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Endocrinology AND Hyperlipidemia [keywords]
- Diagnosis and management of glycogen storage disease type I: a practice guideline of the American College of Medical Genetics and Genomics. [JOURNAL ARTICLE]
- Genet Med 2014 Nov 6.
Disclaimer: This guideline is designed primarily as an educational resource for clinicians to help them provide quality medical services. Adherence to this guideline is completely voluntary and does not necessarily ensure a successful medical outcome. This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed toward obtaining the same results. In determining the propriety of any specific procedure or test, the clinician should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen. Clinicians are encouraged to document the reasons for the use of a particular procedure or test, whether or not it is in conformance with this guideline. Clinicians also are advised to take notice of the date this guideline was adopted and to consider other medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Purpose:Glycogen storage disease type I (GSD I) is a rare disease of variable clinical severity that primarily affects the liver and kidney. It is caused by deficient activity of the glucose 6-phosphatase enzyme (GSD Ia) or a deficiency in the microsomal transport proteins for glucose 6-phosphate (GSD Ib), resulting in excessive accumulation of glycogen and fat in the liver, kidney, and intestinal mucosa. Patients with GSD I have a wide spectrum of clinical manifestations, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Individuals with GSD type Ia typically have symptoms related to hypoglycemia in infancy when the interval between feedings is extended to 3-4 hours. Other manifestations of the disease vary in age of onset, rate of disease progression, and severity. In addition, patients with type Ib have neutropenia, impaired neutrophil function, and inflammatory bowel disease. This guideline for the management of GSD I was developed as an educational resource for health-care providers to facilitate prompt, accurate diagnosis and appropriate management of patients.Methods:A national group of experts in various aspects of GSD I met to review the evidence base from the scientific literature and provided their expert opinions. Consensus was developed in each area of diagnosis, treatment, and management.Results:This management guideline specifically addresses evaluation and diagnosis across multiple organ systems (hepatic, kidney, gastrointestinal/nutrition, hematologic, cardiovascular, reproductive) involved in GSD I. Conditions to consider in the differential diagnosis stemming from presenting features and diagnostic algorithms are discussed. Aspects of diagnostic evaluation and nutritional and medical management, including care coordination, genetic counseling, hepatic and renal transplantation, and prenatal diagnosis, are also addressed.Conclusion:A guideline that facilitates accurate diagnosis and optimal management of patients with GSD I was developed. This guideline helps health-care providers recognize patients with all forms of GSD I, expedite diagnosis, and minimize adverse sequelae from delayed diagnosis and inappropriate management. It also helps to identify gaps in scientific knowledge that exist today and suggests future studies.Genet Med advance online publication 06 November 2014Genetics in Medicine (2014); doi:10.1038/gim.2014.128.
- Dietary rapeseed/canola oil supplementation reduces serum lipids and liver enzymes and alters postprandial inflammatory responses in adipose tissue compared to olive oil supplementation in obese men. [JOURNAL ARTICLE]
- Mol Nutr Food Res 2014 Nov 18.
Obesity is associated with hyperlipidemia, hepatic steatosis and low-grade inflammation. Studies have shown that MUFA as well as PUFA have beneficial effects on blood lipids and the inflammatory state.This study investigates a daily supplementation of either 50 g of rapeseed/canola (RA) or olive (OL) oil over four weeks on serum lipids, serum liver enzymes and inflammatory gene expression in subcutaneous (s. c.) adipose tissue in obese men. Consuming RA resulted in increased serum n-3 fatty acids and a reduction in total cholesterol, LDL cholesterol and serum aspartate aminotransferase compared to OL. In s. c. adipose tissue gene expression of the pro-inflammatory cytokine IL6 was reduced in RA compared to OL. However, after four hours after a test meal, containing the appropriate oil, white bread and 400 mL of liquid diet drink (835 kcal in total), gene expression of IL6, IL1B and EMR1 was increased in RA and of monocyte chemoattractant protein-1 (CCL2) in both, RA and OL.This demonstrates that consuming RA for four weeks improves serum lipids, liver enzymes and basal inflammation in s. c. adipose tissue, but mediates an acute pro-inflammatory response in adipose tissue upon consuming a meal. This article is protected by copyright. All rights reserved.
- Predicting of trend of hemoglobin a1c in type 2 diabetes: a longitudinal linear mixed model. [Journal Article]
- Int J Prev Med 2014 Oct; 5(10):1274-80.
There are some evidences that control the blood sugar decreasing the risk of diabetes complications, and even fatal. There are so many studies, but they are mostly cross-sectional and ignore the trend and hence it is necessary to implement a longitudinal study. The aim of this prospective study is to find the trend of glycosylated hemoglobin (HbA1c) over time and the associative factors on it.Participants of this longitudinal study were 3440 eligible diabetes patients referred to Isfahan Endocrine and Metabolism Research Center during 2000-2012 who are measured 2-40 times. A linear mixed model was applied to determine the association between HbA1c and variables, including lipids, systolic, diastolic blood pressure and complications such as nephropathy, and retinopathy. Furthermore, the effect of mentioned variables on trend of HbA1c was determined.The fitted model showed total cholesterol, retinopathy, and the method of therapy including oral antidiabetic drugs (OADs) plus insulin and insulin therapy decreased the trend of HbA1c and high-density lipoprotein, weight, hyperlipidemia and the method of therapy including diet, and OADs increased the trend of HbA1c.The present study shows that regular visits of diabetic patients as well as controlling blood pressure, lipid profile, and weight loss can improve the trend of HbA1c levels during the time.
- Correlation between Renal Function and Common Risk Factors for Chronic Kidney Disease in a Healthy Middle-Aged Population: A Prospective Observational 2-Year Study. [Journal Article]
- PLoS One 2014; 9(11):e113263.
Age, proteinuria, metabolic syndrome, and hyperuricemia are the reported risk factors for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the best predictor of changes in renal function in the early stages of renal disease in a healthy middle-aged population is still unknown. Our study evaluated the correlation between changes in renal function and common risk factors to determine such a predictor.In total, 2,853 healthy persons aged ≤50 years participated in the study. They had no proteinuria and were not on medications for hypertension, diabetes mellitus, hyperlipidemia, or hyperuricemia. Over 2 years, participants underwent annual health screening. The relationship between changes in estimated glomerular filtration rate (eGFR) and changes in risk factors for CKD was evaluated using univariate and multivariate linear regression analyses.Over 2 years, eGFR showed a significant decrease. Univariate regression analysis revealed that changes in fasting plasma glucose (FPG), total cholesterol, LDL-cholesterol, serum uric acid levels, and hemoglobin showed a significant negative correlation with changes in eGFR. Multiple regression analysis confirmed that changes in FPG, serum uric acid levels, in particular, and hemoglobin had a significant negative correlation with changes in eGFR.The changes in eGFR and other variables over 2 years were small and could be within expected biologic variation. A longer observational study is needed to elucidate whether FPG, serum uric acid and hemoglobin represent the earliest markers of eGFR decline.
- The association of neighborhood characteristics with obesity and metabolic conditions in older women. [Journal Article]
- J Nutr Health Aging 2014; 18(9):792-8.
Previous studies exploring the relationship of neighborhood characteristics with metabolic conditions have focused on middle-aged adults but none have comprehensively investigated associations in older adults, a potentially vulnerable population. The aim was to explore the relationship of neighborhood characteristics with metabolic conditions in older women.Cross-sectional analysis.We studied 384 women aged 70-79 years, representing the two-thirds least disabled women in the community, enrolled in the Women's Health and Aging Study II at baseline. Neighborhood scores were calculated from census-derived data on median household income, median house value, percent earning interest income, percent completing high school, percent completing college, and percent with managerial or executive occupation. Participants were categorized by quartile of neighborhood score with a higher quartile representing relative neighborhood advantage. Logistic regression models were created to assess the association of neighborhood quartiles to outcomes, adjusting for key covariates.Primary outcomes included metabolic conditions: obesity, diabetes, hypertension, and hyperlipidemia. Secondary outcomes included BMI, HbA1c, blood pressure and lipids.Higher neighborhood quartile score was associated with a lower prevalence of obesity (highest quartile=13.5% versus lowest quartile=36.5%; p<0.001 for trend). A lower prevalence of diabetes was also observed in highest (6.3%) versus lowest (14.4%) neighborhood quartiles, but was not significantly different (p= 0.24 for trend). Highest versus lowest neighborhood quartile was associated with lower HbA1c (-0.31%, p=0.02) in unadjusted models. Women in the highest versus lowest neighborhood quartile had lower BMI (-2.01 kg/m2, p=0.001) and higher HDL-cholesterol (+6.09 mg/dL, p=0.01) after accounting for age, race, inflammation, and smoking.Worse neighborhood characteristics are associated with adiposity, hyperglycemia, and low HDL. Further longitudinal studies are needed and can inform future interventions to improve metabolic status in older adults.
- Estimating the prevalence of comorbid conditions and their effect on health care costs in patients with diabetes mellitus in Switzerland. [Journal Article]
- Diabetes Metab Syndr Obes 2014.:455-65.
Estimating the prevalence of comorbidities and their associated costs in patients with diabetes is fundamental to optimizing health care management. This study assesses the prevalence and health care costs of comorbid conditions among patients with diabetes compared with patients without diabetes. Distinguishing potentially diabetes- and nondiabetes-related comorbidities in patients with diabetes, we also determined the most frequent chronic conditions and estimated their effect on costs across different health care settings in Switzerland.Using health care claims data from 2011, we calculated the prevalence and average health care costs of comorbidities among patients with and without diabetes in inpatient and outpatient settings. Patients with diabetes and comorbid conditions were identified using pharmacy-based cost groups. Generalized linear models with negative binomial distribution were used to analyze the effect of comorbidities on health care costs.A total of 932,612 persons, including 50,751 patients with diabetes, were enrolled. The most frequent potentially diabetes- and nondiabetes-related comorbidities in patients older than 64 years were cardiovascular diseases (91%), rheumatologic conditions (55%), and hyperlipidemia (53%). The mean total health care costs for diabetes patients varied substantially by comorbidity status (US$3,203-$14,223). Patients with diabetes and more than two comorbidities incurred US$10,584 higher total costs than patients without comorbidity. Costs were significantly higher in patients with diabetes and comorbid cardiovascular disease (US$4,788), hyperlipidemia (US$2,163), hyperacidity disorders (US$8,753), and pain (US$8,324) compared with in those without the given disease.Comorbidities in patients with diabetes are highly prevalent and have substantial consequences for medical expenditures. Interestingly, hyperacidity disorders and pain were the most costly conditions. Our findings highlight the importance of developing strategies that meet the needs of patients with diabetes and comorbidities. Integrated diabetes care such as used in the Chronic Care Model may represent a useful strategy.
- 3,5-Diiodo-L-thyronine (3,5-T2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male dietinduced obese mice. [JOURNAL ARTICLE]
- Endocrinology 2014 Oct 16.:en20141604.
Effective and safe anti-obesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with 3,5,3'-triiodo-L-thyronine (T3) administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2 treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase (Dio1) activity after application of 3,5-T2 (2.5 μ g/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity.
- Ezetimibe prevents the development of non‑alcoholic fatty liver disease induced by high‑fat diet in C57BL/6J mice. [Journal Article]
- Mol Med Rep 2014 Dec; 10(6):2917-23.
There is currently no established treatment for non‑alcoholic fatty liver disease (NAFLD), including its most extreme form, non‑alcoholic steatohepatitis (NASH). Ezetimibe, an inhibitor of Niemann‑Pick C1 Like 1‑dependent cholesterol absorption, improves diet‑induced hyperlipidemia and attenuates liver steatosis and insulin resistance. The aim of the present study was to determine whether ezetimibe treatment is able to inhibit the development of NAFLD, and to elucidate the underlying mechanism, using C57BL/6J (B6) mice maintained on a high‑fat diet. Male B6 mice (20 weeks of age) were divided into the following two groups (n=7 in each group): Mice fed a high‑fat diet for four weeks and mice fed a high‑fat diet with 0.0064% (wt/wt) ezetimibe (5 mg/kg/day) for four weeks. Administration of ezetimibe significantly reduced liver steatosis and fibrosis. Ezetimibe reduced serum cholesterol, hepatic fat accumulation and insulin resistance in the liver of mice fed the high‑fat diet. Furthermore, ezetimibe significantly reduced hepatic mRNA expression of Acc1 and Scd1, which are involved in hepatic fatty acid synthesis. Ezetimibe significantly reduced hepatic Cd36 gene expression, upregulation of which is significantly associated with insulin resistance, hyperinsulinemia and increased steatosis. The protein expression of SKP2, a viable therapeutic target in human cancer, was also reduced by ezetimibe. These findings suggest that ezetimibe may be an effective therapy for high fat‑induced NAFLD, including NASH.
- Deletion of serum amyloid A3 improves high fat high sucrose diet-induced adipose tissue inflammation and hyperlipidemia in female mice. [Journal Article, Research Support, N.I.H., Extramural]
- PLoS One 2014; 9(9):e108564.
Serum amyloid A (SAA) increases in response to acute inflammatory stimuli and is modestly and chronically elevated in obesity. SAA3, an inducible form of SAA, is highly expressed in adipose tissue in obese mice where it promotes monocyte chemotaxis, providing a mechanism for the macrophage accumulation that occurs with adipose tissue expansion in obesity. Humans do not express functional SAA3 protein, but instead express SAA1 and SAA2 in hepatic as well as extrahepatic tissues, making it difficult to distinguish between liver and adipose tissue-specific SAA effects. SAA3 does not circulate in plasma, but may exert local effects that impact systemic inflammation. We tested the hypothesis that SAA3 contributes to chronic systemic inflammation and adipose tissue macrophage accumulation in obesity using mice deficient for Saa3 (Saa3(-/-)). Mice were rendered obese by feeding a pro-inflammatory high fat, high sucrose diet with added cholesterol (HFHSC). Both male and female Saa3(-/-) mice gained less weight on the HFHSC diet compared to Saa3(+/+) littermate controls, with no differences in body composition or resting metabolism. Female Saa3(-/-) mice, but not males, had reduced HFHSC diet-induced adipose tissue inflammation and macrophage content. Both male and female Saa3(-/-) mice had reduced liver Saa1 and Saa2 expression in association with reduced plasma SAA. Additionally, female Saa3(-/-) mice, but not males, showed improved plasma cholesterol, triglycerides, and lipoprotein profiles, with no changes in glucose metabolism. Taken together, these results suggest that the absence of Saa3 attenuates liver-specific SAA (i.e., SAA1/2) secretion into plasma and blunts weight gain induced by an obesogenic diet. Furthermore, adipose tissue-specific inflammation and macrophage accumulation are attenuated in female Saa3(-/-) mice, suggesting a novel sexually dimorphic role for this protein. These results also suggest that Saa3 influences liver-specific SAA1/2 expression, and that SAA3 could play a larger role in the acute phase response than previously thought.
- Statin therapy and hepatotoxicity: Appraisal of the safety profile of atorvastatin in hyperlipidemic patients. [Journal Article]
- Adv Biomed Res 2014.:168.
Statins are one of the most frequently prescribed medications to reduce the risk of cardiovascular events. Statins appear to be safe however, there are contradictory data regarding their adverse effects, which might be due to genetic variation in their metabolism. Hence, this prospective study was aimed to evaluate the effects of atorvastatin on liver transaminase changes in a clinical setting, in north Iran.This prospective semi-experimental study was performed on hyperlipidemic adults in 2010-2011. Patients received atorvastatin (5-40 mg/d) based on the American National Cholesterol Education Program guidelines. Liver aminotransferases were measured in three occasions of baseline, 8 and 16 weeks period.A total of 206 patients were included in the study. Of which 178 were female and 30 were male. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were in normal range before intervention in the majority, except in 25 (12.1%) and 16 (7.8%) of patients, respectively. In general, ALT and AST remained in normal range over the study period (23.3 IU/L and 21.8 IU/L, respectively). There was found no relationship between different doses of atorvastatin prescribed and ALT/AST changes in the patients. The males' ALT means at baseline (26.9 IU/L), 8 weeks (30 IU/L) and 16 weeks (28.8 IU/L) after statin therapy were significantly higher than females (22 IU/L, 22.2 IU/L and 22.1 IU/L, respectively; P < 0.05 for all).The absence of any hepatic adverse effect in the present study supports safety of atorvastatin and emerging opinion that routine screening of liver function tests is not necessary in patients on statins.