Elsevier

Clinical Biochemistry

Volume 40, Issues 3–4, February 2007, Pages 201-205
Clinical Biochemistry

Relationships between leptin, insulin, IGF-1 and IGFBP-3 in children with energy malnutrition

https://doi.org/10.1016/j.clinbiochem.2006.11.008Get rights and content

Abstract

Objectives:

Leptin has a key role in energy homeostasis and there may be a link between leptin and insulin-like growth factor-1 (IGF-1) system. The aim of this study was to analyze the relationships between long-lasting insufficient caloric intake (marasmus), leptin and IGF-1 system.

Design and methods:

The study group consisted of 30 marasmic children and control group included 28 healthy children. After an overnight fasting; leptin, insulin, IGF-1 and IGFBP-3 levels were measured.

Results:

Marasmic children had significantly lower body weight, height, mid-arm circumference (MAC), skinfold thickness, mean serum leptin, insulin, IGF-1 and IGFBP-3 levels compared with healthy subjects (P < 0.05). Serum IGF-1 and IGFBP-3 levels were significantly correlated with insulin, MAC and height Z score in patients (P < 0.05). In controls, significant positive correlations were found between BMI, IGF-1 and leptin (P < 0.05).

Conclusions:

Energy malnutrition is characterized by the important decreases in the leptin, insulin, IGF-1 and IGFBP-3 levels. Understanding details of these changes may lead to new therapeutic approaches in disease states associated with malnutrition.

Introduction

Protein-energy malnutrition (PEM) is one of the most common health problems in the world. Growth retardation due to this condition generally occurs in children of post-weaning age, which is a result of dietary deficiency. PEM could be defined as marasmus or kwashiorkor based on the severity and features at the presentation; marasmus results from inadequate energy intake and a chronic wasting condition of energy deficiency, whereas kwashiorkor results primarily from insufficient protein intake and distinguished by oedema and anaemia [1].

In the presence of a relative insufficient food intake, a higher cortisol–insulin ratio, associated with lower levels of insulin like growth factor-1 (IGF-1) will lead to lower muscle gain and linear growth [1]. The insulin like growth factor binding proteins (IGFBPs) play an important role in controlling the transport of IGF-1 in the circulation and their delivery to body fluids and tissues [2], thus the biological effects of IGF-1 are regulated by IGFBPs [3]. It is well known that nutritional status is an important determinant of the growth hormone (GH)–IGF axis and children with PEM show high blood levels of GH and low levels of IGF-1 [4].

Leptin, the Ob gene protein, is an adipocyte-secreted hormone that plays a key role in energy homeostasis of the body by controlling food intake [5]. Leptin concentrations correlate with the amount of fat mass, with higher levels in more obese people. The decrease in leptin after energy restriction is a starvation signal to the brain [6], [7] that probably has a protective effect.

Although the amount of fat is an important determinant of leptin concentrations, some other factors including gender, adipocyte size and visceral versus subcutaneous fat distribution and other hormones (e.g., insulin, glucocorticoids) are also relevant [8]. Human and in vitro studies have shown that a decreased glucose metabolism results in a reduction in leptin production [9]. Falling leptin concentrations might mediate the neuroendocrine responses to fasting [10].

Experimental models have provided evidences of leptin functions as a neuromodulator of the GH-releasing factor–GH–IGF axis by connecting this hormonal system with nutritional status [11]. Although it is well known that long-term insufficient nutritional intake decreases leptin concentration [12], relationship between leptin, IGF-1 and IGFBPs in caloric deprivation is poorly understood [13], which was aimed to be investigated in this study.

Section snippets

Patients

Severely malnourished 30 patients (16 female, 14 male) were included. All of patients had minimal subcutaneous tissue, had no oedema and were defined as marasmus according to Wellcome criteria of classification [14]. Briefly body weight for age of study group was below 60%, body weight for height was below 70% and no patient had clinical findings of oedema. Most of the children had not received sufficient breast milk or proper supplemental food before and after weaning. Control group consisted

Results

The study group consisted of 30 marasmic children with a mean age of 14.4 ± 9.3 months (median 12 months, range 4–36) (Table 1), who were admitted to Dicle University Hospital. The mean ages of marasmic children and controls were similar (P > 0.05). The anthropometric data for the study and the control groups are presented in Table 1. Marasmic children had significantly lower body weight, height, head and mid-arm circumference, BMI and skinfold thickness compared with the healthy subjects (P < 

Discussion

In the present study, serum leptin, insulin, IGF-1 and IGFBP-3 levels were found to be markedly reduced in marasmic children compared with healthy control subjects. Serum leptin, insulin and IGF-1 levels have been reported to be decreased in children with PEM compared with normal subjects in previous studies [13], [17], [18]. Also, it has been reported that the decreasing insulin level may also play an important role in the decrease of leptin production by the adipocyte during starvation [18].

Acknowledgment

We thank to Dr. Julide Sisman (Albany Medical Center, US) for her help in revising the English of the manuscript.

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