Interleukin-10 promotor -592A/C polymorphism is associated with slow coronary flow in Han Chinese.

An accumulating body of evidence suggests that slow coronary flow (SCF) phenomenon seems to be an early-form of atherosclerosis and low-grade inflammation plays a major role in the atherosclerotic vascular processes. Interleukin (IL)-10 is a multifunctional cytokine involved in both innate and adaptive immune response. The aim of the present study is to investigate the association of IL-10 gene -592A/C polymorphism with SCF in Han Chinese. 250 patients who underwent coronary angiography and had angiographically normal coronary arteries of varying coronary flow rates without any atherosclerotic lesion were enrolled in this study. Patients who had thrombolysis in myocardial infarction frame counts (TFC) above the normal cutoffs were considered to have SCF and those within normal limits were considered to have normal coronary flow (NCF). The PCR-based restriction fragment length polymorphism (PCR-RFLP) technique was used to assess the genotypes frequencies. The distribution of the IL-10 -592A/C genotypes (AA, AC, and CC) was 46.34%, 41.46%, and 12.20% in the NCF group, and 66.51%, 28.71%, and 4.78% in SCF subjects, respectively (P = 0.0280). The frequency of the A allele in the SCF group was significantly higher than that in the NCF group (80.86% vs. 67.07%, P = 0.0054). Compared with the CC genotype, the AA genotype had increased risk of SCF in both unadjusted and adjusted analyses. In SCF patients, the average serum IL-10 levels in AA genotype were statistically lower than in AC + CC genotype (P = 0.0000). These findings suggest that IL-10 -592A/C polymorphism is associated with SCF and the A allele has increased risk for SCF in Han Chinese.

Gamma-glutamyltransferase, insulin resistance and cardiometabolic risk profile in a middle-aged African population.

BACKGROUND: Mechanisms linking liver functions with cardiometabolic risk may involve insulin resistance (IR) and non-alcoholic fatty liver disease. We assessed the associations of gamma-glutamyltransferase (GGT) levels with IR and metabolic syndrome (MetS) in an adult South African urban cohort. METHODS: 1198 participants aged >15 years (297 men) were drawn from the Bellville-South suburb (Cape Town). The homeostatic model assessment of insulin (HOMA-IR), ß-cells function (HOMA-B%), fasting insulin resistance index (FIRI) and the quantitative insulin-sensitivity check index (QUICKI) were calculated, and MetS defined according to the Join Interim Statement 2009 criteria. Associations of GGT levels with covariates were assessed on a continuous scale and across sex-specific quarters of GGT, with adjustment for confounders via generalized linear and logistic regressions. RESULTS: Indicators of IR (HOMA-IR, FIRI and fasting insulin) increased, whereas those for insulin sensitivity (Sib and QUICKI) diminished significantly linearly and across increasing GGT quarters. In multivariable-adjusted models, adjustment for sex, age, BMI, cigarette smoking and alcohol intake yielded the strongest, significant associations between GGT and all markers of IR/IS and glycemia excluding glucose insulin ratio. In a similar level of adjustments, with/without further adjustment for markers of IR/insulin sensitivity, the prevalence of MetS significantly increased across quarters of GGT. CONCLUSIONS: GGT levels were independently associated with insulin sensitivity and MetS in this population. Unaccounted, chronic elevation of GGT may therefore be a cue to screen and monitor individuals for MetS and diabetes, and may warrant consideration as an indicator of high risk for the development of these metabolic disorders.

Age-related patterns of the clustering of cardiovascular risk variables of syndrome X from childhood to young adulthood in a population made up of black and white subjects: the Bogalusa Heart Study.

The age-related patterns of clustering of cardiovascular risk variables of Syndrome X from childhood to adulthood were examined in a community-based sample of black and white children (aged 5-10 years, n = 2,389), adolescents (aged 11-17 years, n = 3,371), and young adults (aged 18-37 years, n = 2,115). In the analysis of clustering, insulin resistance index, BMI, triglycerides/ HDL cholesterol ratio, and mean arterial pressure were used either as categorical variables (age-, race- and sex-specific values >75th percentiles) to calculate risk ratios (observed frequency/expected frequency) or as continuous variables (normal scores based on ranks) to compute intraclass correlations. In the total sample, the risk ratio for clustering of adverse levels of all 4 variables was 9.8 for whites (P < 0.01) versus 7.4 for blacks (P < 0.01); the intraclass correlation was 0.33 for whites (P < 0.001) versus 0.26 for blacks (P < 0.001). Both the risk ratio and intraclass correlation were significantly higher in whites than in blacks in the total sample. The intraclass correlations of the 4 variables were significant (P < 0.001) in all race and age-groups, and they were higher during preadolescence and adulthood than during adolescence. Furthermore, unlike risk ratios, intraclass correlations showed a continuous increase with age during adulthood. When BMI was adjusted, the intraclass correlations involving the other 3 variables were reduced by approximately 50%, and the age-related pattern was no longer evident. These results suggest that the degree of clustering of risk variables of Syndrome X varies with age from childhood to adulthood and is likely influenced by the age-related changes in obesity and the attendant insulin resistance.

Correlation of fasting serum C-peptide and insulin with markers of metabolic syndrome-X in a homogenous Chinese population with normal glucose tolerance.

We surveyed 1447 men and 1800 women aged 30 years (mean 46.7 years) with normal glucose tolerance in Kin-Chen, Kinmen. Correlations of fasting serum insulin and C-peptide with various clinical and biochemical parameters were analyzed by multiple linear regression analysis. Women had significantly higher levels of insulin than men (98+/-43 vs. 91+/-43 pM, p<0.0001), yet they also had a more favorable cardiovascular risk profile. Insulin was positively associated with the female sex, height, body mass index, waist-to-hip ratio, serum triglyceride, total cholesterol, uric acid, and fasting plasma glucose, and was negatively associated with age, smoking, and high-density lipoprotein cholesterol. Independent correlates for C-peptide were similar to those of insulin, except for the addition of mean blood pressure and the exclusion of age and total cholesterol. Significant interaction of sex-body mass index (coefficient = -0.0051, p = 0.0232) was detected for C-peptide only. In conclusion, both fasting serum insulin and C-peptide are quantitatively associated with cardiovascular risk factors in this homogeneous Chinese population with normal glucose tolerance. The female sex is independently associated with higher insulin and C-peptide levels, and the strength of the positive association between the female sex and C-peptide reduces when the body mass index increases.

Premature adrenarche: findings in prepubertal African-American and Caribbean-Hispanic girls.

Premature adrenarche was previously thought to be a benign condition. However, the authors and several other research groups have noted hyperinsulinism and insulin resistance in many girls with premature adrenarche. African-American and Caribbean-Hispanic girls with premature adrenarche are frequently obese with marked hyperandrogenism, signs which correlate with the degree of insulin resistance (i.e., those girls who are obese and insulin resistant tend to have higher levels of adrenocorticotropic hormone-stimulated androgens). Also, girls with premature adrenarche and reduced insulin sensitivity can have subtle decreases in their high-density lipoprotein (HDL) profile. Many of these girls have a strong family history of type 2 diabetes mellitus. Preliminary data regarding long-term follow-up of girls with premature adrenarche indicate that those girls who remain obese are at risk of developing polycystic ovary syndrome (PCOS). The term 'syndrome X' refers to the constellation of laboratory and clinical findings associated with hyperinsulinism stemming from insulin resistance. These findings include obesity, acanthosis nigricans, glucose intolerance, type 2 diabetes mellitus, dyslipidaemia with reduced HDL and elevated low-density lipoprotein, cardiovascular disease and PCOS. Hence, for certain girls, premature adrenarche may be a part of the clinical spectrum of syndrome X.

Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study.

OBJECTIVE: Although the level of hyperglycemia is clearly a risk factor for microvascular complications in diabetic patients, its role in macrovascular complications remains controversial. We followed 4,875 subjects (65% Mexican-American) for 7-8 years to investigate the effects of diabetes and hyperglycemia on all-cause and cardiovascular disease (CVD) mortality. These end points were also analyzed according to quartiles of baseline fasting plasma glucose among diabetic participants. RESEARCH DESIGN AND METHODS: The Cox proportional hazards model was used to estimate the relative risks (RRs) for all-cause and CVD mortality. RESULTS: Diabetes was significantly associated with increased all-cause mortality (RR [95% CI] = 2.1 [1.3-3.5] in men; 3.2 [1.9-5.4] in women) and increased CVD mortality (3.2 [1.4-7.1] in men; 8.5 [2.8-25.2] in women). Among diabetic subjects, those in quartile 4 had a 4.2-fold greater risk of all-cause mortality (P < 0.001) and a 4.7-fold greater risk of CVD mortality (P = 0.01) than those in quartiles 1 and 2 combined. After further adjustment for other potential risk factors, subjects in quartile 4 had a 4.9-fold greater risk of all-cause mortality and a 4.9-fold greater risk of CVD mortality than those in quartiles 1 and 2. In addition, hypertension, current smoking, and cholesterol > 6.2 mmol/l were significant predictors of CVD mortality using Cox models. CONCLUSIONS: We conclude that diabetes is a predictor of both all-cause and CVD mortality in the general population and that both hyperglycemia and common CVD risk factors are important predictors of all-cause and CVD mortality in diabetic subjects.