Applied nutritional investigationAssociation between serum zinc and later development of metabolic syndrome in middle aged and older men: The Kuopio Ischaemic Heart Disease Risk Factor Study
Introduction
Metabolic syndrome is characterized by hypertension, excess abdominal fat, and dyslipidemia, all of which have been shown to be involved in the development of a number of chronic diseases, including type 2 diabetes, coronary heart disease, and stroke. Besides the genetic factors, which may have an important role in predisposition to cardiometabolic syndrome [1], unhealthy lifestyle behaviors such as smoking and adherence to a poor diet are implicated in the development of metabolic syndrome [2], [3]. Zinc plays a role in the insulin homeostasis including the synthesis, storage, and secretion of insulin [4], [5].
Insulin resistance has been suggested to play a noteworthy role in the pathogenesis of metabolic syndrome [6], and some evidence suggests a direct association between serum zinc and insulin resistance [7]. The information about the association of zinc with insulin resistance, however, is scarce. Recent cross-sectional studies have reported that higher serum zinc concentration may be a risk factor for metabolic syndrome [8], [9]. Nevertheless, the causality and mechanisms are uncertain because of the cross-sectional study design.
To our knowledge, no prospective study has been conducted of the relation of serum zinc with development of metabolic syndrome. Due to limited research data, more studies are clearly needed. The aim of this prospective study was to assess the relation of serum zinc with metabolic syndrome and its components, which includes waist circumference, fasting blood glucose, serum high-density lipoprotein (HDL) cholesterol, triacylglycerols, and hypertension after 11 y of follow-up among middle-aged and older Finnish men.
Section snippets
Study population
The Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) was designed to investigate risk factors for cardiovascular disease, atherosclerosis, and related outcomes in a population-based, randomly selected sample of men from Eastern Finland [10]. The baseline examinations were carried out from 1984 to 1989. A total of 2682 men aged 42, 48, 54, or 60 y at baseline (82.9% of those eligible) were recruited in two cohorts (Fig. 1). The first cohort consisted of 1166 men aged 54 y, enrolled from
Results
Table 1 shows the baseline characteristics of the study participants free of type 2 diabetes and metabolic syndrome based on the tertiles of serum zinc. Men with higher serum zinc were younger, smoked less, and had a lower alcohol consumption and HOMA of insulin sensitivity. Higher serum zinc concentration was also associated with higher education, waist circumference, BMI, total cholesterol, and low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol and
Discussion
The present study shows a direct association between higher serum zinc concentration and increased risk of incident metabolic syndrome in middle-aged and older men. Serum zinc was also directly associated with higher waist circumference and hypertension and inversely associated with HDL cholesterol at the 11 y examinations. In addition, adjusting for the components of metabolic syndrome at the 11-y follow-up attenuated the associations between serum zinc and risk of metabolic syndrome, which
Conclusion
Overall, we found a direct association between higher serum zinc and incidence of metabolic syndrome and three of its components, increased waist circumference, hypertension, and low serum HDL cholesterol, in middle-aged and older men from Eastern Finland. Further prospective studies in other study populations are warranted to confirm our results and to explore the mechanisms.
References (30)
- et al.
Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and akt in 3 T3-L1 fibroblasts and adipocytes
J Nutr
(2001) - et al.
The key role of insulin resistance in the cardiometabolic syndrome
Am J Med Sci
(2005) - et al.
Serum zinc and risk of type 2 diabetes incidence in men: The Kuopio ischaemic heart disease risk factor study
J Trace Elem Med Biol
(2016) - et al.
Serum levels of polyunsaturated fatty acids are low in Chinese men with metabolic syndrome, whereas serum levels of saturated fatty acids, zinc, and magnesium are high
Nutr Res
(2012) - et al.
Dietary intakes of zinc and heme iron from red meat, but not from other sources, are associated with greater risk of metabolic syndrome and cardiovascular disease
J Nutr
(2012) - et al.
Zinc bioavailability and homeostasis
Am J Clin Nutr
(2010) - et al.
Excessive zinc in diet induces leptin resistance in wistar rat through increased uptake of nutrients at intestinal level
J Trace Elem Med Biol
(2012) - et al.
Zinc supplements and serum lipids in young adult white males
Am J Clin Nutr
(1988) Zinc toxicity
Am J Clin Nutr
(1990)- et al.
The CoLaus study: A population-based study to investigate the epidemiology and genetic determinants of cardiovascular risk factors and metabolic syndrome
BMC Cardiovasc Disord
(2008)
Smoking and metabolic syndrome
Eur Respir J
Endocr Metab Immune Disord Drug Targets
Protein tyrosine phosphatases as targets of the combined insulinomimetic effects of zinc and oxidants
Biometals
Gender differences in the relationship between serum zinc concentration and metabolic syndrome
Ann Hum Biol
Is there a continuing need for longitudinal epidemiologic research? the Kuopio ischaemic heart disease risk factor study
Ann Clin Res
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We thank all participants and other staff members for encouraging and supporting this study. We wish to express our sincerest appreciation to Jalmari and Rauha Ahokas Foundation, Centre for International Mobility (CIMO) Fellowship (TM-14-9374) and University of Eastern Finland for supporting this research. It should be noted that the funding agencies had no role in the collection, analysis or interpretation of data neither in writing of the manuscript.