Louisa Y.F. Wong

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.

Prevalence of the Metabolic Syndrome in the United States National Health and Nutrition Examination Survey 1999–2002 According to Different Defining Criteria

The authors studied the prevalence of the metabolic syndrome in the 1999‐2002 National Health and Nutrition Examination Survey (NHANES) according to the World Health Organization, National Cholesterol Education Program (NCEP), and International Diabetes Federation (IDF) definitions. There was 92.9% agreement between the NCEP and IDF definitions. The IDF prevalence was higher (p=0.001) due to more men fulfilling its criteria than the NCEPs (39.9+1.7% vs. 33.6+1.6%; p=0.007). If central obesity were not a prerequisite, the IDF prevalence would increase slightly to 40.3+1.1 %. Subjects categorized as having the metabolic syndrome under IDF but not NCEP tended to be men, younger, and leaner. Their prevalence of self‐reported coronary heart disease was not significantly different from that of other metabolic syndrome patients. Whether waist circumference is a prerequisite does not affect the diagnosis of the metabolic syndrome in the United States. The IDF definition identifies additional individuals at risk for cardiovascular disease.

Haplotypes in the urotensin II gene and urotensin II receptor gene are associated with insulin resistance and impaired glucose tolerance.

We studied single nucleotide polymorphisms (SNPs) and haplotypes in the urotensin-II (UTS2) and urotensin-II receptor gene (UTS2R) in Hong Kong Chinese (224 hypertensive and 306 normotensive unrelated subjects) and their relation to hypertension and the metabolic syndrome. For UTS2, the GGT haplotype (-605G, 143G and 3836T) was associated with higher plasma level of U-II and insulin, and higher homeostasis model assessment of insulin resistance index and beta-cell function. For UTS2R, the AC haplotype (-11640A and -8515C) was associated with higher 2 h plasma glucose after a 75 g oral glucose load. Therefore, U-II and its receptor may play a role in insulin resistance.

Elevated serum alkaline phosphatase and peripheral arterial disease in the United States National Health and Nutrition Examination Survey 1999–2004

BACKGROUND Alkaline phosphatase (ALP) is elevated in peripheral arterial disease (PAD). We therefore examined the relationship of PAD with ALP and other liver enzymes in the United States National Health and Nutrition Examination Survey 1999-2004. METHODS The analysis included 5995 men and non-pregnant women aged >or=40 years with no missing data in variables of interest. PAD was defined as ankle-brachial blood pressure index (ABI) <0.90 in either leg. RESULTS Serum alkaline phosphatase (ALP) level was associated significantly with lower ABI after adjustment for confounding factors (p=0.019). No significant association of ABI with other liver enzymes was found. Serum ALP level increased with increasing age, body mass index, C-reactive protein, monocyte count, serum uric acid, lead, cadmium, and prevalence of hypercholesterolemia, diabetes, smoking, non-alcohol drinking, and cardiovascular diseases after adjusting for age, sex, race/ethnicity, and survey years (p<0.02). The highest quartile of serum ALP was associated with an odds ratio of 1.89 (95% confidence interval [CI]: 1.25-2.85) for PAD after adjustment for confounding factors (p for trend=0.023). In subjects with normal kidney function (glomerular filtration rate >90 ml/min/1.73 m(2)), the odds ratio increased to 4.22 (95% CI 1.45-12.35) (p=0.010). CONCLUSION Elevated serum ALP is correlated with PAD, independent of other traditional cardiovascular risk factors.

The role of urotensin II in the metabolic syndrome

Urotensin II is a potent vasoconstrictive peptide that mediates both endothelium-independent vasoconstriction and endothelium-dependent vasodilatation. Its plasma level correlates positively with body weight and is raised in diabetes, renal failure, hypertension, and other cardiovascular diseases including congestive heart failure and carotid atherosclerosis. It can inhibit glucose-induced insulin secretion, and genetic variants in urotensin II gene are associated with insulin resistance and type 2 diabetes. Urotensin II also affects lipid metabolism in fish and food intake in mice. Recent studies have also demonstrated a role of urotensin II in inflammation and endothelial dysfunction. These findings suggest a close relationship between urotensin II and at least some components of the metabolic syndrome, including hypertension, insulin resistance, hyperglycemia, and inflammation.

Association between plasma alkaline phosphatase and C-reactive protein in Hong Kong Chinese.

Abstract Background: Alkaline phosphatase (ALP) is a biomarker for hepatobiliary and skeletal diseases. It is also raised in sepsis. In atherosclerotic plaques, ALP is expressed. Similar to C-reactive protein (CRP), it may be another marker of systemic inflammation. Therefore, we investigated their association in a Hong Kong Chinese population. Methods: Plasma ALP and CRP were measured in 205 subjects (110 men, 95 women; age 55.2±11.6 years) in the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 cohort. Results: The blood levels of ALP and CRP were significantly correlated (r=0.30, p<0.001), which was due to a significant correlation in women (r=0.43, p<0.001). In a multivariate model, CRP level was related to ALP (β=0.18, p=0.008). After adjusting for confounding factors and other liver enzymes, the relationship between ALP and CRP remained significant in women (β=0.28, p=0.019), but in men, ALP was not an independent determinant of CRP levels. Conclusions: ALP may be another marker of systemic inflammation, especially in women. Whether it provides clinical information additional to CRP requires further study. Clin Chem Lab Med 2008;46:523–7.

Association of a Polymorphism in the Lipin 1 Gene With Systolic Blood Pressure in Men

BACKGROUND Lipin 1 plays a role in abdominal obesity, insulin resistance, and hypertriglyceridemia. The gene is located at 2p25.1, a susceptibility locus for hypertension. We studied the association of tagging single-nucleotide polymorphisms (SNPs) in the lipin 1 (LPIN1) gene with hypertension and blood pressure. METHODS Twelve tagging SNPs from the HapMap database were genotyped using Sequenom MassArray in 268 hypertensive subjects and 407 normotensive controls, of whom 268 matched the cases in age and sex. RESULTS None of the tagging SNPs were found to be associated with hypertension after correcting for multiple testing, although carriers of the minor allele of rs10520097 had nominally lower odds for hypertension (P = 0.014). After excluding subjects who were on antihypertensive medications, the minor allele of rs10495584 was nominally associated with lower mean systolic and diastolic blood pressures in men (121.1 +/- 14.2 and 76.3 +/- 10.2 mm Hg vs. 127.4 +/- 15.2 and 80.1 +/- 10.5 mm Hg, P = 0.002 and 0.007, respectively), but not in women (P > 0.05). The association of rs10495584 with systolic blood pressure in men remained significant after correcting for multiple testing and adjustment for age, waist circumference, insulin resistance, triglyceride, and high-density lipoprotein (HDL) cholesterol (beta = -0.158, P = 0.005). An analysis of statistically similar SNPs (ssSNPs) in the regions surrounding rs10495584 suggested that its effect may be caused by its high linkage disequilibrium (LD) with the SNP, rs11524, in which the major allele forms an exonic splicing silencer sequence. CONCLUSION Our study provides further evidence that lipin 1 may play a role in blood pressure regulation, especially in men.

Elevated Plasma Level of Soluble F11 Receptor/Junctional Adhesion Molecule-A (F11R/JAM-A) in Hypertension

BACKGROUND The F11 receptor (F11R, also known as junctional adhesion molecule A (JAM-A)) plays a role in the development of hypertension in rat. Genetic variants in the human F11R gene were demonstrated to influence systolic blood pressure. In the present study, we investigated the relationship between F11R and hypertension by examining the levels of a circulating soluble form of F11R (sF11R) in hypertensive patients. METHODS Plasma sF11R was measured by enzyme-linked immunosorbent assay in 152 hypertensive and 166 normotensive subjects in whom seven tagging single-nucleotide polymorphisms (SNPs) in the F11R gene had been genotyped. RESULTS Plasma sF11R levels were significantly higher in hypertensive subjects than in normotensive subjects (median (interquartile) range): 162.8 (85.5-293.2) vs. 116.5 (74.1-194.8) pg/ml, P = 0.004), which remained significantly higher after adjusting for age, sex, body mass index (BMI), and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.028). In stepwise multiple logistic regression, sF11R level (log-transformed) (P = 0.040), triglycerides (log-transformed) (P = 0.024), and HOMA-IR (log-transformed) (P < 0.001) were independently associated with hypertension. Plasma sF11R level correlated with systolic and diastolic blood pressures (r = 0.15, P < 0.001, and r = 0.13, P = 0.024, respectively). In stepwise multiple linear regression, hypertension (P = 0.013) and fibrinogen levels (P = 0.027) were significant independent predictors of sF11R level. A seven-locus haplotype, present in 2.1% of the subjects, was associated with higher sF11R level (P = 0.024). CONCLUSIONS These results further support a role of F11 receptor in the pathophysiology of human hypertension.

Adrenomedullin gene expression and levels in the cardiovascular system after treatment with lipopolysaccharide

To study the effect of septicaemia, the temporal changes in tissue adrenomedullin (AM) and preproAM mRNA levels were studied in the heart and blood vessels after lipopolysaccharide (LPS) injection. Radioimmunoassay and solution hybridization-RNase protection assays were used to follow the changes in AM and its mRNA levels respectively after intraperitoneal injection of 10 mg/kg LPS in rats. The preproAM mRNA levels increased at 1 h in the right atrium after LPS injection, while the AM contents decreased at 1 h in the left atrium. The preproAM mRNA levels increased at 3 and 6 h in the left ventricle, whereas it increased at 6 h in the right ventricles after LPS injection. There was an increase in preproAM mRNA levels at 1 and 3 h in the mesenteric artery, while AM levels were increased at 1, 3 and 6 h. However, there were no such changes in the thoracic aorta. There were also increases in tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6 in the heart, and in the mesenteric artery (TNF-alpha and IL-1beta) and in thoracic aorta (IL-1beta and IL-6). The present results suggest that the biosynthesis and secretion of AM may be increased in cardiovascular tissues of rats injected with LPS, and that AM may play multiple roles in inflammation.

Polymorphisms of the fibrinogen-beta gene are related to 2-hour glucose level after oral glucose tolerance test in Hong Kong Chinese

Fibrinogen, an acute phase protein, is an important inflammatory marker that is associated with cardiovascular diseases. We studied the association of three common human fibrinogen-β gene (FGB) variants, −455G>A, −249C>T, and −148C>T with glycemic parameters in 265 non-diabetic Hong Kong Chinese subjects. Both FGB variants, −455G>A and −148C>T were in complete linkage disequilibrium and were associated with higher levels of plasma fibrinogen and 2-h glucose after a 75-g oral glucose load (p <0.01). Carriers of FGB AC-haplotype, comprising the two nucleotide variants at positions −455 and −249, had higher fibrinogen level (2.64 ± 0.65 vs 2.42 ± 0.52 g/L, p = 0.002) and 2-h glucose after a 75-g oral glucose load (5.87 ± 1.14 vs 5.47 ± 1.22 g/L, p = 0.006). The associations were significant in men, but not women. In stepwise multiple regression analysis, AC-haplotype was independently associated with plasma fibrinogen level and 2-h glucose (p = 0.002 and 0.010 respectively). This suggests that fibrinogen may play a role in the development of impaired glucose tolerance.