A new oral model of free fatty acid kinetics to assess lipolysis in subjects with and without type 2 diabetes

• Published in: American journal of physiology: endocrinology and metabolism 2023-08, Vol.325 (2), p.E163-E170
• Main Authors: Bonet, J, Yadav, Y, Miles, J, Basu, A, Cobelli, C, Basu, R, Dalla Man, C
• Format: Article
• Language: English
• Subjects: Blood Glucose; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Humans; Insulin - metabolism; Insulin Resistance; Kinetics; Lipolysis; Obesity
• ISSN: 0193-1849; 1522-1555; 1522-1555
• DOI: 10.1152/ajpendo.00091.2023

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.