AUTHOR=Newman John W. , Krishnan Sridevi , Borkowski Kamil , Adams Sean H. , Stephensen Charles B. , Keim Nancy L. 

TITLE=Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test

JOURNAL=Frontiers in Nutrition

VOLUME=9

YEAR=2022

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2022.877696

DOI=10.3389/fnut.2022.877696

ISSN=2296-861X

ABSTRACT=<p>The use of meal challenge tests to assess postprandial responses in carbohydrate and fat metabolism is well established in clinical nutrition research. However, challenge meal compositions and protocols remain a variable. Here, we validated a mixed macronutrient tolerance test (MMTT), containing 56-g palm oil, 59-g sucrose, and 26-g egg white protein for the parallel determination of insulin sensitivity and postprandial triglyceridemia in clinically healthy subjects. The MMTT was administered in two study populations. In one, women with overweight/obese BMIs (<italic>n</italic> = 43) involved in an 8-week dietary intervention were administered oral glucose tolerance tests (OGTTs) and MMTTs within 2 days of each other after 0, 2, and 8 weeks of the dietary intervention. In the other, 340 men and women between 18 and 64 years of age, with BMI from 18–40 kg/m<sup>2</sup>, completed the MMTT as part of a broad nutritional phenotyping effort. Postprandial blood collected at 0, 0.5, 3, and 6 h was used to measure glucose, insulin, and clinical lipid panels. The MMTT postprandial insulin-dependent glucose disposal was evaluated by using the Matsuda Index algorithm and the 0- and 3 h blood insulin and glucose measures. The resulting MMTT insulin sensitivity index (ISI<sub>MMTT</sub>) was strongly correlated (<italic>r</italic> = 0.77, <italic>p</italic> &lt; 0.001) with the OGTT-dependent 2 h composite Matsuda index (ISI<sub>Composite</sub>), being related by the following equation: Log (ISI<sub>Composite</sub>) = [0.8751 x Log(ISI<sub>MMTT</sub>)] –0.2115. An area under the triglyceride excursion curve &gt;11.15 mg/mL h<sup>–1</sup> calculated from the 0, 3, and 6 h blood draws established mild-to-moderate triglyceridemia in agreement with ∼20% greater prevalence of hypertriglyceridemia than fasting indications. We also demonstrated that the product of the 0 to 3 h and 3 to 6 h triglyceride rate of change as a function of the triglyceride incremental area under the curve optimally stratified subjects by postprandial response patterns. Notably, ∼2% of the population showed minimal triglyceride appearance by 6 h, while ∼25% had increasing triglycerides through 6 h. Ultimately, using three blood draws, the MMTT allowed for the simultaneous determination of insulin sensitivity and postprandial triglyceridemia in individuals without clinically diagnosed disease.</p><sec><title>Clinical Trial Registration</title><p>[<ext-link ext-link-type="uri" xlink:href="https://clinicaltrials.gov/" xmlns:xlink="http://www.w3.org/1999/xlink">https://clinicaltrials.gov/</ext-link>], identifier [NCT02298725; NCT02367287].</p></sec>