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Metab Syndr Relat Disord [journal]
- Effects of Simvastatin and Ezetimibe in Lowering Low-Density Lipoprotein Cholesterol in Subjects with Type 1 and Type 2 Diabetes Mellitus. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Dec 9.
Objective:Statins are used to lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels among patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). However, there are no studies of statin efficacy among T1DM patients. T1DM patients have higher gut cholesterol absorption than synthesis; hence cholesterol absorption inhibitors such as ezetimibe may also be effective in T1DM. Here, we compare the effects of simvastatin and ezetimibe among subjects with T1DM and T2DM. Research Design and
Methods:Subjects with T1DM (n=20, 45% female) or T2DM (n=27, 56% female) were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design.
Results:Among T2DM subjects, simvastatin lowered TC and LDL-C from the baseline (-25±4% and -40±5%, respectively, P<0.001), whereas ezetimibe was not as effective (-2±4% and -3±5%, respectively). Among T1DM subjects, both statin and ezetimibe showed significant decreases in TC and LDL-C from baseline, although ezetimibe lowered LDL-C much more than simvastatin (-32±12 (P<0.001) and -19±5% (P<0.01), respectively). Effect of simvastatin on LDL-C was much lower among T1DM subjects compared to T2DM subjects (P=0.02).
Conclusions:This study shows that the cholesterol synthesis inhibitor simvastatin was less effective in lowering LDL-C in T1DM than T2DM subjects, whereas the cholesterol absorption inhibitor ezetimibe was at least as effective in lowering LDL-C as simvastatin among T1DM subjects.
- Effect of Hyperketonemia (Acetoacetate) on Nuclear Factor-κB and p38 Mitogen-Activated Protein Kinase Activation Mediated Intercellular Adhesion Molecule 1 Upregulation in Endothelial Cells. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Dec 9.
Abstract Background: Hyperketonemia is a pathological condition observed in patients with type 1 diabetes and ketosis-prone diabetes (KPD), which results in increased blood levels of acetoacetate (AA) and β-hydroxybutyrate (BHB). Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. We examined the hypothesis that hyperketonemia activates the nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that regulate intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells. Methods: Human umbilical vein endothelial cells (HUVECs) were cultured with AA (0-8 mM) or BHB (0-10 mM) for 0-24 hr. Western blotting was used to determine NF-κB activation in whole-cell lysates. ICAM-1 expression was measured using flow cytometry. Results: Results show a 2.4-fold increase in NF-κB activation in cells treated with 8 mM AA compared to the control. BHB had little or no effect on NF-κB activation. Pretreatment with a reactive oxygen species (ROS) inhibitor [N-acetyl-l-cysteine (NAC)] reduced NF-κB to near-control levels. The expression of AA-induced ICAM-1 was significantly reduced when cells were pretreated with either NAC or p38 MAPK inhibitor. Conclusions: These results suggest that NF-κB and p38 MAPK mediate upregulation of ICAM-1 expression in endothelial cells exposed to elevated levels of AA, which may contribute to the development of vascular disease in diabetes.
- Relationships Among the Metabolic Syndrome, Bone Mineral Density, Bone Turnover Markers, and Hyperglycemia. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Dec 3.
Abstract Background: This study investigated the possible effects of metabolic syndrome on bone mineral density (BMD) and bone turnover markers in Turkish postmenopausal women. Method: This prospective case-control study included a total of 230 postmenopausal women, between 45 and 65 years old, including 63 with metabolic syndrome and 167 without metabolic syndrome on the basis of the International Diabetes Federation criteria. The height, weight, body mass index (BMI), waist circumference, hip circumference, and waist-to-hip ratio of each subject were measured. Fasting and nonfasting blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), parathyroid hormone (PTH), thyroid-stimulating hormone (TSH), calcium, phosphorus, glycated hemoglobin (HbA1c), bone-specific alkaline phosphatase (ALP), 25-hydroxyvitamin D3 [25(OH) D], osteocalcin, and the β-isomerized form carboxy-terminal telopeptide of type I collagen (β-CTx) were measured. Bone mineral densities in the lumbar spine and femoral neck were measured by dual energy X-ray absorptiometry. Results: The mean age was 58.49±5.7 years in metabolic syndrome patients and 56.13±5.0 years in patients without metabolic syndrome. There was a statistically significant difference in the age of the patients. The mean BMI was 33.96±5.3 and 30.867±3.8 kg/m(2) in metabolic syndrome patients and patients without metabolic syndrome, respectively, indicating a statistically significant difference. Serum calcium, osteocalcin, and β-CTx were statistically significantly lower in metabolic syndrome patients. There was no significant difference in the levels of phosphorus, 25-hydroxyvitamin D3, and bone-specific ALP, TSH, and PTH among the patients with metabolic syndrome and without metabolic syndrome. The statistical analysis, after adjusting for age and BMI, revealed no significant difference between the two groups in terms of lumbar and femoral BMD. When the patients in the metabolic syndrome group were split into two groups on the basis of those with a T score -2.5 or less and those with a normal score, a statistically significant difference was identified between the two groups in terms of the fasting blood glucose (FBG) and HbA1c values (P<0.05). Furthermore, a negative correlation was identified between the lumbar T score and the FBG and HbA1c values (P<0.05). Conclusion: After adjusting for age and BMI in a comparison of BMD between postmenopausal women with and without metabolic syndrome, it was revealed that metabolic syndrome has no positive or negative effect on BMD. In contrast, a negative correlation was identified between FBG and HbA1c levels and lumbar BMD, suggesting that poor glycemic control may have a negative effect on lumbar BMD in this group of patients.
- Serum Ferritin, Insulin Resistance, and Metabolic Syndrome: Clinical and Laboratory Associations in 769 Non-Hispanic Whites Without Diabetes Mellitus in the HEIRS Study. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Nov 25.
Background:In some reports, serum ferritin (SF) has been associated with insulin resistance and metabolic syndrome.
Methods:We studied non-Hispanic whites without diabetes mellitus in a postscreening examination. Participants included cases [HFE C282Y homozygosity; and transferrin saturation (TS) >50% and SF >300 μg/L (males) and TS >45% and SF >200 μg/dL (females), regardless of HFE genotype] and controls [HFE wild-type (wt/wt) and TS/SF 25th-75th percentiles]. We excluded participants with overnight fasts <8 hr, cirrhosis, hepatitis B or C, pregnancy, or missing data. Observations were age, sex, C282Y homozygosity, body mass index (BMI), systolic and diastolic blood pressures (SBP, DBP), lymphocytes, alanine aminotransferase (ALT), aspartate aminotransferase (AST), C-reactive protein (CRP), TS, SF, and glucose/insulin. Insulin resistance was defined as homeostasis model assessment of insulin resistance (HOMA-IR) 4th quartile (≥2.70).
Results:A total of 407 women and 362 men (mean age 54 years) included 188 C282Y homozygotes and 371 wt/wt. Significant trends across HOMA-IR quartiles included age, male sex, BMI, SBP, DBP, lymphocytes, ALT, CRP >0.5 mg/dL (positive), and TS (negative). Multiple regression on HOMA-IR revealed significant associations with male sex, BMI, SBP, lymphocytes, ALT, CRP>0.5 mg/dL (positive), and DBP and SF (negative). Logistic regression on HOMA-IR 4th quartile revealed significant positive associations with age, male sex, BMI, and lymphocytes. Metabolic syndrome occurred in 53 participants (6.9%). Logistic regression on metabolic syndrome revealed these odds ratios: HOMA-IR 4th quartile [9.1 (4.8, 17.3)] and CRP >0.5 mg/dL [2.9 (1.6, 5.4)].
Conclusions:Age, male sex, BMI, and lymphocytes were positively associated with HOMA-IR after correction for other factors. HOMA-IR 4th quartile and CRP >0.5 mg/dL predicted metabolic syndrome.
- Obese First-Degree Relatives of Patients with Type 2 Diabetes with Elevated Triglyceride Levels Exhibit Increased β-Cell Function. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Nov 25.
Background:Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and β-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT).
Methods:We studied 372 FDR-T2DM subjects (ages,18-65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob-) or obese (Ob+)] and TGs levels (TG-, <150 mg/dL, or TG+, ≥150 mg/dL). β-cell function, IR, and IS were determined by the homeostasis model assessment of β-cell function (HOMA2-β), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively.
Results:The obese subjects with elevated TGs levels had 21%-60% increased β-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with β-cell function (ρ=0.502, P<0.001).
Conclusion:We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and β-cell function, which may precede PT2DM.
- Plasma Levels of Lysine, Tyrosine, and Valine During Pregnancy Are Independent Risk Factors of Insulin Resistance and Gestational Diabetes. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Nov 24.
Background:This study compared plasma concentrations of amino acids in pregnant women with and without gestational diabetes mellitus (GDM) and identified the association between plasma amino acid levels and GDM, insulin resistance, and insulin secretion at 24-28 weeks of pregnancy.
Methods:Circulating amino acid levels were evaluated using high-performance liquid chromatography at 24-28 weeks of pregnancy in 25 non-GDM and 64 GDM women after adjusting for covariates such as maternal age, body mass index (BMI) before pregnancy, BMI and gestational age at screening GDM, and daily caloric intake. Backward stepwise logistic regression analysis was used to identify the predictors of developing GDM, and homeostatic model assessments for insulin resistance (HOMA-IR) and β-cell function (HOMA-B).
Results:Circulating levels of amino acids except threonine and tyrosine were significantly higher in GDM women than non-GDM women. Along with the intakes of energy, protein, and fat from animal sources, the intakes of each amino acid were significantly higher in the GDM group without a direct correlation to plasma amino acid levels. The variation in GDM development was explained by maternal age, diastolic blood pressure, and plasma lysine levels (R(2)=0.691). Height, BMI before pregnancy, systolic blood pressure, and plasma tyrosine and valine levels accounted for the variation in HOMA-IR (R(2)=0.589). The 53.3% variation of HOMA-B was explained by maternal age, BMI at GDM screening, plasma insulin level at 1 h during the oral glucose tolerance test (OGTT), and plasma valine level.
Conclusions:Circulating concentrations of lysine, tyrosine, and valine were independently and positively associated with GDM through modifying insulin resistance and secretion.
- Type 2 Diabetes Mellitus, Metabolic Syndrome, and Mixed Dyslipidemia: How Similar, How Different, and How to Treat? [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Nov 17.
Abstract Individuals with mixed atherogenic dyslipidemia, type 2 diabetes mellitus (T2DM), and metabolic syndrome are at high risk of developing cardiovascular disease (CVD) and can often benefit greatly from preventive lifestyle and medical interventions. These conditions typically co-exist in an individual, and the lipid profiles associated with them have several features in common. The worldwide prevalence of T2DM, atherogenic dyslipidemia, and metabolic syndrome is increasing, particularly in southern Asia and the Middle East. Statins can lower low-density lipoprotein-cholesterol and reduce the risk of CVD in these high-risk individuals, but there is a residual risk of CVD associated with additional lipid abnormalities, such as high levels of triglycerides and low levels of high-density lipoprotein cholesterol. These abnormalities are commonly found in patients with T2DM and metabolic syndrome. Additional lipid-modifying therapies that target these abnormalities, such as fibrates and omega-3 polyunsaturated fatty acids, may be able to improve lipid profiles and further reduce the risk of CVD in these patients.
- Are Metabolic Syndrome and Its Components Associated with 5-Year Mortality in Chronic Obstructive Pupmonary Disease Patients? [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Oct 29.
Abstract The aim of this study was to evaluate the risk of mortality according to the presence of metabolic syndrome in chronic obstructive pulmonary disease (COPD) patients who were followed for 5 years. We did not establish the influence of metabolic syndrome on mortality rate. However, an increase of 100 mg of triglycerides was associated with a 39% increase in the probability of death in the period of the study (hazard ratio 1.39, 95% confidence interval 1.06-1.83).
- Genetic and Environmental Relationships of Metabolic and Weight Phenotypes to Metabolic Syndrome and Diabetes: The Healthy Twin Study. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Oct 21.
Background:We aimed to examine the relationships, including genetic and environmental correlations, between metabolic and weight phenotypes and factors related to diabetes and metabolic syndrome. Design and
Methods:Participants of the Healthy Twin Study without diabetes (n=2687; 895 monozygotic and 204 dizygotic twins, and 1588 nontwin family members; mean age, 42.5±13.1 years) were stratified according to body mass index (BMI) (<25 vs. ≥25 kg/m(2)) and metabolic syndrome categories at baseline. The metabolic traits, namely diabetes and metabolic syndrome, metabolic syndrome components, glycated hemoglobin (HbA1c) level, and homeostasis model assessment of insulin resistance (HOMA-IR), were assessed after 2.5±2.1 years.
Results:In a multivariate-adjusted model, those who had metabolic syndrome or overweight phenotypes at baseline were more likely to have higher HbA1C and HOMA-IR levels and abnormal metabolic syndrome components at follow-up as compared to the metabolically healthy normal weight subgroup. The incidence of diabetes was 4.4-fold higher in the metabolically unhealthy but normal weight individuals and 3.3-fold higher in the metabolically unhealthy and overweight individuals as compared with the metabolically healthy normal weight individuals. The heritability of the metabolic syndrome/weight phenotypes was 0.40±0.03. Significant genetic and environmental correlations were observed between the metabolic syndrome/weight phenotypes at baseline and the metabolic traits at follow-up, except for incident diabetes, which only had a significant common genetic sharing with the baseline phenotypes.
Conclusions:The genetic and environmental relationships between the metabolic and weight phenotypes at baseline and the metabolic traits at follow-up suggest pleiotropic genetic mechanisms and the crucial role of lifestyle and behavioral factors.
- Lifestyle Changes Followed by Bariatric Surgery Lower Inflammatory Markers and the Cardiovascular Risk Factors C3 and C4. [JOURNAL ARTICLE]
- Metab Syndr Relat Disord 2014 Oct 20.
Abstract Background: Morbidly obese patients are at risk of developing insulin resistance and cardiovascular disease. Low-grade systemic inflammation is an important factor for this development. We evaluated the effect of bariatric surgery on markers of inflammation, coagulation and glucose metabolism. Methods: Ninety-seven morbidly obese patients and 17 lean subjects (control group) participated. Anthropometric measurements as well as fasting blood samples were obtained at first admission, prior to surgery, and 1 year after surgery. Results: At admission, the morbidly obese group had significantly elevated levels of the complement components C3 and C4 compared to the lean control group (P<0.0001). Levels of C3 and C4 dropped significantly in the morbidly obese group over time (P<0.0001), and, 1 year after the operation, levels were comparable to those of the control group. The same changes were seen for markers of inflammation (high-sensitivity C-reactive protein, tumor necrosis factor-α, interferon-γ, interleukin-1 receptor antagonist, IL-6, and IL-13), coagulation (fibrinogen and plasminogen activator inhibitor-1), and glucose metabolism (leptin and insulin). There was a positive correlation between changes in C3 and body mass index, weight, coagulation parameters, inflammatory parameters, and leptin, respectively. Conclusions: Bariatric surgery in morbidly obese patients reduced weight effectively. Even more importantly, the increased levels of several risk factors associated with diabetes and cardiovascular co-morbidity normalized 1 year after surgery.