Abstract

Introduction

We sought to evaluate the ability of various metabolic syndrome definitions in predicting primary cardiovascular disease (CVD) outcomes in a vast multiethnic U.S. cohort.

Methods

This study included 6,814 self-identified men and women aged 45–84 years enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA) study. Gender-stratified analyses were performed to calculate hazard ratios of CVD, stroke, and mortality associated with various metabolic syndrome definitions and their individual constructs.

Results

The hazard ratios [95% confidence interval (CI)] for all-cause CVD in men were 2.90 (2.18–3.85), 2.64 (1.98–3.51), 2.16 (1.62–2.88), 2.56 (1.91–3.44), 1.82 (1.35–2.46), and 2.92 (2.15–3.95) for the National Cholesterol Education Program (NCEP), American Heart Association (AHA), World Health Organization (WHO), International Diabetes Federation (IDF), European Group for the Study of Insulin Resistance (EGIR), and the newly defined consensus criteria. Hazard ratios in women were 2.11 (1.41–3.15), 2.17 (1.45–3.27), 2.04 (1.37–3.06), 1.91 (1.27–2.88), 1.85 (1.23–2.79), and 2.08 (1.37–3.14), respectively. Metabolic syndrome was strongly associated with stroke risk only in males. In men, all constitutive metabolic syndrome components were continuously and strongly associated with CVD. In women, high-density lipoprotein and triglycerides did not appear to be associated with short term CVD risk.

Conclusion

We found the newly defined consensus criteria for metabolic syndrome to be similarly predictive of cardiovascular events when compared to existing definitions. Significant gender differences exist in the association between metabolic syndrome, its individual components, and CVD.

Abstract

Background

Elevated insulin resistance (IR), triglycerides (TG), body mass index (BMI), and waist circumference (WC) are features of the metabolic syndrome. Although several single-nucleotide polymorphisms (SNPs) associated with these traits have been reported, no study has reported their risk allele frequencies and effect sizes among the major U.S. race/ethnic groups in a nationally representative sample.

Methods

We compared the risk allele frequencies of eight SNPs previously associated with IR, TG, BMI, or WC by race/ethnicity (non-Hispanic white, non-Hispanic black, Mexican American) in 3,030 participants of the National Health and Nutrition Examination Study III (NHANES III). In regression models predicting IR, TG, BMI, WC, and metabolic syndrome, we tested whether the SNP effect sizes on these traits varied by race/ethnicity.

Results

Risk allele frequencies varied by race/ethnicity for all eight loci (P<0.0001). The directionality of effects of the variants on IR, TG, WC, and BMI was generally consistent with previous observations and did not differ by race/ethnicity (P>0.001), although our study had low power for this test. No SNP predicted metabolic syndrome in any of the three groups (P>0.05).

Conclusions

The significance of racial/ethnic differences in risk allele frequencies merits consideration if genetic discoveries are to have clinical and public health applicability.

Abstract

Background

This study investigates ethnic disparities in metabolic syndrome in Malaysia.

Methods

Data were obtained from the Malaysia Non-Communicable Disease Surveillance-1 (2005/2006). Logistic regressions of metabolic syndrome health risks on sociodemographic and health–lifestyle factors were conducted using a multiracial (Malay, Chinese, and Indian and other ethnic groups) sample of 2,366 individuals.

Results

Among both males and females, the prevalence of metabolic syndrome amongst Indians was larger compared to both Malays and Chinese because Indians are more likely to exhibit central obesity, elevated fasting blood glucose, and low high-density lipoprotein cholesterol. We also found that Indians tend to engage in less physical activity and consume fewer fruits and vegetables than Malays and Chinese. Although education and family history of chronic disease are associated with metabolic syndrome status, differences in socioeconomic attributes do not explain ethnic disparities in metabolic syndrome incidence. The difference in metabolic syndrome prevalence between Chinese and Malays was not statistically significant. Whereas both groups exhibited similar obesity rates, ethnic Chinese were less likely to suffer from high fasting blood glucose.

Conclusions

Metabolic syndrome disproportionately affects Indians in Malaysia. Additionally, fasting blood glucose rates differ dramatically amongst ethnic groups. Attempts to decrease health disparities among ethnic groups in Malaysia will require greater attention to improving the metabolic health of Malays, especially Indians, by encouraging healthful lifestyle changes.

Abstract

In 2010, more than 45 years after the initial discovery of lipoprotein(a) [Lp(a)] by Kare Berg, an European Atherosclerosis Society Consensus Panel recommended screening for elevated Lp(a) in people at moderate to high risk of atherosclerotic cardiovascular disease (CVD). This recommendation was based on extensive epidemiological findings demonstrating a significant association between elevated plasma Lp(a) levels and coronary heart disease, myocardial infarction, and stroke. In addition to those patients considered to be at moderate to high risk of heart disease, statin-treated patients with recurrent heart disease were also identified as targeted for screening of elevated Lp(a) levels. Taken together, recent findings have significantly strengthened the notion of Lp(a) as a causal risk factor for CVD. It is well established that Lp(a) levels are largely determined by the size of the apolipoprotein a [apo(a)] gene; however, recent studies have identified several other LPA gene polymorphisms that have significant associations with an elevated Lp(a) level and a reduced copy number of K4 repeats. In addition, the contribution of other genes in regulating Lp(a) levels has been described. Besides the strong genetic regulation, new evidence has emerged regarding the impact of inflammation as a modulator of Lp(a) risk factor properties. Thus, oxidized phospholipids that possess a strong proinflammatory potential are preferentially carried on Lp(a) particles. Collectively, these findings point to the importance of both phenotypic and genotypic factors in influencing apo(a) proatherogenic properties. Therefore, studies taking both of these factors into account determining the amount of Lp(a) associated with each individual apo(a) size allele are valuable tools when assessing a risk factor role of Lp(a).

Abstract

Background

Central obesity measured by waist circumference is a cardiovascular disease (CVD) risk factor; however, the waist circumference of risk in populations of African descent has not been identified. The International Diabetes Federation currently suggests that cutoffs established in men of European descent be applied to sub-Saharan men—a waist circumference ≥94 cm.

Subjects and Methods

Participants were 203 South African black men with type 2 diabetes mellitus (T2DM). They were divided into quartiles of waist circumference (>88 cm, 88–94 cm, 95–103 cm, >103 cm). Cardiovascular risk factors, including insulin resistance (IR), measured by modified homeostasis model assessement of IR (HOMA-IR), and the triglycerides-to-high-density lipoprotein cholesterol (TG-to-HDL-C) ratio, were compared across quartiles.

Results

Age, duration of diabetes, glycosylated hemoglobin (HbA1c), blood pressure, urinary albumin excretion, and smoking were similar across waist circumference quartiles. Overall, for both lipids and measures of IR, there was variation across waist circumference quartiles, but no significant differences between quartiles 2 and 3. Therefore, data from these two quartiles were pooled. Between the first and second+third (88–103 cm) quartiles, there were significant differences in HDL-C (1.30±0.43, 1.10±0.43 mmol/L, P=0.003), TG (medians 1.10, 1.60 mmol/L P<0.001), low-density lipoprotein cholesterol (LDL-C; 2.40±0.93, 2.85±1.03 mmol/L, P=0.01), non-HDL-C (3.05±1.18, 3.70±1.16 mmol/L, P=0.002), HOMA-IR (medians 0.90, 2.10, P<0.001), and TG-to-HDL-C ratio (medians 0.89, 1.17, P<0.001). Additional comparisons were made between men with waist circumference <90 cm and 90–93 cm. Values for each lipid and for IR parameters were more favorable in the <90-cm group (all P<0.05).

Conclusions

For black South African diabetic men, CVD risk substantially increased with waist circumference >90 cm. The waist circumference cut point of >94 cm has the potential to misclassify many black South African diabetic men at risk for CVD.

Abstract

Background

Skeletal muscle adipose tissue (AT) infiltration, or myosteatosis, appears to be greater in African compared with European ancestry individuals and may play a role in type 2 diabetes mellitus (T2DM), a disease that disproportionally affects African ancestry populations. Inflammation is one mechanism that may link myosteatosis with increased T2DM risk, but studies examining the relationship between inflammation and myosteatosis are lacking.

Methods

To examine these associations, we measured skeletal muscle subcutaneous AT, intermuscular AT, and skeletal muscle density using quantitative computed tomography and serum markers of inflammation in 471 individuals from 8 Afro-Caribbean multigenerational families [mean family size 67; mean age 43 years; mean body mass index (BMI) 28 kg/m2].

Results

After removing the variation attributable to significant covariates, heritabilities of inflammation markers [C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)] ranged from 33% (TNFα) to 40% (CRP); all P<0.01. Higher CRP, IL-6, and TNF-α were associated with lower subcutaneous AT around skeletal muscle (r=−0.13 to −0.19, P<0.05). Higher CRP was additionally associated with lower skeletal muscle density, indicative of greater intramuscular AT (r=−0.10, P<0.05), hyperinsulinemia (r=0.12, P<0.05), and increased homeostasis model assessment of insulin resistance (HOMA-IR) (r=0.17, P<0.01).

Conclusions

Our findings suggest that heredity may play a significant role in the determination of several markers of inflammation in African ancestry individuals. Higher concentrations of CRP appear to be associated with greater skeletal muscle AT infiltration, lower subcutaneous AT, hyperinsulinemia, and insulin resistance. Longitudinal studies are needed to further evaluate the relationship between inflammation with changes in skeletal muscle AT distribution with aging and the incidence of T2DM.

Abstract

Background

We examined associations between elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) with physical activity and obesity measures in middle-aged urban Chinese men. The associations between elevated aminotransferases with impaired fasting glucose, newly diagnosed type 2 diabetes (T2D), and metabolic syndrome were also evaluated in this population.

Methods

The study included 3,978 urban Chinese men 40–74 years of age from a population-based cohort study, the Shanghai Men's Health Study, who were free of T2D at baseline and had provided fasting blood samples. Elevated AST and ALT levels were defined as >40 U/L. Anthropometric measurements and information on lifestyle factors and disease history were collected by in-person interviews.

Results

A total of 11.13% and 5.85% study participants had elevated serum ALT and AST levels, respectively. Both body mass index (BMI) and waist-to-hip ratio (WHR) were positively associated with elevated ALT and AST. We found stronger associations between ALT and BMI/WHR than between AST and BMI/WHR. Physical activity was inversely associated with ALT and AST, but the association was attenuated after adjustment for BMI and WHR. Elevated serum aminotransferase levels were associated with T2D and metabolic syndrome.

Conclusions

In this representative sample of middle-aged Chinese men, elevated ALT and AST were associated with a prevalence of metabolic syndrome and T2D. These findings suggest that the relationship between obesity and T2D might involve liver injury. Physical activity might reduce the levels of ALT and AST, probably mediated through weight reduction.

Abstract

Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosisworsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.

Abstract

Background

The aim of this study was to examine the distribution of alanine aminotrasferase (ALT) and its association with metabolic syndrome variables and their clustering in apparently healthy children.

Methods

A cross-sectional study of 1,524 preadolescents (age, 4–11 years, 62% white, 51% male) and 1,060 adolescents (age, 12–18 years, 58% white, 51% male) enrolled in the Bogalusa Heart Study was performed.

Results

ALT levels showed a significant race (whites > blacks) difference in preadolescents and a gender (males > females) difference in adolescents. Both preadolescents and adolescents in the age, race, and gender-specific top versus bottom quartiles of ALT had significant increases in the prevalence of adverse levels (>75th percentile specific for age, race, and gender) of body mass index (BMI), systolic blood pressure, total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio (adolescents only), insulin resistance index (HOMA-IR), and clustering of all four of these metabolic syndrome variables. In multivariate analyses, BMI was the major independent predictor of ALT in both preadolescents and adolescents; other independent predictors were total cholesterol to HDL-C ratio, HOMA-IR, white race in preadolescents and male gender in adolescents. With respect to the ability of ALT to identify children with clustering of the metabolic syndrome variables, area under the receiver operating characteristic curve analysis (c-statistics) adjusted for age, race, and gender yielded a value of 0.67 for preadolescents and 0.82 for adolescents.

Conclusion

An elevation in serum ALT within the reference range relate adversely to all of the major components of metabolic syndrome and their clustering in children and, thus, may be useful as a biomarker of the presence of metabolic syndrome and related risk in pediatric population, especially adolescents.

Abstract

Background

Carotid artery intima-media thickness (IMT) is greater in adults with elevated metabolic risk profiles. However, the influence of body mass index (BMI) or waist circumference (WC) on the relationship between IMT and metabolic risk is unclear.

Methods

Adults from the Bogalusa Heart Study were classified as normal weight, overweight, or obese and into WC categories (men, low <94 cm, moderate 94–101.9 cm, high ≥102 cm; women, low <80 cm, moderate 80–87.9 cm, high ≥88 cm). Elevated metabolic risk was defined by cardiovascular risk factor clustering (≥2 abnormal risk factors or insulin resistance (upper quartile of homeostasis model of insulin resistance). Carotid ultrasound measurements were obtained and mean IMT was calculated. General linear models compared IMT between elevated versus normal metabolic risk groups, adjusting for sex, age, race/ethnicity, and either BMI or WC category.

Results

Adults were 24–43 years of age (n = 991) and 41% had elevated metabolic risk (42% male, 28% African American, 38% obese). IMT (mm) was greater in adults with elevated metabolic risk (0.83 ± 0.007) versus normal risk (0.80 ± 0.006) whether adjusted by BMI or WC (both P < 0.0005). IMT was greater in adults with elevated compared to normal metabolic risk within normal-weight (0.84 ± 0.016 vs. 0.79 ± 0.008; P = 0.002), and obese adults (0.86 ± 0.009 vs. 0.80 ± 0.01; P = 0.03), but not significantly different between risk groups in overweight adults. Similar results were found when stratified by WC category.

Conclusion

Adults with elevated metabolic risk have greater IMT than those with normal risk in normal-weight, overweight, low WC, and high WC, but not significant for overweight or moderate WC categories.

Abstract

Background

The associations between adiposity and metabolic risk factors have been suggested to vary across ethnicities. Studies in Caucasians have shown that after adjusting for waist circumference and body mass index (BMI), a larger hip circumference may be protective for metabolic risk factors. To our knowledge, these associations have never been examined in a Chinese population.

Methods

Baseline (1987–1988) and follow-up (1993–1994) data were from the People's Republic of China Study (n = 1,144 men, n = 1,776 women). Logistic models were stratified by sex and adjusted for age, smoking, center, and education. Incidence differences (ID) comparing the sex specific 85th percentile to the 15th percentile of hip circumference were computed for elevated blood pressure, blood glucose and triglycerides, low high-density lipoprotein cholesterol (HDL-C), and multiple metabolic abnormalities (three or more of the aforementioned).

Results

In models adjusted for waist circumference and BMI, the ID [95% confidence interval (CI)] per 1,000 persons associated with a 12-cm larger hip were −132 (−237, −26) for low HDL-C; −85 (−138, −31) for elevated triglycerides; and −49 (−83, −4) for multiple metabolic abnormalities. In males, a larger hip circumference was not associated with a reduction of incident risk factors, although the ID tended to be negative.

Conclusions

In Chinese women, greater mass in the lower trunk region was inversely associated with incident high triglycerides, low HDL-C, and multiple metabolic abnormalities when adjusted for general and central adiposity. This association was not detected in men. Additional research is needed to better understand the mechanisms by which fat at different depots results in differential risk.

Abstract

Diabetes mellitus is a major cause of morbidity and mortality among transplanted patients. This study evaluated the role of the ENPP1 K121Q polymorphism and other variables known to affect diabetes risk in 115 nondiabetic and unrelated patients who underwent kidney transplant at our institution and had consented for use of genetic material (30% whites, 48% blacks, and 22% Hispanics). Thirty-six of these patients (30%) developed posttransplant diabetes mellitus (PTDM) within 1 year of observation from transplant. Black race, ENPP1 K121Q polymorphism, age, body mass index (BMI), and immunosuppressive medications were found to have the strongest associations with PTDM in the logistic regression and receiver operator characteristic (ROC) analysis. However, because ENPP1 K121Q is more common in Hispanics and in blacks, who also have higher PTDM prevalence, the studied genetic polymorphism did not exert independent predictive effect, whereas ethnicity, specifically black versus non-black, was the most robust predictor of PTDM. The model with the largest ROC area under the curve (AUC) of 0.80 was comprised of black/non-black, age, BMI, and tacrolimus treatment as significant predictors. A reduced model containing only ethnicity (black/non-black) and age as predictors yielded similar results (ROC AUC 0.78). We conclude that black race and age are major and not modifiable risk factors for PTDM. The specific role of ENPP1 K121Q on ethnic susceptibility to PTDM deserves further investigation in larger cohorts of transplanted patients.

Abstract

Objective

The aim of this study was to examine whether there are ethnic differences in the association of triglycerides (TG) with waist circumference (WC), blood pressure, high-density lipoprotein cholesterol (HDL-C), fasting glucose, and insulin resistance and to examine the disparities in the prevalence of the metabolic syndrome components between African Americans and non-Hispanic whites who do not have hypertriglyceridemia.

Methods

This study used the baseline data from the Multi-Ethnic Study of Atherosclerosis (MESA) study. The analysis included non-Hispanic whites (N = 2,427) and African Americans (N = 1,519) aged 45–84 years free of clinically evident cardiovascular disease and diabetes at baseline. The revised National Cholesterol Education Program (NCEP) criteria were used to define the metabolic syndrome and its components.

Results

African Americans had lower prevalence of elevated TG as compared with non-Hispanic whites. The association of TG with other components of the metabolic syndrome appeared to be similar between African Americans and non-Hispanic whites except for one. There was significant association of TG with WC among white women but not among African American women after adjusting for demographic and other variables (P for interaction of TG with ethnicity <0.001). In participants with TG < 150 mg/dL, African American women had higher prevalence rates than white women of abdominal obesity, elevated blood pressure, low HDL-C, elevated fasting glucose and homeostasis model assessment of insulin resistance (HOMA-IR). In men, the prevalence rates of high blood pressure, elevated fasting glucose, and HOMA-IR were significantly higher in African Americans than in whites.

Conclusions

The study findings suggest that further evaluation is warranted regarding the cutoffs for elevated TG and its clustering effect with other cardiometabolic risk factors on predicting risk for diabetes and cardiovascular disease (CVD) in African Americans.

Abstract

Background

Leptin is an important adipose tissue–derived hormone that has been shown to be involved in pathophysiological mechanisms related to cardiovascular disease and diabetes. However, few studies have examined the association between plasma leptin and diabetes mellitus in humans. Also, it is not clear if this association is present among women as well as in men. Therefore, we examined the association between plasma leptin levels and diabetes mellitus in a representative multiethnic sample of U.S. adults.

Methods

We examined the 1988–1994 third National Health and Nutrition Examination Survey (NHANES III) participants >20 years of age (n = 5,599, 54.7% women). Plasma leptin levels were categorized into quartiles (women, <7.68 fg/L, 7.68–13.18 fg/L, 13.19–21.70 fg/L, >21.70 fg/L; men, <2.64 fg/L, 2.64–4.36 fg/L, 4.37–7.12 fg/L, >7.12 fg/L). Diabetes mellitus was defined as fasting glucose ≥126 mg/dL, non-fasting glucose ≥200 mg/dL or use of oral hypoglycemic medication or insulin (n = 395).

Results

Higher plasma leptin levels were initially found to be associated with diabetes mellitus after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, hypertension, serum cholesterol and C-reactive protein [odds ratio (OR), 3.79; confidence interval (CI), 2.05–7.00; P trend <0.0001). However, when we additionally adjusted for body mass index (BMI), the association between plasma leptin levels and diabetes mellitus disappeared in both men (OR, 1.07; CI, 0.59–1.94; P trend = 0.5004) and women (OR, 0.86; CI, 0.49–1.51; P trend = 0.2819).

Conclusion

Higher plasma leptin levels are not independently associated with diabetes mellitus after adjustment for BMI. The null association was evident both in women as well as in men.

Abstract

Background

Apolipoprotein E (ApoE) plays a major role in lipoprotein metabolism and genetic variability of ApoE confers susceptibility to coronary artery disease (CAD). Beyond variability in the coding region, promoter polymorphisms in the ApoE gene impact on ApoE transcription.

Methods

We determined the ApoE − 491 A/T promoter polymorphism, ApoE isoforms, lipid and lipoprotein levels, and CAD risk factors in 313 Caucasians and 215 African Americans.

Results

Caucasians had a lower ApoE T allele frequency compared to African Americans (18.1% vs. 32.3%, P < 0.05). Among T/* carriers, ApoB levels were significantly lower in Caucasians, but significantly higher among African Americans, in both cases compared to A/A homozygotes (P = 0.017, and P = 0.012). For a given −491A/T genotype, levels of atherogenic lipoproteins differed across ApoE2/E3/E4 isoforms among African Americans, but not Caucasians, as T/* carriers with ApoE4 had significantly higher ApoB levels compared to T/* carriers with ApoE2 (P = 0.010). Among patients with CAD, Caucasian A/A homozygotes and African American T/* carriers had higher ApoB levels compared to the same genotype without CAD (P = 0.007, P = 0.049, respectively).

Conclusions

We observed an ethnicity-specific variability in ApoB levels across the ApoE − 491 A/T polymorphism and a modulatory impact on this pattern by ApoE2/E3/E4 isoforms.

Abstract

Background

Compared to whites, insulin-resistant African Americans have worse outcomes. Screening programs that could identify insulin resistance early enough for intervention to affect outcome often rely on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels. Racial differences in TG and HDL-C may compromise the efficacy of these programs in African Americans. A recommendation currently exists to use the TG/HDL-C ratio ≥2.0 to predict insulin resistance in African Americans. The validity of this recommendation needs examination. Therefore, our aim was to determine the ability of TG/HDL-C ratio to predict insulin resistance in African Americans.

Methods

In 1,903 African Americans [895 men, 1,008 women, age 55 ± 12 years, mean ± standard deviation (SD), range 35–80 years, body mass index (BMI) 31.0 ± 6.4 kg/m2, range 18.5–55 kg/m2] participating in the Jackson Heart Study, a population-based study of African Americans, Jackson, Mississippi tricounty region, insulin resistance was defined by the upper quartile (≥4.43) of homeostasis model assessment of insulin resistance (HOMA-IR). An area under the receiver operating characteristic curve (AUC-ROC) of >0.70 was required for prediction of insulin resistance by TG/HDL-C. The optimal test cutoff was determined by the Youden index.

Results

HOMA-IR was similar in men and women (3.40 ± 2.03 vs. 3.80 ± 2.46, P = 0.60). Women had lower TG (94 ± 49 vs. 109 ± 65 mg/dL P < 0.001) and TG/HDL-C (1.9 ± 1.4 vs. 2.7 ± 2.1, P < 0.001). For men, AUC-ROC for prediction of insulin resistance by TG/HDL-C was: 0.77 ± 0.01, mean ± standard error (SE), with an optimal cutoff of ≥2.5. For women, the AUC-ROC was 0.66 ± 0.01, rendering an optimal cutoff indefinable. When women were divided in two groups according to age, 35–50 years and 51–80 years, the results did not change.

Conclusions

In African-American men, the recommended TG/HDL-C threshold of 2.0 should be adjusted upward to 2.5. In African-American women, TG/HDL-C cannot identify insulin resistance. The Jackson Heart Study can help determine the efficacy of screening programs in African-Americans.

Abstract

Background

Fibroblast growth factor 23 (FGF-23), a phosphaturic peptide hormone secreted by the osteoblasts, is an important regulator of phosphorus and vitamin D metabolism. In chronic kidney disease, FGF-23 levels rise with declining kidney function. Increasing FGF-23 levels are associated with increasing risk of mortality in dialysis patients. Two assays for FGF-23 have been reported. One assay detects only full-length/intact FGF-23. In contrast, the carboxy-terminal assay recognizes both intact and carboxy-terminal FGF-23.

Aim/Methods

The aim of this study was to evaluate both assays for FGF-23. Test samples were analyzed with both the intact and carboxy-terminal FGF-23 enzyme-linked immunosorbent assay (ELISA) kits according to manufacturers' instructions.

Results

Carboxy-terminal FGF-23 showed very good precision with coefficients of variation (CV) ranging from 4% to 10.5%, whereas the CVs for intact FGF-23 were not very good (6–37.5%). The carboxy-terminal assay was linear, stable in plasma samples, and was not affected by common interferents. Also, the carboxy-terminal FGF-23 assay appeared to correlate better with worsening of kidney function as assessed by plasma creatinine and calculated estimated glomerular filtration rate (eGFR).

Conclusion

Thus, the carboxy-terminal FGF-23 assay is robust and can be used in prospective trials to validate its utility as a biomarker of adverse outcomes in patients with renal disease.

Abstract

Diabetes is a global epidemic. The recommended goals for glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and blood pressure are achieved only in a very small minority of patients. In this supplement to Metabolic Syndrome and Related Disorders, we review the data showing that the bile acid sequestrant colesevelam lowers both HbA1c and LDL-C in patients with diabetes. These data make colesevelam an attractive therapy to get more patients to achieve their LDL-C and HbA1c goals.

Abstract

The prevalence of type 2 diabetes (T2DM) and cardiovascular disease (CVD) continues to escalate globally. There is now abundant clinical trial evidence that the optimal treatment of CVD risk factors, with lifestyle changes aimed at weight loss in most patients, and pharmacologic management of dyslipidemia and hyperglycemia, can help mitigate the CVD burden. Yet more than 50% of patients are still not achieving glycosylated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) goals. Over the past 15 years, many novel and emerging drugs have made it possible to achieve optimal glycemic control, generally in combination therapy, without untoward effects of weight gain, hypoglycemia, and other adverse effects with traditional agents. Although the long-term efficacy and safety of some of the newer classes of agents are yet to be determined, bile acid sequestrants represent a unique long-standing class of agents. These drugs have the dual efficacy in glycemic control and LDL-C reduction, and an established record of long-term safety. Colesevelam HCl is the only drug approved for this dual indication and is an adjunct in the treatment of both hyperglycemia and hypercholesterolemia that frequently co-exist in adults with T2DM.

Abstract

Objective

In vitro studies suggest that adiponectin plays an important role in nitric oxide (NO) generation. We studied the relationship between plasma adiponectin and skeletal muscle nitric oxide synthase (NOS) activity in type 2 diabetic (T2DM) patients.

Methods

We determined NOS activity in skeletal muscle of 7 T2DM and 8 nondiabetic control subjects under basal conditions and after a 4-h euglycemic insulin (80 mU/m2 · min) clamp.

Results

Insulin-stimulated glucose disposal (Rd) (5.2 ± 0.4 vs. 9.0 ± 0.9 mg/kg-min, P < 0.01) and basal NOS activity (107 ± 45 vs. 459 ± 100 pmol/min-mg protein, P < 0.05) were reduced in T2DM versus controls. In response to hyperinsulinemia, NOS activity increased approximately two-fold in controls (757 ± 244, P < 0.05 vs basal) but failed to increase in T2DM (105 ± 38, P < 0.01 vs. T2DM). Basal NOS protein content was similar in controls and T2DM and did not change following insulin. Plasma adiponectin was decreased in T2DM (4.5 ± 0.8 vs. 7.0 ± 1.0 μg/mL, P < 0.02) and correlated with insulin-stimulated NOS activity (r = 0.49, P < 0.05) and with Rd (r = 0.50, P < 0.05). In controls and T2DM collectively, Rd correlated with insulin-stimulated NOS activity (r = 0.48, P < 0.05).

Conclusion

Decreased plasma adiponectin correlates with impaired insulin-stimulated NOS activity and severity of insulin resistance in T2DM. Because impaired NO generation plays a central role in endothelial dysfunction and development of atherosclerosis, our results may provide a link between reduced plasma adiponectin levels and accelerated atherosclerosis in T2DM.

Abstract

Polycystic ovary syndrome (PCOS) is a common disorder characterized by hyperandrogenism and disordered gonadotropin secretion, often associated with insulin resistance. The syndrome, which modulates both hormonal and metabolic processes, is the most common endocrinopathy in reproductive-age women and increases a woman's risk of infertility, endometrial pathology, and cardiometabolic disease. As it is currently defined, PCOS most likely encompasses several distinct diseases with similar clinical phenotypes but different underlying pathophysiological processes. However, hyperandrogenism remains the syndrome's clinical hallmark. The clinical manifestations of PCOS often emerge during childhood or in the peripubertal years, suggesting that the syndrome is influenced by fetal programming and/or early postnatal events. However, given that the full clinical spectrum of PCOS does not typically appear until puberty, a “two-hit” hypothesis has been proposed: (1) a girl develops hyperandrogenism via one or more of many different potential mechanisms; (2) the preexisting hyperandrogenism subsequently disturbs the hypothalamic–pituitary–ovarian axis, resulting in ovulatory dysfunction and sustained hyperandrogenism. No consensus guidelines exist regarding the diagnosis and management of PCOS in the pediatric population; however, because the syndrome is a diagnosis of exclusion, the clinical evaluation of girls suspected of having PCOS is aimed at excluding other causes of androgen excess and menstrual dysfunction. For the syndrome's management, emphasis is placed on lifestyle and symptom-directed treatment.

Abstract

Objectives

Psoriasis (PsO) is a common chronic T cell-mediated inflammatory disorder traditionally thought to manifest in the skin and joints (psoriatic arthritis, PsA). Recently, it has been shown that these patients have an increased risk for myocardial infarction and this was greater with increasing severity of psoriasis. Patients with psoriasis have reported to have cardiometabolic disturbances including obesity, insulin resistance, and dyslipidemia. This constellation of risk factors, referred to as the metabolic syndrome, increases the risk for atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes mellitus. The aim of this study was to determine the prevalence of metabolic syndrome in PsA.

Methods

In our study, we examined the records of 105 patients with PsA to determine the prevalence of metabolic syndrome in PsA. This was a retrospective analysis of the Sacramento Veterans Affairs database.

Results

Our results demonstrated an increased prevalence of the metabolic syndrome in patients with PsA (61/105 patients or 58.1%) compared to the 35.2 % reported for the Third National Health and Nutrition Examination Survery (NHANES III) data.

Conclusions

Thus, patients with PsA have a very high prevalence of metabolic syndrome, which predisposes them to an increased risk of both diabetes and ASCVD.

Abstract

Background

The metabolic syndrome is an interaction of risk factors that may lead to cardiovascular disease and type 2 diabetes.

Methods

Given the need for data in Puerto Rico, this cross-sectional study aimed to determine the association between demographic, lifestyles, and reproductive characteristics and the metabolic syndrome among a sample of women (N = 564) in the San Juan Metropolitan Area. The metabolic syndrome was defined based on the revised National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria.

Results

In multivariate logistic regression models, women aged 40–59 and 60–79 years were 3.03 [95% confidence interval (CI), 1.70, 5.40] and 7.05 (95% CI, 3.69, 13.49) times more likely, respectively, to have the metabolic syndrome as compared to those aged 21–39 years. A dose–response relationship was also observed between body mass index (BMI) and metabolic syndrome. Physical activity reduced the odds for metabolic syndrome [prevalence odds ratios (POR) = 0.64; 95% CI, 0.41, 1.01]; however, this association was marginally significant (P = 0.05). Among reproductive characteristics, only women who had a history of gestational diabetes (GDM) were 2.14 (95% CI, 1.02, 4.51) times more likely to have metabolic syndrome.

Conclusions

Consistent with previous studies, increased age and BMI, physical inactivity, and GDM are associated with the metabolic syndrome in this population. This information is relevant for the development of preventive interventions for the metabolic syndrome.

Abstract

Background

Hyperuricemia is associated with metabolic syndrome and has emerged as a marker for both type 2 diabetes and cardiovascular disease. We estimated the prevalence and lifestyle risk factors of hyperuricemia in middle-aged, urban Chinese men.

Methods

The study included 3,978 urban Chinese men 40–74 years of age from a population-based cohort study, the Shanghai Men's Health Study, who were free of type 2 diabetes at baseline and had provided fasting blood samples. Uric acid concentrations were measured by the uricase method. Hyperuricemia was defined as >7.0 mg/dL. Anthropometric measurements and information on lifestyle factors and disease history were collected by in-person interviews.

Results

One quarter of the study subjects had hyperuricemia. Participants with metabolic syndrome had a higher prevalence of hyperuricemia. Body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and weight gain (since age 20) were positively associated with the prevalence of hyperuricemia. Physical activity was inversely related to the prevalence of hyperuricemia. The odds ratios for hyperuricemia for quintiles of nonoccupational physical activity were 1.00, 0.80, 0.73, 0.75, and 0.57 (P trend <0.001). Participants with hyperuricemia were less likely to be current smokers, but were more likely to drink alcohol regularly. Beer consumption was associated with higher risk of hyperuricemia compared with consumption of wine or liquor.

Conclusions

In this representative sample of middle-aged, urban Chinese men, hyperuricemia is highly prevalent. Obesity, weight gain in adulthood, and alcohol intake were associated with a higher prevalence of hyperuricemia, whereas daily physical activity and smoking were inversely related to the prevalence of hyperuricemia.

Abstract

Background

Individuals from South Asia have high diabetes prevalence despite low body weight. We compared the prevalence of diabetes among South Asian Indians with other U.S. ethnic groups and explored correlates of diabetes.

Methods

This was a cross-sectional study of 150 South Asian Indians (ages 45–79) in California, using similar methods to the Multi-Ethnic Study of Atherosclerosis (MESA). Type 2 diabetes was classified by fasting plasma glucose (FPG) ≥126 mg/dL, 2-h postchallenge glucose ≥200 mg/dL, or use of hypoglycemic medication.

Results

A total of 29% of Asian Indians had diabetes, 37% had prediabetes, and 34% had normal glucose tolerance. After full adjustment for covariates, Indians still had significantly higher odds of diabetes compared to whites and Latinos, but not significantly different from African Americans and Chinese Americans in MESA: Indians [odds ratio (OR), 1.0], whites [OR, 0.29; 95% confidence interval (CI), 0.17–0.49], Latinos (OR, 0.59; CI, 0.34–1.00) African Americans (OR, 0.77; CI 0.45–1.32), Chinese Americans (OR, 0.78, CI, 0.45–1.32). Variables associated with prediabetes or diabetes among Indians included hypertension, fatty liver, visceral adiposity, microalbuminuria, carotid intima media thickness, and stronger traditional Indian beliefs.

Conclusions

Indian immigrants may be more likely to have diabetes than other U.S. ethnic groups, and cultural factors may play a role, suggesting that this is a promising area of research.