The Journal of clinical endocrinology and metabolism
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J. Clin. Endocrinol. Metab. · Jun 2003
Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus.
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones secreted in response to meal ingestion, thereby enhancing postprandial insulin secretion. Therefore, an attenuated incretin response could contribute to the impaired insulin responses in patients with diabetes mellitus. The aim of the present investigation was to investigate incretin secretion, in obesity and type 1 and type 2 diabetes mellitus, and its dependence on the magnitude of the meal stimulus. ⋯ Incremental GLP-1 responses were normal in type 1 diabetic patients. Increased fasting concentrations of GIP and an early enhanced postprandial GIP response were seen in obese, compared with lean healthy subjects, whereas GLP-1 responses were the same in the two groups. beta-cell sensitivity to glucose, evaluated as the slope of insulin secretion rates vs. plasma glucose concentration, tended to increase in both type 2 diabetic patients (29%, P = 0.19) and obese healthy subjects (22% P = 0.04) during the large meal, compared with the small meal, perhaps reflecting the increased incretin response. We conclude: 1) that a decreased GLP-1 secretion may contribute to impaired insulin secretion in type 2 diabetes mellitus, whereas GIP and GLP-1 secretion is normal in type 1 diabetic patients; and 2) that it is possible to modulate the beta-cell sensitivity to glucose in obese healthy subjects, and possibly also in type 2 diabetic patients, by giving them a large meal, compared with a small meal.
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J. Clin. Endocrinol. Metab. · May 2003
Rationale for central and bilateral lymph node dissection in sporadic and hereditary medullary thyroid cancer.
A retrospective study was performed on 101 consecutive medullary thyroid cancer (MTC) patients who underwent at Institut Gustave-Roussy (IGR) total thyroidectomy with central and bilateral lymph node dissection. At histology, lymph node metastases were found in 55% of patients. In sporadic MTC, lymph node metastases were observed in the central compartment in 50% of patients, in the ipsilateral jugulocarotid chain in 57%, and in the contralateral jugulocarotid chain in 28%. In hereditary MTC, lymph node metastases were identified in the central compartment in 45% of patients, in the ipsilateral jugulocarotid chain in 36%, and in the contralateral jugulocarotid chain in 19%. Contralateral lymph nodes were found in 37% of metastatic patients with an unilateral tumoral involvement of the thyroid gland. A strong association was observed between tumor size and lymph node involvement for both hereditary and sporadic MTC (P < 0.02). Permanent hypoparathyroidism occurred in 4% of patients and laryngeal nerve palsy in 5%. An undetectable calcitonin level was obtained after surgery in 61% of patients, in 95% of patients without lymph node metastases, and in 32% of patients with lymph node metastases. Among patients with lymph node involvement, undetectable calcitonin level was obtained in 57% of patients with less than or with 10 lymph node metastases and in 4% of patients with more than 10 (P < 0.01). ⋯ 1) lymph node metastases occur early in the course of MTC; 2) the pattern of lymph node metastatic distribution in neck areas varied between patients and was not related to the thyroid tumor size; 3) contralateral lymph node metastases were observed even in patients with small thyroid tumor; 4) total thyroidectomy with central and complete bilateral neck dissection should be performed routinely in all patients with sporadic and hereditary MTC, even in those with small thyroid tumors-a contralateral neck dissection may be avoided only in sporadic MTC patients with unilateral involvement of the thyroid gland in the absence of central and ipsilateral neck involvement; and 5) the number of lymph node metastases was predictive of biological cure after surgery.
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J. Clin. Endocrinol. Metab. · Apr 2003
Comparative StudyBody fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans.
The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. ⋯ Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum adiponectin or resistin concentrations and total energy or macronutrient intake. Thus, total energy intake and macronutrient composition of the diet are associated with sOB-R and free leptin index but do not play a role of comparable significance in predicting adiponectin and resistin concentrations in healthy young subjects.
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J. Clin. Endocrinol. Metab. · Jan 2003
Randomized Controlled Trial Comparative Study Clinical TrialMetformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study.
Metformin, an insulin-sensitizing drug, has been shown to improve ovarian function and glucose metabolism in obese women with polycystic ovary syndrome (PCOS), but its effects and possible benefits in nonobese PCOS subjects are not well known. Seventeen nonobese (body mass index < 25 kg/m(2)) women with PCOS were randomized to receive either metformin (500 mg twice daily for 3 months, then 1000 mg twice daily for 3 months; n = 8) or ethinyl estradiol (EE, 35 microg)-cyproterone acetate (CA, 2 mg) oral contraceptive pills (EE-CA; n = 9). Waist to hip ratio; serum concentrations of sex steroids, glucose, and insulin during a 75-g oral glucose tolerance test; early phase insulin and C-peptide secretion; and insulin sensitivity using a euglycemic hyperinsulinemic clamp were assessed at baseline and at 3 and 6 months of treatment. ⋯ In conclusion, EE-CA seems to be an efficient mode of therapy for hyperandrogenic symptoms associated with PCOS, but its possible negative effects on insulin and glucose metabolism also have to be taken into consideration in nonobese subjects. Metformin improved hyperandrogenism, hyperinsulinemia, and menstrual cyclicity, most likely through its positive effect on insulin clearance and abdominal adiposity. Thus, similarly to obese PCOS women, nonobese PCOS subjects with anovulation may also benefit from metformin treatment.
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J. Clin. Endocrinol. Metab. · Dec 2002
Randomized Controlled Trial Clinical TrialRegulation of insulin-like growth factor binding protein-1 during protracted critical illness.
IGF binding protein-1 (IGFBP-1), an important regulator of IGF bioavailability, has been shown to correlate with mortality in critically ill patients. In the liver, IGFBP-1 is transcriptionally repressed by insulin, and it is therefore a potential marker of hepatic insulin sensitivity. We have recently shown that, compared with conventional treatment, maintenance of normoglycemia with intensive insulin therapy decreased morbidity and mortality of continuously fed critically ill patients. ⋯ The predictive value of serum IGFBP-1 for mortality was similar to that of the APACHE-II score. Like circulating IGFBP-1, hepatic mRNA levels of IGFBP-1 and the similarly insulin-regulated gene, phosphoenolpyruvate carboxykinase, were not significantly different between conventional and intensive insulin therapy groups. These data suggest that hepatic insulin resistance in prolonged critically ill patients, reflected by high serum IGFBP-1 levels, is not overcome by intensive insulin therapy, and that this may affect patient outcome.