Body composition, metabolic syndrome, and lifestyle in treatment-naïve gender-diverse youth in Israel.

BACKGROUND: There is a scarcity of published studies evaluating transgender/gender-diverse youth before initiating gender-affirming hormones. AIM: To study the body composition, metabolic syndrome (MetS) components and lifestyle habits in treatment-naïve transgender youth. METHODS: Cross-sectional study evaluating 153 transgender youth [median age 15.7 years, 94 transgender males] who attended The Israeli Children and Adolescents Gender Clinic between 6/2021-12/2022. Clinical, metabolic data and lifestyle habits (diet, physical activity and sleep patterns) were retrieved from the medical files. Body composition was determined by bioelectrical impedance analysis. Body mass index and muscle-to-fat ratio z-scores were calculated by sex designated at birth. RESULTS: Weight categories differed between genders, with a greater proportion of subjects classified as underweight among transgender females, and a greater proportion affected by overweight/obese/severe obese among transgender males (p = 0.035). The odds for MetS components were increased by 2.2 for every 1 standard deviation decrease in the muscle-to-fat ratio z-score (95%CI: 1.45 to 3.26, p < 0.001). About one-third of the cohort did not meet any of the three lifestyle recommendations. Transgender males had increased odds for MetS components by 3.49 (95%CI: 1.63 to 7.44, p = 0.001). CONCLUSIONS: Treatment-naïve transgender-male adolescents have an imbalance between muscle and adipose tissue, which places them at increased susceptibility for MetS components even prior to hormonal treatment.

Body Composition and Metabolic Syndrome Components in Transgender/Gender Diverse Adolescents and Young Adults.

Purpose: The objective of this study was to examine the association of designated sex at birth, body composition, and gender-affirming hormone treatment (GAHT) with the components of metabolic syndrome (MetS) (overweight/obesity, elevated blood pressure [BP], altered glucose metabolism, and dyslipidemia) in transgender/gender diverse (TGD) adolescents and young adults. Methods: TGD individuals underwent body composition studies by bioelectrical impedance analysis according to designated sex at birth, and their muscle-to-fat ratio (MFR) z-scores were calculated. Generalized estimating equations with binary logistic models (n = 326) were used to explore associations while adjusting for potential confounders. Results: A total of 55 TGD females and 111 TGD males, with mean age of 18 ± 1.9 years and median duration of GAHT of 1.4 years (interquartile range = 0.6-2.5), were enrolled. Overall, 118/166 (71%) of the TGD cohort showed evidence of at least one MetS component, with a significantly higher rate among TGD males compared with TGD females (91.1% vs. 50.9%, p < 0.001). TGD males were at increased odds for overweight/obesity, elevated/hypertensive BP, elevated triglycerides (TGs), and an atherogenic dyslipidemia index (TG/high-density lipoprotein cholesterol [HDL-c], TG:HDL-c). The odds of overweight/obesity increased by 44.9 for each standard deviation decrease in the MFR z-score, while the odds for an elevated TG:HDL-c index increased by 3.7. Psychiatric morbidity increased the odds for overweight/obesity by 2.89. Conclusions: After considering confounding variables, the TGD males on GAHT were found to be at an increased risk for cardiometabolic disease. Our observations support the importance of targeted medical nutrition intervention in this group of individuals.

Muscle-to-fat ratio in children and adolescents with type 1 diabetes in predicting glycaemic control and partial clinical remission.

BACKGROUND: Advances in treatment could mitigate the expected adverse changes in the body composition of children and adolescents with type 1 diabetes (T1D). OBJECTIVES: To examine the evolution of weight status and body composition and their association with glycaemic control and partial clinical remission in youth with T1D. METHODS: Ninety-nine participants with T1D (median age 9.5 years [interquartile range 7.3, 12.9], 59.6% boys) were longitudinally followed for 3 years since diagnosis. Data at seven pre-determined time points were extracted from medical files. Outcome measures included body mass index (BMI) z-scores, muscle-to-fat ratio (MFR) z-scores, haemoglobin A1c (HbA1c) levels, continuous glucose monitoring metrics, and insulin dose-adjusted HbA1c (IDAA1c) levels. RESULTS: The BMI z-scores increased significantly (p < 0.001) for both sexes, with no significant change in MFR z-scores over time. The girls had higher BMI z-scores (p < 0.001) and lower MFR z-scores than the boys (p = 0.016). The mean HbA1c levels decreased during the first month and at 3 months since diagnosis (p < 0.001), then plateaued and achieved a median overall HbA1c of 7.1% for the entire cohort. At 12 months, 37 participants (37.6%) were in partial clinical remission, as evidenced by IDAA1c ≤ 9. The odds of partial clinical remission at 2 years increased by 2.1-fold for each standard deviation increase in the MFR z-score (p < 0.001). Higher MFR z-scores were associated with better metabolic control. CONCLUSIONS: Integration of body composition assessments could mitigate adverse body changes in paediatric patients with T1D.

Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy.

AIM: Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses. METHODS: Case scenarios and review of the literature. RESULTS: Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of -2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m2, 212% of the 95th percentile, 63.7% FP and MFR z-score of -2.34], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of -1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of -1.13) with normalization of liver transaminases. Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications. CONCLUSIONS: Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.