[Insulin resistance and metabolic syndrome in type 1 diabetes mellitus].
Insulin resistance (IR) plays a larger role in the type 1 diabetes mellitus (T1DM) disease process than commonly recognized. Overweight and physical inactivity have increased steadily for the last 20-30 years in children and adolescents in many populations, concurrently with a rising incidence of T1DM. The role of IR in T1DM has only recently been gaining acceptance. This review will focus on how IR influences our current understanding of disease development and metabolic syndrome (MS) in T1DM. Increases in IR by weight gain and sedentarism, associated to decreased beta cell mass by autoimmune process, may disrupt normoglycemia in pre-T1DM individuals. IR may reflect a more aggressive form of autoimmune disease mediated by immuno-inflammatory factors that also mediate beta cell destruction (TNF-alpha and IL-6). These concepts are included in the "accelerator hypothesis". Moreover, family history of T2DM and chronic hyperglycemia (glucotoxicity), occurring after T1DM diagnosis, contribute to decrease peripheral glucose uptake. The onset of diabetic nephropathy (DN) might also contribute to IR and metabolic syndrome (MS) via low-grade inflammation and increased oxidative stress. MS is found between 12 to 40% in T1DM, especially in patients with advanced DN and poor glycemic control. These findings have therapeutic and cardiovascular prognostic implications as children make the transition toward adolescence and young adulthood T1DM.
Dib
Sergio Atala
SA
Centro de Diabetes, Departamento de Medicina, EPM, UNIFESP, São Paulo, SP. sadib@endocrino.epm.br
D002318:Cardiovascular Diseases / Q000209:etiology; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D018450:Disease Progression; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D024821:Metabolic Syndrome / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha