Pathogenesis of Type 2 Diabetes Mellitus

  • Marcia F. KalinEmail author
  • Marcus GoncalvesEmail author
  • Jennifer John-Kalarickal
  • Vivian FonsecaEmail author
Reference work entry


Type 2 diabetes affects about 3% of the worldwide population and about 9% of the US population, and its prevalence is accelerating rapidly. Twin studies suggest that genetics account for 60–90% of the susceptibility to type 2 diabetes. Environmental factors, including physical inactivity, obesity, diet, and altered intestinal microbiota, account for the remaining risk. The earliest detectable defect in the development of type 2 diabetes is insulin resistance, which may occur in the muscle, fat, or liver. The primary cause of insulin resistance in type 2 diabetes appears to be a post-receptor defect. Because insulin resistance in type 2 diabetes is evident in several different actions of insulin, the primary defect likely involves an early step in the insulin signaling pathway, possibly phosphatidylinositol-3-kinase, the insulin receptor substrates IRS-1 or IRS-2, or the glucose transporter, Glut-4. During the natural course of diabetes, insulin levels rise with the increasing obesity and insulin resistance that precede the onset of diabetes, peak around the time of the onset of diabetes, and fall progressively thereafter. The progressive deterioration in insulin secretion results from β-cell loss and β-cell dysfunction. Possible contributors to β-cell loss or β-cell dysfunction include amyloid deposition in the pancreatic islet, β-cell dedifferentiation, glucotoxicity, and lipotoxicity. Other contributors to hyperglycemia in type 2 diabetes include a diminished incretin effect and increased hepatic glucose output.


Pathogenesis Pathophysiology Type 2 diabetes 


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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Endocrinology Service, Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  2. 2.Section of EndocrinologyTullis Tulane Alumni Chair in Diabetes, Tulane University Health Sciences CenterNew OrleansUSA
  3. 3.EndocrinologyNortheast Georgia Diagnostic ClinicGainesvilleUSA

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