Günay Can

Neck circumference as a measure of central obesity: Associations with metabolic syndrome and obstructive sleep apnea syndrome beyond waist circumference

BACKGROUND & AIMS To investigate the relationship of neck circumference (NC) to metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS) and whether it adds information to that provided by waist circumference. METHODS Cross-sectional analysis of a population sample of 1,912 men and women, aged 55.1 +/- 12 years, representative of Turkish adults. MetS was identified based on modified criteria of the ATP-III, OSAS when habitual snoring and episodes of apnea were combined with another relevant symptom. RESULTS NC measured 36.7 (+/- 3.5) cm in the total sample. It was significantly correlated with numerous risk factors, above all body mass index and waist girth (r > or = 0.6), homeostatic model-assessed insulin resistance, blood pressure and, inversely, with smoking status and sex hormone-binding globulin. Sex- and age-adjusted NC was associated significantly with MetS, at a 2-3-fold increased likelihood for 1 standard deviation (SD) increment. After further adjustment for waist circumference and smoking status, a significant residual odds ratio (OR, 1.13 [95% CI 1.08; 1.19]) persisted, corresponding to ORs of 1.53 and 1.27 in males and females, respectively, for 1 SD increment. Even when adjusted for all MetS components, a residual OR (1.08 [95% CI 1.000; 1.17]) remained. Sex- and age-adjusted NC was associated significantly also with OSAS in genders combined, independent of waist girth, yielding an added OR of 1.3 for 1 SD increment. CONCLUSIONS NC contributes to MetS likelihood beyond waist circumference and the MetS components. Regarding association with OSAS, NC is of greater value than WC among Turkish men, not women.

Enhanced proinflammatory state and autoimmune activation: a breakthrough to understanding chronic diseases.

Insight is provided herein into the novel mechanisms of cardiometabolic risk. Previous reports, including the epidemiological work of the Turkish Adult Risk Factor study, indicated that proinflammatory state and oxidative stress are crucial for evaluating cardiometabolic risk. Autoimmune pathways in the course of oxidative stress are major determinants of cardiorenal and metabolic risk. The latter encompasses metabolic syndrome, type 2 diabetes, coronary heart disease, and chronic kidney disease (CKD). Along with platelet-activating factor acetylhydrolase, creatinine, thyroid stimulating hormone, acylation-stimulating protein, asymmetric dimethylarginine, and serum lipoprotein[Lp](a) are triggers of systemic low-grade inflammation and enhanced autoimmune reactions. Related studies are analyzed in the current review. Lp(a) plays a crucial role by taking part in the immune activation, thereby accelerating the course of diabetes, CKD, and other chronic disorders. Populations prone to impaired glucose tolerance, and particularly peri- and postmenopausal women, are at high risk of developing related vascular complications.

Complement C3 and cleavage products in cardiometabolic risk.

This review summarizes available evidence on the role of serum complement component 3 (C3), produced by liver, adipocytes and activated macrophages at inflammation sites, and C3 cleavage products linking lipoproteins and metabolism to immunity. C3 and cleavage products are modified in several associated metabolic disorders including obesity, insulin resistance, type-2 diabetes, dyslipidemia, and cardiovascular diseases. Circulating C3 is independently and linearly associated with serum triglycerides, C-reactive protein (CRP), waist circumference and in some populations inversely with current smoking. The complement cascade is activated during myocardial ischemia and likely mediates immune and inflammatory responses in ischemic myocardium. Serum complement activation is elevated in unstable rather than stable angina pectoris suggesting added contribution to damage extension in acute coronary syndromes. In logistic regression models for incident metabolic syndrome (MetS), increasing C3 concentrations predicted MetS in women, after adjusting for continuous values of 3 major MetS components and other confounders, with a relative risk similar in magnitude to an established component suggesting elevated C3 likely constitutes part of the cluster of MetS in women. C3 interacts with MetS in men for independently conferring risk of incident type-2 diabetes and coronary heart disease (CHD). In women, though C3 is equally predictive of cardiometabolic risk, it is less so additively to MetS components or to CRP. Evidence suggests that circulating C3 might serve as a signal for an immune process that enhances - via mediation of increased apolipoprotein (apo) E levels - the development of dysfunctional apoA-I particles rendering them diabetogenic and atherogenic in populations prone to MetS or subsets of populations harboring impaired glucose tolerance. C3 activation also leads to production of chemoattractants C3a and C5a, and acylation stimulating protein (ASP, C3adesArg), a lipogenic hormone, which contribute additionally to the metabolic phenotypes generated. These observations have clinical and public health implications.

Impaired protection against diabetes and coronary heart disease by high-density lipoproteins in Turks

The issue of whether or not incident type 2 diabetes mellitus and coronary heart disease (CHD) can be predicted by high-density lipoprotein (HDL) cholesterol in both sexes needs investigation. A representative sample of 3035 middle-aged Turkish adults free of CHD at baseline was studied with this purpose prospectively over a mean of 7.8 years. High-density lipoprotein cholesterol levels were found to be correlated in women positively with plasma fibrinogen and weakly with waist girth and C-reactive protein, and to be not correlated with fasting insulin. High-density lipoprotein cholesterol protected men against future CHD risk (for a 12-mg/dL increment: relative risk = 0.80 [95% confidence interval, 0.69-0.95]) after multivariable adjustment in logistic regression analyses for age, smoking status, physical activity grade, hypertension, abdominal obesity, diabetes, and lipid-lowering drugs. However, men were not protected against risk of diabetes. In women, HDL cholesterol was not associated with risk for CHD, whereas intermediate (40-60 mg/dL) compared with lower HDL cholesterol levels proved protective against risk of diabetes (relative risk = 0.57 [95% confidence interval, 0.36-0.90]) after adjustments that included apolipoprotein A-I tertiles. Yet higher serum concentrations failed to yield protection against diabetes. It was concluded that HDL particles confer partially lacking protection against cardiometabolic risk among Turks, and this impairment is modulated by sex. This highly important observation may result from a setting of prevailing chronic subclinical inflammation.

Cross-sectional study of complement C3 as a coronary risk factor among men and women.

In the present study, we examined (i) whether C3 (complement C3) was an independent marker of prevalent CHD (coronary heart disease), and (ii) which preferential associations existed between C3 and some cardiovascular risk factors when jointly analysed with CRP (C-reactive protein) and fibrinogen. In a cohort of 756 unselected adults, 39% of whom had the metabolic syndrome, C3 and other risk variables were evaluated in a cross-sectional manner. In a logistic regression model for the likelihood of CHD, a significant OR (odds ratio) of 3.5 [95% CI (confidence intervals), 1.27 and 9.62)] for C3 was obtained after adjustment for smoking status, TC (total cholesterol) and usage of statins. A similar model, also comprising systolic blood pressure, with a cut-off point of >or=1.6 g/l C3 exhibited a 1.9-fold risk (95% CI, 1.01 and 3.58) compared with individuals below the cut-off point. Both analyses displayed an adjusted OR of 1.37 for each S.D. increment in C3. The significant relationship of C3 with a likelihood of CHD also proved to be independent of CRP. In multiple linear regression models, associations were tested for each acute-phase protein with measures of obesity, fasting insulin, triacylglycerols (triglycerides), TC, HDL (high-density lipoprotein)-cholesterol, physical activity, smoking status, diagnosis of metabolic syndrome and family income. When both genders were combined, C3 was independently associated with serum triacylglycerols, waist circumference, BMI (body mass index) and TC. CRP was independently associated with waist circumference, TC, family income (inversely) and physical activity, and fibrinogen with BMI, TC, smoking status and metabolic syndrome. In summary, elevated levels of complement C3 are associated with an increased likelihood of CHD independent of standard risk factors and regardless of the presence of acute coronary events, suggesting that C3 might be actively involved in coronary atherothrombosis. Unlike CRP and fibrinogen, C3 was preferentially associated with waist girth and serum triacylglycerols.

The paradox of high apolipoprotein A-I levels independently predicting incident type-2 diabetes among Turks

BACKGROUND Predictive value of apolipoprotein (apo) A-I for incident hypertension, metabolic syndrome (MetS), type 2 diabetes (DM) and coronary heart disease (CHD) needs further exploration. METHODS A representative sample of Turkish adults was studied with this purpose prospectively. Sex-specific apoA-I tertiles were examined regarding cardiometabolic risk. RESULTS AND CONCLUSIONS A total of 1044 men and 1067 women (aged 49+/-12 years at baseline) were followed up over 7.4 years. High serum apoA-I levels were significantly associated in multivariable analysis with female sex, aging, alcohol intake, (inversely) cigarette smoking and, in women, with systolic blood pressure. Risk of diabetes was predicted in logistic regression in both genders by top versus bottom apoA-I tertile (RR 1.98; [95%CI 1.31; 3.0]), additive to age, body mass index (BMI), C-reactive protein (CRP), HDL-cholesterol and lipid lowering drugs. By adding sex hormone-binding globulin to the model in a subset of the sample, the association between high apoA-I and incident diabetes was attenuated only in women. ApoA-I tertiles tended to be positively associated also with hypertension and CHD only in women but this did not reach significance. High compared with low serum apoA-I levels nearly double the risk for incident diabetes, additively to age, BMI, CRP, HDL-cholesterol among Turks. Systemic inflammation concomitant with prevailing MetS might turn apoA-I into proinflammatory particles.

Serum complement C3: a determinant of cardiometabolic risk, additive to the metabolic syndrome, in middle-aged population

We studied whether serum complement C3 (C3) is an independent determinant of incident cardiometabolic risk (coronary heart disease [CHD], metabolic syndrome [MetS], and type 2 diabetes mellitus). A cohort of 1220 adults of a general population (age, 53 +/- 10.5 years) was evaluated prospectively at 3.3 years follow-up using Cox proportional hazard regressions. Cardiometabolic risk factors were measured. Metabolic syndrome was identified by Adult Treatment Panel III criteria modified for male abdominal obesity. The C3 levels were associated significantly and linearly with serum triglycerides, waist circumference, and C-reactive protein (CRP), and inversely with current smoking but not with the marker of insulin resistance. In regression models for incident MetS, increasing C3 quartiles strongly predicted MetS in women and in both sexes combined after adjusting for all 5 MetS components and other confounders. Circulating C3 significantly predicted in each sex incident CHD independent of age, smoking status, and presence of MetS. Even after entering CRP, C3 predicted CHD with a relative risk of 1.35 (95% confidence interval, 1.09-1.67) for 1-SD increment of C3 in the total sample. Complement C3 tended to contribute, additively to MetS, to the association with diabetes with a relative risk of 1.36 in women alone, not in men. In conclusion, elevated serum complement C3 is part of the MetS cluster and confers CHD risk, additively to MetS components and CRP, in a population in which MetS prevails. Levels contribute, additively to MetS, to the diabetes risk in women alone.

Serum γ‐Glutamyltransferase: Independent Predictor of Risk of Diabetes, Hypertension, Metabolic Syndrome, and Coronary Disease

Serum γ‐glutamyltransferase (GGT) is associated with oxidative stress and hepatic steatosis. The extent to which its value in determining incident cardiometabolic risk (coronary heart disease (CHD), metabolic syndrome (MetS), hypertension and type 2 diabetes) is independent of obesity needs to be further explored in ethnicities. After appropriate exclusions, a cohort of 1,667 adults of a general population (age 52 ±11 years) was evaluated prospectively at 4 years follow‐up using partly Cox proportional hazard regressions. GGT activity was measured kinetically, and values were log‐transformed for analyses. MetS was identified by Adult Treatment Panel‐III criteria modified for male abdominal obesity. Median (interquartile range) GGT activity was 24.9 (17.0; 35.05) U/l in men, 17.0 (12.3; 24.0) U/l in women. In linear regression analysis, while smoking status was not associated, (male) sex, sex‐dependent age, alcohol usage, BMI, fasting triglycerides and C‐reactive protein (CRP) were significant independent determinants of circulating GGT. Each 1‐s.d. increment in (= 0.53 ln GGT) GGT activity significantly predicted in each sex incident hypertension (hazard ratio (HR) 1.20 (95% confidence interval (CI) 1.10; 1.31)), and similarly MetS, after adjustment for age, alcohol usage, smoking status, BMI and menopause. Strongest independent association existed with diabetes (HR 1.3 (95% CI 1.1; 1.5)) whereas GGT activity tended to marginally predict CHD independent of total bilirubin but not of BMI. Higher serum total bilirubin levels were protective against CHD risk in women. We conclude that elevated serum GGT confers, additively to BMI, risk of hypertension, MetS, and type 2 diabetes but only mediates adiposity against CHD risk.

Serum apolipoprotein C‐III in high‐density lipoprotein: a key diabetogenic risk factor in Turks

Aims  We studied determinants of serum apolipoprotein C‐III (apoC‐III) and whether levels of apoC‐III or its fractions predict metabolic syndrome (MetS), Type 2 diabetes and coronary heart disease (CHD).

Obstructive sleep apnea syndrome is associated with metabolic syndrome rather than insulin resistance

The aim of this study was to investigate cross-sectionally the prevalence and covariates of obstructive sleep apnea syndrome (OSAS) and its relationship to metabolic syndrome (MS), insulin resistance (IR), and coronary heart disease (CHD) in a population sample of 1,946 men and women representative of Turkish adults. OSAS was identified when habitual snoring and episodes of apnea were combined with another relevant symptom. MS was diagnosed based on modified criteria of the Adult Treatment Panel III and IR by homeostatic model assessment (HOMA). OSAS was identified in 61 men (6.4%) and 58 women (5.8%), at a similar prevalence, after adjusting for covariates. Among individuals with OSAS, significantly higher odds ratios (ORs), adjusted for age, body mass index (BMI), and waist girth, were observed for MS, hypertension, and prevalent CHD, but not for HOMA or menopause. Significantly higher C-reactive protein existed only in women with OSAS who were also more frequent smokers. In logistic regression models, waist circumference, but not BMI nor hypertension, was significantly associated with OSAS among men. In women, by contrast, current cigarette smoking and hypertension were the significant independent covariates. Regression models controlling for sex, age, and smoking revealed that MS (and not IR per se) was associated significantly with OSAS (OR 1.94) in nondiabetic individuals. To conclude, abdominal rather than overall obesity in men and smoking among women are significant independent determinants of OSAS in Turkish adults. OSAS is associated with MS rather than IR per se. Relatively high prevalence of OSAS is observed in Turkish women in whom it is significantly associated with CHD.