Circulating
leptin,
insulin,
insulin-like growth factor-I (
IGF-I),
cortisol, and
albumin concentrations and the
growth hormone (GH) response to provocation were measured in 30 children with severe
protein-energy malnutrition (PEM), 20 with
marasmus and 10 with
kwashiorkor, as well as 10 age-matched normal children (body mass index [BMI] >50th and <90th percentile for age and sex) and 10 prepubertal obese children (BMI >95th percentile for age and sex). Patients with PEM had a significantly lower BMI, midarm circumference (MAC), and skinfold thickness (SFT) compared with the age-matched control group. Basal
cortisol and GH concentrations were significantly higher in the malnourished groups versus controls.
Leptin and
IGF-I were significantly lower in the marasmic and
kwashiorkor groups versus normal children. Fasting
insulin levels were significantly decreased in the
kwashiorkor group compared with marasmic and normal children. The BMI correlated significantly with
leptin (r = .77, P < .001), basal
insulin (r = .61, P < .001), and
IGF-I (r = .77, P < .001) and negatively with basal GH (r = -.52, P < .001). These findings suggest that during prolonged nutritional deprivation, the decreased energy intake, diminished subcutaneous fat mass, and declining
insulin (and possibly
IGF-I) concentration suppress
leptin production. In support of this view, serum
leptin levels were positively correlated with triceps, scapular, and abdominal SFT (r = .763, .75, and .744, respectively, P < .0001) in all of the children. Moreover, basal
insulin and circulating
IGF-I were correlated significantly with
leptin concentrations (
r = .47 and .62, respectively, P < .001). Basal levels of
cortisol and GH were significantly elevated in the 2 groups with severe PEM. It is suggested that low
leptin levels can stimulate the hypothalamic-pituitary-adrenal (HPA) axis and possibly the hypothalamic-pituitary-GH axis to maintain the high
cortisol and GH levels necessary for effective lipolysis to ensure a fuel (
fatty acids) supply for the metabolism of brain and peripheral tissue during nutritional deprivation. In summary, during prolonged PEM, the decreased synthesis of
IGF-I and the low level of
insulin and/or its diminished effect due to an
insulin-resistant status in the presence of high circulating GH and
cortisol levels ensure substrate diversion away from growth toward metabolic homeostasis.
Leptin appears to be an important signal in the process of metabolic/endocrine adaptation to prolonged nutritional deprivation.