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Endocrinology AND Hyperlipidemia [keywords]
- Serum Lipid Responses to Weight Loss Differ between Overweight Adults with Familial Hypercholesterolemia and Those with Familial Combined Hyperlipidemia. [Journal Article]
- J Nutr 2014 Aug; 144(8):1219-26.
The effect of weight loss on lipids differs among individuals, although whether it can modify the management of hereditary hyperlipidemias has not yet been explored. The objective of this study was to examine the effect of weight loss on cholesterol metabolism, assessed by circulating noncholesterol sterols, in overweight adults with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL). We conducted a 6-mo weight loss intervention in untreated individuals (FH: n = 28; FCHL: n = 50) with a body mass index of >25 kg/m(2) and mean age of 46.9 ± 11.3 y, of whom 53.8% were men. A hypocaloric diet was implemented and serum lipid analyses, including noncholesterol sterols, were assessed. Global significant mean weight losses of 5.7 kg (-6.6%) and 6.6 kg (-7.6%) were achieved after 3 and 6 mo, respectively. Mean non-HDL cholesterol and triglyceride (TG) changes at 3 and 6 mo compared with baseline were -5.8% (P = 0.004) and -7.1% (P = 0.014), and -30.1% (P < 0.001) and -31.4% (P < 0.001), respectively. Among participants who lost ≥5% body weight, only significant changes in TGs and non-HDL cholesterol were observed in FCHL participants. Sterol precursors of cholesterol synthesis decreased significantly by 10.4% at 6 mo in FCHL participants, mostly because of a 23.9% lathosterol reduction. Baseline synthesis precursors were associated with TG reduction in FCHL participants (P = 0.039; R(2) = 0.20), and intestinally derived sterols were inversely associated with non-HDL cholesterol changes in FH participants (P = 0.036; R(2) = 0.21). Thus, FCHL participants had a better lipid-lowering response to weight loss than did FH participants. This response was positively associated with baseline cholesterol synthesis, which was reduced by weight loss. Our results confirm the cholesterol overproduction mechanism of FCHL and its interaction with fat mass, while also supporting the differential management of familial hyperlipidemias if obesity coexists. This trial was registered at clinicaltrials.gov as NCT01995149.
- Guidelines for Cardiovascular Risk Assessment and Cholesterol Treatment-Reply. [JOURNAL ARTICLE]
- JAMA 2014 Jun 4; 311(21):2236.
- Impact of comorbidities on pharmacotherapy of painful diabetic neuropathy in clinical practice. [JOURNAL ARTICLE]
- J Diabetes Complications 2014 Apr 18.
We evaluated the impact of baseline comorbidities on the effectiveness of duloxetine and anticonvulsants (pregabalin/gabapentin) in patients with painful diabetic neuropathy in clinical care.Outcomes from a 6-month, observational study with 2575 patients initiating/switching DPNP treatment were analyzed post-hoc. Propensity scoring was used to adjust for baseline factors influencing treatment choice in 1523 patients receiving duloxetine or anticonvulsants. Analysis of covariance models with fixed effects for baseline pain, treatment, propensity score, baseline characteristics or comorbidities, and their interaction with treatment were used to estimate LSmean effects on Brief Pain Inventory (BPI) average pain and interference scores.89.5% of patients reported comorbidities, including hypertension (70.5%), hyperlipidemia (39.2%), and depression (24.8%). Macrovascular complications (37.0%) and 'other chronic pain' (41.5%), particularly joint pain had an impact on both pain treatments, i.e. less improvement of average pain and interference of pain. Better treatment responses with duloxetine vs. anticonvulsants were observed in patients with depression, those with high baseline BPI total interference score, especially general activity, and in patients with joint pain.Comorbidities such as macroangiopathy and depression as well as pain characteristics should be considered in the treatment of DPNP as they may predict the effectiveness of duloxetine and anticonvulsants.
- Polycystic ovary syndrome: update on diagnosis and treatment. [REVIEW]
- Am J Med 2014 May 21.
Polycystic ovary syndrome is now a well-recognized condition affecting 6-25% of reproductive aged women, depending on the definition. Over the past 3 decades, research has launched it from relative medical obscurity to a condition increasingly recognized as common in internal medicine practices. It affects multiple systems, and requires a comprehensive perspective on health care for effective treatment. Metabolic derangements and associated complications include insulin resistance and diabetes, hyperlipidemia, hypertension, fatty liver, metabolic syndrome and sleep apnea. Reproductive complications include oligo/amenorrhea, sub-fertility, endometrial hyperplasia and cancer. Associated psychosocial concerns include depression and disordered eating. Additionally, cosmetic issues include hirsutism, androgenic alopecia and acne. This review organizes this multi-system approach around the mnemonic "MY PCOS" and discusses evaluation and treatment options for the reproductive, cosmentic and metabolic complications of this condition.
- [Association of abdominal fat distribution by computed tomography with body mass index and metabolic syndrome in Chinese elders]. [English Abstract, Journal Article]
- Zhonghua Yi Xue Za Zhi 2014 Apr; 94(12):908-12.
To explore the gender and age difference of abdominal fat distribution in Chinese older adults and examine the effects of metabolic syndrome (MS) on abdominal fat distribution by computed tomography (CT).Chinese elders (aged ≥ 65 years old) undergoing abdominal CT scanning at our hospital from January 2009 to December 2010 were collected through retrospective analysis. A total of 52 healthy normal-weight subjects and gender-specific body mass index (BMI)-matched middle-aged adults were selected (28 males, 24 females) to compare the difference of abdominal fat during the same period. Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured at the cross-sections of L4 and L5 intervertebral space.A total of 390 subjects were enrolled. There were 252 males and 138 females. Total abdominal fat (TAF) was not significantly different in both genders [female (323 ± 122 cm(2)) vs male (303 ± 141 cm(2)) , P = 0.146]. However, females had higher TAF than males after height correction (128 ± 49 vs 105 ± 49 cm(2)/m(2), P = 0.000). VFA and SFA were higher with higher BMI values across lean, normal weight, overweight and obese groups in both genders. VFA and SFA were not significantly different in both genders among 3 different age groups (>65-75, >75-85, >85 years; P > 0.05). Compared with healthy normal weight elders and BMI-matched middle-aged adults, VFA and SFA increased with more components of MS except in only one component group. When the patients were excluded suffering from 2 or more components of MS, VFA was not significantly different between normal weight elders and those with only one component of MS (diabetes/hyperlipidemia/hypertension). Logistic regression analysis showed VFA was a risk factor for elders with MS (male: OR = 1.03, 95%CI: 1.012- 1.047; female: OR = 1.06, 95%CI: 1.026-1.088) . However, SFA and age were not.The elder females have more TAF than the elder males while abdominal fat does not increase with age in elders. TAF, VFA and SFA have a highly positively correlation with BMI. Visceral fat, not subcutaneous fat, is a risk factor for elders with MS and it increases with an increment of more than 2 components of MS.
- Palmitate induces reactive oxygen species production and β-cell dysfunction by activating nicotinamide adenine dinucleotide phosphate oxidase through Src signaling. [Journal Article]
- J Diabetes Investig 2014 Feb 12; 5(1):19-26.
Chronic hyperlipidemia impairs pancreatic β-cell function, referred to as lipotoxicity. We have reported an important role of endogenous reactive oxygen species (ROS) overproduction by activation of Src, a non-receptor tyrosine kinase, in impaired glucose-induced insulin secretion (GIIS) from diabetic rat islets. In the present study, we investigated the role of ROS production by Src signaling in palmitate-induced dysfunction of β-cells.After rat insulinoma INS-1D cells were exposed to 0.6 mmol/L palmitate for 24 h (palmitate exposure); GIIS, ROS production and nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity were examined with or without exposure to10 μmol/L 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2), a Src inhibitior, for 30 or 60 min.Exposure to PP2 recovered impaired GIIS and decreased ROS overproduction as a result of palmitate exposure. Palmitate exposure increased activity of NOX and protein levels of NOX2, a pathological ROS source in β-cells. Palmitate exposure increased the protein level of p47 (phox) , a regulatory protein of NOX2, in membrane fraction compared with control, which was reduced by PP2. Transfection of small interfering ribonucleic acid of p47 (phox) suppressed the augmented p47 (phox) protein level in membrane fraction, decreased augmented ROS production and increased impaired GΙIS by palmitate exposure. In addition, exposure to PP2 ameliorated impaired GIIS and decreased ROS production in isolated islets of KK-A(y) mice, an obese diabetic model with hyperlipidemia.Activation of NOX through Src signaling plays an important role in ROS overproduction and impaired GΙIS caused by chronic exposure to palmitate, suggesting a lipotoxic mechanism of β-cell dysfunction of obese mice.
- Impaired β Cell Function in Chinese Newly Diagnosed Type 2 Diabetes Mellitus with Hyperlipidemia. [Journal Article]
- J Diabetes Res 2014.:493039.
The objective is to explore the effects of hyperlipidemia on β cell function in newly diagnosed type 2 diabetes mellitus (T2DM). 208 patients were enrolled in the study and were divided into newly diagnosed T2DM with hyperlipidemia (132 patients) and without hyperlipidemia (76 patients). Demographic data, glucose levels, insulin levels, lipid profiles, homeostasis model assessment for β cell function index (HOMA- β ), homeostasis model assessment for insulin resistance index (HOMA-IR), and quantitative insulin-sensitivity check index (QUICKI) were compared between the two groups. We found that comparing with those of normal lipid levels, the subjects of newly diagnosed T2DM with hyperlipidemia were younger, and had declined HOMA- β . However, the levels of HOMA- β were comparable regardless of different lipid profiles (combined hyperlipidemia, hypertriglyceridemia, and hypercholesterolemia). Multiple stepwise linear regression analysis showed that high fasting plasma glucose (FPG), decreased fasting insulin level (FINS), and high triglyceride (TG) were independent risk factors of β cell dysfunction in newly diagnosed T2DM. Therefore, the management of dyslipidemia, together with glucose control, may be beneficial for T2DM with hyperlipidemia.
- Cardiovascular risk and statin use in the United States. [Journal Article]
- Ann Fam Med 2014 May-Jun; 12(3):215-23.
PURPOSE Statins reduce the risk of mortality and coronary artery disease in individuals at high cardiovascular risk. Using nationally representative data, we examined the relationships between statin use and cardiovascular risk, diagnosis of hyperlipidemia, and other risk factors.
METHODSWe analyzed data from the 2010 Medical Expenditure Panel Survey, a nationally representative survey of the US civilian noninstitutionalized population. The study sample had a total of 16,712 individuals aged 30 to 79 years. Those who reported filling at least 2 statin prescriptions were classified as statin users. We created multiple logistic regression models for statin use as the dependent variable, with cardiovascular risk factors and sociodemographic factors as independent variables.
RESULTSOverall, 58.2% (95% CI, 54.6%-61.7%) of individuals with coronary artery disease and 52.0% (95% CI, 49.4%-54.6%) of individuals with diabetes aged older than 40 years were statin users. After adjusting for cardiovascular risk factors and sociodemographic factors, the probability of being on a statin was significantly higher among individuals with both hyperlipidemia and coronary artery disease, at 0.44 (95% CI, 0.40-0.48), or hyperlipidemia only, at 0.32 (95% CI, 0.30-0.33), than among those with coronary artery disease only, at 0.11 (95% CI, 0.07-0.15). A similar pattern was seen in people with diabetes.
CONCLUSIONSIn this nationally representative sample, many people at high risk for cardiovascular events, including those with coronary artery disease, diabetes, or both, were not receiving statins despite evidence that these agents reduce adverse events. This undertreatment appears to be related to placing too much emphasis on hyperlipidemia and not enough on cardiovascular risk. Recently released guidelines from the American College of Cardiology and the American Heart Association offer an opportunity to improve statin use by focusing on cardiovascular risk instead of lipid levels.
- Familial combined hyperlipidemia: from molecular insights to tailored therapy. [JOURNAL ARTICLE]
- Curr Opin Lipidol 2014 Jun; 25(3):176-182.
This review presents recent basic and clinical developments in familial combined hyperlipidemia (FCHL).A variety of experiments have contributed to the elucidation of this complex disease. They consist of dynamic and gene expression studies in adipocytes, confirming the role of dysfunctional adipose tissue in the pathogenesis of FCHL and identifying potential new pathways, such as complement activation. Whole exome sequencing and classical linkage studies in FCHL pedigrees, some conducted with new traits (e.g. plasma proprotein convertase subtilisin/kexin type 9 [PCSK9] and phospholipid transfer protein activity), have revealed new genes of interest, among which SLC25A40 and LASS4. Finally, gene expression studies in liver biopsies and liver cell culture experiments have gained further insight in the role of upstream stimulatory factor 1, one of the most replicated genes in FCHL, in its pathogenesis.On the basis of these observations and recent phase II clinical trials, PCSK9 antagonizing is the most promising lipid-lowering therapy to be added to our current arsenal of statins and fibrates in FCHL treatment.Ongoing basic research provides a steady growth in our knowledge on the genes that are involved in FCHL as well as their metabolic function(s). This field of research may be enhanced when data are expanded and integrated for systems biology approaches. Our growing insights in the cause of FCHL allow for better, targeted treatment of dyslipidemia and prevention of cardiovascular complications.
- Electrocardiogram abnormalities and risk of cardiovascular mortality and all-cause mortality in old age: The Kahrizak Elderly Study (KES). [JOURNAL ARTICLE]
- Arch Gerontol Geriatr 2014 Apr 5.
Resting electrocardioghic (ECG) abnormalities might be value for mortality prediction. The aim of this study is to evaluate whether ECG abnormalities are associated with increased mortality in older residents of Kahrizak Charity Foundation (KCF). A total of 247 participants ≥60-years of KES were enrolled in this study. Adjudicated all cause mortality was collected over 3 years between 2006 and 2009. The subjects were classified as having major, minor or no ECG abnormalities according to the Minnesota Code. The addition of ECG to risk factors were examined to predict cardiovascular diseases (CVD) and all-cause mortality by using Cox proportional hazards regression models. At baseline, 104(42.1%) had major ECG abnormalities and 73(29.6%) had minor abnormalities. During a median follow-up of 3.2 years, 73 participants died from all-cause mortality and 31deaths from CVD. Major ECG abnormalities were associated with an increased risk of CVD mortality in all models. The associations between minor ECG abnormalities at baseline and CVD mortality were not statistically significant. After adjustment for age and sex, Body mass index (BMI), smoking, diabetes, hypertension (HTN), hyperlipidemia and history of CVD, the participants with the major ECG abnormalities had higher risks of CVD mortality (HR: 3.12(95% CI, 1.02-9.57) and all-cause mortality (HR: 2.45(95% CI, 1.23-4.85) compared with those with normal ECG.