c-peptide and Hypogonadism

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Topics: Adrenal Glands; Adult; Antipsychotic Agents; beta-Endorphin; Blood Glucose; C-Peptide; Endocrine System; Female; Gonadal Steroid Hormones; Humans; Hypogonadism; Insulin; Insulin Resistance; Leptin; Lipids; Multivariate Analysis; Obesity; Prolactin; Sex Hormone-Binding Globulin; Thyroid Hormones

We report 34 patients (aged 5-18 years) with acute (n = 26) or chronic (n = 1) leukemia, non-Hodgkin's lymphoma (n = 3) or severe aplastic anemia (n = 4) evaluated for pancreatic beta-cell function 9 months to 10.2 years after autologous (n = 19) or allogeneic (n = 15) BMT. Before BMT, all patients received cytotoxic drugs, combined with total body irradiation (TBI) in 24 cases or thoracoabdominal irradiation (TAI) in 4 children. Patients were investigated for fasting blood glucose (FBG), HbA1C, anti-insulin (IAA) and islet cell antibodies (ICA), first-phase insulin response (FPIR) and insulinemia/glycemia (I/G) ratio on i.v. glucose tolerance test (GTT) and C-peptide response after glucagon 1 mg i.v. Results were compared with those obtained in 21 age- and sex-matched controls. None of the patients or controls had IAA and/or ICA. FBG and HbA1C were normal in all children. In the patients, glycemia on i.v. GTT was similar to controls whereas insulin levels I/G ratio and FPIR were significantly higher in patients than in controls, as well as C-peptide levels. We divided the patients on the basis of the radiotherapy into group I with TBI (n = 18), group II with TAI (n = 4) and group III who were not irradiated (n = 4). The I/G ratio, FPIR on i.v. GTT and C-peptide response were significantly higher in group I compared with the other two groups and controls. The increased insulin and C-peptide levels in our patients with normal glycemia might be interpreted as a state of insulin resistance, more evident in patients who received TBL.

Topics: Adolescent; Anemia, Aplastic; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Blood Glucose; Bone Marrow Transplantation; C-Peptide; Child; Child, Preschool; Female; Glucagon; Glycated Hemoglobin; Growth Hormone; Humans; Hypogonadism; Hypothyroidism; Insulin; Insulin Resistance; Insulin Secretion; Islets of Langerhans; Leukemia; Lymphoma, Non-Hodgkin; Male; Prospective Studies; Radiation Injuries; Radioisotope Teletherapy; Whole-Body Irradiation