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Adipose tissue insulin resistance, not muscle insulin resistance, is associated with impaired metabolic health in humans.

Created on 03 Aug 2026

Authors

Kiana Meshkat, Anouk Gijbels, Lydia A Afman, Gijs H Goossens, Ellen E Blaak, Ruth C R Meex

Published in

Diabetes research and clinical practice. Pages 113480. Aug 02, 2026. Epub Aug 02, 2026.

Abstract

Obesity is a major contributor to insulin resistance (IR) and cardiometabolic diseases, but IR can manifest in a tissue-specific manner, resulting in discordant IR phenotypes. This study characterized metabolic and clinical differences between individuals with adipose and muscle IR.
Baseline data from 229 adults (40-75 years, BMI 25-40 kg/m2) in the PERSON study were analyzed. Participants were categorized into four groups based on indices of muscle and adipose insulin sensitivity. Muscle IR was assessed with a 7-point oral glucose tolerance test, and adipose IR was determined from fasting plasma insulin and non-esterified fatty acids. Detailed phenotyping was performed under controlled conditions and daily life.
42% of participants displayed discordant IR patterns. Independent of muscle IR, adipose IR was associated with an adverse cardiometabolic profile, including abdominal fat accumulation, higher fasting insulin, HOMA-IR and triglycerides, greater glycemic variability, and more liver fat and hepatic IR. In contrast, individuals with isolated muscle IR maintained a relatively healthy cardiometabolic profile, though women exhibited higher muscle fat infiltration and hepatic IR.
These findings demonstrate that adipose IR is more strongly and consistently linked to impaired metabolic health than muscle IR, highlighting the importance of phenotype-specific strategies for prevention and treatment.

PMID:
42543083
Bibliographic data and abstract were imported from PubMed on 03 Aug 2026.

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