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Objective: To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM)., Research Design and Methods: Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11.1 +/- 2.7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls., Results: Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects., Conclusions: The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.