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1.  Associations of serum uric acid with cardiovascular events and mortality in moderate chronic kidney disease 
Nephrology Dialysis Transplantation  2008;24(4):1260-1266.
Background. It is unclear whether the presence of kidney disease modifies the associations of uric acid with cardiovascular events and death.
Methods. In the limited access, public use Atherosclerosis Risk In Communities (ARIC) database, associations of serum uric acid levels with cardiovascular events and death were analysed using a parametric proportional hazards model and the modification of these associations by the presence of CKD was assessed using a likelihood ratio test.
Results. Of the 15 366 ARIC participants included in this analysis, 461 had CKD (eGFR <60 ml/min/1.73 m2). In both non-CKD and CKD sub-groups, participants with hyperuricaemia (≥ 7 mg/dl in men and ≥ 6 mg/dl in women) compared to those with normal serum uric acid levels had higher waist circumference and fasting serum insulin levels. In the entire cohort, in a multivariate parametric proportional hazards model, each mg/dl increase in serum uric acid was associated with an increased hazard of cardiovascular events (HR 1.09, 95% CI 1.05–1.12) and death. A multiplicative interaction term of serum uric acid and CKD when added to the above models was significant (P < 0.001). The likelihood ratio test of the models with and without the interaction term was also significant (P < 0.001). In the non-CKD population, a multivariate analysis after adjusting for comorbidities and metabolic syndrome showed a significant association between hyperuricaemia and mortality (HR 1.18, 95% CI 1.04–1.33) but not for cardiovascular events (HR 1.07, 95% CI 0.96–1.19). In the CKD population, the association was not significant for both mortality and cardiovascular events.
Conclusion. We conclude that hyperuricaemia is associated with insulin resistance and mortality in the non-CKD population. The presence of CKD attenuates the associations of uric acid with mortality. Interventional studies are warranted to establish the biological role of hyperuricaemia in mortality in non-CKD and CKD populations.
PMCID: PMC2721426  PMID: 19033255
cardiovascular events; chronic kidney disease; insulin resistance; mortality; uric acid
2.  Uric Acid as a Risk Factor for Cardiovascular Disease and Mortality in Overweight/Obese Individuals 
PLoS ONE  2013;8(3):e59121.
The predictive value of serum uric acid (SUA) for adverse cardiovascular events among obese and overweight patients is not known, but potentially important because of the relation between hyperuricaemia and obesity.
The relationship between SUA and risk of cardiovascular adverse outcomes (nonfatal myocardial infarction, nonfatal stroke, resuscitated cardiac arrest or cardiovascular death) and all-cause mortality, respectively, was evaluated in a post-hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial. Participants enrolled in SCOUT were obese or overweight with pre-existing diabetes and/or cardiovascular disease (CVD). Cox models were used to assess the role of SUA as an independent risk factor.
9742 subjects were included in the study; 83.6% had diabetes, and 75.1% had CVD. During an average follow-up time of 4.2 years, 1043 subjects had a primary outcome (myocardial infarction, resuscitated cardiac arrest, stroke, or cardiovascular death), and 816 died. In a univariate Cox model, the highest SUA quartile was associated with an increased risk of cardiovascular adverse outcomes compared with the lowest SUA quartile in women (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.20–2.10). In multivariate analyses, adjusting for known cardiovascular risk factors the increased risk for the highest SUA quartile was no longer statistically significant among women (HR: 0.99; 95% CI: 0.72–1.36) nor was it among men. Analyses of all-cause mortality found an interaction between sex and SUA. In a multivariate Cox model including women only, the highest SUA quartile was associated with an increased risk in all-cause mortality compared to the lowest SUA quartile (HR: 1.51; 95% CI: 1.08–2.12). No relationship was observed in men (HR: 1.06; 95% CI: 0.82–1.36).
SUA was not an independent predictor of cardiovascular disease and death in these high-risk overweight/obese people. However, our results suggested that SUA was an independent predictor of all-cause mortality in women.
PMCID: PMC3606441  PMID: 23533601
3.  A prospective study of gout in New Zealand Maoris. 
Annals of the Rheumatic Diseases  1978;37(5):466-472.
Results are reported from the first prospective study of gout in New Zealand Maoris based on a sample of 388 males and 378 females. At baseline, high mean levels of serum uric acid (SUA) were found, 0.422 +/- 0.092 mmol/1 (7.05 +/- 1.54 mg/100 ml) in males and 0.350 +/- 0.091 mmol/1 (5.85 +/- 1.52 mg/100 ml) in females. On the basis of traditional criteria (SUA above 0.42 mmol/1 (7.0 mg/100 ml) in males and above 0.36 mmol/1 (6.0 mg/100 ml) in females) the prevalence of hyperuricaemia was 49% in males and 42% in females. The baseline prevalence of gout (8.8% for males and 0.8% for females) and the subsequent 11-year incidence rates (10.3% for males and 4.3% for females) are discussed in relation to specified SUA classes. When traditional, sex-specific criteria for hyperuricaemia were used, no relationship was found between the prevalence of hyperuricaemia and the incidence of gout. There was, however, a sharp increase in the incidence rate of gout in both sexes when SUA levels were above 0.48 mmol/1 (8.0 mg/100 ml). In subjects with a baseline SUA above this level, the age-standardised 11-year incidence rate of gout was 29.1% for males and 37.2% for females. A previously unreported relationship linking muscle size to the incidence of gout in males is presented as a major finding of the study. Other risk factors associated with gout were body mass and blood pressure.
PMCID: PMC1000277  PMID: 718280
4.  Hyperthyroid and Hypothyroid Status Was Strongly Associated with Gout and Weakly Associated with Hyperuricaemia 
PLoS ONE  2014;9(12):e114579.
The aim of this study was to estimate the risk of hyperuricaemia and gout in people with hypothyroid or hyperthyroid status.
This study analyzed data from individuals who participated in health screening programs at Chang Gung Memorial Hospital in northern Taiwan (2000–2010). Participants were categorized as having euthyroid, hypothyroid, or hyperthyroid status according to their thyroid-stimulating hormone (TSH) levels. Multinomial logistic regression models were used to calculate the odds ratios (95% CI) for hyperuricaemia and gout in participants with thyroid dysfunction compared to euthyroid participants.
A total of 87,813 (euthyroid, 83,502; hypothyroid, 1,460; hyperthyroid, 2,851) participants were included. The prevalence of hyperuricaemia was higher in hyperthyroid subjects (19.4%) than in euthyroid subjects (17.8%) but not in hypothyroid subjects (19.3%). The prevalence of gout was significantly higher in both hypothyroid (6.0%) and hyperthyroid (5.3%) subjects than in euthyroid subjects (4.3%). In men, hypothyroid or hyperthyroid status was not associated with hyperuricaemia. However, hypothyroid or hyperthyroid status was associated with ORs (95% CI) of 1.47 (1.10–1.97) and 1.37 (1.10–1.69), respectively, for gout. In women, hypothyroid status was not associated with hyperuricaemia or gout. However, hyperthyroid status was associated with ORs (95% CI) of 1.42 (1.24–1.62) for hyperuricaemia and 2.13 (1.58–2.87) for gout.
Both hyperthyroid and hypothyroid status were significantly associated with gout and weakly associated with hyperuricaemia. A thyroid function test for gout patients may by warranted.
PMCID: PMC4259336  PMID: 25486420
5.  Hyperuricaemia, chronic kidney disease, and outcomes in heart failure: potential mechanistic insights from epidemiological data 
European Heart Journal  2011;32(6):712-720.
To determine if the association between hyperuricaemia and poor outcomes in heart failure (HF) varies by chronic kidney disease (CKD).
Methods and results
Of the 2645 systolic HF patients in the Beta-Blocker Evaluation of Survival Trial with data on baseline serum uric acid, 1422 had hyperuricaemia (uric acid ≥6 mg/dL for women and ≥8 mg/dL for men). Propensity scores for hyperuricaemia, estimated for each patient, were used to assemble a matched cohort of 630 pairs of patients with and without hyperuricaemia who were balanced on 75 baseline characteristics. Associations of hyperuricaemia with outcomes during 25 months of median follow-up were examined in all patients and in those with and without CKD (estimated glomerular filtration rate of <60 mL/min/1.73 m2). Hyperuricaemia-associated hazard ratios (HRs) and 95% confidence intervals (CI) for all-cause mortality and HF hospitalization were 1.44 (1.12–1.85, P = 0.005) and 1.27 (1.02–1.58, P = 0.031), respectively. Hazard ratios (95% CIs) for all-cause mortality among those with and without CKD were 0.96 (0.70–1.31, P = 0.792) and 1.40 (1.08–1.82, P = 0.011), respectively (P for interaction, 0.071), and those for HF hospitalization among those with and without CKD were 0.99 (0.74–1.33, P = 0.942) and 1.49 (1.19–1.86, P = 0.001), respectively (P for interaction, 0.033).
Hyperuricaemia has a significant association with poor outcomes in HF patients without CKD but not in those with CKD, suggesting that hyperuricaemia may predict poor outcomes when it is primarily a marker of increased xanthine oxidase activity, but not when it is primarily due to impaired renal excretion of uric acid.
PMCID: PMC3056205  PMID: 21199831
Heart failure; Hyperuricaemia; Chronic kidney disease; Outcomes
6.  Serum Uric Acid Level and Diverse Impacts on Regional Arterial Stiffness and Wave Reflection 
Both increased arterial stiffness and hyperuricaemia are associated with elevated cardiovascular risks. Little is known about the relations of serum uric acid (UA) level to regional arterial stiffness and wave reflection. The aim of the study was to investigate the gender-specific association of serum UA and indices of arterial function in a community-based investigation in China.
Cross-sectional data from 2374 adults (mean age 58.24 years) who underwent routine laboratory tests, regional pulse wave velocity (PWV) and pulse wave analysis measurements were analyzed in a gender-specific manner. None of the participants had atherosclerotic cardiovascular disease, chronic renal failure, systemic inflammatory disease, gout, or were under treatment which would affect serum UA level.
Men had higher serum UA level than women. Subjects with hyperuricaemia had significantly higher carotid-ankle PWV in both genders (P< 0.05), and the carotid-femoral PWV (PWVc-f) was higher in women (P< 0.001) while the augmentation index was marginally lower in men (P = 0.049). Multiple regression analysis showed that serum UA was an independent determinant only for PWVc-f in women (β = 0.104, P = 0.027) when adjusted for atherogenic confounders. No other independent relationship was found between UA level and other surrogates of arterial stiffness.
Serum UA levels are associated with alterations in systemic arterial stiffness that differ in men and women. Women might be more susceptible to large vascular damage associated with hyperuricaemia.
PMCID: PMC3469023  PMID: 23113222
Arterial stiffness; Gender; Public health; Pulse wave velocity; Uric acid; Wave reflection
7.  Prevalence and determinants of obesity - a cross-sectional study of an adult Northern Nigerian population 
Obesity is assuming an epidemic dimension globally. It is important to appreciate factors associated with the disease so that a holistic approach can be taken in tackling the rising burden. The objective of this study was to determine the prevalence of overweight and obesity and the factors independently associated with obesity in an urban Nigerian population.
A cross-sectional study of 300 healthy adult subjects was conducted in the urban city of Katsina, northern Nigeria. Relevant sociodemographic and clinical information were obtained. Screening for obesity was done using the Body Mass Index while relevant laboratory investigations were conducted. Univariate and multivariate logistic regression analyses were performed to determine the predictors of obesity.
Overweight and obesity was found in 53.3% and 21.0% respectively with a significantly higher prevalence in females compared to males (overweight: 62.0% vs 41.9%, p < 0.001; obesity: 29.8% vs 9.3%, p < 0.001). In univariate analysis, the odds of obesity were higher in women and in the presence of hypertension, hypercholesterolaemia and hyperuricaemia. However, in multivariate analysis, factors independently associated with obesity were female sex (OR 6.119, 95% CI 2.705-13.842, p < 0.001), hypercholesterolaemia (OR 2.138, 95% CI 1.109-4.119, p = 0.023) and hyperuricaemia (OR 2.906, 95% CI 1.444-5.847, p = 0.003).
There is a high prevalence of obesity in northern Nigeria and women are significantly more affected. The high prevalence is independently associated with female sex, hypercholesterolaemia and hyperuricaemia. Public health education is urgently needed in order to reduce this burden and prevent other non-communicable cardiovascular disorders.
PMCID: PMC3055810  PMID: 21362196
8.  Serum uric acid levels are associated with hypertension and metabolic syndrome but not atherosclerosis in Chinese inpatients with type 2 diabetes 
Journal of Hypertension  2015;33(3):482-490.
Serum uric acid (SUA) is associated with many cardiovascular risk factors such as hypertension (HTN) and metabolic syndrome (MetS). However, the association of SUA with atherosclerosis remains controversial. Our aim was to investigate the relationships of SUA with HTN, MetS and atherosclerosis in Chinese inpatients with type 2 diabetes.
This cross-sectional study was performed with a sample of 2388 hospitalized Chinese patients with type 2 diabetes. Both carotid and lower limb atherosclerotic lesions were assessed for intima–media thickness, plaque and stenosis by Doppler ultrasound. Atherosclerotic plaque and stenosis were defined as the presence of either carotid or lower limb plaques and stenoses, respectively.
There were significant increases in the prevalence of both HTN and MetS across the SUA quartiles (HTN: 43.4, 49.6, 56.1 and 66.3% for the first, second, third and fourth quartiles, respectively, P < 0.001; MetS: 59.9, 68.8, 74.7 and 84.9% for the first, second, third and fourth quartiles, respectively, P < 0.001). A fully adjusted multiple logistic regression analysis revealed that SUA quartile was independently associated with the presence of HTN (P = 0.001) and MetS (P = 0.006). The prevalence of atherosclerotic plaque and stenosis was obviously higher in the patients with either HTN or MetS than in those without HTN or MetS. However, there was no significant association of SUA quartile with the presence of atherosclerotic lesions.
SUA levels were closely associated with HTN and MetS, but not with atherosclerosis in type 2 diabetes. Our findings strongly suggest that, in select populations such as those with type 2 diabetes, the role of uric acid in atherosclerosis might be attributable to other cardiovascular risk factors, such as HTN and MetS.
PMCID: PMC4309490  PMID: 25405332
atherosclerosis; hypertension; hyperuricemia; metabolic syndrome; type 2 diabetes; uric acid
9.  Serum Uric Acid and Non-Alcoholic Fatty Liver Disease in Non-Diabetic Chinese Men 
PLoS ONE  2013;8(7):e67152.
Increased serum uric acid (SUA) levels may be involved in the development of non-alcoholic fatty liver disease (NAFLD) in men presenting with metabolic syndrome (MetS) and/or insulin resistance. We aimed to determine the independent relationship between SUA and NAFLD in non-diabetic Chinese male population, and to explore the determinants of SUA levels among indexes of adiposity, lipid, and genotypes pertaining to triglycerides metabolism, inflammation, oxidative stress, and SUA concentrations. A total of 1440 men, classified depending on the presence of ultrasonographically detected NAFLD, underwent a complete healthy checkup program. Genotypes were extracted from our previously established genome-wide association study database. After adjusting for age, smoking, drinking, body mass index, homeostasis model assessment of insulin resistance, C-reactive protein, creatinine, alanine aminotransferase (ALT) and components of metabolic syndrome, the odds ratio for NAFLD, comparing the highest with the lowest SUA quartile, was 2.81 (95% confidence interval 1.66–4.76). A stepwise multivariate linear regression analysis (R2 = 0.238, P<0.001) retained age, waist circumference, serum creatinine, triglycerides, the Q141K variant in ABCG2 (rs2231142) and NAFLD as significant predictors of SUA levels (all P<0.001). Besides, ALT and Met196Arg variant in TNFRSF1B (rs1061622) additionally associated with SUA among individuls with NAFLD. Our data suggest that in Chinese men, elevated SUA is significantly associated with NAFLD, independent of insulin resistance and other metabolic disorders, such as central obesity or hypertriglyceridemia. Meanwhile, among subjects with NAFLD, index of liver damage, such as elevated ALT combined with genetic susceptibility to inflammation associated with increased SUA levels.
PMCID: PMC3720733  PMID: 23935829
10.  Gout is on the increase in New Zealand 
OBJECTIVE—To determine the current prevalence of hyperuricaemia and gout in New Zealand Maori and Europeans for comparison with previous studies.
METHODS—342 Maori and 315 European men and women aged 15 years and older were studied by personal interview and a musculoskeletal system examination. The 1977 ARA criteria for gout in a survey setting were used and serum uric acid was determined by a uricase method. The data were compared with those of previous New Zealand studies.
RESULTS—Gout was significantly more common in Maori (6.4%) than Europeans (2.9%) (Δ = 3.6%, 95% confidence interval 0.4 to 6.8) and in Maori men (13.9%) than in European men (5.8%) (Δ = 8.1%, 95% CI 1.0 to 15.2). Hyperuricaemia was significantly more common in Maori men (27.1%) than in European men (9.4%) (Δ = 17.7%, 95% CI 8.3 to 27.1) and in Maori women (26.6%) than in European women (10.5%) (Δ = 16.1%, 95% CI 8.5 to 23.7). At least 14% of hyperuricaemic individuals were receiving diuretics, of whom 78% were women. Comparison with previous studies shows that the prevalence of gout has increased in both Maori and Europeans, particularly in men. In Maori men the prevalence of gout has risen from 4.5-10.4% previously to 13.9%, and in European men from 0.7%-2.0% previously to 5.8%. Clinical differences included a stronger family history, earlier age at onset, and a higher frequency of tophi and polyarticular gout in Maori than Europeans. Of those with gout, 62% of Maori and 63% of Europeans were hyperuricaemic on the day surveyed and six (19.4%) were on diuretics. Treatment of gout was inadequate in most cases.
CONCLUSIONS—Hyperuricaemia and gout remain common among Maori. Of concern is that the prevalence of gout appears to be on the increase, not only in Maori but also in Europeans in New Zealand.

PMCID: PMC1752259  PMID: 9059136
11.  The potential impact of family history of metabolic syndrome and risk of type 2 diabetes mellitus: In a highly endogamous population 
This study aims to determine the potential impact of positive family history of Metabolic Syndrome (MetS) among two generations, on developing Type 2 Diabetes Mellitus (T2DM) and the potential relation of consanguineous marriage among patients with MetS to the risk of developing T2DM among a sample of Qataris.
A cross-sectional study.
Primary healthcare (PHC) centers.
Materials and Methods:
The survey and measurement were conducted from April 2011 to December 2012 among Qatari nationals above 20 years of age. Of the 2,182 subjects, who were approached to participate in the study, 1,552 (71%) gave their consent. Face-to-face interviews were conducted using a structured questionnaire followed by anthropometric measurements and laboratory tests. Metabolic syndrome was defined using the National Cholesterol Education Program-Third Adult Treatment Panel (ATP III) as well as International Diabetes Federation (IDF).
Overall, the prevalence of MetS was 26.2% according to ATP III and 36.9% according to IDF (P < 0.0001). The mean age of MetS patients with T2DM was significantly higher than those without T2DM (Mean 48 ± 9.9 vs. 42.5 ± 9.2; P < 0.001). The proportion of females was higher among MetS patients with T2DM as compared to those without T2DM (61% vs. 51%; P = 0.053). In addition, there were significant differences between MetS patients with and without DM in terms of co-morbidities of hypertension, coronary heart disease, and high cholesterol. The proportion of MetS patients with positive family history for MetS was significantly higher in MetS patients with T2DM as compared to those without T2DM (46.7% vs. 33.8%; P = 0.009). The proportion of positive family history of MetS among fathers (35% vs. 21.9%; P = 0.005), mothers (30.5% vs. 18.8%; P = 0.008), maternal aunt (18.3% vs. 11.2%; P = 0.055), and maternal grand father (19.5% vs. 10%; P = 0.010) were significantly higher in MetS patients with T2DM as compared to the counterpart. The proportion of consanguineous marriages was almost two times higher among MetS patients with T2DM as compared to those without T2DM (80.9% vs. 41.9%; P < 0.001). The proportion of MetS patients with T2DM was lower than MetS patients without DM below 45 years, but after 45 years, the proportion of MetS patients with T2DM remained higher than their counterparts.
Family history of MetS among parents, maternal aunt, maternal grandfather, and consanguineous marriages among patients of MetS are significantly associated with the development of T2DM in Qatar. These results support the necessity of earlier screening for T2DM among MetS patients with positive family history of MetS.
PMCID: PMC3987271  PMID: 24741517
Consanguinity; correlates; diabetes mellitus; genetics; metabolic syndrome; prevalence
12.  Community-based study on CKD subjects and the associated risk factors 
Nephrology Dialysis Transplantation  2009;24(7):2117-2123.
Background. The study was performed to investigate the prevalence, awareness and the risk factors of chronic kidney disease (CKD) in the community population in Shanghai, China.
Methods. A total of 2596 residents were randomly recruited from the community population in Shanghai, China. All were screened for albuminuria, haematuria, morning spot urine albumin-to-creatinine ratio and renal function. Serum creatinine, uric acid, cholesterol, triglyceride and haemoglobin were assessed. A simplified MDRD equation was used to estimate the glomerular filtration rate (eGFR). All studied subjects were screened by kidney ultrasound. Haematuria, if present in the morning spot urine dipstick test, was confirmed by microscopy. The associations among the demographic characteristics, health characteristics and indicators of kidney damage were examined.
Results. Two thousand five hundred and fifty-four residents (n = 2554), after giving informed consent and with complete data, were entered into this study. Albuminuria and haematuria were detected in 6.3% and 1.2% of all the studied subjects, respectively, whereas decreased kidney function was found in 5.8% of all studied subjects. Approximately 11.8% of subjects had at least one indicator of kidney damage. The rate of awareness of CKD was 8.2%. The logistic regression model showed that age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis each contributed to the development of CKD.
Conclusion. This is the first Shanghai community-based epidemiological study data on Chinese CKD patients. The prevalence of CKD in the community population in Shanghai is 11.8%, and the rate of awareness of CKD is 8.2%. All the factors including age, central obesity, hypertension, diabetes, anaemia, hyperuricaemia and nephrolithiasis are positively correlated with the development of CKD in our studied subjects.
PMCID: PMC2698090  PMID: 19193736
awareness; chronic kidney disease; epidemiology; prevalence; risk factors
13.  Serum urate levels and consumption of common beverages and alcohol among Chinese in Singapore 
Arthritis care & research  2013;65(9):1432-1440.
Western studies suggest that beverages may affect serum urate (SU) levels but data from Asian populations are scarce. We evaluated the associations between beverages and SU levels in Singapore Chinese.
The study population consisted of 483 subjects from the Singapore Chinese Health Study cohort, aged 45-74 years, recruited between 1993 and 1998. Lifestyle factors, medical histories and diet were collected through in-person interviews. SU and other biomarkers were measured from blood collected between 1994 and 1996.
Mean age was 57.6 years and 44% were men. The geometric mean of SU was 321 μmol/L (range 157-719 μmol/L). Mean SU levels increased with alcohol consumption (P for trend = 0.024). The mean SU level of daily alcohol drinkers was 42.6 μmol/L higher than that of non-drinkers. Similarly, increasing frequency of green tea intake was associated with rising SU levels. The highest mean SU level was observed in daily green tea drinkers (difference of 25.0 μmol/L) relative to non-drinkers (P for trend = 0.009). Compared to non-drinkers, daily alcohol drinkers had an almost 5-fold increase in association with hyperuricaemia [odds ratio (OR) = 4.83; 95% confidence interval (CI) = 1.10-21.23) while daily green tea drinkers had a 2-fold increase in association with hyperuricaemia (OR=2.12, 95% CI=1.03-4.36). The present study did not show elevated levels of SU in individuals who consumed black tea, coffee, fruit juice or soda.
Alcohol consumption increases SU levels. The finding that daily drinking of green tea is associated with hyperuricaemia needs validation in future studies.
PMCID: PMC3710722  PMID: 23463601
serum urate; coffee; tea; soft drinks; fruit juice; alcohol; Chinese
14.  Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study 
Increased ferritin concentrations are associated with metabolic syndrome (MetS). The association between ferritin as well as hemoglobin level and individual MetS components is unclear. Erythropoietin levels in subjects with MetS have not been determined previously. The aim of this study was to compare serum erythropoietin, ferritin, haptoglobin, hemoglobin, and transferrin receptor (sTFR) levels between subjects with and without MetS and subjects with individual MetS components.
A population based cross-sectional study of 766 Caucasian, middle-aged subjects (341 men and 425 women) from five age groups born in Pieksämäki, Finland who were invited to a health check-up in 2004 with no exclusion criteria. Laboratory analyzes of blood samples collected in 2004 were done during year 2010. MetS was defined by National Cholesterol Education Program criteria.
159 (53%) men and 170 (40%) women of study population met MetS criteria. Hemoglobin and ferritin levels as well as erythropoietin and haptoglobin levels were higher in subjects with MetS (p < 0.001, p = 0.018). sTFR level did not differ significantly between subjects with or without MetS. Hemoglobin level was significantly higher in subjects with any of the MetS components (p < 0.001, p = 0.002). Ferritin level was significantly higher in subjects with abdominal obesity or high TG or elevated glucose or low high density cholesterol component (p < 0.001, p = 0.002, p = 0.02). Erythropoietin level was significantly higher in subjects with abdominal obesity component (p = 0.015) but did not differ significantly between subjects with or without other MetS components. Haptoglobin level was significantly higher in subjects with blood pressure or elevated glucose component o MetS (p = 0.028, p = 0.025).
Subjects with MetS have elevated hemoglobin, ferritin, erythropoietin and haptoglobin concentrations. Higher hemoglobin levels are related to all components of MetS. Higher ferritin levels associate with TG, abdominal obesity, elevated glucose or low high density cholesterol. Haptoglobin levels associate with blood pressure or elevated glucose. However, erythropoietin levels are related only with abdominal obesity. Higher serum erythropoietin concentrations may suggest underlying adipose tissue hypoxemia in MetS.
PMCID: PMC3471017  PMID: 23016887
Erythropoietin; Ferritin; Hemoglobin; Metabolic syndrome
15.  Serum uric acid in England and Scotland. 
Annals of the Rheumatic Diseases  1977;36(5):420-427.
Serum uric acid (SUA) was measured in 512 men and 254 women from two English regions and in 337 men from one Scottish region. Mean SUA levels were the same in the men (5-5 mg/100 ml) and similar in the women (3-9 and 4-1 mg/100 ml). The apparent rarity of gout in Scotsmen cannot be explained by regional differences in SUA levels or in the prevalence of hyperuricaemia (defined as SUA of 7-0 mg/100 ml or over) which was present in 6-6% of the English men and 8% of the Scots. SUA was positively correlated with weight and serum urea, and with age in women, but no variation was found with social class. Body weight was the most important predictor of SUA in both men and women and superior to measurements involving correction for height, such as ponderal index and calculated lean body mass.
PMCID: PMC1000133  PMID: 921341
16.  Prevalence, components and associated demographic and lifestyle factors of the metabolic syndrome in type 2 diabetes mellitus 
Adults with the metabolic syndrome (MetS) are twice as likely to die from and three times as likely to have a heart attack or stroke compared with people without the syndrome. About 70-80% of type 2 diabetes mellitus (type 2 DM) patients are diagnosed with the MetS. Investigating the occurrence of the MetS in type 2 DM patients is critical for cardiovascular disease prevention. We evaluated the prevalence and components of the MetS and its associated clinical and demographic factors in a Ghanaian adult population with DM 2.
This cross-sectional study was conducted among 200 previously diagnosed type 2 DM patients receiving care from an outpatient clinic of the Tamale Teaching Hospital, Ghana. Anthropometric measurements of waist circumference (cm), weight (Kg) and height (m) were measured appropriately. Clinical data were obtained from the personal health record files of the participants. MetS was defined according to the International Diabetes Federation criteria.
The prevalence of MetS was 24.0% (n=48). The prevalence was higher in women (27.3%, n= 42) compared to men (13.0%, n=6). The commonest occurring components of the MetS included abdominal obesity (77.0%) and elevated FPG (77.0%) denoting uncontrolled diabetes. The prevalence of elevated BP was found to be 44.0%(n=88) and was higher in men (56.5%) than in women (40.3%). Factors that were found to be associated to the MetS were being overweight/obese (Crude OR = 2.9, 95% CI = 1.43 – 5.90, p=0.004), ever tried to lose weight (Crude OR = 2.5, 95% CI = 1.24 – 4.94, p=0.015) and having diabetes for over 5 years (Crude OR = 11.3, 95% CI = 5.26 – 24.08, p<0.001). Other factors that were associated to the MetS were current smokers (Crude OR = 6.8, 95% CI = 1.21- 38.49, p=0.030) and alcohol drinkers (Crude OR = 3.1, 95% CI = 1.23 – 7.65, p=0.018).
A comparatively low prevalence of the MetS was found. More females than males had the MetS. Uncontrolled diabetes and abdominal obesity were prevalent. The factors identified by our univariate logistic regression model were not significant predictors of the MetS in our multivariate model.
PMCID: PMC4106220  PMID: 25054102
Metabolic syndrome; Type 2 diabetes mellitus; Clinical factors; Demographic factors; Tamale; Ghana
17.  Prevalence and gender distribution of the metabolic syndrome 
The Metabolic syndrome (MetS) is a cardiovascular risk factor of public health significance and of recent has become a topical issue. The prevalence of diabetes mellitus (DM) is on the increase and with this scenario, a possible increase in burden of DM which may be largely attributed to cardiovascular complications is expected. The objective of this report is to determine the prevalence of the MetS and compare gender characteristics in subjects with type 2 DM.
Subjects with type 2 DM were recruited from an urban hospital for the study. Clinical data was obtained by interviewing the patients and referring to their Case folders. The anthropometric indices and blood pressure measurements were documented. Laboratory parameters analysed for included total cholesterol, high density and low density cholesterol, triglyceride and glycosylated haemoglobin. Statistical analysis included usage of Student's t test and chi square.
963 patients with type 2 DM aged between 35-85 years were recruited for the study. The main outcome measures included the prevalence of the metabolic syndrome and the gender differences of its components. The prevalence of the metabolic syndrome was 86%. The frequency of occurrence of the MetS was similar for men (83%) and women (86%) and increased with age in both sexes. The prevalence of MetS increased from 11% among participants aged 20 through 29 years to 89% in participants aged 70 through 79. In our patients with DM, the commonest occurring and least detected MetS defining parameters are central obesity and elevated triglyceride levels respectively. The components of the MetS that differed significantly in both sexes was HDL-C. The combination of the components of the MetS were comparable in both genders and 5.8% of the subjects with the MetS had all components of the MetS.
The prevalence of the MetS in type 2DM is high in both genders and increases with age thus posing a potential high cardiovascular risk in this group of patients. The modifiable risk factors for the MetS should be a focus point in the management of subjects with type 2 DM,
PMCID: PMC2836983  PMID: 20180954
18.  Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex Difference in a Chinese Community Elderly Population 
Objective. This study aimed to evaluate the association between serum uric acid (SUA) levels within a normal to high range and the risk of metabolic syndrome (MetS) among community elderly and explore the sex difference. Design and Methods. A cross-sectional study was conducted in a representative urban area of Beijing between 2009 and 2010. A two-stage stratified clustering sampling method was used and 2102 elderly participants were included. Results. The prevalence of hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong association between hyperuricemia and four components of MetS in women and three components in men. Multiple logistic regression analysis showed ORs of hyperuricemia for MetS were 1.67 (95% CI: 1.11–2.50) in men and 2.73 (95% CI: 1.81–4.11) in women. Even in the normal range, the ORs for MetS increased gradually according to SUA levels. MetS component number also showed an increasing trend across SUA quartile in both sexes (P for trend < 0.01). Conclusion. This study suggests that higher SUA levels, even in the normal range, are positively associated with MetS among Chinese community elderly, and the association is stronger in women than men. Physicians should recognize MetS as a frequent comorbidity of hyperuricemia and take early action to prevent subsequent disease burden.
PMCID: PMC4129973  PMID: 25136366
19.  Metabolic syndrome and gallstone disease 
AIM: To investigate the association between metabolic syndrome (MetS) and the development of gallstone disease (GSD).
METHODS: A cross-sectional study was conducted in 7570 subjects (4978 men aged 45.0 ± 8.8 years, and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital. The subjects included 918 patients with gallstones (653 men and 265 women) and 6652 healthy controls (4325 men and 2327 women) without gallstones. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG) and serum lipids and lipoproteins levels were measured. Colorimetric method was used to measure cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Dextrose oxidizing enzyme method was used to measure FPG. Subjects were asked to complete a questionnaire that enquired about the information on demographic data, age, gender, histories of diabetes mellitus, hypertension, and chronic liver disease and so on. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III (ATP III) criteria. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.
RESULTS: Among the 7570 subjects, the prevalence of the gallstone disease was 12.1% (13.1% in men and 10.2% in women). BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose and serum triglyceride (TG) in cases group were higher than in controls, while serum high-density lipid was lower than in controls. There were significant differences in the waist circumference, blood pressure, FPG and TG between cases and controls. In an age-adjusted logistic regression model, metabolic syndrome was associated with gallstone disease. The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95% confidence interval (CI), 1.09-1.52; P = 0.0030], and 1.68 (95% CI, 1.26-2.25; P = 0.0004) in women; the overall age-adjusted odds ratio of MetS for GSD was 1.42 (95% CI, 1.23-1.64; P < 0.0001). The men with more metabolic disorders had a higher prevalence of gallstone disease, the trend had statistical significance (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 3.4 times (P < 0.0001). The prevalence of GSD in women who had 5 components of MetS was 5 times higher than in those without MetS component. The more the components of MetS, the higher the prevalence of GSD (P < 0.0001). The presence of 5 components of the MetS increased the risk of gallstone disease by 4.0 times.
CONCLUSION: GSD appears to be strongly associated with MetS, and the more the components of MetS, the higher the prevalence of GSD.
PMCID: PMC3422804  PMID: 22919256
Gallstone disease; Obesity; Hypertension; Dyslipidemia; Metabolic syndrome
20.  Serum uric acid levels among thirty-four thousand people in Japan. 
Annals of the Rheumatic Diseases  1982;41(3):272-274.
During 1978 a survey was carried out on 34 036 people in Nagano Prefecture, Japan, in an epidemiological study of hyperuricaemia; 15 713 males and 18 324 females were examined by means of our health examination car. The subjects of the survey were all volunteers. The results have shown that the serum uric acid (SUA) levels were related to sex and age. The male group had a mean SUA level of 5.82 mg/dl (range 0.9 to 11.8 mg/dl, standard deviation 1.14 mg/dl) (0.35, range 0.05-0.7, SD 0.07 mmol/l), and the female group had a mean of 4.33 mg/dl (range 0.5 to 9.7 mg/dl, standard deviation 0.91 mg/dl) (0.26, range 0.03-0.58, SD 0.05 mmol/l). The distribution curve for SUA was almost normal in both sexes. Lower levels of SUA were found in males from the 2nd to the 6th decade, but they increased again after the 7th decade. In females they gradually decreased and were at the lowest in the 4th and 5th decades, and then increased again. The values were always lower in females than males with the difference ranging from 1.84 to 0.81 mg/dl (0.11-0.05 mmol/l).
PMCID: PMC1000926  PMID: 7092340
21.  Metabolic Syndrome Derived from Principal Component Analysis and Incident Cardiovascular Events: The Multi Ethnic Study of Atherosclerosis (MESA) and Health, Aging, and Body Composition (Health ABC) 
Background. The NCEP metabolic syndrome (MetS) is a combination of dichotomized interrelated risk factors from predominantly Caucasian populations. We propose a continuous MetS score based on principal component analysis (PCA) of the same risk factors in a multiethnic cohort and compare prediction of incident CVD events with NCEP MetS definition. Additionally, we replicated these analyses in the Health, Aging, and Body composition (Health ABC) study cohort. Methods and Results. We performed PCA of the MetS elements (waist circumference, HDL, TG, fasting blood glucose, SBP, and DBP) in 2610 Caucasian Americans, 801 Chinese Americans, 1875 African Americans, and 1494 Hispanic Americans in the multiethnic study of atherosclerosis (MESA) cohort. We selected the first principal component as a continuous MetS score (MetS-PC). Cox proportional hazards models were used to examine the association between MetS-PC and 5.5 years of CVD events (n = 377) adjusting for age, gender, race, smoking and LDL-C, overall and by ethnicity. To facilitate comparison of MetS-PC with the binary NCEP definition, a MetS-PC cut point was chosen to yield the same 37% prevalence of MetS as the NCEP definition (37%) in the MESA cohort. Hazard ratio (HR) for CVD events were estimated using the NCEP and Mets-PC-derived binary definitions. In Cox proportional models, the HR (95% CI) for CVD events for 1-SD (standard deviation) of MetS-PC was 1.71 (1.54–1.90) (P < 0.0001) overall after adjusting for potential confounders, and for each ethnicity, HRs were: Caucasian, 1.64 (1.39–1.94), Chinese, 1.39 (1.06–1.83), African, 1.67 (1.37–2.02), and Hispanic, 2.10 (1.66-2.65). Finally, when binary definitions were compared, HR for CVD events was 2.34 (1.91–2.87) for MetS-PC versus 1.79 (1.46–2.20) for NCEP MetS. In the Health ABC cohort, in a fully adjusted model, MetS-PC per 1-SD (Health ABC) remained associated with CVD events (HR = 1.21, 95%CI 1.12–1.32) overall, and for each ethnicity, Caucasian (HR = 1.24, 95%CI 1.12–1.39) and African Americans (HR = 1.16, 95%CI 1.01–1.32). Finally, when using a binary definition of MetS-PC (cut point 0.505) designed to match the NCEP definition in terms of prevalence in the Health ABC cohort (35%), the fully adjusted HR for CVD events was 1.39, 95%CI 1.17–1.64 compared with 1.46, 95%CI 1.23–1.72 using the NCEP definition. Conclusion. MetS-PC is a continuous measure of metabolic syndrome and was a better predictor of CVD events overall and in individual ethnicities. Additionally, a binary MetS-PC definition was better than the NCEP MetS definition in predicting incident CVD events in the MESA cohort, but this superiority was not evident in the Health ABC cohort.
PMCID: PMC3318892  PMID: 22536533
22.  Serum Uric Acid Is More Strongly Associated with Impaired Fasting Glucose in Women than in Men from a Community-Dwelling Population 
PLoS ONE  2013;8(6):e65886.
Serum uric acid (SUA) levels are associated with metabolic syndrome (MetS) and its components such as glucose intolerance and type 2 diabetes. It is unknown whether there are gender-specific differences regarding the relationship between SUA levels, impaired fasting glucose (IFG) and newly detected diabetes. We recruited 1,209 men aged 60±15 (range, 19–89) years and 1,636 women aged 63±12 (range, 19–89) years during their annual health examination from a single community. We investigated the association between SUA levels and six categories according to fasting plasma glucose (FPG) level {normal fasting glucose (NFG), <100 mg/dL; high NFG-WHO, 100 to 109 mg/dL; IFG-WHO, 110 to 125 mg/dL; IFG-ADA, 100 to 125 mg/dL; newly detected diabetes, ≥126 mg/dL; known diabetes} SUA levels were more strongly associated with the different FPG categories in women compared with men. In women, the associations remained significant for IFG-WHO (OR, 1.23, 95% CI, 1.00–1.50) and newly detected diabetes (OR, 1.33, 95% CI, 1.03–1.72) following multivariate adjustment. However, in men all the associations were not significant. Thus, there was a significant interaction between gender and SUA level for newly detected diabetes (P = 0.005). SUA levels are associated with different categories of impaired fasting glucose in participants from community-dwelling persons, particularly in women.
PMCID: PMC3681777  PMID: 23785457
23.  Impaired fasting glucose: Pro-diabetic, “atheroprotective” and modified by metabolic syndrome 
World Journal of Diabetes  2013;4(5):210-218.
AIM: To investigate whether impaired fasting glucose (IFG) confers cardiovascular risk.
METHODS: A non-diabetic population-based sample representative of middle-aged and elderly Turks was studied at 8.5 years’ follow-up for incident diabetes and coronary heart disease (CHD). Metabolic syndrome (MetS) was defined by ATP-III criteria modified for male abdominal obesity, and IFG and type 2 diabetes were identified by criteria of the American Diabetes Association. Stratification by presence of MetS was used. Outcomes were predicted providing estimates for hazard ratio (HR) obtained by use of Cox proportional hazards regression analysis in models that controlled for potential confounders.
RESULTS: In 3181 adults (aged 52 ± 11.5 years at baseline), analysis stratified by MetS, gender and IFG status distinguished normoglycemic subjects by a “hypertriglyceridemic waist” phenotype consisting of significantly higher waist circumference, fasting triglyceride and lower high-density lipoprotein-cholesterol, regardless of gender and MetS. Additionally, lipoprotein (Lp) (a) tended to be lower in (especially female) participants with MetS. Multivariable linear regression in a subset of the sample demonstrated decreased Lp (a) levels to be associated with increased fasting glucose and insulin concentrations, again particularly in women. In Cox regression analysis, compared with normoglycemia, baseline IFG adjusted for major confounders significantly predicted incident diabetes at a 3-fold HR in men and only women with MetS. Cox models for developing CHD in 339 individuals, adjusted for conventional risk factors, revealed that IFG status protected against CHD risk [HR = 0.37 (95%CI: 0.14-0.998)] in subjects free of MetS, a protection that attenuated partly in male and fully in female participants with MetS.
CONCLUSION: IFG status in non-diabetic people without MetS displays reduced future CHD risk, yet is modulated by MetS, likely due to autoimmune activation linked to serum Lp (a).
PMCID: PMC3797886  PMID: 24147205
Autoimmune activation; Coronary disease risk; Diabetes, type 2; Impaired fasting glucose; Lipoprotein (a); Metabolic syndrome
24.  Adiponectin in eutrophic and obese children as a biomarker to predict metabolic syndrome and each of its components 
BMC Public Health  2013;13:88.
Obesity is associated with the rise of noncommunicable diseases worldwide. The pathophysiology behind this disease involves the increase of adipose tissue, being inversely related to adiponectin, but directly related to insulin resistance and metabolic syndrome (MetS). Therefore, this study aimed to determine the relationship between adiponectin levels with each component of MetS in eutrophic and obese Mexican children.
A cross sectional study was conducted in 190 school-age children classified as obese and 196 classified as eutrophic. Adiponectin, glucose, insulin, high density lipoprotein cholesterol (HDL-C) and triglycerides were determined from a fasting blood sample. Height, weight, waist circumference, systolic and diastolic blood pressures (BP) were measured; MetS was evaluated with the IDF definition. The study groups were divided according to tertiles of adiponectin, using the higher concentration as a reference. Linear regression analysis was used to assess the association between adiponectin and components of the MetS. Finally, stepwise forward multiple logistic regression analysis controlling for age, gender, basal HOMA-IR values and BMI was performed to determine the odds ratio of developing MetS according to adiponectin tertiles.
Anthropometric and metabolic measurements were statistically different between eutrophic and obese children with and without MetS (P <0.001). The prevalence of MetS in obese populations was 13%. Adiponectin concentrations were 15.5 ± 6.1, 12.0 ± 4.8, 12.4 ± 4.9 and 9.4 ± 2.8 μg/mL for eutrophic and obese subjects, obese without MetS, and obese with MetS, respectively (P <0.001). Obese children with low values of adiponectin exhibited a higher frequency of MetS components: abdominal obesity, 49%; high systolic BP, 3%; high diastolic BP, 2%; impaired fasting glucose, 17%; hypertriglyceridemia, 31%; and low HDL-C values, 42%. Adjusted odds ratio of presenting MetS according to adiponectin categories was 10.9 (95% CI 2.05; 48.16) when the first tertile was compared with the third.
In this sample of eutrophic and obese Mexican children we found that adiponectin concentrations and MetS components have an inversely proportional relationship, which supports the idea that this hormone could be a biomarker for identifying individuals with risk of developing MetS.
PMCID: PMC3570482  PMID: 23363707
Obesity; Adiponectin; Child; Insulin resistance; Metabolic syndrome; Biomarker
25.  FABP 2 gene polymorphism and metabolic syndrome in elderly people of Croatian descent 
Biochemia Medica  2012;22(2):217-224.
Metabolic syndrome (MetS) is a multifactorial disorder in which dyslipidemia plays an important role. Fatty acid-binding protein 2 (FABP 2) is responsible for transport of free fatty acids in the intestinal endothelium cells. FABP2-genetic variants might affect plasma lipid concentrations and intracellular lipid transport. The aim of this study was to investigate the association between FABP2 Ala54Thr genetic polymorphism and metabolic syndrome and some biochemical and anthropological parameters in elderly subjects.
Materials and methods:
This cross-sectional study included 140 men and 176 women older than 70 years. Fasting serum concentration of glucose, lipid parameters, total proteins and C-reactive protein were determined by standardized methods. Presence (MetS(+)) or absence (MetS(−)) of MetS was determined according to criteria of the International Diabetes Federation. FABP2 genetic polymorphism Ala54Thr (rs1799883) was genotyped with PCR-RFPL.
The genotype frequencies for Ala/Ala, Ala/Thr and Thr/Thr genotype were 60, 36 and 6 in MetS(−), and 131, 70 and 13 in MetS(+), respectively, without statistical significance (P = 0.567). Ala/Ala genotype was a subgroup of non-carriers, while Ala/Thr and Thr/Thr genotypes were Thr54-carriers. Median triglyceride concentration was significantly lower in carriers then in non-carriers for whole MetS(+) group (P = 0.050); there were no significant difference between men with MetS (P = 0.144), but there was a difference between women with MetS (P = 0.020). T-test showed that mean HDL cholesterol concentrations in MetS(+) group for Thr54-carriers was significantly higher in whole group (P = 0.001), and for both genders (men P = 0.039; women P = 0.004) as compared to non-carriers.
FABP2 genetic polymorphism is associated with lower triglyceride and higher HDL-cholesterol concentrations in elderly subjects with MetS. This genetic variation might be a useful marker for understanding dyslipidemia in MetS.
PMCID: PMC4062340  PMID: 22838187
fatty acid-binding proteins (FABPs); FABP2; genetic polymorphism; metabolic syndrome

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