Serum Immunoglobulin M Concentration Is Positively Related to Metabolic Syndrome in an Adult Population: Tianjin Chronic Low-Grade Systemic Inflammation and Health (TCLSIH) Cohort Study

Persistent low-grade systemic inflammation has been increasingly recognized as a common pathological process, and an important contributing factor to cardiovascular diseases and its risk factor, metabolic syndrome. Immunoglobulin M is reactive to multiple autoantigens and is inferred to be important for autoimmunity, implying that immunoglobulin M may be a potential risk factor for metabolic syndrome. However, few epidemiological studies are available which are related to this potential link. Therefore, we designed a cross-sectional study of 9,379 subjects to evaluate the relationship between immunoglobulin M and metabolic syndrome in an adult population. Subjects who received health examinations were recruited from the Tianjin Medical University General Hospital-Health Management Center in Tianjin, China. Immunoglobulin M was determined with an immunonephelometric technique. Metabolic syndrome was defined according to the criteria of the American Heart Association scientific statements of 2009. Multiple logistic regression analysis was used to examine the relationships between the quartiles of immunoglobulin M and the prevalence of metabolic syndrome. After adjustment for covariates, the odds ratio of having metabolic syndrome in the fourth quartile compared with the first quartile of immunoglobulin M was 1.19 times for males (95% confidence interval, 1.002–1.41) and 1.39 times for females (95% confidence interval, 1.07–1.80). Immunoglobulin M levels also showed positive relationships with the ratio of elevated triglycerides and reduced high-density lipoprotein cholesterol in males. The study is the first to show that immunoglobulin M is independently related to metabolic syndrome and its individual components (elevated triglycerides and reduced high-density lipoprotein cholesterol) in males, whereas immunoglobulin M is independently related to metabolic syndrome in females but not to its individual components. Further studies are needed to explore the causality and the exact role of immunoglobulin M in metabolic syndrome.

[1]  P. Marzullo,et al.  Lymphocytes and immunoglobulin patterns across the threshold of severe obesity , 2014, Endocrine.

[2]  O. Ohara,et al.  Obesity-associated autoantibody production requires AIM to retain the immunoglobulin M immune complex on follicular dendritic cells. , 2013, Cell reports.

[3]  Bernadette A. Thomas,et al.  Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010 , 2012, The Lancet.

[4]  S. Shoelson,et al.  Metabolic Syndrome, Insulin Resistance, and Roles of Inflammation – Mechanisms and Therapeutic Targets , 2012, Arteriosclerosis, thrombosis, and vascular biology.

[5]  Ling Qi,et al.  Mechanisms of inflammatory responses in obese adipose tissue. , 2012, Annual review of nutrition.

[6]  N. Kadoglou,et al.  Obesity and metabolic syndrome as related to cardiovascular disease , 2012, Expert review of cardiovascular therapy.

[7]  N. Jenny.  Inflammation in aging: cause, effect, or both? , 2012, Discovery medicine.

[8]  J. Anaya,et al.  IgM predominance in autoimmune disease: genetics and gender. , 2012, Autoimmunity reviews.

[9]  Michael N. Alonso,et al.  B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies , 2011, Nature Medicine.

[10]  S. Weitzman,et al.  Chronic inflammation and cancer: the role of the mitochondria. , 2011, Oncology.

[11]  M. Ehrenstein,et al.  The importance of natural IgM: scavenger, protector and regulator , 2010, Nature Reviews Immunology.

[12]  J. Eckel,et al.  Adipose tissue inflammation: novel insight into the role of macrophages and lymphocytes , 2010, Current opinion in clinical nutrition and metabolic care.

[13]  J. Francis,et al.  Central Adiposity, Systemic Inflammation, and the Metabolic Syndrome , 2010, Current hypertension reports.

[14]  E. Maury,et al.  Adipokine dysregulation, adipose tissue inflammation and metabolic syndrome , 2010, Molecular and Cellular Endocrinology.

[15]  G. Knudsen.  Gender bias in autoimmune diseases X chromosome inactivation in women with multiple sclerosis , 2009, Journal of the Neurological Sciences.

[16]  S. Grundy,et al.  Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International As , 2009, Circulation.

[17]  P. Calabrò,et al.  Adipose tissue-mediated inflammation: the missing link between obesity and cardiovascular disease? , 2009, Internal and emergency medicine.

[18]  P. Matarrese,et al.  Redox state, cell death and autoimmune diseases: a gender perspective. , 2008, Autoimmunity reviews.

[19]  C. Nathan.  Epidemic Inflammation: Pondering Obesity , 2008, Molecular medicine.

[20]  S. Grundy.  Metabolic Syndrome Pandemic , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[21]  F. Gudé,et al.  Serum levels of immunoglobulins (IgG, IgA, IgM) in a general adult population and their relationship with alcohol consumption, smoking and common metabolic abnormalities , 2007, Clinical and experimental immunology.

[22]  G. Kolovou,et al.  The Prevalence of Metabolic Syndrome in Various Populations , 2007, The American journal of the medical sciences.

[23]  D. Barad,et al.  Gender as risk factor for autoimmune diseases. , 2007, Journal of autoimmunity.

[24]  S. Yamaoka,et al.  Role of the Toll-like Receptor 4/NF-&kgr;B Pathway in Saturated Fatty Acid–Induced Inflammatory Changes in the Interaction Between Adipocytes and Macrophages , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[25]  J. Flier,et al.  TLR4 links innate immunity and fatty acid-induced insulin resistance. , 2006, The Journal of clinical investigation.

[26]  H. Vollmers,et al.  Natural IgM antibodies: the orphaned molecules in immune surveillance. , 2006, Advanced drug delivery reviews.

[27]  G. Licata,et al.  Obesity: a main factor of metabolic syndrome? , 2006, Panminerva medica.

[28]  M. Heineman,et al.  Sex hormones and the immune response in humans. , 2005, Human reproduction update.

[29]  K. Shirai.  Obesity as the core of the metabolic syndrome and the management of coronary heart disease , 2004, Current medical research and opinion.

[30]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[31]  Gary L Myers,et al.  Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. , 2003, Circulation.

[32]  A. Martí,et al.  Obesity and immune function relationships , 2001, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[33]  P. Kovanen,et al.  Prediction of myocardial infarction in dyslipidemic men by elevated levels of immunoglobulin classes A, E, and G, but not M. , 1998, Archives of internal medicine.

[34]  J. Marchalonis,et al.  Natural human antibodies to synthetic peptide autoantigens: correlations with age and autoimmune disease. , 1993, Gerontology.