Muscle Ultrasound Echo Intensity Detects Insulin Resistance Before Changes in HbA_1c or Fasting Glucose, Independent...

To quantify the association between skeletal muscle echo intensity (MEI), measured by ultrasound, and clinical markers of insulin resistance and glycemic control, and evaluate MEI's diagnostic accuracy in identifying insulin resistance.

In this cross-sectional study, 20 adults with obesity (mean body mass index [BMI] 34.4 ± 2.6 kg/m², mean age 33 years, 40% female) and 8 healthy, lean adults (mean BMI 22.5 ± 1.4 kg/m², mean age 25 years, 75% female), all without diabetes or metabolic disease, underwent laboratory testing (HbA_1c, 2-hour oral glucose tolerance testing with insulin for Matsuda Index), muscle ultrasound (deltoid, vastus lateralis), and DEXA for sarcopenia indices. Two blinded research assistants independently analyzed 336 ultrasound images to quantify MEI.

Increased MEI was significantly associated with greater insulin resistance (lower Matsuda Index; r = -.47, p = .011), particularly in women (r = -.56, p = .039). MEI z-scores identified insulin resistance with an AUROC of 0.872 (95% CI 0.742-1.000). At the optimal threshold of z = 1.96, sensitivity was 94.4%, specificity 80%, accuracy 89.3%, and Youden's index 0.744. MEI accurately identified insulin resistance despite normal HbA_1c and fasting glucose. Increased MEI in both muscles suggested global skeletal muscle changes. Among participants with obesity, MEI did not correlate with BMI but was negatively correlated with sarcopenia indices (r = -.56, p = .0096) and body weight (r = -.50, p = .0233).

MEI is an accurate, noninvasive biomarker for insulin resistance and may detect muscle alterations before conventional markers emerge. Its independence from BMI and conventional markers supports MEI's use in early risk stratification and identification of individuals at risk for metabolic dysfunction who might otherwise go undetected.