The aim of this study is to compare the risk for future development of nonalcoholic fatty liver disease (NAFLD) according to different status of metabolic health and obesity.
A total of 3,045 subjects without NAFLD and diabetes at baseline were followed for 4 years. Subjects were categorized into four groups according to the following baseline metabolic health and obesity statuses: metabolically healthy, non-obese (MHNO); metabolically healthy, obese (MHO); metabolically unhealthy, non-obese (MUHNO); and metabolically unhealthy, obese (MUHO). Being metabolically healthy was defined as having fewer than two of the following five components: high blood pressure, high fasting blood glucose, high triglyceride, low high density lipoprotein cholesterol, and being in the highest decile of the homeostasis model assessment-insulin resistance index. Obesity was defined as a body mass index >25 kg/m2. The presence of NAFLD was assessed by ultrasonography.
The proportions of subjects included in the MHNO, MHO, MUHNO, and MUHO groups were 71.4%, 9.8%, 13.0%, and 5.8%, respectively. The proportions of subjects who developed NAFLD were 10.5%, 31.4%, 23.2%, and 42% in the MHNO, MHO, MUHNO, and MUHO groups, respectively. The risk for developing NAFLD was highest in subjects who were metabolically unhealthy both at baseline and after 4 years compared with subjects who were consistently metabolically healthy during the follow-up period (odds ratio, 2.862). Using the MHNO group as reference, the odds ratios for the MHO, MUHNO, and MUHO groups were 1.731, 1.877, and 2.501, respectively.
The risk for NAFLD was lower in MHO subjects than in MUNO subjects.
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Recent studies have shown an association between thyroid hormone levels and metabolic syndrome (MetS) among euthyroid individuals; however, there have been some inconsistencies between studies. Here, we evaluated the relationship between thyroid hormone levels and MetS in euthyroid middle-aged subjects in a large cohort.
A retrospective analysis of 13,496 euthyroid middle-aged subjects who participated in comprehensive health examinations was performed. Subjects were grouped according to thyroid stimulating hormone, total triiodothyronine (T3), total thyroxine (T4), and T3-to-T4 ratio quartile categories. We estimated the odds ratios (ORs) for MetS according to thyroid hormone quartiles using logistic regression models, adjusted for potential confounders.
Of the study patients, 12% (
Serum T3 levels and T3-to-T4 ratio are independently associated with MetS in euthyroid middle-aged subjects. Longitudinal studies are needed to define this association and its potential health implications.
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Fibroblast growth factor 21 (FGF21) is an attractive target for treating metabolic disease due to its wide-ranging beneficial effects on glucose and lipid metabolism. Circulating FGF21 levels are increased in insulin-resistant states; however, endogenous FGF21 fails to improve glucose and lipid metabolism in obesity, suggesting that metabolic syndrome is an FGF21-resistant state. Therefore, transcription factors for FGF21 are potential drug targets that could increase FGF21 expression in obesity and reduce FGF21 resistance. Despite many studies on the metabolic effects of FGF21, the transcriptional regulation of FGF21 gene expression remains controversial and is not fully understood. As the FGF21 transcription factor pathway is one of the most promising targets for the treatment of metabolic syndrome, further investigation of FGF21 transcriptional regulation is required.
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Recently, we reported the antiapoptotic effect of ghrelin in spinal cord injury-induced apoptotic cell death of oligodendrocytes. However, how ghrelin inhibits oligodendrocytes apoptosis, is still unknown. Therefore, in the present study, we examined whether ghrelin inhibits microglia activation and thereby inhibits oligodendrocyte apoptosis.
Using total cell extracts prepared from BV-2 cells activated by lipopolysaccharide (LPS) with or without ghrelin, the levels of p-p38 phosphor-p38 mitogen-activated protein kinase (p-p38MAPK), phospho-c-Jun N-terminal kinase (pJNK), p-c-Jun, and pro-nerve growth factor (proNGF) were examined by Western blot analysis. Reactive oxygen species (ROS) production was investigated by using dichlorodihydrofluorescein diacetate. To examine the effect of ghrelin on oligodendrocyte cell death, oligodendrocytes were cocultured in transwell chambers of 24-well plates with LPS-stimulated BV-2 cells. After 48 hours incubation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and terminal deoxynucleotidyl transferase 2'-deoxyuridine, 5'-triphosphate nick end labeling staining were assessed.
Ghrelin treatment significantly decreased levels of p-p38MAPK, p-JNK, p-c-Jun, and proNGF in LPS-stimulated BV-2 cells. ROS production increased in LPS-stimulated BV-2 cells was also significantly inhibited by ghrelin treatment. In addition, ghrelin significantly inhibited oligodendrocyte cell death when cocultured with LPS-stimulated BV-2 cells.
Ghrelin inhibits oligodendrocyte cell death by decreasing proNGF and ROS production as well as p38MAPK and JNK activation in activated microglia as an anti-inflammatory hormone.
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The natural course of cytologically benign thyroid nodules remains unclear. The aim of this study was to evaluate whether ultrasonographic (US) changes are associated with changes in nodule volume during follow-up.
We retrospectively reviewed over 4 years of clinical records of patients with benign thyroid nodules as confirmed by fine needle aspiration (FNA). In total, 186 patients with 202 benign thyroid nodules were included for study. We assessed for changes in nodule volume and examined the cystic portion of the nodule as well as four US features (echogenicity, margin, calcification pattern, and shape).
During follow-up (mean, 21.7±10.7 months) and using 50% as a cutoff value, nodule volumes increased in 11.8%, exhibited no change in 79.9%, and decreased in 8.3% of patients. Proportion of nodules demonstrating at least one US change was 20.8% (42/202). The most common US changes (in descending order of frequency) were cystic change, margin change, and calcification pattern change. Nodule shape and echogenicity rarely changed. Increased nodule volume was not significantly associated with any US features or with the number of FNAs but was associated with younger age at time of diagnosis.
Although a portion of thyroid nodules confirmed as benign showed US changes or volume changes during the follow-up period, these findings may only represent the natural course of benign nodules. Frequent follow-up with US might be needed for only a small number of cases with suspicious US findings.
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Metabolic syndrome (MetS), a cluster of multiple metabolic abnormalities, is one of the major public health challenges worldwide. The current study was conducted to evaluate the association between sugar-sweetened beverage (SSB) consumption and MetS and its components in Iranian adults.
This cross-sectional study was conducted among 5,852 men and women, aged 19 to 70 years, who participated in the fourth phase (2009 to 2011) of the Tehran Lipid and Glucose Study. Demographics, anthropometrics, biochemical measurements, and blood pressure (BP) were assessed and MetS was defined by National Cholesterol Education Program Adult Treatment Panel III definition. Frequency and quantity of SSB intakes including carbonated drinks and synthetic fruit juices were collected using a validated semiquantitative food frequency questionnaire.
Mean age of participants (43%, men) was 40.6±12.9 years. Significant positive associations between SSBs and waist circumference, triglyceride level, systolic and diastolic BP in the third and fourth quartile of SSBs were observed, after adjustment for all potential confounding variables. The odds of MetS in the third and fourth quartiles compared to the first quartile category of SSBs was 1.21 (95% confidence interval [CI], 1.01 to 1.45) and 1.30 (95% CI, 1.06 to 1.58), respectively (
Higher intake of SSBs was associated with the higher odds of MetS in adults. It is suggested that reducing consumption of SSBs could be a practical approach to prevent metabolic abnormalities.
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The nuclear receptor peroxisome proliferator-activator gamma (PPARγ) is a useful therapeutic target for obesity and diabetes, but its role in protecting β-cell function and viability is unclear.
To identify the potential functions of PPARγ in β-cells, we treated mouse insulinoma 6 (MIN6) cells with the PPARγ agonist pioglitazone in conditions of lipotoxicity, endoplasmic reticulum (ER) stress, and inflammation.
Palmitate-treated cells incubated with pioglitazone exhibited significant improvements in glucose-stimulated insulin secretion and the repression of apoptosis, as shown by decreased caspase-3 cleavage and poly (adenosine diphosphate [ADP]-ribose) polymerase activity. Pioglitazone also reversed the palmitate-induced expression of inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], and IL-1β) and ER stress markers (phosphor-eukaryotic translation initiation factor 2α, glucose-regulated protein 78 [GRP78], cleaved-activating transcription factor 6 [ATF6], and C/EBP homologous protein [CHOP]), and pioglitazone significantly attenuated inflammation and ER stress in lipopolysaccharide- or tunicamycin-treated MIN6 cells. The protective effect of pioglitazone was also tested in pancreatic islets from high-fat-fed KK-Ay mice administered 0.02% (wt/wt) pioglitazone or vehicle for 6 weeks. Pioglitazone remarkably reduced the expression of ATF6α, GRP78, and monocyte chemoattractant protein-1, prevented α-cell infiltration into the pancreatic islets, and upregulated glucose transporter 2 (Glut2) expression in β-cells. Moreover, the preservation of β-cells by pioglitazone was accompanied by a significant reduction of blood glucose levels.
Altogether, these results support the proposal that PPARγ agonists not only suppress insulin resistance, but also prevent β-cell impairment via protection against ER stress and inflammation. The activation of PPARγ might be a new therapeutic approach for improving β-cell survival and insulin secretion in patients with diabetes mellitus
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To compare pain, tolerability, and complications associated with fine needle aspiration (FNA) versus core needle biopsy (CNB).
FNAs were performed using 23-gauge needles and CNBs were performed using 18-gauge double-action spring-activated needles in 100 patients for each procedure. Patients were asked to record a pain score using a 10-cm visual analog scale and procedure tolerability. Complications and number of biopsies were recorded.
The median pain scores were similar for the FNA and CNB approaches during and 20 minutes after the biopsy procedures (3.7 vs. 3.6,
FNA and CNB show no significant differences for diagnosing thyroid nodules in terms of pain, tolerability, or complications.
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Intraoperative parathyroid hormone monitoring (IPM) has been shown to be a useful adjunct during parathyroidectomy to ensure operative success at many specialized medical centers worldwide. Using the Miami or “>50% intraoperative PTH drop” criterion, IPM confirms the complete excision of all hyperfunctioning parathyroid tissue before the operation is finished, and helps guide the surgeon to identify additional hyperfunctioning parathyroid glands that may necessitate further extensive neck exploration when intraoperative parathyroid hormone (PTH) levels do not drop sufficiently. The intraoperative PTH assay is also used to differentiate parathyroid from non-parathyroid tissues during operations using fine needle aspiration samples and to lateralize the side of the neck harboring the hypersecreting parathyroid through differential jugular venous sampling when preoperative localization studies are negative or equivocal. The use of IPM underscores the recognition and understanding of sporadic primary hyperparathyroidism (SPHPT) as a disease of function rather than form, where the surgeon is better equipped to treat such patients with quantitative instead of qualitative information for durable long-term operative success. There has been a significant paradigm shift over the last 2 decades from conventional to focused parathyroidectomy guided by IPM. This approach has proven to be a safe and rapid operation requiring minimal dissection performed in an ambulatory setting for the treatment of SPHPT.
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Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disease that is characterized by the formation of heterotopic bone tissues in soft tissues, such as skeletal muscle, ligament, and tendon. It is difficult to remove such heterotopic bones via internal medicine or invasive procedures. The identification of activin A receptor, type I (
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