Background: The Irisin is a myokine associated with the improvement on insulin resistance caused by diet and increased physical energy expenditure. Recent studies have shown that patients with Type 2 Diabetes Mellitus (T2DM) have reduced levels of irisin, showing it as a potential marker for various endocrine and cardiovascular diseases. This study aimed to verify if T2DM patients never treated or without ongoing treatment have reduced levels of irisin when compared to individuals with other metabolic profiles. Methods and Findings:Systematic review of the literature, considering the primary studies published in 2012 to 2016, with the outcome Irisin levels in patients never treated or without current treatment in the ambience of Type 2 Diabetes Mellitus. The search was conducted through the electronic database Scopus (Elsevier), using the key words: "Irisin", "Human" and "Diabetes Mellitus". From the 91 studies found, 8 met the eligibility criteria. Significant differences were found on levels of irisin in patients with T2DM compared to normoglycemic individuals, obese and/or pre-diabetic. On average, there was a reduction of 15 pg/ml in plasma levels of irisin in diabetics. However, a minority of studies says that this relationship does not exist. Conclusion:Irisin reduced levels were found in patients with T2DMand is also related to lipid profile, with the risk of developing endocrine diseases, such as diabetes and obesity, and high risk for cardiovascular diseases because of its relationship with endothelial dysfunction. This Low Irisin Levels in Patients with IntroductionDiabetes mellitus is the most common chronic disease characterized by hyperglycemia resulting from defects in insulin secretion and/or activity [1].Its incidence increases gradually each year. The worldwide prevalence of diabetes among adults was 6.4%, affecting 285 million people in 2010, and is expected to increase to 7.7% (ie, 439 million adults) in 2030 [2]. Obesity, especially visceral is one of the most important factors in the development of diabetes through various mechanisms, including increased circulating free fatty acids, secretion of cytokines by white adipose tissue, which ultimately exacerbates insulin resistance, and decreased adiponectin [3], a derived from white adipose tissue cytokine that has been linked to insulin sensitizing activity and cardiovascular protective properties [4]. The brown adipose tissue acts oxidizing chemical energy to produce heat as a defense against hypothermia and obesity [5], may alter insulin sensitivity [6,7,8,9].The reduction in physical activity has also been associated with an increase in the development of chronic diseases, including type 2 diabetes mellitus (T2DM) [10]. One possible explanation for this is the secretion of myokine by the muscular system [11]. Contraction of the skeletal muscle secretes a spectrum of bioactive molecules known as 'myokine', coordinating the flow of energy needed to sustain muscle activity and stimulating the adaptive plasticity of muscle and various ...