Lipotoxicity , originally used to describe the destructive effects of excess fat accumulation on glucose metabolism, causes functional impairments in several metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. Lipotoxicity has roles in insulin resistance and pancreatic beta cell dysfunction. Increased circulating levels of lipids and the metabolic alterations in fatty acid utilization and intracellular signaling, have been related to insulin resistance in muscle and liver. Different pathways, like novel protein kinase c pathways and the JNK-1 pathway are involved as the mechanisms of how lipotoxicity leads to insulin resistance in nonadipose tissue organs, such as liver and muscle. Mitochondrial dysfunction plays a role in the pathogenesis of insulin resistance. Endoplasmic reticulum stress, through mainly increased oxidative stress, also plays important role in the etiology of insulin resistance, especially seen in non-alcoholic fatty liver disease. Visceral adiposity and insulin resistance both increase the cardiometabolic risk and lipotoxicity seems to play a crucial role in the pathophysiology of these associations.

This study shows that 25(OH)D deficiency is associated with endothelial dysfunction and increased lipid peroxidation. Replacement of vitamin D has favorable effects on endothelial function. Vitamin D deficiency can be seen as an independent risk factor of atherosclerosis. Hypovitaminosis D-associated endothelial dysfunction may predispose to higher rates of cardiovascular disease in the winter.

Although only 4.5% to 16% of ovarian cysts in children are malignant, oophorectomy is common in such patients. Conservative expectant management and ovarian sparing surgery would avoid bilateral oophorectomies in children with ovarian cysts at low risk of malignancy. Pediatric or general surgeons who have limited expertise with pediatric gynecology often manage these children because of limited availability of pediatric and adolescent gynecologists with the special skills needed.The objective of this retrospective case-note study was to investigate the nature and surgical management of ovarian cysts in children at a large children's hospital to determine whether current management practices could be improved. Between 1991 and 2007, 155 cases identified through use of clinical coding of surgical cases and pathology databases were analyzed by use of Snap 9.Sixty-two ovarian cysts were found in children under 9 years of age who were prepubertal. There were 58 neoplastic cysts, but 36 (62%) were benign teratomas. Ten of the cysts were malignant. Preoperative diagnostic investigation was preformed in a minority of the patients: Of the 155 children, only 16 (10%) were investigated for tumor markers; 61 (39%) had an ultrasound scan; and 16 (10%) had a computed tomography or magnetic resonance imaging scan. An oophorectomy was performed in 90 (58%) of the children and an ovarian cystectomy was performed in 40 (26%). The ovary was removed in all cases with malignant cysts, and in 75 cases with benign or normal pathology (including 5 benign epithelial, 9 functional and 4 paraovarian cysts; 5 cases with normal ovarian tissue; 30 oophorectomies for benign teratomas, 21 for torsion and 1 for hemorrhage). Referral to a pediatric gynecologist occurred for only 24 (15.5%) of the patients following surgery for an ovarian cyst. This number excluded the 10 girls who were still in pain. None of the referrals were before surgery.These findings show that a large number of young girls with benign cysts who are at low risk of malignancy have cystectomy or oophorectomy when a conservative expectant management approach or ovarian-sparing surgery could have been justified. To prevent this practice, the investigators recommend greater use of preoperative diagnostic investigations including tumor markers and imaging, and the training of more gynecologists with the special skills in pediatric and adolescent gynecology needed to manage these patients. EDITORIAL COMMENT(In this retrospective analysis of ovarian cysts in children and adolescents from England, a surprisingly large number of patients were man-aged by oophorectomy and open laparotomy. Cases in this review (and certainly in most reports) were identified by searching the pathol- GYNECOLOGY Volume 65, Number 3 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTBecause hysterectomy, the standard treatment option for women of reproductive age with menorrhagia, is associated with serious complications and requires a relatively long-recovery period, the levonorgestrel-releasing intrauterine sys...

BACKGROUND/OBJECTIVE: Artificial sweeteners were thought to be metabolically inactive, but after demonstrating that the gustatory mechanism was also localized in the small intestine, suspicions about the metabolic effects of artificial sweeteners have emerged. The objective of this study was to determine the effect of artificial sweeteners (aspartame and sucralose) on blood glucose, insulin, c-peptide and glucagon-like peptide-1 (GLP-1) levels. SUBJECTS/METHODS: Eight newly diagnosed drug-naive type 2 diabetic patients (mean age 51.5 ± 9.2 years; F/M: 4/4) and eight healthy subjects (mean age 45.0 ± 4.1 years; F/M: 4/4) underwent 75 g oral glucose tolerance test (OGTT). During OGTT, glucose, insulin, c-peptide and GLP-1 were measured at 15-min intervals for 120 min. The OGTTs were performed at three settings on different days, where subjects were given 72 mg of aspartame and 24 mg of sucralose in 200 ml of water or 200 ml of water alone 15 min before OGTT in a single-blinded randomized order. RESULTS: In healthy subjects, the total area under the curve (AUC) of glucose was statistically significantly lower in the sucralose setting than in the water setting (P = 0.002). There was no difference between the aspartame setting and the water setting (P = 0.53). Total AUC of insulin and c-peptide was similar in aspartame, sucralose and water settings. Total AUC of GLP-1 was significantly higher in the sucralose setting than in the water setting (P = 0.04). Total AUC values of glucose, insulin, c-peptide and GLP-1 were not statistically different in three settings in type 2 diabetic patients. CONCLUSIONS: Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.