Relation of Some Steroids, SHBG, IGF-1, IGF BP-3, and Growth Hormone
to Glucose Metabolism Disorders During Long-term Treatment with Low-doses of Glucocorticoids
Vondra K., Hampl R., Němcová D., Hill M.,Hoza J., Koťátková A., Stárka L., Vrbíková J., Zamrazil V.
Endokrinologický ústav, Praha Klinika dětského a dorostového lékařství 1. LF UK a VFN, Praha |
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Summary:
Background. The relationships between selected steroids, SHBG, growth hormone, IGF-1, IGF BP-3 and
indicators of glucose metabolism were studied in the group of 20 female patients (15–20 yrs) on long-term treatment
with low prednison doses (<0.3 mg/kg/day) (baseline phase) and after adding 1000 mg of metformin per day for
following 6 months to improve impaired glucose metabolism (control phase).
Methods and Results. Lower basal DHEAS and DHEA (DHEA/S) levels were found as compared with reference
values. Only DHEAS level returned into the reference range after the treatment with metformin. Decrease of DHEA/S
depended on the doses (DHEAS -0.7621, DHEA -0.7685). Positive correlations between DHEA/S and of the results
insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the
metformin administration (+0.7549, resp. +0.6073). Testosterone (T) and dihydrotestosteronu (DHT) values were
within the reference range during the whole study. Due to very low SHBG levels higher free androgen index (FAI)
was recorded in more than half of the patients. Significant relationships were revealed between former gonadal
androgens and indicators of glucose metabolism deterioration at the control phase: T correlated: with fasting insulin
(+0.6005), with HOMA IR (+0.5380), with insulin/glucose (+0.5261), with fasting glucose (+0.9268), with AUC
glucose (+0.6792), FAI: with fasting insulin (+0.5560), with HOMA IR (+0.5269), with fasting glucose (+0.9025),
with AUC glucose (+0.7143), DHT: with fasting C peptide (+0.7921), with AUC C peptide (+0.7143). SHBG
correlated: with fasting glucose (-0.6519), and with AUC glucose (-0.5868). The tendency of GH to lower, and
IGF-1, IGF BP-3 to higher values at the baseline changed at the control phase: fasting and AUC value of GH increased
(signif.), while were IGF-1 (nonsignif.) and IGF BP-3 (signif.) levels decreased. Surprisingly, no correlation was
observed between GH and parameters of glucose metabolism. Contrary to GH, baseline IGFBP-3 values correlated:
with HOMA IR (+0.5002), with insulin/glucose (+0.4860). The same relationships were found between AUC IGF
BP-3 (+0.5676, +0.5559), IGF-1 (HOMA IR only +0.5412), IGF-1/IGF BP-3 (+0.5059, +0.5716) and parameters of
insulin sensitivity (HOMA IR , insulin/glucose) in the control period. For the first time negative correlations between
IGF-1, IGF-1 AUC, IGF BP-3, IGF-1/IGF BP-3 and somatostatin blood levels were discovered at the control phase.
Conclusions. The study brought a number of new information about the importance of the „non-classical“
glucoregulatory hormones in impairment of glucose metabolism, during long-term administration of low prednison
(89) doses. The results suggest, that without normalisation of low DHEA/S, SHBG and high FAI levels it would not be
possible to correct glucose metabolism properly in patients with long-term glucocorticoid therapy.
Key words:
glucose metabolism, metformin, prednison, insulin resistance, androgens, IGF-1, growth hormone,
IGF BP-3, sex hormone binding globulin, somatostatin.
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