Kelsey, Megan Moriarty

ABSTRACT Background Adolescents with youth‐onset type 2 diabetes (YO‐T2D) have an increased risk for cardiometabolic complications. The impact of vertical sleeve gastrectomy (VSG) on fat distribution and cardiac morphology/function in YO‐T2D is unknown. Objectives To evaluate changes in body composition, abdominal and cardiac fat depots, and cardiometabolic health in adolescents with YO‐T2D undergoing VSG. Methods Anthropometrics, labs and imaging were used to assess participants pre‐surgery and 3–12 months post‐surgery. MRI quantified pericardial (PAT), epicardial (EAT), subcutaneous (SAT) and visceral adipose tissue (VAT), hepatic fat fraction (HFF) and cardiac morphology/function. Mixed‐effects models assessed longitudinal changes. Results By 12 months, weight decreased from 134.3 ± 5.1 to 103.3 ± 5.2 kg, VAT 1943 ± 148 to 1248 ± 150 cm 3 , HFF 23.2% ± 2.3% to 5.3% ± 2.3% and PAT and EAT by 27% and 33% (all p < 0.01). Homeostatic model assessment of insulin resistance (HOMA‐IR) improved (7.8 ± 1.2 to 1.7 ± 1.2 [ p < 0.01]). BMI, SAT, resting heart rate (RHR), left ventricular (LV) mass and cardiac output (CO) also decreased (all p < 0.05). VAT decreases correlated with decreases in HFF ( r = 0.70, p = 0.01), HOMA‐IR ( r = 0.60, p = 0.04) and CO ( r = 0.70, p = 0.03). HFF decreases correlated with decreases in BMI ( r = 0.70, p = 0.03), HOMA‐IR ( r = 0.90, p < 0.001), RHR ( r = 0.90, p = 0.002), CO ( r = 0.80, p = 0.007) and LV mass ( r = 0.70, p = 0.02). Conclusions VSG reduces ectopic and regional fat and improves associated insulin sensitivity and cardiac health in adolescents with YO‐T2D.

Conditions related to cardiometabolic disease, including metabolic syndrome and type 2 diabetes, are common among men with Klinefelter syndrome (KS). The molecular mechanisms underlying this aberrant metabolism in KS are largely unknown, although there is an assumption that chronic testosterone deficiency plays a role. This cross-sectional study compared plasma metabolites in 31 pubertal adolescent males with KS to 32 controls of similar age (14 ± 2 years), pubertal stage, and body mass index z -score of 0.1 ± 1.2 and then between testosterone-treated ( n = 16) and untreated males with KS. The plasma metabolome in males with KS was distinctly different from that in controls, with 22% of measured metabolites having a differential abundance and seven metabolites nearly completely separating KS from controls (area under the curve > 0.9, P < 0.0001). Multiple saturated free fatty acids were higher in KS, while mono- and polyunsaturated fatty acids were lower, and the top significantly enriched pathway was mitochondrial β-oxidation of long-chain saturated fatty acids (enrichment ratio 16, P < 0.0001). In contrast, there were no observed differences in metabolite concentrations between testosterone-treated and untreated individuals with KS. In conclusion, the plasma metabolome profile in adolescent males with KS is distinctly different from that in males without KS independent of age, obesity, pubertal development, or testosterone treatment status and is suggestive of differences in mitochondrial β-oxidation.