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

John W Newman; Sridevi Krishnan; Kamil Borkowski; Sean H Adams; Charles B Stephensen; Nancy L Keim

doi:10.3389/fnut.2022.877696

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

Front Nutr. 2022 May 11:9:877696. doi: 10.3389/fnut.2022.877696. eCollection 2022.

Authors

John W Newman^{1

2

3}, Sridevi Krishnan², Kamil Borkowski³, Sean H Adams^{4

5}, Charles B Stephensen^{1

2}, Nancy L Keim^{1

2}

Affiliations

¹ Western Human Nutrition Research Center, Agricultural Research Service, USDA, Davis, CA, United States.
² Department of Nutrition, University of California, Davis, Davis, CA, United States.
³ West Coast Metabolomics Center, Genome Center, University of California, Davis, Davis, CA, United States.
⁴ Department of Surgery, Davis School of Medicine, University of California, Davis, Sacramento, CA, United States.
⁵ Center for Alimentary and Metabolic Science, Davis School of Medicine, University of California, Davis, Sacramento, CA, United States.

Abstract

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 (n = 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/m², 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_MMTT) was strongly correlated (r = 0.77, p < 0.001) with the OGTT-dependent 2 h composite Matsuda index (ISI_Composite), being related by the following equation: Log (ISI_Composite) = [0.8751 x Log(ISI_MMTT)] -0.2115. An area under the triglyceride excursion curve >11.15 mg/mL h^-1 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.

Clinical trial registration: [https://clinicaltrials.gov/], identifier [NCT02298725; NCT02367287].

Keywords: fat tolerance test; insulin patterns; insulin sensitivity; meal challenge test; phenotyping; postprandial triglyceridemia; triglyceridemia.

Associated data

ClinicalTrials.gov/NCT02367287
ClinicalTrials.gov/NCT02298725