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Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist

By August 1, 1999September 24th, 2020No Comments

LINK TO RESEARCH
https://pubmed.ncbi.nlm.nih.gov/10431109/

PUBLICATION
The Journal of Pediatrics

AUTHORS
R H Lustig 1 ,
S R Rose,
G A Burghen,
P Velasquez-Mieyer,
D C Broome,
K Smith,
H Li,
M M Hudson,
R L Heideman,
L E Kun

ABSTRACT
Objective: Hypothalamic obesity is a rare sequela of cranial insult, for which
pathogenesis and treatment remain obscure. In rodents ventromedial
hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and
insulin resistance. Reduction of insulin secretion in humans may attenuate
weight gain.
Methods: Eight children with intractable obesity after therapy for leukemia or
brain tumors underwent oral glucose tolerance testing (OGTT) with
simultaneous insulin levels before and after treatment with octreotide for
6 months.
Results: In comparison with a 6-month pre-study observation period, patients
exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P =.04) and
decrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2);
P =.0001). Recall calorie count decreased during the 6 months of treatment
(P =. 015). OGTT demonstrated biochemical glucose intolerance in 5 of 8
patients initially and in 2 of 7 at study end, whereas insulin response was
decreased (281 +/- 47 microU/mL vs 114 +/- 35 microU/mL; P =.04). Percent
weight change correlated with changes in insulin response (r = 0.72, P
=.012) and changes in plasma leptin r = 0.76, P =.0004).
Conclusions: Patients with hypothalamic obesity demonstrate excessive insulin
secretion. Octreotide administration promoted weight loss, which correlated
with reduction in insulin secretion on OGTT and with reduction in leptin
levels. Pre-study biochemical glucose tolerance improved in several
patients while they were receiving octreotide. These results suggest that
normalization of insulin secretion may be an effective therapeutic strategy
in this syndrome.

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