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

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.

Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model

“…There is growing interest surrounding the field of precision nutrition, whereby dietary interventions will be targeted toward an individual’s specific metabolic aberrations ( Ben-Yacov et al., 2021 ; Berry et al., 2020 ; Gijbels et al., 2021 ; Zeevi et al., 2015 ). In order to achieve this transition toward the provision of personalized interventions it is necessary to be able to objectively quantify metabolic resilience.…”

Can nutrition interventions tackle the global insulin affordability via improving diabetes management and reducing insulin demand?

“…After summarizing the technologies used to help T1D patients, the ADS/ADEA/APEG/ADIPS Working Group in Australia has recommended that focus of diabetes treatment should shift from strict trial-based glycemic criteria to personalized approaches to consider the broad spectrum of benefits obtained by these technologies [ 9 ]. Personalized or precision nutrition studies have shown some promise to control glycemia [ 10 ]. The benefits may have long-term impacts on the health of the individuals and populations as the nutrition exposure has memories in the form of epigenetics.…”

Distinct metabolic phenotypes towards cardiometabolic diseases

“…The studies investigated the effect of diets that were slightly different in macronutrient composition and study duration (ranging between 3-12 weeks) (Table 1). However, these studies consistently reported no significant effects of a LFHCC or a lowfat high-carbohydrate (LFHC) diet on IR, determined by either HOMA-IR or the M-value (12,(109)(110)(111) (12,110), while the study by Parente et al (111) showed a 49% increase in IMCL content after a 4-week LFHC diet. It was not clear whether the carbohydrates were mainly complex or not.…”

“…Nevertheless, BMI predicts disease risk less well on an individual level, implying that body weight and height per se do not reflect the complexity of the disease (7)(8)(9). Obesity is a highly complex, multifactorial, relapsing adiposity-based chronic disease (ABCD) (10)(11)(12). A better insight into the underlying metabolic disturbances in obesity is essential to understand the complex relationship between excess body weight and metabolic complications.…”

“…Diet and physical activity are key modifiable risk factors that play a significant role in the development, progression and reversal of IR and ectopic fat accumulation (5,10). Related to the diet, not only caloric intake, but also the macronutrient quantity and quality of the diet may affect insulin sensitivity, which may be mediated by changes in ectopic fat accumulation (11)(12)(13)(14). Interestingly, however, recent evidence has shown that the metabolic phenotype of an individual seems to contribute to the inter-individual differences in response to dietary intervention (13, 15).…”