Obesity in the Natural History of Type 1 Diabetes Mellitus: Causes and Consequences

There has been a worldwide epidemic increasing in the prevalence of sedentary, overweight and obesity that comes with modernity and urbanization (Wang et al., 2002). The consequence is the development of insulin resistance (IR) and type 2 diabetes (T2D). This is classically defined as a metabolic disease that occurs due to a higher IR that leads to a slow setting of lower insulin production (more relative than absolute), in general in adult age. T2D is associated also with a genetic predisposition. The majority of T2D individuals are overweight or obese and the ones who do not, at least present increased abdominal adipose mass (ADA, 1997). The rising prevalence of overweight and obesity is happening also in children and adolescents (Pinhas-Hamiel et al., 1996; Willi & Egede, 2000; Rosenbloom et al., 1999). The metabolic syndrome (MS), which physiopathology is based on IR, shows the same trend in children and adolescents (Jago et al., 2008), as well as isolated pre-diabetes (Li et al., 2009). In parallel, it has been seen an elevation in the number of type 1 diabetes (T1D) cases and its establishment at a younger age (EURODIAB ACE Study Group, 2000). T1D is characterized primarily by a pancreatic beta cell destruction, which may lead to ketosis. It can be classified as autoimmune (with positive anti-islet, anti-insulin, anti-GAD, anti-IA2 and/or anti-IA2 beta antibodies) or idiopathic, in which no autoantibodies can be detected, and occurs more frequently in individuals of African-American or Asian origin. Multiple genetic predisposition and environmental factors are involved with T1D (ADA, 1997). At least one of those autoantibodies is present in 85-90% of T1D on diagnosis. The treatment for T1D consists of multiple insulin injections, known as intensive treatment, to obtain adequate glycemic control and therefore prevent micro (The DCCT Research Group, 1993) and macrovascular (Nathan et al., 2005 and 2003) chronic complications. However, it can be followed by weight gain most of the times (Arai et al., 2008), which can amplify the risk of cardiovascular disease (CVD) in spite of good glycemic control. This weight gain can start on puberty and persist along adulthood (Särnblad et al., 2007). Therefore, some of these patients present clinical features of both T1D and T2D, confounding its classification. This phenotype was initially called double diabetes (DD) (Libman & Becker, 2003; Becker et al.,