Department of Information Engineering, University of Padova, Padova, Italy.
Division of Endocrinology, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Virginia, United States.
Am J Physiol Endocrinol Metab. 2023 Aug 1;325(2):E163-E170. doi: 10.1152/ajpendo.00091.2023. Epub 2023 Jun 28.
Assessing free fatty acids (FFAs) kinetics and the role of insulin and glucose on FFA lipolysis and disposal may improve our understanding of the pathogenesis of type 2 diabetes (T2D). Some models have been proposed to describe FFA kinetics during an intravenous glucose tolerance test and only one during an oral glucose tolerance test. Here, we propose a model of FFA kinetics during a meal tolerance test and use it to assess possible differences in postprandial lipolysis in individuals with type 2 diabetes (T2D) and individuals with obesity without type 2 diabetes (ND). We studied 18 obese ND and 16 T2D undergoing three meal tolerance tests (MTT) on three occasions (breakfast, lunch, and dinner). We used plasma glucose, insulin, and FFA concentrations collected at breakfast to test a battery of models and selected the best one based on physiological plausibility, ability to fit the data, precision of parameter estimates, and the Akaike parsimony criterion. The best model assumes that the postprandial suppression of FFA lipolysis is proportional to the above basal insulin, while FFA disposal is proportional to FFA concentration. It was used to compare FFA kinetics in ND and T2D along the day. The maximum lipolysis suppression occurred significantly earlier in ND than T2D (39 ± 6 min vs. 102 ± 13 min, 36 ± 4 min vs. 78 ± 11 min, and 38 ± 6 min vs. 84 ± 13 min, < 0.01, at breakfast, lunch, and dinner, respectively), making lipolysis significantly lower in ND than T2D. This is mainly attributable to the lower insulin concentration in the second group. This novel FFA model allows to assess lipolysis and insulin antilipolytic effect in postprandial conditions. In this study, we propose a new mathematical model able to quantify postprandial FFA kinetics and adipose tissue insulin sensitivity in both subjects with obesity without type 2 diabetes (ND) and subjects with type 2 diabetes (T2D). Results show that the slower postprandial suppression of lipolysis in T2D contributes to the higher free fatty acid (FFA) concentration that, in turn, may contribute to hyperglycemia.
评估游离脂肪酸 (FFA) 的动力学以及胰岛素和葡萄糖对 FFA 脂肪分解和处置的作用，可能有助于我们理解 2 型糖尿病 (T2D) 的发病机制。已经提出了一些模型来描述静脉葡萄糖耐量试验期间的 FFA 动力学，而仅有一种模型用于口服葡萄糖耐量试验。在这里，我们提出了一种在餐耐量试验期间 FFA 动力学的模型，并使用它来评估 2 型糖尿病 (T2D) 患者和非 2 型糖尿病肥胖 (ND) 患者餐后脂肪分解的可能差异。我们研究了 18 名肥胖的 ND 和 16 名 T2D 患者，他们在三个时间点（早餐、午餐和晚餐）进行了三次餐耐量试验 (MTT)。我们使用早餐时收集的血浆葡萄糖、胰岛素和 FFA 浓度来测试一系列模型，并根据生理学合理性、拟合数据的能力、参数估计的精度和赤池信息量准则选择最佳模型。最佳模型假设餐后 FFA 脂肪分解的抑制与基础胰岛素呈比例，而 FFA 处置与 FFA 浓度呈比例。它用于比较 ND 和 T2D 患者在一天中的 FFA 动力学。ND 患者的最大脂肪分解抑制发生得明显早于 T2D 患者（早餐时为 39±6 分钟比 102±13 分钟，午餐时为 36±4 分钟比 78±11 分钟，晚餐时为 38±6 分钟比 84±13 分钟，均 <0.01），使 ND 患者的脂肪分解明显低于 T2D 患者。这主要归因于第二组的胰岛素浓度较低。这种新型 FFA 模型可用于评估餐后脂肪分解和胰岛素抗脂肪分解作用。在这项研究中，我们提出了一种新的数学模型，能够定量评估肥胖非 2 型糖尿病 (ND) 患者和 2 型糖尿病 (T2D) 患者的餐后 FFA 动力学和脂肪组织胰岛素敏感性。结果表明，T2D 患者餐后脂肪分解抑制较慢，导致游离脂肪酸 (FFA) 浓度升高，进而导致高血糖。
