The MetaboHealth Score Enhances Insulin Resistance Metabotyping for Targeted Fat Loss: The PERSON Study.

No significant four-way interaction between IR metabotype, diet, MetaboHealth tertile, and time was observed for cardiometabolic outcomes.

• Outcomes assessed included a 7-point oral glucose tolerance test
• 242 adults aged 40-75 with insulin resistance were randomized; 184 had complete data and were included in analyses
• Participants were randomized to either a low-fat, high-protein, high-fiber diet or a high-monounsaturated fatty acid diet for 12 weeks
• Linear mixed models were used to assess four-way interactions

Significant four-way interactions were found between IR metabotype, diet assignment, MetaboHealth tertile, and time for android fat percentage, gynoid fat percentage, total fat percentage, and fat mass index.

• Body composition was assessed using DXA-based measurements
• Outcomes showing significant interactions included android fat percentage, gynoid fat percentage, total fat percentage, and fat mass index
• 184 participants with complete data were grouped into MetaboHealth tertiles, where higher tertile indicated poorer health
• The study population consisted of middle-aged and older adults (aged 40-75) with insulin resistance

In the healthiest MetaboHealth tertile, diet-metabotype matching led to greater fat loss compared to mismatched diets.

• Participants in the lowest (healthiest) MetaboHealth tertile showed differential fat loss responses depending on whether they received their metabotype-matched diet
• The muscle IR group was matched to a low-fat, high-protein, high-fiber diet
• The liver IR group was matched to a high-monounsaturated fatty acid diet
• Fat loss outcomes included android, gynoid, and total fat percentage as well as fat mass index

In the poorest MetaboHealth tertile, both matched and unmatched diets were similarly effective for fat loss.

• Participants in the highest (poorest health) MetaboHealth tertile did not show differential responses to matched versus unmatched diets
• This pattern suggests MetaboHealth status modifies the benefit of diet-metabotype matching specifically for body composition outcomes
• The finding was observed across multiple fat distribution measures (android, gynoid, total fat percentage, and fat mass index)

The MetaboHealth score itself remained unchanged over the 12-week dietary intervention period.

• The MetaboHealth score reflects risks of mortality, frailty, and cognitive decline
• Neither the low-fat, high-protein, high-fiber diet nor the high-monounsaturated fatty acid diet altered the MetaboHealth score over 12 weeks
• This finding was observed regardless of IR metabotype assignment or MetaboHealth tertile

The PERSON study previously demonstrated that a low-fat, high-protein, high-fiber diet benefits the muscle IR metabotype while a high-monounsaturated fatty acid diet benefits the liver IR metabotype.

• Two distinct IR metabotypes were identified in middle-aged and older adults: muscle IR and liver IR
• The dietary intervention was isocaloric and lasted 12 weeks
• 242 adults aged 40-75 with insulin resistance were randomized in the PERSON study