly represented among the ethnicity WPI metabolome model, implicating a dysregulation in ammonia and nitrogen metabolism among Chinese participants. Uric acid and purine synthesis pathways were enriched within the high IPFD cohort's WPI metabolome response, implicating adipogenesis and insulin resistance pathways. In conclusion, the discrimination of ethnicity from WPI metabolome profiles was a stronger prediction model than IPFD in overweight women with prediabetes. Each models' discriminatory metabolites enriched different metabolic pathways that help to further characterize prediabetes in Asian Chinese women and women with increased IPFD, independently.
“外瘦内胖”（TOFI）亚洲研究发现，与性别和体重指数（BMI）相匹配的欧洲白种人相比，华裔亚洲人更容易患2型糖尿病（T2D）。这受到内脏脂肪沉积程度以及肝脏和胰腺等关键器官中异位脂肪积累的影响，导致空腹血糖改变、胰岛素抵抗以及血浆脂质和代谢物谱的差异。胰腺内脂肪沉积（IPFD）如何影响与华裔亚洲人相关的TOFI表型相关T2D风险因素仍不清楚。牛乳清蛋白分离物（WPI）是一种胰岛素促分泌剂，可抑制糖尿病前期的高血糖。在这项饮食干预中，我们使用非靶向代谢组学来表征24名超重糖尿病前期女性的餐后WPI反应。参与者按种族（华裔亚洲人，n = 12；欧洲白种人，n = 12）和IPFD（低IPFD < 4.66%，n = 10；高IPFD≥4.66%，n = 10）进行分类。采用交叉设计，参与者被随机安排在不同时间饮用三种WPI饮料；0克（水对照）、12.5克（低蛋白，LP）和50克（高蛋白，HP），在空腹时饮用。实施了一个用于分离具有时间（T）WPI反应的代谢物的排除流程，并使用支持向量机递归特征消除（SVM-RFE）算法按种族和IPFD类别对相关代谢物进行建模。代谢网络分析确定甘氨酸是种族和IPFD WPI反应网络中的核心枢纽。在华裔和高IPFD参与者中，与WPI浓度相比，甘氨酸含量减少，且与BMI无关。尿素循环代谢物在种族WPI代谢组模型中占比很高，这表明华裔参与者的氨和氮代谢失调。尿酸和嘌呤合成途径在高IPFD队列的WPI代谢组反应中富集，这与脂肪生成和胰岛素抵抗途径有关。总之，在超重糖尿病前期女性中，从WPI代谢组谱中区分种族比IPFD是更强的预测模型。每个模型的鉴别代谢物丰富了不同的代谢途径，有助于分别进一步表征华裔亚洲女性和IPFD增加的女性的糖尿病前期情况。
