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Endocrinology AND Hyperlipidemia [keywords]
- Carotid Artery Intima Media Thickness and HsCRP; Predictors for Atherosclerosis in Prediabetic Patients? [Journal Article]
- Pak J Med Sci 2013 Apr; 29(2):495-9.
Objective:We aimed to assess carotid intima media thickness (CIMT) and serum high-sensitivity C-reactive protein (hs-CRP) levels as estimated markers of subclinical atherosclerosis and inflammation in prediabetic patients. Methodology: One hundred and ten patients were defined as prediabetic and seventy-six subjects (age and sex matched) were assigned as control group in our cross sectional study. Bilateral CIMT measurements and hs-CRP levels were evaluated.
Results:The prevalance of hypertension, hyperlipidemia, angiotensin receptor blockers and antihyperlipidemic medication use were statistically higher in the prediabetic group. Serum hs-CRP levels, left, right and maximum CIMT were statistically higher among prediabetics compared to control group. There was a positive, significant correlation between left, right, maximum CIMT and fasting blood glucose, HbA1c, hs-CRP levels and BMI.
Conclusion:Recognising and focusing on the intervention of prediabetic state as early as possible and identifying the susceptible patients who may benefit from more aggressive preventive therapy is an important issue of primary prevention of diabetes and cardiovascular diseases.
- Adherence of Healthcare Professionals to American Diabetes Association 2004 guidelines for the care of patients with type 2 diabetes at Peripheral Diabetes Clinics in Karachi, Pakistan. [Journal Article]
- Pak J Med Sci 2013 Apr; 29(2):474-8.
Objective:To observe the adherence of Healthcare Professionals to American Diabetes Association (ADA) 2004 guidelines for the care of patients with type 2 diabetes at Peripheral Diabetes Clinics (PDCs) in Karachi, Pakistan. Methodology: The study was conducted using a retrospective medical chart review of patients with type 2 diabetes at four PDCs in four townships of Karachi district from January 2005 to December 2006. Entire medical records of patients were evaluated for the evidence of documentation of testing and treatment.
Results:Medical records of 691 patients (332 males and 359 females) with type 2 diabetes were reviewed. Mean age of the patients was 50.79 ± 10.75 years. Deficiencies were observed in most areas of diabetes care. Blood pressure was documented in 85.81% patients, whereas, serum creatinine, HbA1c and lipid profile were noted in 56%, 44.57% and 40.08% of the patients respectively. Similarly, lower leg examination was registered in 44% patients, while in 30.53% of the patients fundoscopic examination was recorded. Co-morbid conditions like hypertension and hyperlipidemia were documented in 92.7% and 84.6% patients respectively. HbA1c < 7% was achieved by 59.04% patients, while 27.50% of the patients attained the recommended level of serum cholesterol. Likewise, ADA recommended goal for blood pressure and LDL was achieved by13.02% and 12.16% patients respectively.
Conclusions:The study showed that adherence of healthcare professionals to ADA guidelines was suboptimal. Moreover, insufficient documentation of medical records reflected inadequate care of patients with type 2 diabetes.
- Myopathy after switching from brand to generic atorvastatin. [Case Reports, Letter]
- J Am Geriatr Soc 2013 Dec; 61(12):2254-5.
- Differences in cholesterol management among states in relation to health insurance and race/ethnicity across the United States. [Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't]
- J Clin Lipidol 2013 Nov-Dec; 7(6):675-82.
Across the United States, hyperlipidemia remains inadequately controlled and may vary across states according to differences in health insurance coverage and/or race/ethnicity.To examine relationships between states' health insurance and race/ethnicity characteristics with measures of hyperlipidemia management across the 50 U.S. states and the District of Columbia.Cross-validated, multiple linear regression modeling was used to analyze associations between states' health insurance patterns or proportions of racial minorities (from the 2010 U.S. Census data) and states' aggregate frequency of checking cholesterol within the previous 5 years or prescriptions written for lipid-lowering medications (from national survey and population-adjusted retail prescription data, respectively), with adjustments for age, sex, body mass index, race/ethnicity, and poverty.In states with proportionately more uninsured, cholesterol levels are checked less often, but in states with proportionately more private, Medicare, or Medicaid coverage, providers are not necessarily more likely to check cholesterol or to write more prescriptions. In states with proportionately more African-Americans and/or Hispanics, cholesterol is more likely to be checked, but in states with more African-Americans, more prescriptions were written, whereas in states with more Hispanics, fewer statin prescriptions were written.Variations across states in insurance and racial/ethnicity mix are associated with variations in hyperlipidemia management; less-insured states may be less effective whereas states with more private, Medicare, or Medicaid coverage may not be more effective. In states with proportionately more African-Americans vs. Hispanics, lipid medications may be prescribed differently. Our findings warrant further investigations.
- Inherited lipemic splenomegaly and the spectrum of apolipoprotein E p.Leu167del mutation phenotypic variation. [Journal Article]
- J Clin Lipidol 2013 Nov-Dec; 7(6):566-72.
We review disorders associated with splenomegaly and dyslipidemia with an emphasis on the APOE p.Leu167del mutation. Recent studies suggest that this rare mutation may present more often without splenomegaly in patients with familial combined hyperlipidemia or autosomal dominant hypercholesterolemia. We supplement the literature review by reporting a new kindred.We reviewed our 3405-patient lipid clinic database to identify persons with dyslipidemia and splenomegaly. Identified patients were evaluated for relevant disorders, including genetic testing for a 3-base pair deletion in APOE that causes deletion of leucine at position 167 of apolipoprotein E.We identified 4 patients with splenomegaly and dyslipidemia, one of whom had a heterozygous APOE p.Leu167del mutation. This proband is a 76-year-old man with a history of splenomegaly first noted at age 13 and subsequent diagnosis of hypertriglyceridemia, low high-density lipoprotein cholesterol, leukopenia, and thrombocytopenia in his third decade. He never required splenectomy, and his splenic enlargement regressed over time with medical management of his hypertriglyceridemia. The APOE p.Leu167del mutation was also found in the proband's son and granddaughter, neither of whom has splenomegaly or marked dyslipidemia.Splenomegaly in association with dyslipidemia may indicate the presence of an underlying disorder. We discuss possible causes, review the literature relating to the rare APOE p.Leu167del mutation, and present a 3-generation kindred with variable phenotypic expression of this mutation. Severity of expression may depend on genotype, sex, or effective medical management of dyslipidemia or a combination of these factors. Aggressive lipid treatment may improve or prevent splenomegaly among patients with this disorder.
- Circulating PCSK9 is a strong determinant of plasma triacylglycerols and total cholesterol in homozygous carriers of apolipoprotein ε2. [Journal Article]
- Clin Sci (Lond) 2014 May 1; 126(9):679-84.
Homozygous carriers of the apolipoprotein ε2 allele are at risk of type III hyperlipidaemia, but do not necessarily develop this lipid disorder. In the present study, we have investigated the role of circulating PCSK9 (pro-protein convertase subtilisin kexin type 9), an important regulator of LDL (low-density lipoprotein) receptor expression, in the development of this hyperlipidaemic phenotype. In an observational study, plasma PCSK9 was measured in homozygous carriers of apolipoprotein ε2 (ε2/ε2; n=12), normal controls (n=72) and hypertriglyceridaemic patients with FCHL (familial combined hyperlipidaemia; n=38), who served as a hyperlipidaemic reference group. Cholesterol, triacylglycerols (triglycerides) and apolipoprotein B content in VLDL (very-low-density lipoprotein) and LDL particles was determined by ultracentrifugation in ε2/ε2 and FCHL patients. Median circulating PCSK9 levels did not differ between ε2/ε2 carriers compared with controls and hypertriglyceridaemic FCHL patients (84.5 compared with 82.0 and 84.9 ng/ml; P=0.2 and 0.6 respectively). Circulating PCSK9 was associated with total cholesterol and triacylglycerols levels in ε2/ε2 carriers (P<0.05). These associations were stronger in ε2/ε2 carriers when compared with controls (P values for interaction=0.01 and 0.02 respectively). A direct comparison with FCHL patients demonstrated a similar discrepancy for the association with plasma triacylglycerols and also VLDL-apolipoprotein B, cholesterol and triacylglycerols (P value for interaction=0.01, 0.01, 0.03 and 0.03 respectively). Plasma PCSK9 is associated with type III hyperlipidaemia. Its strong relationship with plasma triacylglycerols and total cholesterol distinguishes ε2/ε2 carriers from controls and another type of dyslipidaemia, which provides valuable information regarding the pathogenesis of this complex dyslipidaemia. Furthermore, these results suggest that patients with type III hyperlipidaemia may benefit from PCSK9-antagonizing therapy.
- Decreased prevalence of hypercholesterolaemia and stabilisation of obesity trends in 5-year-old children: possible effects of changed public health policies. [Journal Article, Research Support, Non-U.S. Gov't]
- Eur J Endocrinol 2014 Feb; 170(2):293-300.
Overweight/obesity in children is a worldwide public health problem. Together with hypercholesterolaemia they are associated with early atherosclerotic complications.In this study, we aimed to investigate the anthropometric characteristics and total cholesterol (TC) levels in a population of 5-year-old children, to determine trends in the prevalence of overweight/obesity and hypercholesterolaemia in 5-year-old children over a period of 8 years (2001-2009) and to assess the impact of modified national nutritional guidelines for kindergartens implemented in 2005.Cross-sectional studies of overweight/obesity prevalence in the years 2001, 2003-2005 and 2009, and hypercholesterolaemia in years 2001 and 2009, in 5-year-old children.Altogether, 12 832 (6308 girls/6524 boys) children were included.Overweight/obesity was defined by IOTF criteria. Hypercholesterolaemia was defined by TC level >5 mmol/l. Multivariable logistic regression models were used.NO CORRELATION BETWEEN BMI VALUES AND TC LEVELS WAS FOUND. OVERWEIGHT AND OBESITY PREVALENCE WERE STABILISED FROM 2001 TO 2009 (ODDS RATIO (OR) (95% CI): 1.13 (0.99-1.3) and 1.13 (0.89-1.42) respectively). Girls were more frequently overweight/obese than boys (OR (95% CI): 0.71 (0.65-0.79) and 0.75 (0.64-0.89) respectively). Prevalence of hypercholesterolaemia significantly decreased from 2001 to 2009 (OR (95% CI): 0.47 (0.41-0.55)). It was less frequent in boys than in girls (OR (95% CI): O.7 (0.61-0.8)).This is the first study to describe a negative trend in the prevalence of hypercholesterolaemia in pre-pubertal children. In addition, the prevalence of overweight/obesity in these children has been stabilised. Nationwide changes in public health policies could have influenced these observations.
- Association of RXR-Gamma Gene Variants with Familial Combined Hyperlipidemia: Genotype and Haplotype Analysis. [Journal Article]
- J Lipids 2013.:517943.
Background.Familial combined hyperlipidemia (FCHL), the most common genetic form of hyperlipdemia, is characterized by a strong familial clustering and by premature coronary heart disease. The FCHL locus has been mapped to human chromosome 1q21-q23. This region includes the retinoid X receptor gamma (RXRG), a nuclear factor member of the RXR superfamily, which plays important roles in lipid homeostasis.
Objective.To investigate the possible role of the RXRG gene in the genetic susceptibility to FCHL. Methods. Variations in RXRG gene were searched by direct sequencing, and the identified SNPs were genotyped by PCR-RFLP in 192 FCHL individuals from 74 families and in 119 controls.
Results.We identified 5 polymorphisms in the RXRG gene (rs1128977, rs2651860, rs2134095, rs283696, and rs10918169). Genotyping showed that the A-allele of rs283696 SNP was significantly associated with FCHL (corrected P, P c < 0.01). Also the alleles of the rs10918169 and of the rs2651860 SNP were more frequent in FCHL subjects compared to those in controls, although not significantly after correction. When the clinical characteristics of the FCHL subjects were stratified by allele carrier status for each SNP, the rs2651860 SNP was significantly associated with increased levels of LDL-cholesterol and of Apo-B in T-allele carriers (P < 0.04). Finally, haplotypes analysis with all 5 SNPs confirmed the significant association of RXRG gene with FCHL. Specifically, the haplotype containing all 3 "at-risk" alleles, significantly associated with FCHL (A-allele of rs283696, G-allele of rs10918169, and T-allele of rs2651860), showed an OR (Odds Ratio) of 2.02, P c < 0.048. Conversely, the haplotype without all these 3 alleles was associated with a reduced risk for FCHL (OR = 0.39, P c < 0.023). The "at-risk" haplotype CTTAG was also associated with higher LDL-C (P < 0.015). In conclusion, variation in the RXRG gene may contribute to the genetic dyslipidemia in FCHL subjects.
- Abnormal metabolic phenotype in middle-aged GH-deficient adults despite long-term recombinant human GH replacement. [Journal Article, Research Support, Non-U.S. Gov't]
- Eur J Endocrinol 2014 Feb; 170(2):263-72.
Adult GH deficiency (GHD) is associated with increased cardiovascular mortality. Recombinant human GH (rhGH) replacement has beneficial short-term metabolic effects. Although these positive effects sustain during longer follow-up, the prevalence of the metabolic syndrome (MS) remains increased in comparison with population data not adjusted for the higher mean BMI in GHD adults.To explore whether middle-aged patients with proposed physiological rhGH replacement have been normalized with respect to MS and its individual components in comparison with the general population, adjusted for age, sex, and BMI.One hundred and sixty-one GHD patients (aged 40-70 years) were studied before the start and after 5 years of rhGH replacement, and were compared with 1671 subjects (aged 45-66 years) from the general population (NEO Study).MS PROPORTION IN GHD PATIENTS WAS 41.0% BEFORE THE START OF RHGH SUPPLETION, INCREASING TO 53.4% AFTER 5 YEARS (P=0.007). DESPITE CHRONIC RHGH REPLACEMENT, GHD PATIENTS HAD A 1.3-TIMES HIGHER MS PROPORTION THAN THE GENERAL POPULATION, INDEPENDENTLY OF AGE, SEX, AND BMI (95% CI 1.11.5, P=0.008). THE GHD POPULATION SHOWED A DIFFERENT METABOLIC PROFILE THAN THE GENERAL POPULATION WITH SIMILAR BMI: an increased risk of hypertriglyceridemia (adjusted prevalence ratio (PR) 2.0, 95% CI 1.7-2.3) and low HDL-C (adjusted PR 1.8, 95% CI 1.5-2.2), but less hyperglycemia (adjusted PR 0.5, 95% CI 0.4-0.7).Despite 5 years of rhGH replacement, GHD patients still have a different metabolic profile and more frequently MS than the general population. These differences were independent of BMI, and resemble the unfavorable metabolic profile of untreated GHD patients, pointing to question the long-term benefits of rhGH replacement.
- Thyroid function testing in patients with newly diagnosed hyperlipidemia. [Journal Article]
- JAMA Intern Med 2014 Feb 1; 174(2):287-9.