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Endocrinology AND Hyperlipidemia [keywords]
- Ovarian leydig cell hyperplasia: an unusual case of virilization in a postmenopausal woman. [Journal Article]
- Case Rep Endocrinol 2014.:762745.
Objective.To report an unusual case of ovarian Leydig cell hyperplasia resulting in virilization in a postmenopausal woman. Methods. Patient's medical history and pertinent literature were reviewed.
Results.A 64-year-old woman presented with virilization with worsening hirsutism, deepening of her voice, male musculature, and male pattern alopecia. Her pertinent past medical history included type 1 diabetes, hyperlipidemia, and hypertension. Her pertinent past surgical history included hysterectomy due to fibroids. On further work-up, her serum total testosterone was 506 ng/dL (nl range: 2-45) and free testosterone was 40 pg/mL (nl range: 0.1-6.4). After ruling out adrenal causes, the patient underwent an empiric bilateral oophorectomy that showed Leydig cell hyperplasia on pathology. Six weeks postoperatively, serum testosterone was undetectable with significant clinical improvement.
Conclusion.Postmenopausal hyperandrogenism can be the result of numerous etiologies ranging from normal physiologic changes to ovarian or rarely adrenal tumors. Our patient was found to have Leydig cell hyperplasia of her ovaries, a rarely reported cause of virilization.
- Erectile dysfunction and risk of end stage renal disease requiring dialysis: a nationwide population-based study. [Journal Article]
- PLoS One 2014; 9(7):e102055.
Previous studies have suggested that erectile dysfunction (ED) is an independent risk factor for macrovascular disease. Very few studies have evaluated the relationship between ED and risk of end stage renal disease (ESRD) requiring dialysis.A random sample of 1,000,000 individuals from Taiwan's National Health Insurance database was collected. We selected the control group by matching the subjects and controls by age, diabetes, hypertension, coronary heart disease, hyperlipidemia, area of residence, monthly income and index date. We identified 3985 patients with newly-diagnosed ED between 2000 and 2008 and compared them with a matched cohort of 23910 patients without ED. All patients were tracked from the index date to identify which patients subsequently developed a need for dialysis.The incidence rates of dialysis in the ED cohort and comparison groups were 10.85 and 9.06 per 10000 person-years, respectively. Stratified by age, the incidence rate ratio for dialysis was greater in ED patients aged <50 years (3.16, 95% CI: 1.62-6.19, p = 0.0008) but not in aged 50-64 (0.94, 95% CI: 0.52-1.69, p = 0.8397) and those aged ≧ 65 (0.69, 95% CI: 0.32-1.52, p = 0.3594). After adjustment for patient characteristics and medial comorbidities, the adjusted HR for dialysis remained greater in ED patients aged <50 years (adjusted HR: 2.08, 95% CI: 1.05-4.11, p<0.05). The log-rank test revealed that ED patients <50-years-old had significantly higher cumulative incidence rates of dialysis than those without (p = 0.0004).Patients with ED, especially younger patients, are at an increased risk for ESRD requiring dialysis later in life.
- Protection against high-fat diet-induced obesity in helz2-deficient male mice due to enhanced expression of hepatic leptin receptor. [Journal Article]
- Endocrinology 2014 Sep; 155(9):3459-72.
Obesity arises from impaired energy balance, which is centrally coordinated by leptin through activation of the long form of leptin receptor (Leprb). Obesity causes central leptin resistance. However, whether enhanced peripheral leptin sensitivity could overcome central leptin resistance remains obscure. A peripheral metabolic organ targeted by leptin is the liver, with low Leprb expression. We here show that mice fed a high-fat diet (HFD) and obese patients with hepatosteatosis exhibit increased expression of hepatic helicase with zinc finger 2, a transcriptional coactivator (Helz2), which functions as a transcriptional coregulator of several nuclear receptors, including peroxisome proliferator-activated receptor γ in vitro. To explore the physiological importance of Helz2, we generated Helz2-deficient mice and analyzed their metabolic phenotypes. Helz2-deficient mice showing hyperleptinemia associated with central leptin resistance were protected against HFD-induced obesity and had significantly up-regulated hepatic Leprb expression. Helz2 deficiency and adenovirus-mediated liver-specific exogenous Leprb overexpression in wild-type mice significantly stimulated hepatic AMP-activated protein kinase on HFD, whereas Helz2-deficient db/db mice lacking functional Leprb did not. Fatty acid-β oxidation was increased in Helz2-deficeint hepatocytes, and Helz2-deficient mice revealed increased oxygen consumption and decreased respiratory quotient in calorimetry analyses. The enhanced hepatic AMP-activated protein kinase energy-sensing pathway in Helz2-deficient mice ameliorated hyperlipidemia, hepatosteatosis, and insulin resistance by reducing lipogenic gene expression and stimulating lipid-burning gene expression in the liver. These findings together demonstrate that Helz2 deficiency ameliorates HFD-induced metabolic abnormalities by stimulating endogenous hepatic Leprb expression, despite central leptin resistance. Hepatic HELZ2 might be a novel target molecule for the treatment of obesity with hepatosteatosis.
- Clinical association of circulating VEGF-B levels with hyperlipidemia and target organ damage in type 2 diabetic patients. [Journal Article]
- Int J Immunopathol Pharmacol 2014 Jul-Sep; 28(2):225-36.
Vascular endothelial growth factor-B (VEGF-B is an important member of the VEGF protein family. Recent animal studies indicated that VEGF-B signaling had determinant roles in insulin resistance, lipid distribution and metabolism in type 2 diabetes. The clinical significance of VEGF-B in type 2 diabetes is still not clear. This study aimed to correlate VEGF-B levels with biochemistry characteristics and target organ damage in type 2 diabetic patients. Serum VEGF-B levels were measured using ELISA. A crosssectional control study, which included 180 type 2 diabetic patients and 62 healthy subjects, was carried out. Diabetic patients who were undergoing insulin therapy were not included. This results showed that serum VEGF-B levels did not differ between the type 2 diabetic patients and the healthy controls (169.2∓118.8 vs 163.5∓115.2 pg/mL; P=0.734). VEGF-B levels in type 2 diabetic patients were significantly associated with the levels of c-peptide, total cholesterol and triglyceride. T-test analysis showed that the associations of serum VEGF-B levels with insulin resistance, pancreatic reserve, HDL and LDL were not significant. Regression analysis showed that VEGF-B levels were significantly correlated with diabetic retinopathy and nephropathy. No significant association between VEGF-B and macro-vasculopathy was found. In conclusion, our study findings suggested that VEGF-B levels did not differ between the type 2 diabetic patients and the normal controls. High VEGF-B levels might correlate with the presence of hyperlipidemia and target organ damage in type 2 diabetic patients.
- New drug therapies for the treatment of overweight and obese patients. [Journal Article]
- Am Health Drug Benefits 2013 Sep; 6(7):423-30.
Obesity is a serious and costly disease that is growing in epidemic proportions. Obesity-related hospitalizations have nearly tripled from 1996 to 2009. If the current trend in the growth of obesity continues, the total healthcare costs attributable to obesity could reach $861 billion to $957 billion by 2030. The American Medical Association has officially recognized obesity as a disease. Obesity is a public health crisis affecting approximately more than 33% of Americans and costing the healthcare system more than $190 billion annually.To review the 2 new drugs that were recently approved by the US Food and Drug Administration (FDA) for the treatment of obesity, lorcaserin HCl (Belviq) and phentermine/topiramate (Qsymia) and their potential impact on the treatment of obese patients.Lifestyle modification is the first and mainstay treatment for obesity. Antiobesity drugs are indicated as adjuncts to a healthy, low-fat, low-calorie diet and an exercise plan. Currently, 4 drugs are approved by the FDA for the treatment of obesity, 2 of which were approved after June 2012. These 2 drugs, Belviq and Qsymia, have added new tools for the treatment of obesity. In addition to reducing body mass index, these drugs have been shown to reduce hemoglobin A1c levels in patients with diabetes and blood pressure levels in patients with hypertension, as well as to decrease lipid levels in patients with hyperlipidemia. This article reviews the drugs' mechanisms of action, evaluates landmark clinical studies leading to the FDA approval of the 2 drugs, their common side effects, and the benefits these new drugs can provide toward the management of the obesity epidemic that are different from other medications currently available.The weight loss seen in patients who are using the 2 new medications has been shown to further improve other cardiometabolic health parameters, including blood pressure, blood glucose levels, and serum lipid levels. Based on clinical trials evidence, it is likely that many obese patients could benefit from these therapies, if used appropriately.
- Prevalence of metabolic syndrome in the family members of women with polycystic ovary syndrome from North India. [Journal Article]
- Indian J Endocrinol Metab 2014 May; 18(3):364-9.
Polycystic ovary syndrome (PCOS) is the most complex and common endocrine disorder of women in reproductive years. In addition to irregular menstrual cycles, chronic anovulation and hyperandrogenism, it has many metabolic manifestations such as obesity, hyperlipidemia, hyperinsulinemia, insulin resistance, dysglycemia, increased risk of cardiovascular disease or possibly endometrial cancer. Familial clustering of PCOS in consistence with the genetic susceptibility has been described.The present study assessed the clinical, biochemical and hormonal parameters including prevalence of metabolic syndrome by two different criteria in the first- degree relatives of patients with PCOS.The average age of 37 index patients was 23 ± 3.6 years, with the mean age of menarche as 13.3 ± 1.2 years. The mean age and age of menarche in mothers (n = 22) was 48.8 ± 5.1 and 13 ± 1.3 years, respectively, whereas as it was 23.5 ± 4.7 and 13.3 ± 1.2 years in sisters (n = 22), respectively. Metabolic syndrome (MS) defined by International Diabetes Federation (IDF) criteria was present in 10 index patients, 1 brother, 4 sisters, 17 mothers and 15 fathers while as by Adult Treatment Panel III (ATP III) it was in 8 index patients, 5 sisters, 16 mothers and 11 fathers.The presence of MS or related metabolic derangements is high in the family members of women with PCOS.
- Effect of Atorvastatin on Pancreatic Beta-Cell Function and Insulin Resistance in Type 2 Diabetes Mellitus Patients: A Randomized Pilot Study. [JOURNAL ARTICLE]
- Can J Diabetes 2014 Jun 3.
Statins are commonly used for the management of dyslipidemia in type 2 diabetes mellitus patients. We hypothesized that atorvastatin could modulate the beta-cell function by altering the levels of proapoptotic and antiapoptotic lipoproteins and could also have an effect on insulin resistance. The aim of the present pilot study was to assess the effect of atorvastatin 10 mg on pancreatic beta-cell function and insulin resistance in patients with hyperlipidemia and type 2 diabetes by using the homeostasis model assessment-2 (HOMA2) index.Fifty-one type 2 diabetes patients receiving oral antidiabetes drugs, not taking statins, with baseline low-density lipoprotein cholesterol between 2.6 mmol/L and 4.1 mmol/L were included. Forty-three patients (21 in placebo group and 22 in atorvastatin group) completed the study and were taken up for final analysis. Fasting blood samples were obtained at baseline and at 12 weeks to determine levels of blood glucose, lipid profile, insulin, C-peptide and glycosylated hemoglobin (A1C).Atorvastatin nonsignificantly increased fasting serum insulin (+14.29%, p=0.18), accompanied by marginal nonsignificant increases in fasting plasma glucose and A1C. There was a decrease in HOMA2 percent beta-cell function (-2.9%, p=0.72) and increase in HOMA2 insulin resistance (+14%, p=0.16) in the atorvastatin group as compared with baseline, but the difference was not statistically significant.Atorvastatin in the dose used failed to produce significant change in pancreatic beta-cell function and insulin resistance in type 2 diabetes patients as assessed by the HOMA2 index. The possible explanations include absence of lipotoxicity at prevailing levels of dyslipidemia at baseline or inadequacy of statin dose used in the study. (Clinical Trials Registry-India: CTRI/2008/091/000099).
- Understanding the type 2 diabetes mellitus and cardiovascular disease risk paradox. [Journal Article, Review]
- Postgrad Med 2014 May; 126(3):190-204.
Patients with diabetes have approximately a 2-fold increase in the risk for coronary heart disease, stroke, and death from vascular causes compared with patients who do not have diabetes. Interventions targeted at modifiable risk factors, such as smoking cessation and management of hypertension and dyslipidemia, reduce the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). Paradoxically, large randomized studies have failed to conclusively show that intensively lowering glucose reduces CVD event rates in patients with T2DM, despite pathophysiologic and epidemiologic evidence suggesting that hyperglycemia contributes to CVD. Although initiation of intensive glycemic control early in the disease course may be associated with a reduction in the long-term risk of cardiovascular (CV) events, this approach in those with long-standing or complicated T2DM is not of clear benefit and may even be harmful in some. Failure to mitigate risk with antihyperglycemic therapy and the potential for some treatments to increase CVD risk underlies a treatment paradox. New glucose-lowering therapies are now subject to close scrutiny for CV safety before and after drug approval. Results from the first trials designed to meet the recent CV regulatory requirements have shown no increased risk of major adverse CV events but also no CV benefit from dipeptidyl peptidase-4 inhibitor therapy, as well as a potentially increased risk of hospitalization for heart failure. Conclusive evidence of CV risk reduction with glucose-lowering therapy is still lacking and scrutiny of additional agents is necessary. Type 2 diabetes mellitus is a heterogeneous disease, for which patient-centered, individualized care, and goal-setting is appropriate. Interventions that focus on the management of CV risk factors and glucose lowering with medications that are not cardiotoxic represent an optimal and attainable treatment approach.
- Influencing Factors of New-Onset Diabetes after a Renal Transplant and Their Effects on Complications and Survival Rate. [JOURNAL ARTICLE]
- PLoS One 2014; 9(6):e99406.
To discuss the onset of and relevant risk factors for new-onset diabetes after a transplant (NODAT) in patients who survive more than 1 year after undergoing a renal transplant and the influence of these risk factors on complications and long-term survival.A total of 428 patients who underwent a renal transplant between January 1993 and December 2008 and were not diabetic before surgery were studied. The prevalence rate of and relevant risk factors for postoperative NODAT were analyzed on the basis of fasting plasma glucose (FPG) levels, and differences in postoperative complications and survival rates between patients with and without NODAT were compared.The patients in this study were followed up for a mean of 5.65 ± 3.68 years. In total, 87 patients (20.3%) developed NODAT. Patients who converted from treatment with CSA to FK506 had increased prevalence rates of NODAT (P <0.05). Multi-factor analysis indicated that preoperative FPG level (odds ratio [OR] = 1.48), age (OR = 1.10), body mass index (OR = 1.05), hepatitis C virus infection (OR = 2.72), and cadaveric donor kidney (OR = 1.18) were independent risk factors for NODAT (All P <0.05). Compared with the N-NODAT group, the NODAT group had higher prevalence rates (P < 0.05) of postoperative infection, hypertension, and dyslipidemia; in addition, the survival rate and survival time of the 2 groups did not significantly differ.Among the patients who survived more than 1 year after a renal transplant, the prevalence rate of NODAT was 20.32%. Preoperative FPG level, age, body mass index, hepatitis C virus infection, and cadaveric donor kidney were independent risk factors for NODAT. Patients who converted from treatment with CSA to FK506 after a renal transplant had aggravated impairments in glycometabolism. Patients with NODAT were also more vulnerable to postoperative complications such as infection, hypertension, and hyperlipidemia.
- Serum bilirubin concentrations are positively associated with serum C-peptide levels in patients with Type 2 diabetes. [JOURNAL ARTICLE]
- Diabet Med 2014 Jun 9.
To investigate the relationship between physiological serum total bilirubin concentrations and serum C-peptide levels in Korean patients with Type 2 diabetes.A total of 588 patients with Type 2 diabetes were investigated in this cross-sectional study. Fasting C-peptide level, 2-h postprandial C-peptide level and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) level were measured in all patients.Fasting C-peptide level, postprandial C-peptide level and ΔC-peptide level tended to be higher in patients with higher bilirubin concentrations. Partial correlation analysis showed that serum bilirubin levels were significantly correlated with fasting C-peptide level (r=0.159, P < 0.001), postprandial C-peptide level (r=0.209, P < 0.001) and ΔC-peptide level (r=0.186, P < 0.001) after adjustment for other covariates. In the multivariate model, the association between serum bilirubin concentrations and serum C-peptide levels remained significant after adjustment for confounding factors including age, gender, familial diabetes, hypertension, hyperlipidaemia, BMI, HbA1c , duration of diabetes and associated liver function tests (fasting C-peptide level: β=0.083, P=0.041; postprandial C-peptide level: β=0.106, P=0.005; ΔC-peptide level: β=0.096, P=0.015, respectively).Serum bilirubin concentrations within the physiological range were positively associated with serum C-peptide levels in patients with Type 2 diabetes. This article is protected by copyright. All rights reserved.