Catabolic to anabolic transition during nutritional rehabilitation of female adolescents with anorexia nervosa

Anorexia nervosa (AN) is associated with profound changes in glucose homeostasis, activity of the GH-IGF-1 axis, and adipose tissue, bone, and protein metabolism. We aimed to characterize the transition from a catabolic to anabolic state during the nutritional rehabilitation of female adolescent inpatients with AN. The study comprised 41 patients (aged 15.6 ± 1.6 yr). Blood samples were obtained at the time of admission and upon attainment of target weight. A subgroup of 18 patients also had blood samples obtained during the early refeeding period. Changes in body mass index (BMI) and BMI-SDS during hospitalization (5.1 ± 2.0 mo) were positively correlated with changes in markers of anabolism including IGF-1 (<i>r</i> = 0.424, <i>P</i> = 0.006), procollagen type I N-terminal propeptide (P1NP) (<i>r</i> = 0.375, <i>P</i> = 0.016), klotho (<i>r</i> = 0.468, <i>P</i> = 0.002), and alkaline phosphatase (ALP) (<i>r</i> = 0.051, <i>P</i> = 0.001) and were negatively correlated with the change in cortisol levels (<i>r</i> = -0.331, <i>P</i> = 0.035). Furthermore, changes in markers of anabolism were intercorrelated. IGF-1 increased consistently throughout the study period (<i>P</i> < 0.001); however, other variables showed a biphasic pattern. During the early refeeding period, there was a decrease in C-terminal telopeptides of type I collagen (CTX-1) (<i>P</i> < 0.001), uric acid (<i>P</i> < 0.001), cortisol (<i>P</i> = 0.056), fatty acid-binding protein 4 (FABP4) (<i>P</i> = 0.04), and klotho (<i>P</i> = 0.038) levels, whereas urea/creatinine ratio (UCR) (<i>P</i> = 0.045) increased. During the later phase, there was an increase in ALP (<i>P</i> = 0.039), insulin (<i>P</i> = 0.04), homeostatic model assessment for insulin resistance (HOMA-IR) (<i>P</i> = 0.06), and klotho levels (<i>P</i> = 0.02). In conclusion, the early refeeding period was characterized by a decrease in markers of catabolism, whereas the later phase was characterized by an increase in anabolic markers. We suggest that IGF-1, UCR, and klotho may be used as markers of reversal of catabolism and shift toward anabolism in patients with severe malnutrition.<b>NEW & NOTEWORTHY</b> We provide a comprehensive temporal characterization of changes in biochemical markers of glucose homeostasis, GH-IGF-1 axis activity, and adipose tissue, bone, and protein metabolism during refeeding of adolescents with anorexia nervosa. Although IGF-I levels increased continuously, other markers showed a biphasic pattern: an early decrease in catabolic markers, followed by an increase in anabolic markers later during hospitalization. IGF-1, urea/creatinine ratio, and klotho emerged as potential clinical biomarkers of catabolic to anabolic transition in patients with severe malnutrition.