The Journal of clinical endocrinology and metabolism
-
J. Clin. Endocrinol. Metab. · Jun 2004
Multicenter Study Comparative StudyBody size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition: The Study of Women's Health across the Nation (SWAN) Daily Hormone Study.
The dynamics of reproductive hormones that characterize the menopausal transition (perimenopause) are incompletely understood, particularly in non-Caucasian women. The Study of Women's Health across the Nation (SWAN) is a multiethnic cohort study of 3302 women at seven sites who were aged 42-52 yr at baseline. All participants are seen annually to assess a variety of endpoints. ⋯ When compared with cycles of younger control women, the cycles of the SWAN DHS participants had higher gonadotropins, lower total integrated Pdg, and E1c levels that were not different, which suggests that the ovary retains sensitivity to elevated FSH in the early menopausal transition. In this cross-sectional study of women over age 42 who are premenopausal or in the early menopausal transition, there were important differences in the characteristics of cycles related to age, body mass index, and ethnicity. Comparisons to younger women indirectly support the inhibin hypothesis, which proposes that the initiating event in the menopausal transition is the loss of inhibin negative feedback on FSH secondary to a diminished follicular reserve.
-
J. Clin. Endocrinol. Metab. · Jun 2004
Randomized Controlled Trial Clinical TrialNon-acylated ghrelin counteracts the metabolic but not the neuroendocrine response to acylated ghrelin in humans.
Ghrelin possesses strong GH-releasing activity but also other endocrine activities including stimulation of PRL and ACTH secretion, modulation of insulin secretion and glucose metabolism. It is assumed that the GH secretagogue (GHS) receptor (GHS-R) 1a mediates ghrelin actins provided its acylation in Serine 3; in fact, acylated ghrelin only is able to exert endocrine activities. Acylated ghrelin (AG) is present in serum at a 2.5 fold lower concentration than unacylated ghrelin (UAG). ⋯ In conclusion, non-acylated ghrelin does not affect the GH, PRL, and ACTH response to acylated ghrelin but is able to antagonize the effects of acylated ghrelin on insulin secretion and glucose levels. These findings indicate that unacylated ghrelin is metabolically active and is likely to counterbalance the influence of acylated ghrelin on insulin secretion and glucose metabolism. As GHS-R1a is not bound by unacylated ghrelin, these findings suggest that GHS receptor subtypes mediate the metabolic actions of both acylated and unacylated ghrelin.
-
J. Clin. Endocrinol. Metab. · Mar 2004
Randomized Controlled Trial Clinical TrialEffects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men.
Glitazones are used in the treatment of type 2 diabetes as efficient insulin sensitizers. They can, however, induce peripheral edema through an unknown mechanism in up to 18% of cases. In this double-blind, randomized, placebo-controlled, four-way, cross-over study, we examined the effects of a 6-wk administration of pioglitazone (45 mg daily) or placebo on the blood pressure, hormonal, and renal hemodynamic and tubular responses to a low (LS) and a high (HS) sodium diet in healthy volunteers. ⋯ Body weight increased with pioglitazone in most subjects. Pioglitazone stimulates plasma renin activity and favors sodium retention and weight gain in healthy volunteers. These effects could contribute to the development of edema in some subjects treated with glitazones.
-
J. Clin. Endocrinol. Metab. · Jan 2004
Randomized Controlled Trial Clinical TrialContribution of circulating lipids to the improved outcome of critical illness by glycemic control with intensive insulin therapy.
Compared with the conventional approach, which recommended only insulin therapy when blood glucose levels exceeded 12 mmol/liter, strict maintenance of blood glucose levels less than 6.1 mmol/liter with intensive insulin therapy has shown to reduce intensive care mortality, acute renal failure, critical illness polyneuropathy, and bloodstream infections in critically ill patients by about 40%. This study of 363 patients, requiring intensive care for more than 7 d and randomly assigned to either conventional or intensive insulin therapy, examines the effects of intensive insulin therapy on glucose and lipid homeostasis and their respective impact on the improved outcome. Intensive insulin therapy effectively normalized blood glucose levels within 24 h, both in survivors and nonsurvivors. ⋯ Multivariate logistic regression analysis, corrected for baseline univariate risk factors and the effect on inflammation, indicated that lipid rather than glucose control independently determined the beneficial effects of intensive insulin therapy on morbidity and mortality. In postmortem biopsies obtained from 74 patients who died in the intensive care unit, intensive insulin therapy increased mRNA levels of skeletal muscle glucose transporter 4 (P = 0.02) and hexokinase (P = 0.03), unlike those of hepatic glucokinase. In conclusion, our data suggest that intensive insulin therapy normalizes blood glucose levels through stimulation of peripheral glucose uptake and concomitantly partially restores the abnormalities in the serum lipid profile, which may have contributed significantly to the improved outcome of protracted critical illness.