The PERSonalized Glucose Optimization Through Nutritional Intervention (PERSON) Study: Rationale, Design and Preliminary Screening Results

Frontiers in Nutrition

Jun 2021

DOI: 10.3389/fnut.2021.694568

Citations:19

Influential Citations:1

Interventional (Human) Studies

Enhanced Details

Methods

Two-center, randomized, double-blind, parallel 12-week dietary intervention; 240 overweight/obese men and women (BMI 25-40 kg/m2), aged 40-75; tissue-specific insulin resistance phenotypes identified by a 7-point OGTT to determine hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI) and classified as NoMIR/LIR, MIR, LIR, or combined MIR/LIR; randomized to isocaloric diets hypothesized to target their IR phenotype; extensive pre- and post-intervention phenotyping; primary outcome: difference in change in disposition index between those receiving their hypothesized optimal vs suboptimal diet.

Intervention

Beta-glucan fiber supplement (PromOat, DSM Nutritional Products): 2 g beta-glucan per 6 g PromOat, providing 6-12 g additional fiber daily; taken daily during the 12-week intervention.

Results

Preliminary screening (May 2018–March 2020) identified tissue-specific IR phenotypes in about 60% of screened individuals: NoMIR/LIR 40.2%, MIR 21.4%, LIR 10.8%, Combined MIR/LIR 27.6%. Baseline differences by phenotype included higher BMI, waist circumference, and fasting-insulin resistance parameters in MIR/LIR groups; Matsuda index highest in NoMIR/LIR, MISI lowest in Combined MIR/LIR and MIR, and disposition index highest in LIR; DM prevalence was 6.6% (NoMIR/LIR), 8.3% (MIR), 0.0% (LIR), and 10.9% (Combined MIR/LIR). IFG most prevalent in LIR (11.5%), IGT most prevalent in MIR (18.2%), Combined 16.7%. These data support precision nutrition by IR phenotype and suggest that diets tailored to tissue-specific IR may yield greater improvements in glucose metabolism than non-targeted diets; full trial results are needed to determine the actual intervention effects.

Limitations

Preliminary screening data only; not results from the dietary interventions; group sizes differ by phenotype; reliance on self-reported dietary data with misreporting; findings may not generalize beyond overweight/obese adults with tissue-specific IR and across centers.

Abstract

Background: It is well-established that the etiology of type 2 diabetes differs between individuals. Insulin resistance (IR) may develop in different tissues, but the severity of IR may differ in key metabolic organs such as the liver and skeletal muscle. Recent evidence suggests that these distinct tissue-specific IR phenotypes may also respond differentially to dietary macronutrient composition with respect to improvements in glucose metabolism. Objective: The main objective of the PERSON study is to investigate the effects of an optimal vs. suboptimal dietary macronutrient intervention according to tissue-specific IR phenotype on glucose metabolism and other health outcomes. Methods: In total, 240 overweight/obese (BMI 25 – 40 kg/m2) men and women (age 40 – 75 years) with either skeletal muscle insulin resistance (MIR) or liver insulin resistance (LIR) will participate in a two-center, randomized, double-blind, parallel, 12-week dietary intervention study. At screening, participants undergo a 7-point oral glucose tolerance test (OGTT) to determine the hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), classifying each participant as either “No MIR/LIR,” “MIR,” “LIR,” or “combined MIR/LIR.” Individuals with MIR or LIR are randomized to follow one of two isocaloric diets varying in macronutrient content and quality, that is hypothesized to be either an optimal or suboptimal diet, depending on their tissue-specific IR phenotype (MIR/LIR). Extensive measurements in a controlled laboratory setting as well as phenotyping in daily life are performed before and after the intervention. The primary study outcome is the difference in change in disposition index, which is the product of insulin sensitivity and first-phase insulin secretion, between participants who received their hypothesized optimal or suboptimal diet. Discussion: The PERSON study is one of the first randomized clinical trials in the field of precision nutrition to test effects of a more personalized dietary intervention based on IR phenotype. The results of the PERSON study will contribute knowledge on the effectiveness of targeted nutritional strategies to the emerging field of precision nutrition, and improve our understanding of the complex pathophysiology of whole body and tissue-specific IR. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT03708419, clinicaltrials.gov as NCT03708419. show less