The acute effect of dexamethasone on plasma leptin concentrations and the relationships between fasting leptin, the IGF-I/IGFBP system, dehydroepiandrosterone, androstenedione and testosterone in an elderly population.
OBJECTIVE
To investigate the acute effect of dexamethasone administration on serum leptin levels and the relationships between dehydroepiandrosterone (DHEAS), androstenedione, testosterone and the IGF-I/IGFBP system and leptin levels in healthy elderly humans.


METHODS
In 209 healthy elderly individuals (95 men, 114 women, aged 55-80 years) measurements were made in the fasting state (0800 h) and after an overnight dexamethasone suppression test (1 mg p.o. at 2300 h.


RESULTS
Mean leptin levels increased from 6.2 +/- 0.4 (SE) micrograms/l to 7.3 +/- 0.5 (SE) micrograms/l in men and from 18.9 +/- 1.4 (SE) micrograms/l to 23.9 +/- 1.8 (SE) micrograms/l in women after 1 mg dexamethasone overnight ('post treatment')(P < 0.001 for both sexes). There was a significant relationship between post-treatment leptin and dexamethasone levels (men: P = 0.002; women: P < 0.001). The increase in leptin levels after dexamethasone administration was only partially related to the increase in plasma insulin concentrations. Cortisol levels were not related to leptin. In multivariate analyses the relationship between post-treatment leptin and dexamethasone levels remained after adjustment for post-treatment insulin levels, BMI, waist:hip ratio (WHR) and age (men: P < 0.001; women: P = 0.001). Plasma (free and total) IGF-I and IGFBP-3 levels were not related to leptin levels in men or women. IGFBP-1 levels were inversely related to leptin levels (P = 0.02), but this relationship was lost after adjustment for insulin, and/or BMI. In multivariate analyses the relationship between leptin and DHEAS was inverse in women (P = 0.04) (after adjustment for BMI, WHR, insulin and glucose), while there was no relationship between leptin and DHEAS in men.


CONCLUSIONS
Administration of dexamethasone acutely increased leptin levels within 9 h in this elderly population. This increase was only partly related to changes in circulating insulin concentrations, but was independent of BMI and waist:hip ratio. No relation existed between leptin and (free or total) IGF-I and IGFBP-3 in men or women. Dehydroepiandrosterone was inversely related to leptin in women. These findings suggest a contributory regulatory role for corticosteroids in modulating circulating leptin concentrations in elderly healthy individuals of both sexes, which is at least in part independent of insulin, BMI and waist:hip ratio. Dehydroepiandrosterone might play a role in the gender-specific differences in serum leptin levels.
Department of Internal Medicine III, Erasmus University, Rotterdam, The Netherlands.
J A
JA
Janssen
N A
NA
Huizenga
R P
RP
Stolk
D E
DE
Grobbee
H A
HA
Pols
F H
FH
de Jong
A M
AM
Attanasio
W F
WF
Blum
S W
SW
Lamberts
D000368:Aged; D000369:Aged, 80 and over; D000735:Androstenedione / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003907:Dexamethasone / Q000494:pharmacology*; D005215:Fasting / Q000097:blood*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D020738:Leptin; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D012737:Sex Factors; D013268:Stimulation, Chemical; D013739:Testosterone / Q000097:blood
D005938:Glucocorticoids; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018969:Insulin-Like Growth Factor Binding Proteins; D020738:Leptin; D011506:Proteins; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone