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Author(s): Sarah H. Bates [1]; Walter H. Stearns [1]; Trevor A. Dundon [1]; Markus Schubert [1]; Annette W. K. Tso [1]; Yongping Wang [2]; Alexander S. Banks [1]; Hugh J. [...]

Aims To investigate the usefulness of the additional measurement of HbA1c, compared with performing only the oral glucose tolerance test ( OGTT), in identifying participants at increased cardiometabolic risk, in an urban Chinese population. Methods All participants from the fourth visit of the population-based Hong Kong Cardiovascular Risk Factors Prevalence Study, without known diabetes, were included. All had their glycaemic status assessed by OGTT and HbA1c, according to American Diabetic Association 2010 criteria. Results Based on OGTT criteria alone, 3.5% of the study cohort ( N = 1300) had diabetes and 19.2% had prediabetes. Based on HbA1c criteria only, 6.2% had diabetes and 61.2% had prediabetes. The measurement of HbA1c, in addition to the OGTT, increased the proportion of participants with diabetes to 7.8% and with prediabetes to 65.3%. Subjects with prediabetes having raised HbA1c but normal glycaemia ( N = 600) had waist circumference, systolic blood pressure, fasting glucose, insulin resistance index ( HOMA- IR), Gutt Index and Framingham 10-year cardiovascular risk scores intermediate between those with both normal HbA1c and glycaemia ( N = 350), and those with impaired fasting glucose and/or impaired glucose tolerance ( N = 249; all P < 0.01). Conclusion The measurement of HbA1c in our population, in addition to the OGTT, results in the detection of a large number of participants with prediabetes having raised HbA1c but normal glycaemia who have a cardiometabolic risk profile intermediate between impaired fasting glucose and/or impaired glucose tolerance and normal participants, and would benefit from early lifestyle intervention. [ABSTRACT FROM AUTHOR]

Background: Adipose tissue inflammation and dysregulated adipokine secretion are implicated in obesity-related insulin resistance and type 2 diabetes. We evaluated the use of serum adiponectin, an anti-inflammatory adipokine, and several proinflammatory adipokines, as biomarkers of diabetes risk and whether they add to traditional risk factors in diabetes prediction. Methods: We studied 1300 non-diabetic subjects from the prospective Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). Serum adiponectin, tumor necrosis factor-alpha receptor 2 (TNF-a R2), interleukin-6 (IL-6), adipocyte-fatty acid binding protein (A-FABP) and high-sensitivity C-reactive protein (hsCRP) were measured in baseline samples. Results: Seventy-six participants developed diabetes over 5.3 years (median). All five biomarkers significantly improved the log-likelihood of diabetes in a clinical diabetes prediction (CDP) model including age, sex, family history of diabetes, smoking, physical activity, hypertension, waist circumference, fasting glucose and dyslipidaemia. In ROC curve analysis, ''adiponectin + TNF-a R2'' improved the area under ROC curve (AUC) of the CDP model from 0.802 to 0.830 (P = 0.03), rendering its performance comparable to the ''CDP + 2-hour post-OGTT glucose'' model (AUC = 0.852, P = 0.30). A biomarker risk score, derived from the number of biomarkers predictive of diabetes (low adiponectin, high TNF-a R2), had similar performance when added to the CDP model (AUC = 0.829 [95% CI: 0.808-0.849]). Conclusions: The combined use of serum adiponectin and TNF-α R2 as biomarkers provided added value over traditional risk factors for diabetes prediction in Chinese and could be considered as an alternative to the OGTT. [ABSTRACT FROM AUTHOR]

Lipocalin-2 is recently recognized as a biomarker of obesity and inflammation, which are both risk factors for hypertension. We therefore investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding lipocalin-2 ( LCN2) with elevated blood pressure (BP) in Hong Kong Chinese. Five tagging SNPs were genotyped in 1936 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) with a median follow-up time of 6.4 years. Elevated BP was defined as ≥130/85 mmHg or taking anti-hypertensive medication. Haplotype GGTCC was associated with elevated BP at follow-up after adjusting for age and sex (odds ratio (OR) [95%% confidence interval (CI)] == 1.17 [1.01-1.36], P == 0.031). Haplotype GGTCC was also an associated plasma CRP level 11.7%% (95%% CI: 2.6-25.9%%) higher among subjects with elevated BP after adjusting for age and sex ( P == 0.036). Among 1381 subjects without elevated BP at baseline, 321 subjects developed elevated BP at follow-up. Haplotype GGTCC was associated with the development of elevated BP at follow-up after adjusting for baseline age, sex, systolic blood pressure (SBP), and follow-up duration (OR [95%% CI] == 1.30 [1.06-1.58], P == 0.011). Among subjects not taking anti-hypertensive medication, carriers of the haplotype GGTCC had higher SBP than noncarriers (119.7 ± 16.4 mmHg vs. 117.9 ± 17.3 mmHg, P == 0.043). Our findings suggest, for the first time, that genetic variants in LCN2 may affect BP. Further studies on the role of lipocalin-2 in BP regulation are warranted. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) in the apolipoprotein A5 gene ( APOA5) are associated with hypertriglyceridaemia in our population. We studied the associations of SNPs in APOA5 with the metabolic syndrome (MetS) in the Hong Kong and Guangzhou Chinese. We genotyped five tagging SNPs in 1330 unrelated subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort with follow-up after a median interval of 6·4 years; 1952 subjects from the Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort were used to replicate the findings. The MetS was defined according to the consensus criteria proposed jointly by several organizations in 2009. The SNP rs662799 (−1131T>C) was associated with the MetS (odds ratio = 1·47, P = 0·00082) and the number of its components present (regression coefficient = 0·204, P = 4·6 × 10) after adjusting for age, sex, smoking, drinking and education in Hong Kong subjects at baseline. Similar association of this SNP was found in Hong Kong subjects at follow-up ( P = 0·010 and 0·00021, respectively) and in Guangzhou subjects ( P = 0·0041 and 0·017, respectively). The association of rs662799 with the number of the MetS components was significant regardless of age, sex, obesity and alcohol drinking, but almost disappeared after further adjusting for plasma triglycerides. Our results showed that the −1131T>C polymorphism in APOA5 was associated with the MetS because of its strong effect on plasma triglycerides. This may partly explain the higher cardiovascular risk in people with this polymorphism. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple beneficial effects on glucose homeostasis and insulin sensitivity in animal models. This study aimed to investigate the relationship between its serum levels and various cardiometabolic parameters in humans. RESEARCH DESIGN AND METHODS--A newly developed immunoassay was used to measure serum FGF21 levels in 232 Chinese subjects recruited from our previous cross-sectional studies. The mRNA expression levels of FGF21 in the liver and adipose tissues were quantified by real-time PCR. RESULTS--Serum FGF21 levels in overweight/obese subjects were significantly higher than in lean individuals. Serum FGF21 correlated positively with adiposity, fasting insulin, and triglycerides but negatively with HDL cholesterol, after adjusting for age and BMI. Logistic regression analysis demonstrated an independent association between serum FGF21 and the metabolic syndrome. Furthermore, the increased risk of the metabolic syndrome associated with high serum FGF21 was over and above the effects of individual components of the metabolic syndrome. Our in vitro study detected a differentiation-dependent expression of FGF21 in 3T3-L1 adipocytes and human adipocytes. In db/db obese mice, FGF21 mRNA expression was markedly increased in both the liver and adipose tissue compared with that in their lean litterumates. Furthermore, FGF21 expression in subcutaneous fat correlated well with its circulating concentrations in humans. CONCLUSIONS--FGF21 is a novel adipokine associated with obesity-related metabolic complications in humans. The paradoxical increase of serum FGF21 in obese individuals, which may be explained by a compensatory response or resistance to FGF21, warrants further investigation. Diabetes 57:1246-1253, 2008 [ABSTRACT FROM AUTHOR]

Hypertension is an important risk factor for cardiovascular disease, which is the leading cause of death in women. We, therefore, analyzed gender-specific trends in the control of blood pressure and prevalence of 5 other cardiovascular risk factors (central obesity, elevated total cholesterol, low high-density lipoprotein cholesterol, hyperglycemia, and smoking) among adults with diagnosed hypertension in the United States. We included 3475 participants aged >or=18 years with diagnosed hypertension in the National Health and Nutrition Examination Survey 1999-2004. The age-adjusted prevalence of uncontrolled blood pressure was 50.8+/-2.1% in men and 55.9+/-1.5% in women, which were not significantly different and had not changed significantly with time. Central obesity, elevated total cholesterol level, and low high-density lipoprotein cholesterol were significantly more prevalent in women than in men (79.0+/-1.0%, 61.3+/-1.6%, and 39.7+/-1.6% versus 63.9+/-1.6%, 48.1+/-1.8%, and 35.6+/-1.7%, respectively; P<0.05). The age-adjusted proportion with >or=3 of the 6 risk factors studied was higher in women than in men (52.5+/-1.4% versus 40.9+/-1.8%; P<0.001), and this proportion decreased significantly by 7.7% in women from 1999-2000 to 2003-2004 (P<0.05) but not in men. Our study shows that blood pressure control in women with diagnosed hypertension was not significantly inferior compared with men and had not changed significantly in 1999-2004. However, women had higher prevalence of other concomitant cardiovascular risk factors. Although there is room for improvement in blood pressure control, our study has highlighted the importance of addressing concomitant cardiovascular risk factors in women with hypertension. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Low circulating levels of adiponectin, an adipokine with insulin-sensitizing, antiatherogenic, and anti-inflammatory properties, are found in hypertensive patients. Adiponectin replenishment ameliorated hypertension in adiponectin-deficient mice or obese, hypertensive mice with hypoadiponectinemia, suggesting an etiologic role of adiponectin in hypertension. We aimed to determine, in this 5-year prospective study, whether hypoadiponectinemia could predict the development of hypertension in a nondiabetic Chinese cohort. A total of 577 subjects (249 men and 328 women) were recruited from the population-based Hong Kong Cardiovascular Risk Factor Prevalence Study and prospectively followed up for 5 years. The relationship of serum adiponectin with the development of hypertension (sitting blood pressure >or=140/90 mm Hg) was investigated in a nested case-control study consisting of 70 subjects who had developed hypertension on follow-up and 140 age- and sex-matched control subjects who were normotensive both at baseline and at year 5. At baseline, serum adiponectin level in the lowest sex-specific tertile was more likely to be associated with hypertension (P=0.003 versus the highest tertile, after adjusting for age, body mass index, fasting insulin, and high-sensitivity C-reactive protein). At year 5, baseline serum adiponectin was a significant independent predictor of incident hypertension in the nested case-control study (P=0.015; age adjusted), together with mean arterial pressure (P<0.001), high-sensitivity C-reactive protein (P=0.018), and body mass index (P=0.004). Normotensive subjects with baseline serum adiponectin levels in the lowest sex-specific tertile had an increased risk of becoming hypertensive (adjusted odds ratio: 2.76; 95% CIs: 1.06 to 7.16; P=0.037 versus highest tertile). Our data suggest that hypoadiponectinaemia may be involved in the pathogenesis of hypertension in humans. [ABSTRACT FROM AUTHOR]

The article focuses on the findings of "Hypoadiponectinemia as a Predictor for the Development of Hypertension: A 5-Year Prospective Study," by Wing-Sun Chow, Nelson M. S. Wat, Sidney Tam et al. The study aims to investigate the relationship of serum adiponectin with the development of hypertension. It mentions the effect of adiponectin on vasoreactivity. It details the methods used for the study.

Serum leptin levels are decreased in patients with acromegaly and rise after GH is normalized by surgical treatment. We have evaluated the effect of Sandostatin® LAR® on leptin levels in acromegalic patients since there are recent data to suggest that somatostatin, in addition to its GH lowering effect, also reduces serum leptin levels in humans. Nineteen patients with active acromegaly were studied. Eleven patients received monthly injection of Sandostatin® LAR® and eight patients underwent transsphenoidal surgery. Serum concen-trations of leptin, GH, IGF-1 and insulin were measured before and after treatment. Serum leptin concentrations were lower in patients with active acromegaly than controls matched for age, sex and body mass index (BMI) [2·79 µg/l (2·60) vs. 4·41 µg/l (5·07); median (inter-quartile range); P < 0·01]. A positive correlation between serum leptin concentrations and BMI was observed in the controls (r = 0·46, P < 0·05) but not in the acromegalic patients before treatment (r = 0·32, ns). In the group of patients treated with Sandostatin® LAR®, a marked reduction in GH and IGF-1 was achieved by week 8 and GH and IGF-1 remained suppressed throughout the 6 months of treatment. There was no change in BMI. A significant increase in leptin levels only became evident after 6 months of treatment [2·99 µg/l (2·60) vs. 4·21 µg/l (3·84), P < 0·05]. Leptin levels also significantly increased after transsphenoidal surgery [3·05 µg/l (5·73) vs. 5·19 µg/l (4·93), P < 0·05]. The positive correlation between serum leptin concentrations and BMI was restored in acromegalic patients both after treatment with Sandostatin® LAR® (r = 0·62, P < 0·05) and after surgery (r = 0·81, P < 0·05). Leptin concentrations were decreased in patients with active acromegaly and lowering GH by either Sandostatin® LAR® or transsphenoidal surgery led to an increase in leptin concentrations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To investigate whether circulating levels of fibroblast growth factor 21 (FGF21), which previously has been shown to be elevated in obesity, could predict tire 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 FGF2f levels were significantly increased in subjects with prediabetes and diabetes and predicted the development of diabetes in humans. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To compare the use of GHb and fasting plasma glucose (FPG) to define the metabolic syndrome (MetS). RESEARCH DESIGN AND METHODS-- Data from the U.S. National Health and Nutrition Examination Survey 1999-2006 were used. MetS was defined using the consensus criteria in 2009. Raised blood glucose was defined as either FPG ≥100 mg/dl (5.6 mmol/1) or GHb ≥5.7%. RESULTS -- In 2003-2006, there was 91.3% agreement between GHb and FPG when either was used to define MetS. The agreement was good irrespective of age, sex, race/ethnicity, BMI, and diabetes status (≥87.4%). Similar results were found in 1999-2002. Among subjects without diabetes, only the use of GHb alone, but not FPG, resulted in significant association with cardiovascular diseases (odds ratio 1.45, P = 0.005). CONCLUSIONS -- Using GHb instead of FPG to define MetS is feasible. It also identifies individuals with increased cardiovascular risk. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- To investigate the relationships of serum adipocyte fatty acid-binding protein (A-FABP) and epidermal fatty acid-binding protein (E-FABP) with renal dysfunction and macrovascular complications in type 2 diabetic patients. RESEARCH DESIGN AND METHODS-- The associations of serum A-FABP and E-FABP with markers of renal function, nephropathy staging, and macrovascular complications were examined in 237 type 2 diabetic patients. RESULTS -- Serum A-FABP and E-FABP correlated significantly with serum creatinine, mean albumin excretion rate, and glomerular filtration rate (all P < 0.001) and were independently associated with diabetic nephropathy staging (P = 0.001 and P < 0.05, respectively). Circulating levels of both types of FABP were increased (P < 0.01) in subjects with macrovascular complications. Serum A-FABP was independently associated with macrovascular complications (odds ratio 2.92 [95% CI 1.42-6.01]; P = 0.004). CONCLUSIONS -- Serum A-FABP and E-FABP might be novel serum biomarkers for evaluating the progression of nephropathy and its cardiovascular risk in type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between raised blood pressure and dysglycemia.Research Design and Methods: We studied the association between raised blood pressure and dysglycemia in 1,862 subjects in the Hong Kong Cardiovascular Risk Factor Prevalence Study cohort. We determined the factors predicting the development of diabetes and hypertension in 1,496 subjects who did not have either condition at baseline.Results: Diabetes and hypertension were both related to age, obesity indexes, blood pressure, glucose, HDL cholesterol, and triglycerides. Of subjects with diabetes, 58% had raised blood pressure. Of subjects with hypertension, 56% had dysglycemia. BMI and blood glucose 2 h after a 75-g oral glucose load were independent predictors of new-onset diabetes. Age, systolic blood pressure, and 2-h glucose were independent predictors of new-onset hypertension. BMI, systolic blood pressure, and 2-h glucose were independent predictors of the development of diabetes and hypertension together.Conclusions: Diabetes and hypertension share common etiological factors. Patients with diabetes or hypertension should be screened and managed for the precursor of the other condition. [ABSTRACT FROM AUTHOR]

A correction to the article "Serum FGF21 Levels Are Increased in Obesity and Are Independently Associated With the Metabolic Syndrome in Humans," by Xinmei Zhang, Dennis C. Y. Yeung, and colleagues that was published in a 2008 issue is presented.