Sex Differences in the Association of Adiponectin and Low-Grade Inflammation With Changes in the Body Mass Index From Youth to Middle Age

doi:10.1016/j.genm.2012.01.002

Gender Medicine

Volume 9, Issue 1, February 2012, Pages 1-8

https://doi.org/10.1016/j.genm.2012.01.002 Get rights and content

Abstract

Background

There are sex differences in low-grade inflammation markers in obesity-related disorders. Little is known, however, about a possible sex-specific association of relative weight change from youth to adulthood with actual low-grade inflammation.

Objective

The aim of this study was to identify possible sex differences in adiponectin, interleukin-1β (IL-1β), interleukin-1Ra (IL-1Ra), and high-sensitivity C-reactive protein (hs-CRP) levels with respect to the relative change in body mass index (BMI) from youth to middle age.

Methods

The study population consisted of 403 men and 500 women from 1 Finnish town. Weight, height, and adiponectin, IL-1β, IL-1Ra, and hs-CRP levels were measured in 2003 at a mean age of 46 years. Self-reported weight at the age of 20 years was recorded.

Results

In women, even after adjustment for BMI in adulthood, a statistically significantly negative linear association was observed between the quartiles of relative change in BMI and adiponectin levels (P < 0.001 for linearity). Significantly positive linear associations were also observed between the change in BMI and IL-1Ra (P = 0.032 for linearity) and hs-CRP (P = 0.029 for linearity) levels. In men, there was no statistically significant association among the quartiles of relative change in BMI and measured inflammatory markers after adjustment for BMI in adulthood.

Conclusions

A relative increase in weight may be more harmful in women than in men with respect to adiponectin and inflammatory markers.

Introduction

Not only is low-grade inflammation associated with weight gain, metabolic syndrome (MetS), cardiovascular diseases, and type 2 diabetes, it is also considered to be a new risk factor for these conditions.1, 2, 3, 4, 5 It is mediated by cytokines, many of which are mainly produced by adipocytes.⁶

Adiponectin, an adipocytokine primarily secreted by subcutaneous adipose tissue, is believed to act as a regulator of many inflammatory and anti-inflammatory cytokines.6, 7 It is also capable of inducing the production of interleukin (IL)-1Ra (IL-1Ra), an anti-inflammatory cytokine that indicates an inflammatory state.6, 8 IL-1Ra levels are elevated in obesity to the same extent as in systemic inflammation, and it has been speculated that IL-1Ra may be the most sensitive cytokine marker of a prediabetic state.8, 9, 10

High-sensitivity C-reactive protein (hs-CRP) is commonly used as an acute-phase reactant produced by hepatocytes. It predicts future coronary events and correlates positively with body mass index (BMI), MetS, and type 2 diabetes.11, 12, 13, 14 CRP synthesis is stimulated by IL-1 and IL-6.¹⁵ IL-1β is thus to known increase hs-CRP levels, but among patients with type 2 diabetes, elevated CRP-levels were found to increase IL-1β concentrations.16, 17 Il-1β also stimulates the release of IL-1Ra.¹⁸

Sex differences have been observed in the relationship between adiponectin levels and glucose metabolism disorders or obesity and in the association between IL-1Ra levels and obesity-related disorders.19, 20, 21 CRP was found to be a stronger predictor of type 2 diabetes in women than in men.²² Another study found a similar sex difference between CRP and early progression of carotid atherosclerosis.²³ There is also evidence of sex differences in the association of CRP and obesity or obesity-related metabolic disorders.24, 25

Weight loss seems to reduce the levels of inflammatory cytokines and increase the levels of anti-inflammatory cytokines.26, 27 However, the relationship between inflammation and obesity is not fully understood and is even somewhat contradictory. Obesity is often thought to precede low-grade inflammation, but there is also evidence that increased levels of inflammatory markers may predict weight gain in the future.28, 29, 30 However, there are no data available regarding whether long-term weight gain or weight loss has a sex-specific role in the development of low-grade inflammation.

The aim of this study was to retrospectively examine the possible sex differences between the markers of low-grade inflammation and the relative change in BMI from youth to middle age.

Section snippets

Materials and Methods

All inhabitants of Pieksämäki (a town in Eastern Finland), born in 1942, 1947, 1952, 1957, and 1962 (N = 1294) were invited for a health checkup in 1997–1998. Among these individuals, 923 (71.3%) participated in the study. Subjects with hs-CRP >10 mg/L, (n = 18; 11 men and 7 women) were excluded because of the possibility of acute infections.³¹ Information regarding weight in youth was missing for 2 subjects. The final study population consisted of 903 subjects (403 men and 500 women).

All

Results

At the age of 20 years, the mean (SD) weight was 71 (9) kg in men and 57 (8) kg in women. The means (SDs) of the BMI were 22.6 (2.5) kg/m² and 21.2 (2.7) kg/m², respectively (P < 0.001 between sexes). The mean (SD) increase in weight was 12.8 (11.2) kg in men and 13.9 (11.9) kg in women (P = 0.160 between sexes). The demographic, clinical, and biochemical characteristics of the study subjects in adulthood, at a mean age of 46 years, are presented in Table I. There was no significant sex

Discussion

The present study reveals that there is a sex difference in the association between the relative change in BMI from the age of 20 years to adulthood and low-grade inflammation measured by adiponectin, IL-1Ra, and hs-CRP levels after adjusting for BMI in adulthood.

Adiponectin levels are known to decrease with weight gain even before the weight gain reaches the level of obesity.³² There is evidence that adiponectin may act as a promoter in the network of inflammatory and anti-inflammatory

Conclusions

We conclude from our results that the increase in fat mass may be more harmful in women than in men with respect to adiponectin and inflammatory markers. However, further research is needed to confirm these results.

Conflicts of Interest

The authors have indicated that they have no conflicts of interest regarding the content of this article.

Acknowledgments

All authors contributed equally to this study.

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Original researchSex Differences in the Association of Adiponectin and Low-Grade Inflammation With Changes in the Body Mass Index From Youth to Middle Age

Abstract

Background

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Materials and Methods

Results

Discussion

Conclusions

Conflicts of Interest

Acknowledgments

Nutr Metab Cardiovasc Dis

Biochim Biophys Acta

Diabetes Metab

Maturitas

Health Policy

Atherosclerosis

Am J Clin Nutr

The implication of proinflammatory cytokines in type 2 diabetes

Front Biosci

Adipose inflammation, insulin resistance and cardiovascular disease

J Parenter Enteral Nutr

Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states

Obes Rev

Type 2 diabetes as an inflammatory cardiovascular disorder

Curr Mol Med

Adipocytokines: mediators linking adipose tissue, inflammation and immunity

Nat Rev Immunol

Adiponectin: more than just another fat cell hormone?

Diabetes Care

Adipose tissue is a major source of interleukin-1 receptor antagonist: up-regulation in obesity and inflammation

Diabetes

IL-1 receptor antagonist serum levels are increased in human obesity: a possible link to the resistance to leptin?

J Clin Endocrinol Metab

Changes in inflammatory cytokines are related to impaired glucose tolerance in offspring of type 2 diabetic subjects

Diabetes Care

Production of C-reactive protein and risk of coronary artery events in stable and unstable anginaEuropean Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group

Lancet

Association between C-reactive protein and features of the metabolic syndrome: a population-based study

Diabetes Care

Association between low-grade systemic inflammation and type 2 diabetes mellitus among men and women from the ATTICA study

Rev Diabet Stud

Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events

N Engl J Med

Advanced glycation end products upregulate C-reactive protein synthesis by human hepatocytes through stimulation of monocyte IL-6 and IL-1 beta production

Scand J Immunol

Association between serum values of C-reactive protein and cytokine production in whole blood of patients with type 2 diabetes

Clin Sci (Lond)

Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue

Clin Endocrinol Metab

Associations of adiponectin levels with incident impaired glucose metabolism and type 2 diabetes in older men and women; The Hoorn study

Diabetes Care

Gender differences in association of plasma adiponectin with obesity reflect resultant insulin resistance in non-diabetic Japanese patients with schizophrenia

Psychiatry Clin Neurosci

Sex differences in the prediction of type 2 diabetes by inflammatory markers: results from the MONICA/KORA Augsburg case-cohort study, 1984–2002

Diabetes Care

High-sensitivity C-reactive protein is independently associated with early carotid artery progression in women but not in men: the INVADE Study

Stroke

Original research
Sex Differences in the Association of Adiponectin and Low-Grade Inflammation With Changes in the Body Mass Index From Youth to Middle Age