The linkage between inflammation and Type 2 diabetes mellitus

doi:10.1016/j.diabres.2012.09.003

Diabetes Research and Clinical Practice

Volume 99, Issue 2, February 2013, Pages 85-92

https://doi.org/10.1016/j.diabres.2012.09.003 Get rights and content

Abstract

The Type 2 diabetes mellitus (DM2) is considered nowadays as one of the most important chronic disturbances because of the significant number of people with diabetes and its severe complications, responsible for elevated indexes of morbidity and mortality. DM2 is characterized by several degrees of insulin resistance and relative deficiency in its secretion. Genetic and environmental factors have been described as of major importance in the DM2 development as obesity, which is directly correlated with development of resistance in peripheral tissues and inflammatory state in metabolic activated adipose tissue. Inflammatory responses may have a dual role in DM2, since it may have either a causal relationship leading to resistance to insulin or may be intensified by the hyperglycemic state, resulting in DM2 complications. In this review, we discuss the association of polymorphisms in genes encoding inflammatory cytokines and the increased level of these pro-inflammatory markers, associated to chronic pathologic conditions in DM2.

Introduction

The Type 2 diabetes mellitus is considered nowadays as a worldwide epidemic. It is one of the most important chronic disturbances because of the significant number of people with diabetes and its severe chronic complications, responsible for elevated indexes of morbidity and mortality.

The most prevalent form of diabetes mellitus corresponds to Type 2 (DM2), responsible for approximately 90% of all cases of diabetes in the world. According to World Health Organization (WHO) [1] the number of people with this metabolic disturbances tends to increase during the fore coming years. The global forward estimative is that in the year 2030, 366 million people will present the disease. In the past, adults represented the main target segment of the population, but nowadays the number of children and teenagers with DM2 is growing remarkably [1], [2].

The clinical manifestations usually found in DM2 patients can be defined considering the associated metabolic disorders and complications of the clinical outcome. The metabolic disorders are consequences of a framework hyperglycemia, resulting from glucose underutilization in tissues. The chronic complications also are important results of hyperglycemic state and include vascular, neuropathic and visual disturbances [3], [4].

The DM2 is characterized by several degrees of insulin resistance and relative deficiency in its secretion. In most people with this form of diabetes, insulin action is impaired. The insulin resistance can be a consequence of a decrease on insulin receptor numbers or failure in insulin-receptor binding. Also, this resistance can happen due to a failure in glucose transportation into the cell by a specific protein carrier as the glucose transporter (GLUT 4) [5].

Genetic and environmental factors have been described as of major importance in the DM2 development and its complications. Among environmental factors obesity, mainly abdominal fat accumulation, is one factor that stands out and that is often present in individuals with diabetes. Obesity is directly correlated with elevated levels of insulin and consequently the development of resistance in peripheral tissues [6].

Insulin resistance has been attributed to adipose tissue activation associated with an increased release of inflammatory cytokines such as TNF-α, IL-6 and decreasing production of IL-10, an anti-inflammatory cytokine, by macrophages and lymphocytes. High levels of other inflammatory factors such as PAI-1 (plasminogen activator inhibitor), C-reactive protein and monocytes activation also are associated with increased insulin resistance [7]. Other factors have been positively associated as hypertension, sedentary lifestyle, age over 40 years, previous gestational diabetes, medications and hyperglycemic family history [4].

This review will explore the main studies that describe the association of inflammatory cytokines and other inflammatory markers, associated to chronic pathologic conditions in DM2.

Section snippets

The signaling through insulin receptor

Cell insulin signaling starts when insulin binds in to its specific receptor in several tissues, inducing a complex intracellular cascade.

The family of insulin receptor substrates (IRSs) is an important regulatory key in the insulin signaling pathway and includes at least four distinct IRS proteins, among IRS-1 and IRS-2 which are found in several human tissues. They are considered the most important proteins of the family linked to actions of insulin on peripheral lipid and carbohydrate and

Cytokines, obesity and Type 2 diabetes

Obesity can be considered as a common disturbances that affects adults, teenagers and children worldwide, especially in developed and developing countries where fat food and sedentary life styles are common. Obesity can be defined as a disease in which excess body fat has accumulated to such an extent that health may be adversely affected. Several genetic, environmental and psychosocial factors are associated and interact, favoring the fat weight body increase [6].

The fat accumulation occurs

Cytokines polymorphism

Several polymorphisms in cytokine genes have been evaluated with respect to DM2 development and its association with the disease complications.

The gene that encodes the TNF-α is located in the MHC II-major histocompatibility complex II. Among the multiple SNPs (single nucleotide polymorphism) in the promoter region of this gene, the G-238A and G-308A are associated with an increase in transcription and secretion of TNF-α and are frequently studied to assert the association with DM2 in different

Conclusion

According to WHO, an increase of DM2 prevalence has occurred during the years and it is important to act preventively, but it seems increasingly important to detect early the disturbances manifestation, ensuring an early diagnosis and avoiding the appearance of clinical manifestations such as metabolic and vascular disorders.

Several studies have been conducted in different populations toward the discovery of candidate molecular markers, including the cytokine polymorphisms, to establish a panel

Conflict of interest

The authors declare that they have no conflict of interest.

Acknowledgment

We thank Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG) for the financial support.

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ReviewThe linkage between inflammation and Type 2 diabetes mellitus

Abstract

Introduction

Section snippets

The signaling through insulin receptor

Cytokines, obesity and Type 2 diabetes

Cytokines polymorphism

Conclusion

Conflict of interest

Acknowledgment

J Diabetes Complications

J Biol Chem

Lancet

Trends Immunol

Life Sci

Trends Endocrinol Metab

J Biol Chem

Brain Res

Biochem Biophys Res Commun

Cytokine

Increasing prevalence of Type 2 diabetes in Chinese adults in Shanghai

Diabetes Care

Early retinal arteriolar changes and peripheral neuropathy in diabetes

Diabetes Care

Standards of medical care in diabetes

Diabetes Care

Obesity as a medical problem

Nature

The role of inflammatory cytokines in diabetes and its complications

J Periodontol

Identifying the links between obesity, insulin resistance and β-cell function: potencial role of adipocyte-derived cytokines in the pathogenesis of type 2 diabetes

Eur J Clin Invest

Altered function of insulin receptor substrate-1-deficient mouse islets and cultured β-cell lines

J Clin Invest

PI3K/AKT, MAPK and AMPK signalling: protein kinases in glucose homeostasis

Expert Rev Mol Med

Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination

Cytokine

Mechanisms of obesity-associated insulin resistance: many choices on the menu

Genes Dev

Obesity, inflammation, and insulin resistance—a mini-review

Gerontology

Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children

Diabetes

Relationship between plasma leptin level and chronic kidney disease

Int J Nephrol

Leptin and mTOR: partners in metabolism and inflammation

Cell Cycle

The weight of leptin in immunity

Nat Rev Immunol

Review
The linkage between inflammation and Type 2 diabetes mellitus