Metabolic syndrome in a metapopulation of Croatian island isolates

Aim

To investigate the prevalence and factors associated with the metabolic syndrome in 9 isolated populations on Adriatic islands, Croatia, and in the group of immigrants to these islands.

Methods

Random samples of 100 inhabitants from each village and 101 immigrants were collected during 2002 and 2003. Bivariate and multivariate methods were used in data analysis. Age, gender, village, diet, smoking habits, physical activity, education, occupational class, and personal genetic history (a pedigree-based estimate of the individual genome-wide heterozygosity level) were used as independent variables in logistic regression.

Results

A total of 343 (34%) examinees met criteria of the metabolic syndrome diagnosis, with significant differences in the prevalence among villages (P = 0.002). Metabolic syndrome was most frequently detected on Mljet island (53%), where all examinees exhibited fasting plasma glucose over 6.1 mmol/L. Examinees with metabolic syndrome were significantly older than those without it (median age 60.0 vs 53.0; P<0.001). Women were more frequently diagnosed than men (39% vs 28%; P<0.001). The highest prevalence of the metabolic syndrome was found in the autochthonous group, whereas the lowest proportion was recorded in the admixed group (39% vs 21%, respectively, P = 0.017). However, only age (odds ratio [OR], 1.06; 95% confidence intervals [CI], 1.03-1.08) and having a university degree (OR, 0.18; 95% CI 0.04-0.92) were significantly associated with metabolic syndrome in the regression model.

Conclusion

Metabolic syndrome was not associated with pedigree-based individual genome-wide heterozygosity estimate, after controlling for a number of confounding factors. More precise marker based genomic measures are needed to provide a clear answer whether metabolic syndrome development is influenced by the population genetic structure.The metabolic syndrome refers to the clustering of cardiovascular risk factors that greatly increase an individual’s risk for developing diabetes, cardiovascular disease, and renal disease (1,2). It is defined as a concurrence of impaired glucose and insulin metabolism, overweight and abdominal fat excess, dyslipidemia, and hypertension, associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease (3). Other frequently used terms for the metabolic syndrome are syndrome X and insulin resistance syndrome. Although insulin resistance is not a defining component of the metabolic syndrome in the definition proposed by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol Adult Treatment Panel III (4), it is considered to be its core feature (5,6).Metabolic syndrome is a substantial public health problem across the world (1,7). Its diagnosing criteria such as high blood pressure and obesity, are globally among the ten leading risk factors (7). Croatian population does not present an exception from this finding, with elevated blood pressure, smoking, physical inactivity, high alcohol intake, inadequate nutrition, and obesity being identified as the most prevalent cardiovascular risk factors in the general population (8).Beside widely investigated environmental and behavioral risk factors, a number of studies have identified a genetic contribution to the metabolic syndrome development. Metabolic abnormalities related to the metabolic syndrome aggregate in families, suggesting a common genetic component (9). Evidence for the genetic basis of type 2 diabetes and the metabolic syndrome has been derived from various family, twin, and population studies. Identification of genes associated with disease pathogenesis is currently under way, using techniques such as genome scanning by positional cloning and the candidate gene approach (10).Multitude of various risk factors renders epidemiological investigation of metabolic syndrome difficult. Reduced genetic and environmental heterogeneity of isolated human populations could theoretically be useful in the investigation of metabolic syndrome. Isolated populations residing in villages of Croatian islands were already proven to be good models for the investigation of common complex diseases of late onset (11-13). The aim of this study was to investigate the prevalence of metabolic syndrome and factors associated with it, namely personal genetic history in 9 isolated populations of Croatian Adriatic islands, as well as immigrants to the islands. These island populations exhibit a wide range of inbreeding and endogamy, reduced genetic variation at both individual and (sub)population levels, and a relative uniformity of environment (11).