Bernard M.Y. Cheung

Circulating Adipocyte–Fatty Acid Binding Protein Levels Predict the Development of the Metabolic Syndrome A 5-Year Prospective Study

Background— Adipocyte-fatty acid binding protein (A-FABP), a major cytoplasmic protein in adipocytes, plays a central role in the development of diabetes and atherosclerotic cardiovascular disease in experimental animals. We have previously shown that A-FABP is present in the bloodstream and that its circulating levels correlate with metabolic risk factors in a cross-sectional study. In the present study, we further evaluated the prospective association of A-FABP with the metabolic syndrome (MetS) as defined by the updated National Cholesterol Education Program criteria. Methods and Results— In the present study, 495 nondiabetic adults from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study were prospectively followed up for 5 years. The relationship of serum A-FABP with the MetS and its components was investigated. At baseline, high A-FABP levels were associated with the MetS (odds ratio, 4.0; 95% CI, 1.5 to 10.4; highest versus lowest sex-specific tertile, adjusted for age, body mass index, the homeostasis model assessment index for insulin resistance, C-reactive protein, and adiponectin, P=0.005). On long-term follow-up, subjects with higher baseline A-FABP levels had progressively worse cardiometabolic risk profile and increasing risk of the MetS. Among 376 subjects without the MetS at baseline, 50 had developed it at 5 years. Apart from the homeostasis model assessment index for insulin resistance (P=0.001), baseline A-FABP was the only independent predictor of the development of the MetS during the 5-year follow-up (odds ratio, 4.7; 95% CI, 1.8 to 11.9; highest versus lowest sex-specific tertile, P=0.001, adjusted for the homeostasis model assessment index for insulin resistance and body mass index). A-FABP was predictive of the MetS even after adjustment for each of its individual components. Conclusions— Circulating A-FABP predicts the development of the MetS independently of adiposity and insulin resistance.

Prevalence, Treatment, and Control of Diagnosed Diabetes in the U.S. National Health and Nutrition Examination Survey 1999-2004

PURPOSE This study aimed to examine the trends in prevalence, treatment, and control of diagnosed diabetes in United States adults 20 years of age or older. METHODS Data from the National Health and Nutrition Examination Survey 1999-2004 were used. Glycemic, blood pressure, and total cholesterol target levels were defined as having glycosylated hemoglobin <7.0%, blood pressure <130/80 mm Hg, and total cholesterol <200 mg/dL, respectively. RESULTS The prevalence of diagnosed diabetes was 7.8% in 2003-2004 and increased significantly in people aged 40-59 years, women, non-Hispanic whites, and obese people in the period 1999-2004. Although there was no significant change in the pattern of antidiabetic treatment, the age-adjusted percentage of people with diagnosed diabetes achieving glycemic and blood pressure target levels increased from 35.8% to 57.1% (p = 0.002) and from 35.7% to 48.3% (p = 0.04), respectively. However, there were only insignificant increases in percentages of those persons achieving total cholesterol target level (from 48.8% to 50.4%) and those achieving all 3 target levels (from 7.5% to 13.2%). CONCLUSIONS In 1999-2004, the prevalence of diagnosed diabetes increased significantly in some subgroups of the population. However, the increases in percentages of people with diabetes achieving glycemic and blood pressure targets are encouraging, although there is room for improvement.

Serum Adipocyte Fatty Acid–Binding Protein as a New Biomarker Predicting the Development of Type 2 Diabetes: A 10-year prospective study in a Chinese cohort

OBJECTIVE— Adipocyte fatty acid–binding protein (A-FABP) is abundantly expressed in adipocytes and plays a role in glucose homeostasis in experimental animals. We have previously shown that circulating A-FABP levels are associated with the metabolic syndrome, which confers an increased risk of type 2 diabetes. Here we investigated whether serum A-FABP levels could predict the development of diabetes in a 10-year prospective study. RESEARCH DESIGN AND METHODS— Baseline serum A-FABP levels were measured with an enzyme-linked immunosorbent assay in 544 nondiabetic subjects, recruited from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort, who were followed prospectively to assess the development of type 2 diabetes. The role of A-FABP in predicting the development of type 2 diabetes over 10 years was investigated using Cox regression analysis. RESULTS— At baseline, serum sex-adjusted A-FABP levels were higher in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) (P < 0.00001 versus normal glucose tolerance) and correlated positively with adverse cardiometabolic risk factors. Over 10 years, 96 subjects had developed type 2 diabetes. High baseline A-FABP was predictive of type 2 diabetes, independent of obesity, insulin resistance, or glycemic indexes (relative risk [RR] 2.25 [95% CI 1.40–3.65]; P = 0.001; above versus below sex-specific median). High A-FABP levels remained an independent predictor of type 2 diabetes in the high-risk IGT/IFG subgroup (adjusted RR 1.87 [1.12–3.15]; P = 0.018). CONCLUSIONS— Serum A-FABP was associated with glucose dysregulation and predicted the development of type 2 diabetes in a Chinese cohort.

Diabetes and Hypertension: Is There a Common Metabolic Pathway?

Diabetes and hypertension frequently occur together. There is substantial overlap between diabetes and hypertension in etiology and disease mechanisms. Obesity, inflammation, oxidative stress, and insulin resistance are thought to be the common pathways. Recent advances in the understanding of these pathways have provided new insights and perspectives. Physical activity plays an important protective role in the two diseases. Knowing the common causes and disease mechanisms allows a more effective and proactive approach in their prevention and treatment.

High Plasma Level of Fibroblast Growth Factor 21 Is an Independent Predictor of Type 2 Diabetes: A 5.4-year population-based prospective study in Chinese subjects

OBJECTIVE To investigate whether circulating levels of fibroblast growth factor 21 (FGF21), which previously has been shown to be elevated in obesity, could predict the development of type 2 diabetes in a 5.4-year, population-based, prospective study. RESEARCH DESIGN AND METHODS Baseline plasma FGF21 levels were measured using an enzyme-linked immunosorbent assay in 1,900 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). The prospective association of FGF21 with diabetes development over 5.4 years was analyzed using multiple logistic regression. RESULTS At baseline, plasma levels of FGF21 increased progressively with worsening dysglycemia from normal glucose tolerance, through prediabetes, to diabetes (global trend, P < 0.001). Of 1,292 subjects without diabetes at baseline, a high baseline FGF21 level was a strong independent predictor for diabetes development (odds ratio 1.792; P < 0.01), together with waist circumference and fasting plasma glucose levels. CONCLUSIONS Plasma FGF21 levels were significantly increased in subjects with prediabetes and diabetes and predicted the development of diabetes in humans.

Prevalence, Awareness, Treatment, and Control of Hypertension: United States National Health and Nutrition Examination Survey 2001–2002

The prevalence, awareness, treatment, and control of hypertension in the United States are analyzed using the National Health and Nutrition Examination Survey (NHANES) database covering the period 1988–2002. Mean body mass index was 26.1±0.1 kg/m2 in 1988–1991 and 27.9±0.2 kg/m2 in 2001–2002 (p<0.001). In the same period, the prevalence of diabetes mellitus increased from 5.0% to 6.5% (p=0.03). Diastolic blood pressure was 73.3±0.2 mm Hg in 1988–1991 and 71.6±0.4 mm Hg in 2001–2002 (p<0.001). Among the 18–39 years and 60 years and older age groups, the prevalence of hypertension increased significantly since 1988–1991. Multiple regression shows age, body mass index, and being non‐Hispanic black were significantly associated with hypertension. In the period 1988–2002, the percentage receiving treatment and the percentage with blood pressure controlled increased significantly. In 2001–2002, significantly more people with hypertension and diabetes reached a blood pressure target of <130/85 mm Hg. Overall, the control rates were low, especially among middle‐aged Mexican‐American men (8%).

Vitamin D Deficiency Is Associated with Depletion of Circulating Endothelial Progenitor Cells and Endothelial Dysfunction in Patients with Type 2 Diabetes

CONTEXT Vitamin D (Vit-D) deficiency is associated with type 2 diabetes mellitus (DM) and endothelial dysfunction. The relationship of Vit-D deficiency with circulating endothelial progenitor cells and endothelial dysfunction in type 2 DM patients nonetheless remains unclear. OBJECTIVE We aimed to investigate the cross-sectional association of Vit-D status with brachial flow-mediated dilation (FMD) and circulating endothelial progenitor cell (EPC) numbers in type 2 DM patients. DESIGN, SETTING, AND PARTICIPANTS We conducted a cross-sectional study of 280 patients (59% male, aged 68 ± 10 yr) with type 2 DM recruited in outpatient clinics during the winter period. MAIN OUTCOME MEASURE We measured serum 25-hydroxyvitamin D [25(OH)D] by an ELISA kit, circulating CD34+/kinase insert domain-containing receptor (KDR)+ and CD133+/KDR+ EPCs by flow cytometry and brachial artery FMD by vascular ultrasound, respectively. RESULTS The mean serum 25(OH)D concentration was 25.00 ± 9.17 ng/ml, and 34.3% of patients had Vit-D deficiency [25(OH)D < 20 ng/ml]. Serum 25(OH)D concentration had a significant correlation with hemoglobin A1c level [B = -0.018, 95% confidence interval (CI) -0.035 to -0.002, P = 0.032]. Patients with Vit-D deficiency status had significantly lower brachial FMD (mean difference -1.43%, 95% CI -2.31 to -0.55, P = 0.001) and CD133+/KDR+EPC counts (mean difference -0.12%, 95% CI -0.21 to -0.019, P = 0.022) than those with sufficient Vit-D status after adjustment for age, sex, and cardiovascular risk factors, including hemoglobin A1c levels. CONCLUSIONS Our results demonstrate that serum 25(OH)D status was significantly associated with brachial artery FMD and circulating CD133+/KDR+EPCs. This suggests that Vit-D deficiency might contribute to depletion of EPCs and endothelial dysfunction in patients with type 2 DM.

Serum Fibroblast Growth Factor-21 Levels Are Associated With Carotid Atherosclerosis Independent of Established Cardiovascular Risk Factors

Objective—Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects. Approach and Results—The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (r=0.32; P<0.001), but not in men (r=0.06; P=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (P=0.039), together with age (P<0.001) and hypertension (P=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted R2=35.8%; P<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (P=0.01). Conclusions—The present study is the first demonstration that elevated serum FGF21 levels are associated with carotid atherosclerosis in humans, independent of established risk factors including adverse lipid profiles and C-reactive protein. The role of FGF21 as a biomarker or therapeutic target of atherosclerotic diseases warrants further investigation.

Metabolic syndrome increases all‐cause and vascular mortality: the Hong Kong Cardiovascular Risk Factor Study

Objective  The metabolic syndrome has been associated with increased mortality in some Caucasian populations, but data in Asian populations are not available. We present data describing the association of the metabolic syndrome with mortality.

Three endothelial nitric oxide (NOS3) gene polymorphisms in hypertensive and normotensive individuals: meta-analysis of 53 studies reveals evidence of publication bias.

Background Studies on the relationship between endothelial nitric oxide (NOS3) gene variants and hypertension have been conflicting. To explore this hypothesis further, we performed a meta-analysis and re-evaluated the relationship between the three most widely studied NOS3 polymorphisms and hypertension status and blood pressure levels. Methods Data on 40 413 subjects from 53 studies were combined in five distinct meta-analyses, and heterogeneity and publication bias were explored. Results Heterogeneity was observed in all meta-analyses. By a random-effects model, carriers of the four 27-basepair repeat variable number of tandem repeats in intron 4 were associated with a 28% increase in the risk of hypertension compared with those homozygous for the 5 repeat: odds ratio (OR) 1.28, 95% confidence interval (CI) 1.11–1.47, P = 0.001. In Asian individuals, Asp allele carriers displayed a similar association: OR 1.28, 95% CI 1.06–1.54, P = 0.01, as well as a 2 mmHg increase in both systolic (P = 0.04) and diastolic (P = 0.009) blood pressure levels. Furthermore, meta-regression analysis indicated that the effect of the Glu298Asp genotype on the risk of hypertension might be dependent on total cholesterol status. No effect of the T-786C variant on hypertension was detected. There was evidence that such findings might be a result of selectively reporting/publishing positive reports. Conclusion Our results suggest that current data on the relationship between NOS3 variants and hypertension are subject not only to important heterogeneity but also to publication bias. Future research should preferentially focus on gene–environment interactions as well as haplotype analyses.