Muscle Mass and Early Glycaemic Risk in Youth With Prediabetes: A Pilot Study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Obesity is a known risk factor for youth-onset type 2 diabetes (T2D), which follows a more aggressive course than adult-onset disease, marked by rapid β-cell decline, reduced treatment responsiveness, and earlier development of comorbidities [1]. Obesity is often defined using body mass index (BMI). While BMI is an inexpensive screening tool, it does not differentiate fat from lean mass and therefore may misclassify metabolic risk. Body composition provides a more precise assessment of adiposity and lean mass and may better identify youth at highest metabolic risk [2]. Excess visceral fat is strongly associated with insulin resistance and impaired β-cell function, whereas greater lean muscle mass is associated with improved insulin sensitivity [3, 4]. In individuals with established T2D, body composition measures predict haemoglobin A1c (HbA1c) concentrations and continuous glucose monitoring (CGM) metrics [5-7]. Despite obesity being the primary risk factor for youth-onset T2D, fewer than 2% of youth with obesity develop diabetes [8], emphasising variability in metabolic risk and the need for improved risk stratification. CGM provides detailed assessment of glycaemic patterns beyond HbA1c, but the relationship between body composition and CGM-derived glycaemic metrics in youth with obesity and prediabetes (PD) remains unstudied. In this pilot study we aimed to (1) assess baseline and 6-month change in body composition in youth with PD, and (2) determine whether baseline body composition is associated with HbA1c and CGM metrics at 6-month follow-up. We hypothesised that higher adiposity and lower lean muscle mass would be associated with greater glycaemic variability, increased time spent above 140 mg/dL on CGM, and higher HbA1c at follow-up. Youth aged 10–18 with obesity and diagnosis of PD based on HbA1c 5.7%–6.4% were enrolled in a prospective observational cohort study at Cincinnati Children's Hospital (January 2024–September 2025). Participants were excluded if there was clinical concern for type 1 diabetes or if they were using medications known to affect glucose dynamics or body composition. Islet autoantibody testing was performed only if clinically indicated and participants were excluded if positive. Study visits occurred at baseline and 6 months and included demographics, vitals, pubertal examination, HbA1c, body composition assessed by bioelectrical impedance analysis (InBody 270, InBody USA), and a 14-day unblinded CGM (FreeStyle Libre 3). Body composition measures included fat mass index (FMI; fat mass [kg]/body surface area [m2]); muscle mass index (MMI; lean mass [kg]/body surface area [m2]); and fat to muscle mass index ratio (FMI/MMI). CGM metrics included glucose management indicator (GMI) which is a CGM-derived HbA1c proxy, mean amplitude glycaemic excursion (MAGE), coefficient of variability (CV), time in range (TIR; 70–180 mg/dL), and percent of time spent above 140, 180, and 200 mg/dL, derived using R Studio (version 2024.12.1; iglu package) [9]. Wilcoxon signed-rank tests (SAS Studio version 9.4; SAS Institute, Cary, NC) were used to assess within-participant 6-month changes in body composition in the overall cohort. Sex-stratified changes were examined descriptively. Multivariable linear regression evaluated associations between baseline body composition measures and glycaemic outcomes at 6-month follow-up (both CGM and HbA1c). Associations between baseline body composition measures (FMI, MMI, and FMI/MMI ratio) and glycaemic outcomes at follow-up were assessed using Spearman rank correlation due to small sample size. Exploratory partial Spearman correlations adjusted for sex were performed to evaluate whether observed associations were independent of sex differences. Twenty-four youth with PD were enrolled. Demographic data is available in Table S1. Mean (± SD) age was 14.0 (± 2.4) years; 79% were female, 63% Non-Hispanic Black, and 25% Non-Hispanic White. Mean baseline BMI z-score (BMIz) was 2.6 (± 1.1), BMI percentile above the 95th percentile (BMIp95) was 140.0 (± 26.9), and mean PD duration was 1.5 (± 2.1) years (defined by first HbA1c in PD range). On examination, 58% were Tanner V, 8% were each Tanner IV and III, 4% were Tanner I, and 21% declined examinations. Among females, 18/19 had undergone menarche (mean age at menarche 11.6 ± 1.6 years). All participants completed baseline body composition and CGM assessments, and 19 participants had paired baseline and 6-month follow-up data. There was no significant median change in BMIz or BMIp95 over 6 months. In contrast, FMI increased significantly over follow-up, with a median within-participant increase of 0.75 kg (IQR −0.04 to 2.06; p = 0.005) while MMI did not change significantly. As a result, the FMI/MMI ratio increased significantly over 6 months (median change 0.04, IQR −0.02 to 0.15; p = 0.039), indicating a shift in body composition despite stable BMI-based measures (Table 1). Sex-stratified changes are presented descriptively in Table S2. Associations between baseline body composition and glycaemic outcomes at follow-up are shown in Table 2. Baseline MMI demonstrated a moderate inverse association with time spent above 180 mg/dL (ρ = −0.44, p = 0.05), whereas no significant associations were observed with other CGM metrics or HbA1c. In exploratory sensitivity analyses adjusting for sex, the inverse association between MMI and time spent above 180 mg/dL was strengthened (partial ρ = −0.54, p = 0.02), indicating that this relationship was not driven by sex differences. In this pilot study of youth with PD, modest changes in body composition were observed over 6 months, characterised by small increases in FMI and FMI/MMI. In exploratory descriptive analyses, these increases appeared more pronounced among females. These findings align with prior literature demonstrating higher adiposity and greater risk of youth-onset T2D among female adolescents [8, 10], but to our knowledge, this is the first study in youth with PD to examine body composition beyond BMI in relation to CGM metrics. Higher baseline MMI was associated with reduced time spent above 180 mg/dL at follow-up and strengthened after exploratory adjustment for sex, whereas other body composition measure associations were less consistent. This observation is consistent with the central role of skeletal muscle in glucose uptake and insulin sensitivity and warrants further investigation in larger cohorts [11, 12]. Importantly, MMI was associated with CGM metrics but not HbA1c, highlighting the ability of CGM to detect early dysglycaemia not captured by traditional measures. In contrast to adult studies which link greater adiposity, especially central fat, to adverse CGM metrics [7, 13], in this cohort of youth with PD, lean mass emerged as the most consistent correlate of higher glycaemic exposure, suggesting that skeletal muscle may play a particularly important role in early glycaemic regulation during adolescence. This difference may reflect developmental factors unique to youth, including ongoing growth, pubertal insulin resistance, and dynamic changes in muscle mass and insulin sensitivity. Confirmation of this finding is clinically important, as youth-onset T2D is characterised by more rapid disease progression and earlier development of complications compared with adult-onset disease [1]. Strengths of this study include its prospective design and comprehensive CGM assessment. Limitations include small sample size and short follow-up duration, use of bioelectrical impedance rather than direct measures of adiposity distribution, and limited power to assess subgroup differences, particularly sex-specific effects. Accordingly, analyses were exploratory and findings should be interpreted cautiously. Lean mass, particularly skeletal muscle, may play a role in protecting against mildly elevated glucose excursions > 180 mg/dL in youth with PD though larger studies are needed to confirm this relationship. MMI may therefore represent a clinically relevant marker for early glycaemic risk stratification and highlight the potential value of incorporating body composition assessment beyond BMI alone into clinical evaluation. Larger, prospective studies with direct measurements of muscle and fat mass are needed to further define the role of muscle mass in early dysglycaemia among youth with obesity and PD. We thank Katherine Bowers, PhD, for her assistance with answering statistical questions and clarifications. This study was supported by funding from the 2023 Pediatric Endocrine Society Rising Star Award, National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK063929), and National Institute of Environmental Health Sciences (T32 ES010957). CGM product support was obtained by the Investigator-Initiated Studies (IIS) Program at Abbott Diabetes Care. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.70661. Table S1: Participant demographics at baseline. Table S2: Sex-stratified changes in BMI and body composition measures over 6 months. 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Source: Diabetes Obesity and Metabolism
DOI: 10.1111/dom.70661
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7135189646