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...

Metabolic syndrome frequency was increased in our study population compared to the general population. Metabolic syndrome parameters (except HDL) correlated with TT3, FT4, and the FT3/FT4 ratio. FT4 levels were associated with obesity and metabolic syndrome independently of insulin resistance, whereas TT3 levels were associated with both insulin resistance and metabolic syndrome. This relationship can be explained by compensatory effects of TT3, and probably FT4, on energy expenditure and thermogenesis in obese people.

Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

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.

Although the studies are mostly small in size, heterogeneous and have conflicting results, we have demonstrated that serum sclerostin levels were not associated with all-cause and cardiovascular mortality.

ObjectiveAlthough levothyroxine (LT4) replacement therapy for hypothyroidism has been established as safe, inexpensive and effective, many studies from different countries reported out-of-reference range thyroid-stimulating hormone (TSH) values for the hypothyroid patients under LT4 treatment. The aim of this study was to determine TSH levels of primary hypothyroid patients under LT4 treatment and to assess self-reported compliance with daily LT4 intake in tertiary care centers in Turkey.DesignIn this cross-sectional, observational study, adult patients with primary hypothyroidism, receiving LT4 treatment for at least 6 months, were included. The patients were from 12 tertiary care centers in 9 cities of Turkey. TSH and free T4 levels were recorded from patient files and self-reported compliance with daily LT4 intake was assessed by interviewing the subjects at the last visit.ResultsA total of 1,755 subjects (46 ± 13 years; F/M: 89.9/10.1%) with primary hypothyroidism were enrolled. Of the hypothyroid subjects, 44.8% had out-of-reference range serum TSH levels. TSH values were over the reference range (TSH > 4 mIU/L) in 26.2% and were under the reference range (TSH < 0.5 mIU/L) in 18.6% of the patients. Total duration of LT4 treatment was 5.9 ± 4.7 years and mean dose was 1.2 ± 0.6 μg/kg/day. Non-compliant patients (31.1%) had higher TSH levels (6.9 ± 16 vs 3.8 ± 0.9 mIU/L, P = 0.01) compared to compliant patients.ConclusionThe results of this study revealed that nearly half of the hypothyroid patients had out-of-reference range serum TSH values, despite under LT4 treatment. Compliance with LT4 treatment seems to be one of the major determinants to reach the target TSH levels in hypothyroid patients.