- Decreased access to bariatric care: an analysis of referral practices to bariatric specialists. [Journal Article]
- SOSurg Obes Relat Dis 2016; 12(9):1725-1730
- CONCLUSIONS: Most primary care and subspecialists do not discuss bariatric surgical options, resulting in decreased access to bariatric care. The main barrier to referral is noncommunication by the primary care physician or subspecialist, despite the vast majority of physicians having positive attitudes about bariatric surgery. Co-morbidities of diabetes and obstructive sleep apnea are more likely to prompt a referral. Primary care physicians are most likely to refer, while endocrinologists are least likely. Improved familiarity with nationally recognized obesity management algorithms could contribute to improved referral rates.
- Combined effect of obesity and uric acid on nonalcoholic fatty liver disease and hypertriglyceridemia. [Journal Article]
- MMedicine (Baltimore) 2017; 96(12):e6381
- Hyperuricemia is associated with metabolic syndrome (MetS), but the association is often confounded by the shared background of obesity. We sought to explore the modifying effects of obesity on the a...
Hyperuricemia is associated with metabolic syndrome (MetS), but the association is often confounded by the shared background of obesity. We sought to explore the modifying effects of obesity on the association between uric acid (UA), MetS components, and nonalcoholic fatty liver disease (NAFLD).We conducted a cross-sectional study in a Chinese population of 10,069 participants aged ≥20 years. Multiplicative interaction between obesity (BMI ≥25 kg/m) and elevated UA was assessed using an interaction term in a logistic regression analysis. The presence of additive interaction was assessed based on the relative excess risk due to the interaction (RERI) and the attributable proportion due to the interaction (AP).There was no evidence of a multiplicative interaction between obesity and elevated UA on MetS components and NAFLD. However, there was a strong additive interaction between obesity and elevated UA with regard to NAFLD (RERI of 6.47 [95% CI 3.42-9.53] for men and 5.87 [1.55-10.19] for women) and hypertriglyceridemia (RERI of 1.38 [0.57-2.20] for men and 1.38 [0.08-2.67] for women). In addition, 42% and 36% of the increased odds of NAFLD for men and women, respectively, can be explained by an interaction between obesity and elevated UA (AP of 0.42 [95% CI (0.30-0.54)] for men and 0.36 [0.17-0.55] for women). Similarly, the interaction accounted for 27% and 26% of the increased risk of hypertriglyceridemia for men and women (AP of 0.27 [0.14-0.41] for men and 0.26 [0.06-0.47] for women).In this population, obesity and elevated UA synergistically interacted to increase the risk of NAFLD and hypertriglyceridemia.
- Effects of Metreleptin in Pediatric Patients with Lipodystrophy. [Journal Article]
- JCJ Clin Endocrinol Metab 2017 Jan 23
- CONCLUSIONS: Metreleptin lowered A1c and triglycerides, and improved biomarkers of NAFLD, in pediatric patients with lipodystrophy. These improvements are likely to reduce the lifetime burden of disease.
- The anti-diabetic drug exenatide, a glucagon-like peptide-1 receptor agonist, counteracts hepatocarcinogenesis through cAMP-PKA-EGFR-STAT3 axis. [Journal Article]
- OOncogene 2017 Mar 20
- Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 recepto...
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells. The tumor suppression effects of Ex-4 were associated with high expression of GLP-1R and activation of cyclic AMP (cAMP) and protein kinase A (PKA). Importantly, Ex-4 also downregulated epidermal growth factor receptor (EGFR) and signal transducer and activator of transcription 3 (STAT3), which lie downstream of cAMP-PKA signaling, resulting in suppression of multiple STAT3-targeted genes including c-Myc, cyclin D1, survivin, Bcl-2 and Bcl-xl. The growth inhibitory effects of Ex-4 were consistent in GLP-1R-abundant hepatoma cell lines and xenograft mouse model, wherein both PKA and EGFR had obligatory roles in mediating Ex-4 functions. In addition, Ex-4 also effectively suppressed inflammatory and fibrotic phenotypes in mice fed with methionine-choline-deficient (MCD) diet and choline-deficient ethionine-supplemented (CDE) diet, respectively. In summary, Ex-4 elicits protective functions against NAFLD and obesity-associated HCC through cAMP-PKA-EGFR-STAT3 signaling, suggesting its administration as a novel approach to reduce HCC risk in diabetic patients.Oncogene advance online publication, 20 March 2017; doi:10.1038/onc.2017.38.
- Low serum testosterone is associated with impaired graft function early after heart transplantation. [Journal Article]
- CTClin Transplant 2017 Mar 17
- CONCLUSIONS: Low serum testosterone levels appear to be associated with impaired graft function and an increased incidence of low-grade rejection episodes early after heart transplantation.
- The Influence of Lipid and Proinflammatory Status on Maternal Uterine Blood Flow in Women With Late Onset Gestational Diabetes. [Journal Article]
- RSReprod Sci 2017 Jan 01; :1933719117698576
- CONCLUSIONS: The proinflammatory status, hyperlipidemia, and metabolic control correlate with uterine blood flow velocity waveforms in women with gestational diabetes.
- Time-course changes of nLDL-induced erectile dysfunction. [Journal Article]
- IJInt J Impot Res 2017 Mar 16
- Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of nativ...
Hyperlipidemia is an important risk factor for atherosclerosis and is frequently seen in patients with erectile dysfunction (ED). This study was designed to evaluate whether the acute effect of native low-density lipoprotein (nLDL) on intracavernosal pressure (ICP) is reversible and related to plasma asymmetrical dimethylarginine (ADMA), endogenous inhibition of endothelial nitric oxide synthase (eNOS) levels and eNOS expression in cavernous tissues. Hyperlipidemia was induced by a single dose of intravenous 4 mg kg(-1) nLDL. Experiments were performed 72 h (72H), 2 weeks (2W) and 8 weeks (8W) after nLDL injection. Endothelium-dependent relaxations, the ratio of ICP to mean arterial pressure (MAP; ICP/MAP), plasma ADMA levels and eNOS mRNA and protein levels were evaluated. The ICP/MAP ratio decreased in both the 2W and 8W groups. Endothelium-dependent relaxation responses to acetylcholine in the rat thoracic aorta were damaged in the 8W group. Plasma ADMA levels increased in the 8W group. mRNA expression of eNOS decreased in a time-dependent manner, whereas the protein expression increased. These results suggest that acute nLDL injection-induced impairments in erectile functions during an 8-week period are irreversible and might be related to an increase in ADMA levels and changes in the regulation of the eNOS/NO pathway.International Journal of Impotence Research advance online publication, 16 March 2017; doi:10.1038/ijir.2017.5.
- Impact of gain-of-function mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) on glucose and lipid homeostasis. [Journal Article]
- OIOsteoporos Int 2017 Mar 10
- CONCLUSIONS: Although our sample size was small, our data do not support the hypothesis that HBM-causing LRP5 mutations, associated with increased Wnt signaling, improve glucose metabolism in humans. However, it does appear that LRP5 variants may affect LDL metabolism, a major risk factor for coronary artery disease. The molecular mechanisms underpinning this effect warrant further study.
- ENOblock, a unique small molecule inhibitor of the non-glycolytic functions of enolase, alleviates the symptoms of type 2 diabetes. [Journal Article]
- SRSci Rep 2017 Mar 08; 7:44186
- Type 2 diabetes mellitus (T2DM) significantly impacts on human health and patient numbers are predicted to rise. Discovering novel drugs and targets for treating T2DM is a research priority. In this ...
Type 2 diabetes mellitus (T2DM) significantly impacts on human health and patient numbers are predicted to rise. Discovering novel drugs and targets for treating T2DM is a research priority. In this study, we investigated targeting of the glycolysis enzyme, enolase, using the small molecule ENOblock, which binds enolase and modulates its non-glycolytic 'moonlighting' functions. In insulin-responsive cells ENOblock induced enolase nuclear translocation, where this enzyme acts as a transcriptional repressor. In a mammalian model of T2DM, ENOblock treatment reduced hyperglycemia and hyperlipidemia. Liver and kidney tissue of ENOblock-treated mice showed down-regulation of known enolase target genes and reduced enolase enzyme activity. Indicators of secondary diabetic complications, such as tissue apoptosis, inflammatory markers and fibrosis were inhibited by ENOblock treatment. Compared to the well-characterized anti-diabetes drug, rosiglitazone, ENOblock produced greater beneficial effects on lipid homeostasis, fibrosis, inflammatory markers, nephrotoxicity and cardiac hypertrophy. ENOblock treatment was associated with the down-regulation of phosphoenolpyruvate carboxykinase and sterol regulatory element-binding protein-1, which are known to produce anti-diabetic effects. In summary, these findings indicate that ENOblock has potential for therapeutic development to treat T2DM. Previously considered as a 'boring' housekeeping gene, these results also implicate enolase as a novel drug target for T2DM.
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- Rationale and Design of a Genetic Study on Cardiometabolic Risk Factors: Protocol for the Tehran Cardiometabolic Genetic Study (TCGS). [Journal Article]
- JRJMIR Res Protoc 2017 Feb 23; 6(2):e28
- CONCLUSIONS: Investigations conducted within the TCGS will seek to identify relevant patterns of genetic polymorphisms that could be related to cardiometabolic risk factors in participants from Tehran. By linking genome-wide data to the existing databank of TLGS participants, which includes comprehensive behavioral, biochemical, and clinical data on each participant since cohort inception in 1999, the TCGS will also allow exploration of gene-gene and gene-environment interactions as they relate to disease status.