ABSTRACT
Objective
Children with type 1 diabetes mellitus (T1DM) are at risk for reduced muscle mass and strength, which may be influenced by insulin deficiency. Although insulin is known to regulate muscle metabolism, data on its effects in newly diagnosed pediatric patients are limited. To describe changes in muscle mass and muscle strength after insulin treatment in children newly diagnosed with T1DM.
Methods
This was a prospective analysis of hospitalized children with newly diagnosed T1DM and age, sex-matched outpatient healthy controls between 2020 and 2021. The primary outcome was muscle strength, muscle mass measured at diagnosis, and three and six months after insulin initiation in patients with T1DM, compared with age- and sex-matched healthy controls. Total body muscle mass were assessed using bioelectrical impedance analysis and muscle strength was measured by handgrip dynamometry.
Results
The study included 36 children with newly diagnosed T1DM and 43 matched controls. Baseline muscle mass did not differ significantly between T1DM patients and controls (p=0.73), but muscle strength was significantly lower in the T1DM group (p=0.001). During follow-up, both muscle mass and muscle strength increased significantly within the T1DM group compared with baseline (p<0.001 for both). No significant correlations were found between muscle parameters and biochemical markers.
Conclusion
Insulin treatment in children with newly diagnosed T1DM was associated with improvements in muscle mass and strength during early follow-up. However, the honeymoon (partial remission) period was not specifically assessed; therefore, its potential contribution to these improvements could not be determined. Regular glycemic control and insulin therapy may contribute to delaying or mitigating complications related to impaired muscle development. Longitudinal studies are warranted to explore the long-term musculoskeletal outcomes of insulin therapy in pediatric T1DM.
What is already known on this topic?
Children with newly diagnosed type 1 diabetes mellitus (T1DM) often present with reduced muscle strength and altered body composition at diagnosis. Insulin therapy improves metabolic control and may have anabolic effects on muscle tissue. Previous studies have evaluated metabolic and anthropometric changes after insulin initiation, but data on longitudinal changes in both muscle mass and strength in pediatric T1DM remain limited.
What this study adds?
This study is the longitudinally evaluate both muscle mass and muscle strength in children with newly diagnosed T1DM after the initiation of insulin therapy. We demonstrate significant improvements in muscle strength and body composition parameters within six months of treatment, providing novel evidence for the anabolic effects of insulin beyond metabolic control. Our findings highlight the importance of early intervention and comprehensive follow-up for musculoskeletal health in pediatric T1DM patients
Introduction
Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency due to destruction of pancreatic β-cells (1). Insulin plays a key role in glucose uptake, glycogenesis, glucose oxidation, and protein synthesis in skeletal muscle, primarily through the protein kinase B (Akt/PKB) and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK1/2) pathways (2). Insulin deficiency leads to hyperglycemia and increases the risk of various complications (3). In individuals with T1DM, muscle mass, muscle strength, and bone mass are adversely affected due to impaired insulin action. Notably, muscle mass and strength have been shown to be negatively correlated with glycemic control, as reflected by hemoglobin A1c (HbA1c) levels (4).
The musculoskeletal system comprises approximately 40% of total body weight and 50-75% of total body protein content. Techniques such as dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and magnetic resonance imaging (MRI) are commonly used to evaluate adiposity and muscle mass distribution in pediatric and adolescent populations. Among these, BIA is widely utilized owing to its safety, non-invasiveness, affordability, reproducibility, and rapid output.
Muscle function in children can be efficiently assessed using a hand dynamometer, which measures maximal isometric grip strength of the forearm (5). Grip strength serves as a useful indicator of general health status, protein reserves, and nutritional status (6).
Although reduced muscle mass and strength have been linked to cardiovascular and metabolic diseases, impaired bone health, sarcopenia, and osteoporosis in children with T1DM, there is limited evidence about changes in these parameters following insulin therapy. To the best of our knowledge, no previous study has prospectively evaluated alterations in muscle mass and strength after the initiation of insulin therapy in pediatric patients with newly diagnosed T1DM. The aim of this study was to assess the effects of starting insulin treatment on muscle strength, fat mass, and muscle mass in children and adolescents recently diagnosed with T1DM and to explore the relationships between these outcomes and various biochemical parameters.
Methods
Newly diagnosed T1DM patients and age- and sex-matched healthy controls, aged 5-18 years, were enrolled. Exclusion criteria included any history of neuropathic or orthopedic disorders, current medication use that could affect muscle function, or prior upper extremity surgery. The healthy control group was evaluated only once at baseline due to logistical limitations and because repeated assessments were not considered ethically appropriate in healthy children. “Newly diagnosed diabetes” referred to children who presented with diabetic ketoacidosis and were subsequently diagnosed with T1DM at first presentation, with no prior diabetes treatment (glucose >200 mg/dL, ketonemia/ketonuria, venous pH <7.3 or bicarbonate <15 mmol/L). Diagnosis of T1DM was also based on the presence of anti-glutamic acid decarboxylase (anti-GAD), anti-insulin, or anti-islet cell antibodies. Laboratory evaluations were performed on the day of hospital admission. In patients, anthropometric measurements, BIA, and handgrip dynamometry were performed after metabolic stabilization, during the diabetes education period, specifically on the fifth day of hospitalization. Total body muscle mass were assessed using BIA (Tanita MC-780, Tanita Corp., Tokyo, Japan) and muscle strength was measured by isometric handgrip dynamometry using a GRIP-D dynamometer (Takei, Tokyo, Japan).
Ethical Considerations
This study was approved by the Akdeniz University Faculty of Medicine Ethics Committee (approval no: KAEK-157, date: 19.02.2020). Written informed consent, in accordance with the Declaration of Helsinki, was obtained from all participants and/or their legal guardians before inclusion in the study.
Clinical Evaluation
Height, weight, and body mass index (BMI) were recorded, and standard deviation scores (SDS) were calculated using age- and sex-specific reference values for Turkish children (7). BMI was calculated as weight (kg) divided by height squared (m2). Pubertal status was assessed according to the Marshall and Tanner (8) staging system and categorized as prepubertal (stage 1) or pubertal (stages 2-5).
Body Composition Assessment
Total body muscle mass and fat mass were evaluated using BIA with the Tanita MC-780 analyzer (Tanita Corp., Tokyo, Japan). All measurements were performed by a single trained clinician to ensure consistency. Participants were instructed to fast for at least one hour prior to the test, void their bladder, and wear lightweight clothing. During the measurement, individuals stood barefoot on the device platform while grasping the hand electrodes with both hands.
Muscle Strength Assessment
Muscle strength was measured using a GRIP-D hand dynamometer (Takei, Tokyo, Japan), which evaluates isometric grip strength. Three consecutive measurements were obtained from the dominant hand, positioned with the thumb over the other fingers, and the average value was used for analysis. In the T1DM group, both BIA and dynamometer assessments were conducted at baseline (day five of hospitalization), and at three and six months following diagnosis. In the control group, these measurements were performed only at baseline.
Biochemical Assessment
In the T1DM group, venous blood samples were collected at diagnosis, and at the two follow-up time points. The following parameters were analyzed: serum calcium, phosphorus, aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin A1c (HbA1c), thyroid-stimulating hormone (TSH), free thyroxine (FT4), fasting blood glucose, and hemoglobin levels. In the control group, these parameters were measured once at baseline. Comparisons between groups were performed for all relevant variables.
Statistical Analysis
Statistical analyses were performed using SPSS, version 23.0 (IBM Corp., Armonk, NY, USA). Categorical variables are presented as numbers and percentages. Comparisons between groups were performed using the chi-square or Fisher’s exact test for categorical variables, and the Student’s t-test or Mann-Whitney U test for continuous variables, as appropriate based on data distribution. The Friedman test was used to compare repeated measures that did not follow a normal distribution. Pearson’s or Spearman’s correlation analyses were used to assess relationships between continuous variables depending on their distribution. Normality of continuous variables was assessed using the Kolmogorov-Smirnov and Shapiro-Wilk tests, supported by visual inspection of histograms and Q-Q plots. Parametric tests were applied to normally distributed variables, whereas non-parametric tests were used when normality assumptions were not met. Sex-based and pubertal subgroup analyses were considered exploratory; therefore, no formal correction for multiple comparisons was applied, and these results should be interpreted with caution. A two-sided p-value<0.05 was considered statistically significant.
Results
A total of 36 children with newly diagnosed type 1 diabetes mellitus (T1DM) (mean age: 9.99±3.02 years) and 43 age- and sex-matched healthy controls (mean age: 10.32±2.70 years) were enrolled. There were no significant differences between the two groups in terms of age, sex distribution, pubertal stage, height, weight, BMI, BMI SDS, fat mass, or muscle mass (Table 1).
At baseline, muscle strength was significantly lower in the T1DM group [median 10.4 N (5-25.5)] compared with controls [median 15.8 N (6.2-31.9); p=0.001]. Fasting blood glucose levels were significantly higher in the T1DM group. Serum calcium and phosphorus levels were also significantly lower in patients with T1DM (both p<0.001), while other laboratory parameters did not differ between groups (Table 1). During follow-up, significant improvements were observed in anthropometric, metabolic, and musculoskeletal parameters in the T1DM group. Fat mass increased from 6.65 kg (2.0-20.2) at baseline to 8.25 kg (2.2-22.3) at three months and 8.25 kg (2.3-28.3) at six months (p<0.001). BMI increased from 17.5±3.28 kg/m2 at baseline to 18.57±3.28 kg/m2 at six months (p=0.004). Glycemic control improved significantly following insulin initiation, with HbA1c and fasting blood glucose levels decreasing at both three and six months (p<0.001 for both). Muscle strength increased significantly from baseline to six months, representing an approximately 40-50% improvement. Similarly, muscle mass increased from a median of 23.8 kg (10.9-55.5) at baseline to 25.6 kg (11.7-61.5) at three months and remained stable at six months [24.9 kg (1.5-58.8); p<0.001] (Table 2). Sex-based analyses showed that boys had higher muscle strength at baseline (p=0.030); however, no significant sex differences were observed at three or six months. Both sexes demonstrated significant within-group improvements in muscle strength and muscle mass over time (p<0.001) (Table 3). At six months, pubertal children had higher muscle strength (21.15±6.39 N vs 11.9±3.72 N; p<0.001) and muscle mass (36.55±10.25 kg vs 20.76±6.18 kg; p<0.001) compared with prepubertal children. From baseline to six months, muscle strength increased by +5.72 N in pubertal patients and +3.49 N in prepubertal patients (p=0.014), while muscle mass increased by +3.61 kg vs +1.81 kg, respectively (p=0.038) (Table 4). Finally, muscle strength showed strong positive correlation with muscle mass at all time points (r=0.867-0.932; p<0.001), supporting the close relationship between structural and functional muscle parameters.
Discussion
The novelty of the present study lies in the simultaneous longitudinal assessment of both muscle mass and muscle strength in children with newly diagnosed T1DM, providing functional insight beyond body composition alone. At diagnosis, muscle mass and fat mass were comparable between the T1DM and control groups. However, muscle strength was already significantly reduced in T1DM group. In contrast to previous pediatric studies that primarily focused on body composition, the present study demonstrated that muscle strength is already reduced at diagnosis but improves in the short term in parallel with muscle mass following insulin therapy (4, 9, 10, 11). These findings extend the existing pediatric literature by providing functional evidence supporting the anabolic role of insulin beyond changes in body composition. Although percentage-based muscle and fat mass measures could allow a more precise interpretation of compositional changes independent of weight gain, these data were not systematically recorded during the initial data collection period. Therefore, analyses were limited to prospectively collected absolute values to avoid methodological bias. Importantly, the concurrent and significant improvement in muscle strength suggests a true functional recovery rather than a passive increase secondary to weight gain, supporting a functional anabolic contribution of insulin therapy to skeletal muscle. The absence of longitudinal follow-up in the healthy control group represents an important limitation when interpreting these findings. Healthy controls were evaluated only at baseline and soage- and growth-related physiological increases in muscle mass and strength over the 6-month period could not be directly accounted for. Therefore, the observed longitudinal improvements should be interpreted as within-patient changes following insulin initiation rather than direct comparisons with normal growth trajectories.
Age-related and sex-related differences in body composition are well documented. Boys typically have higher muscle mass and lower fat mass than girls (12). Consistent with this, boys in our cohort had higher muscle mass, but both sexes showed significant increases in muscle and fat mass following insulin therapy. Notably, a significant increase in BMI and BMI SDS was observed only in girls at six months, a finding that parallels previous reports of greater weight gain in adolescent girls with T1DM (10, 13, 14). Unlike prior pediatric studies that primarily focused on weight or fat mass changes, our findings highlight sex-specific differences in the pattern of musculoskeletal response to insulin therapy. When analyzed by pubertal status, both muscle and fat mass were significantly greater in pubertal children at all time points. Furthermore, increases in these parameters were more pronounced in pubertal patients compared to prepubertal peers, supporting the known anabolic effects of insulin and the additional contribution of pubertal hormones such as androgens (15, 16, 17). Although BMI was higher in pubertal children, BMI SDS did not significantly differ, suggesting alignment with age- and sex-specific normative data. This may reflect increased bone mass and epiphyseal closure during puberty.
Few studies have assessed muscle strength in children with T1DM. In our cohort, muscle strength was significantly lower at diagnosis compared to controls, corroborating previous reports (18, 19, 20), though some studies have shown no difference (21). Following insulin therapy, muscle strength improved significantly in both sexes. While boys had higher baseline strength, this difference was not sustained after treatment, possibly due to greater relative gains in girls or pubertal effects (22). Pubertal patients demonstrated greater improvements in both muscle mass and strength compared to prepubertal patients, supporting the role of pubertal hormones and insulin in promoting musculoskeletal development (23). We found strong positive correlations between muscle strength and both muscle and fat mass across all time points. Impaired muscle function in T1DM is reported to be multifactorial, involving metabolic, hormonal, and neuromuscular mechanisms (19, 24, 25, 26, 27, 28). Although calcium and phosphorus levels were lower in the T1DM patients, they remained within normal ranges and were not correlated with muscle strength, suggesting that other mechanisms may contribute to the observed improvements. We identified a moderate negative correlation between HbA1c and both muscle mass and strength at the third month of treatment, highlighting the impact of glycemic control on muscle health. The slight increase in HbA1c observed at six months may reflect adolescent insulin resistance or challenges in adherence. These findings suggest that improved glycemic control may contribute to favorable musculoskeletal outcomes in pediatric T1DM. While adult studies have similarly linked better glycemic control with increased skeletal muscle mass (29), conflicting results have also been reported (30), highlighting the complexity of this relationship.
Study Limitations
This study has several limitations. First, the control group was evaluated only at baseline, which precluded longitudinal comparisons of muscle strength and muscle mass trajectories between patients and healthy peers. As a result, normal age- and growth-related increases in musculoskeletal parameters among healthy children could not be accounted for, and the observed longitudinal improvements in the T1DM group may partly reflect physiological growth in addition to treatment-related effects, potentially leading to an overestimation of the insulin effect. Second, bone mass, an important contributor to total body weight and BMI was not assessed, which may limit the interpretation of body composition changes. The absence of bone-related measurements restricts the ability to fully differentiate between lean tissue accumulation and skeletal growth, particularly during puberty. The honeymoon (partial remission) period was not specifically assessed; therefore, its potential influence on changes in muscle mass and strength during early follow-up could not be determined. In addition, serum calcium levels were measured only once in the control group, preventing comparative analysis of dynamic changes over time. Third, physical activity levels, nutritional status, and detailed insulin regimen characteristics (such as insulin dose adjustments) were not included in the analyses. These factors are known to influence muscle mass, fat mass, and muscle strength and may have affected the magnitude and interpretation of the observed relationships. Finally, the relatively small sample size and short follow-up duration may limit the generalizability of our findings. Future studies involving larger cohorts with extended follow-up and comprehensive skeletal and lifestyle assessments are warranted to validate and expand upon these results.
Conclusion
Children and adolescents with newly diagnosed T1DM exhibited reduced muscle strength at diagnosis, despite similar muscle and fat mass compared to healthy controls. Our findings suggest that the first six months of insulin therapy, by restoring glycemic control, may contribute to anabolic processes associated with improvements in both muscle mass and muscle strength, particularly during early treatment. These results highlight the potential importance of optimizing insulin therapy not only for metabolic control but also for musculoskeletal health. Longitudinal monitoring of muscle function and body composition in pediatric T1DM may help identify patients at risk for sarcopenia, osteoporosis, and metabolic complications, and may support early preventive strategies.
