Endocrinology AND Hyperlipidemia [keywords]
- Cardiovascular Risk Factors of Adults Age 20-49 Years in the United States, 1971-2012: A Series of Cross-Sectional Studies. [Journal Article]
- PLoS One 2016; 11(8):e0161770.
The health of younger adults in the U.S. has important public health and economic-related implications. However, previous literature is insufficient to fully understand how the health of this group has changed over time. This study examined generational differences in cardiovascular risk factors of younger adults over the past 40 years.Data were from 6 nationally representative cross-sectional National Health and Nutrition Examination Surveys (1971-2012; N = 44,670). Participants were adults age 20-49 years who self-reported sociodemographic characteristics and health conditions, and had examination/laboratory measures for hypertension, hyperlipidemia, diabetes, obesity, and chronic kidney disease. Prevalences of sociodemographic characteristics and health status were determined by study period. Logistic regression was used to determine the odds [odds ratio (OR), 95% confidence interval] of health conditions by study period: models adjusted only for age, sex, and race, and fully adjusted models additionally adjusted for socioeconomic characteristics, smoking, BMI, diabetes, and/or hypertension (depending on the outcome) were assessed.Participants in 2009-2012 were significantly more likely to be obese and have diabetes compared to those in 1971-1975 (OR = 4.98, 3.57-6.97; OR = 3.49, 1.59-7.65, respectively, fully adjusted). Participants in 2009-2012 vs. 1988-1994 were significantly more likely to have had hypertension but uncontrolled hypertension was significantly less likely (OR = 0.67, 0.52-0.86, fully adjusted). There was no difference over time for high cholesterol, but uncontrolled high cholesterol was significantly less likely in 2009-2012 vs. 1988-1994 (OR = 0.80, 0.68-0.94, fully adjusted). The use of hypertensive and cholesterol medications increased while chronic kidney and cardiovascular diseases were relatively stable.Cardiovascular risk factors of younger U.S. adults have worsened over the past 40 years, but treatment for hypertension and high cholesterol has improved. The sub-optimal and worsening health in younger adults may have a substantial impact on health care utilization and costs, and should be considered when developing health care practices.
- KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting. [JOURNAL ARTICLE]
- Cell Rep 2016 Aug 17.
Hepatic lipogenesis is nutritionally regulated (i.e., downregulated during fasting and upregulated during the postprandial state) as an adaptation to the nutritional environment. While alterations in the expression level of the transcription factor SREBP-1c are known to be critical for nutritionally regulated lipogenesis, upstream mechanisms governing Srebf1 expression remain unclear. Here, we show that the fasting-induced transcription factor KLF15, a key regulator of gluconeogenesis, forms a complex with LXR/RXR, specifically on the Srebf1 promoter. This complex recruits the corepressor RIP140 instead of the coactivator SRC1, resulting in reduced Srebf1 and thus downstream lipogenic enzyme expression during the early and euglycemic period of fasting prior to hypoglycemia and PKA activation. Through this mechanism, KLF15 overexpression specifically ameliorates hypertriglyceridemia without affecting LXR-mediated cholesterol metabolism. These findings reveal a key molecular link between glucose and lipid metabolism and have therapeutic implications for the treatment of hyperlipidemia.
- Triglyceride Treatment in the Age of Cholesterol Reduction. [REVIEW, JOURNAL ARTICLE]
- Prog Cardiovasc Dis 2016 Aug 17.
Cholesterol reduction has markedly reduced major cardiovascular disease (CVD) events and shown regression of atherosclerosis in some studies. However, CVD has for decades also been associated with increased levels of circulating triglyceride (TG)-rich lipoproteins. Whether this is due to a direct toxic effect of these lipoproteins on arteries or whether this is merely an association is unresolved. More recent genetic analyses have linked genes that modulate TG metabolism with CVD. Moreover, analyses of subgroups of hypertriglyceridemic (HTG) subjects in clinical trials using fibric acid drugs have been interpreted as evidence that TG reduction reduces CVD events. This review will focus on how HTG might cause CVD, whether TG reduction makes a difference, what pathophysiological defects cause HTG, and what options are available for treatment.
- Genetic testing of familial hypercholesterolemia in a real clinical setting. [JOURNAL ARTICLE]
- Wien Klin Wochenschr 2016 Aug 19.
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterized by strikingly elevated low-density lipoprotein (LDL) cholesterol levels and premature atherosclerosis. For individuals with a definite or probable diagnosis of FH, molecular genetic testing is recommended. This can be justified in countries where genetic testing is broadly available and covered. On the other hand, in countries with limited access to genetic testing, it can be argued whether it is necessary and cost-effective to perform genetic testing in patients with a proven clinical diagnosis of FH. This article presents a family with FH where different family members manifested different phenotypes and discusses situations where genetic diagnosis can crucially help physicians in clinical decision-making on how to approach and treat patients.
- Differences in the performance of PCL-based vascular grafts as abdominal aorta substitutes in healthy and diabetic rats. [JOURNAL ARTICLE]
- Biomater Sci 2016 Aug 18.
Great progress has been made in the field of vascular tissue engineering, with some artificial vascular grafts already exhibiting promising outcomes in animal models. However, these studies were mostly conducted using healthy animals, which are not representative of actual clinical demands. Indeed, patients who require artificial vascular graft implantation are often accompanied by other comorbidities, such as hyperlipidaemia, hypertension and diabetes which should also be taken into consideration when assessing the potential of vascular grafts that are intended for clinical applications. In the present study, we established a rat model with type 2 diabetes (T2D) for performance evaluation of an electrospun PCL vascular graft. Our data showed that rats with T2D had elevated incidents of adverse event rates, including exacerbated platelet adhesion, inflammation, early calcification and impaired regeneration compared to the non-diabetic controls. Thus, we report that T2D exacerbates the regeneration process after in vivo implantation of vascular grafts. More advanced grafts are in demand for clinical use in patients with clinical complications such as T2D.
- Evaluation of the Association Between Preoperative Clinical Factors and Long-term Weight Loss After Roux-en-Y Gastric Bypass. [JOURNAL ARTICLE]
- JAMA Surg 2016 Aug 10.
Weight loss after bariatric surgery varies, yet preoperative clinical factors associated with long-term suboptimal outcomes are not well understood.To evaluate the association between preoperative clinical factors and long-term weight loss after Roux-en-Y gastric bypass (RYGB).From June 2001 to September 2007, this retrospective cohort study followed up RYGB patients before surgery to 7 to 12 years after surgery. The setting was a large rural integrated health system. Of 1033 eligible RYGB patients who consented to participate in longitudinal research and completed surgery before October 2007, a total of 726 (70.3%) had a weight entered in the electronic medical record 7 or more years after surgery and were included in the analyses after exclusions for pregnancy and mortality. Date of the long-term weight measurement was recorded between August 2010 and January 2016.The primary outcome was percentage weight loss (%WL) at 7 to 12 years after surgery. Preoperative clinical factors (>200) extracted from the electronic medical record included medications, comorbidities, laboratory test results, and demographics, among others.Among the 726 study participants, 83.1% (n = 603) were female and 97.4% (n = 707) were of white race, with a mean (SD) preoperative body mass index (calculated as weight in kilograms divided by height in meters squared) of 47.5 (7.4). From the time of surgery to long-term follow-up (median, 9.3 postoperative years), the mean (SD) %WL was 22.5% (13.1%). Preoperative insulin use, history of smoking, and use of 12 or more medications before surgery were associated with greater long-term postoperative %WL (6.8%, 2.8%, and 3.1%, respectively). Preoperative hyperlipidemia, older age, and higher body mass index were associated with poorer long-term postoperative %WL (-2.8%, -8.8%, and -4.1%, respectively).Few preoperative clinical factors associated with long-term weight loss after RYGB were identified. Preoperative insulin use was strongly associated with better long-term %WL, while preoperative hyperlipidemia, higher body mass index, and older age were associated with poorer %WL. Our findings provide additional insight into preoperative identification of RYGB patients at higher risk for long-term suboptimal outcomes.
- Long-term clinical follow-up and molecular testing for diagnosis of the first Tunisian family with Alström syndrome. [JOURNAL ARTICLE]
- Eur J Med Genet 2016 Aug 11.
Alström syndrome is a clinically complex disorder characterized by progressive degeneration of sensory functions, resulting in visual and audiological impairment as well as metabolic disturbances. It is caused by recessively inherited mutations in the ALMS1 gene, which codes for a centrosomal/basal body protein. The purpose of this study was to investigate the genetic and clinical features of two Tunisian affected siblings with Alström syndrome. Detailed clinical examinations were performed including complete ophthalmic examination, serial audiograms and several biochemical and hormonal blood tests. For the molecular study, first genomic DNA was isolated using a standard protocol. Then, linkage analysis with microsatellite markers was performed and DNA array was used to detect known mutations. Subsequently, all ALMS1 exons were simultaneously sequenced for one affected patient with the TaGSCAN targeted sequencing panel. Finally, segregation of the causal variant was performed by Sanger sequencing. Both affected siblings had cone rod dystrophy with impaired visual acuity, sensorineural hearing loss and truncal obesity. One affected individual showed insulin resistance without diabetes mellitus. Other clinical features including cardiac and pulmonary dysfunction, hypothyroidism, hyperlipidemia, acanthosis nigricans, renal and hepatic dysfunction were absent. Genetic analysis showed the presence of a homozygous splice site mutation (c.10388-2A > G) in both affected siblings. Although Alström syndrome is relatively well characterized disease, this syndrome is probably misdiagnosed in Tunisia. Here, we describe the first report of Tunisian patients affected by this syndrome and carrying a homozygous ALMS1 mutation. The diagnosis was suspected after long-term clinical follow-up and confirmed by genetic testing.
- Rhus Coriaria L. (Sumac) in Patients with Hyperlipidemia; A Double Blind Randomized Clinical Trial. [Journal Article]
- Iran J Med Sci 2016 May; 41(3):S10.
Lipid lowering effect of sumac is investigated in multiple animal studies with promising results. However, its clinical efficacy is not investigated adequately. This study is aimed to evaluate the lipid lowering effect of sumac in patients with Hyperlipidemia in a double blind randomized controlled trial.Eighty patients with Hyperlipidemia according to NCEP-ATP III criteria were randomly allocated to receive the Rhus Coriaria L. (1000 mg/day) or placebo for two months. The patients were evaluated in terms of the serum triglyceride, total LDL, and HDL cholesterol. Systolic and diastolic blood pressures along with serum biochemistry profile including fasting blood sugar, liver and kidney function tests and complete blood count were evaluated before the enrolment of patients and after the intervention.No significant difference was observed between the sumac and placebo groups in term of mean reductions in total and LDL cholesterol and triglyceride levels. A significant increase in mean serum HDL cholesterol level was observed in the sumac group (41.18±8.2 vs. 44.65±8.4, P=0.001) after 2 months of intervention.The study showed significant HDL cholesterol increasing effect of sumac supplementation in patients with Hyperlipidemia.
- Lipid phenotypes in patients with nonalcoholic fatty liver disease. [Journal Article]
- Metabolism 2016 Sep; 65(9):1391-8.
There has been conflicting evidence regarding the role of single lipid species in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We aimed to explore the associations between dyslipidemia phenotypes (combinations of lipid parameters) and the risk of NAFLD.We conducted a cross-sectional analysis using a cohort of 9560 apparently healthy Chinese adults who underwent comprehensive health checkups including abdominal ultrasonography.Of 3709 participants with NAFLD, 41.8% were classified as normolipemia (NL), 3.8% as combined hyperlipidemia, 3.2% as hypercholesterolemia, 17.7% as dyslipidemia of metabolic syndrome (MetS), 10.2% as isolated low high-density lipoprotein cholesterol (HDL-C), and 23.3% as isolated hypertriglyceridemia. The multivariable-adjusted odds ratios (ORs) (with 95% confidence intervals) for NAFLD in those with combined hyperlipidemia, those with hypercholesterolemia, those with MetS dyslipidemia, those with low HDL-C, and those with hypertriglyceridemia compared with those with NL were 4.79 (3.19-7.20), 1.26 (0.94-1.69), 3.31 (2.74-3.99), 1.13 (0.95-1.34), and 2.63 (2.26-3.08), respectively. The associations between combined hyperlipidemia, MetS dyslipidemia, or hypertriglyceridemia and risk of NAFLD were consistently seen in various evaluated subgroups. The interactions between lipid phenotypes and sex, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), or uric acid (UA) were not significant for NAFLD (all P>0.05).There were diverse dyslipidemia phenotypes in patients with NAFLD. Combined hyperlipidemia, MetS dyslipidemia, and hypertriglyceridemia were strongly and independently associated with increased risk of NAFLD. Gender, BMI, BP, FPG, and UA status did not modify the associations between dyslipidemia phenotypes and NAFLD.
- No Postoperative Adrenal Insufficiency in a Patient with Unilateral Cortisol-Secreting Adenomas Treated with Mifepristone Before Surgery. [Journal Article]
- Clin Med Insights Endocrinol Diabetes 2016.:31-6.
Glucocorticoid replacement is commonly required to treat secondary adrenal insufficiency after surgical resection of unilateral cortisol-secreting adrenocortical adenomas. Here, we describe a patient with unilateral cortisol-secreting adenomas in which the preoperative use of mifepristone therapy was associated with recovery of the hypothalamic-pituitary-adrenal (HPA) axis, eliminating the need for postoperative glucocorticoid replacement.A 66-year-old Caucasian man with type 2 diabetes mellitus, hyperlipidemia, hypertension, and obesity was hospitalized for Fournier's gangrene and methicillin-resistant Staphylococcus aureus sepsis. Abdominal computed tomography scan revealed three left adrenal adenomas measuring 1.4, 2.1, and 1.2 cm and an atrophic right adrenal gland. Twenty-four-hour urinary free cortisol level was elevated (237 µg/24 hours, reference range 0-50 µg/24 hours). Hormonal evaluation after resolution of the infection showed an abnormal 8 mg overnight dexamethasone suppression test (cortisol postdexamethasone 14.5 µg/dL), suppressed adrenocorticotropic hormone (ACTH; <5 pg/mL, reference range 7.2-63.3 pg/mL), and low-normal dehydroepiandrosterone sulfate (50.5 µg/dL, male reference range 30.9-295.6 µg/dL). Because of his poor medical condition and uncontrolled diabetes, his Cushing's syndrome was treated with medical therapy before surgery. Mifepristone therapy was started and, within five months, his diabetes was controlled and insulin discontinued. The previously suppressed ACTH increased to above normal range accompanied by an increase in dehydroepiandrosterone sulfate levels, indicating recovery of the HPA axis and atrophic contralateral adrenal gland. The patient received one precautionary intraoperative dose of hydrocortisone and none thereafter. Two days postoperatively, ACTH (843 pg/mL) and cortisol levels (44.8 µg/dL) were significantly elevated, reflecting an appropriate HPA axis response to the stress of surgery, and two weeks postoperatively, ACTH was within normal range and a repeat dexamethasone suppression test was normal. Six months postoperatively, ACTH was within normal limits and cortisol was approaching normal. The patient has exhibited no postoperative signs or symptoms of adrenal insufficiency in 12 months.Preoperative mifepristone therapy was associated with apparent recovery of the HPA axis prior to unilateral adrenalectomy in a patient with unilateral adrenal adenomas. Postoperatively, the patient experienced no signs or symptoms of adrenal insufficiency and no glucocorticoid replacement was required.