PSAT117 Lower Muscle Mass Relative to Body Weight in Pre-pubertal Children with Type 1 Diabetes
Authors: Hendrix Grace , Shankaran Mahalakshmi , Ramaker Megan , Evans William , Hellerstein Marc , Muehlbauer Michael , Rasbach Lisa , Benjamin Robert , Freemark Michael , Balikcioglu Pinar Gumus 
Published: November 2022

Abstract

Introduction/Background
Type 1 diabetes (T1D) is associated with decreased skeletal muscle mass (SMM) and impaired muscle function in adults. Despite the importance of skeletal muscle in insulin action and metabolic homeostasis, our understanding of skeletal muscle health in children with T1D is very limited. Here we used a novel, non-invasive methodology to compare muscle mass (MM) in children with T1D and sex and age-matched healthy children without diabetes.

Objectives
We hypothesized that: (a) children with T1D have lower MM than age, sex, and BMI-matched children without T1D; (b) MM in children with T1D correlates with insulin sensitivity and glycemic control.

Methods
Weight (BW), height, BMI%, body fat% (BF%), daily insulin requirement, CGM data, HbA1c, and total and HMW adiponectin were measured in 24 young children (15 females, 9 males; age 6-11 years) with T1D. BF% and fat-free-mass (FFM) was measured by bioelectrical impedance. Insulin sensitivity was assessed by total and HMW-adiponectin and daily insulin requirements. Glycemic control was assessed by glucose time in range, mean blood glucose, and HbA1c. MM was measured using the D3creatine dilution method in 22 of the children with T1D (14 females, 8 males) and, in a separate study, in 34 children without T1D (17 females and 17 males). This method involves an oral 10 mg dose of deuterated creatine (methyl-d3, D3Cr). Creatine is converted in vivo to creatinine, including D3Cr to D3creatinine, in muscle by an irreversible, nonenzymatic reaction and then excreted. A single fasting urine sample is collected to determine D3creatinine enrichment. MM/BW (%) was calculated to normalize for body weight.

Results
There were strong positive associations between MM and body weight (r=0.85, p&lt;0.0001), BMI (r=0.61, p=0.0028), and FFM (r=0.72, p=0.0040). Although children with T1D were slightly older (9.2 ±1.3 vs 8.1± 1.2 yo, p=0.003) and had higher BMI (18± 2.3 vs16.0 ±2.0, p=0.001) than controls, they had lower %MM/BW than children without diabetes (37.8± 4.6 vs 43.1±4.5%, p&lt;0.0001). The lower %MM/BW in T1D compared to controls was confirmed in sub-cohorts matched for age and in males and females analyzed separately. Mean daily insulin requirement and HbA1c in the children with T1D were 0.76±0.15 IU/kg/day and 7.1±1.1%, respectively. MM, FFM, %BF, FM, %MM/BW did not correlate with metrics of insulin sensitivity or glycemic control.

Conclusions
This is the first study to quantitate MM directly in young children with T1D. Our results demonstrate a lower %MM in 6–11-year-old pre-pubertal children with T1D with stable and reasonable glycemic control. The cause for the lower % MM in T1D is not clear; however future studies could examine the rates of muscle protein and fat synthesis and breakdown in healthy and diabetic children along with their relations to insulin administration, metabolic control, growth, and pubertal development.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.