Decreased steroidogenic enzyme 17,20-lyase and increased 17-hydroxylase activities in type 2 diabetes mellitus.
OBJECTIVE
To analyze activities of adrenal steroidogenic enzymes in type 2 diabetes mellitus, serum levels of 11 steroid hormones were measured simultaneously.


METHODS
We studied 130 patients with type 2 diabetes mellitus (74 men and 56 women between the ages of 40 and 69 years), whose blood glucose control had been poor (more than 10% in HbA(1c)). Age-matched normal subjects served as the control group.


METHODS
Serum levels of steroid hormones (pregnenolone (Preg), progesterone (Prog), deoxycorticosterone (DOC), corticosterone (B), 17-hydroxypregnenolone (17-OH-Preg), 17-hydroxyprogesterone (17-OHP), 11-deoxycortisol (S), cortisol (F), dehydroepiandrosterone (DHEA) and Delta4-androstenedione (Delta4A)) were measured by HPLC/RIA methods. Fasting plasma glucose (FPG), HbA(1c), ACTH, serum immunoreactive insulin (IRI) and DHEA sulfate (DHEA-S) were also measured. We analyzed product/precursor ratios to assess relative activities of adrenal steroidogenic enzymes.


RESULTS
Serum levels of ACTH and F were high and DHEA and DHEA-S were low in both male and female patients under poor blood glucose control. Following 6-months treatment with diet only or with sulfonylurea, FPG and HbA(1c) improved, and blood concentrations of ACTH and F decreased while DHEA and DHEA-S levels increased to within the normal range. DHEA/17-OH-Preg and Delta4A/17-OHP ratios, reflecting 17,20-lyase activity, were low before treatment and recovered to the normal range after treatment, and 17-OH-Preg/Preg and 17-OHP/Prog ratios, reflecting 17-hydroxylase activity, were high before treatment, and fell within the normal range after treatment. 3beta-Hydroxysteroid dehydrogenase, 21-hydroxylase and 11beta-hydroxylase activities remained within the normal range both before and after treatment.


CONCLUSIONS
These data suggest that the decrease in DHEA and DHEA-S concentrations together with the high F levels that occur in patients with type 2 diabetes mellitus is associated with low 17,20-lyase and high 17-hydroxylase activity in the adrenal steroidogenic enzymes. High insulin concentrations may further lower DHEA and DHEA-S levels.
Ueshiba
Hajime
H
First Department of Internal Medicine, Toho University School of Medicine, 6-11-1 Ohmori-nishi, Ohta-ku, Tokyo 143-0015, Japan. ueshiba@med.toho-u.ac.jp
Shimizu
Yusuke
Y
Hiroi
Naoki
N
Yakushiji
Fumiatsu
F
Shimojo
Masako
M
Tsuboi
Kumiko
K
Miyachi
Yukitaka
Y
D000311:Adrenal Glands / Q000201:enzymology; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008297:Male; D008875:Middle Aged; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism*; D013255:Steroid 21-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000097:blood
D001786:Blood Glucose; D013256:Steroids; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D013255:Steroid 21-Hydroxylase; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D006854:Hydrocortisone