Pathogenesis of Type 2 Diabetes Mellitus

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Scopus citations


Type 2 diabetes is characterized by multiple pathophysiologic abnormalities which collectively have been referred to as the Ominous Octet: – Muscle insulin resistance → reduced glucose uptake – Hepatic insulin resistance → excessive glucose production – Adipocyte insulin resistance → accelerated lipolysis and elevated circulating levels of FFA and insulin-resistance provoking adipocytokines – Progressive β-cell failure and apoptosis – Increased alpha cell secretion of glucagon and increased hepatic sensitivity to glucagon – Reduced incretin effect due to beta cell resistance to GLP-1 and GIP – Increased renal glucose production – Elevated renal tubular glucose reabsorption – Brain insulin resistance and altered neurotransmitter dysfunction leading to impaired appetite suppression and weight gain. • Insulin resistance in muscle and liver are the earliest detectable abnormalities in the natural history of type 2 diabetes. • With time, progressive β-cell failure ensues and, in the presence of insulin resistance, individuals progress from normal glucose tolerance to impaired glucose tolerance to overt type 2 diabetes.

Original languageEnglish (US)
Title of host publicationEndocrinology (Switzerland)
PublisherSpringer Science and Business Media Deutschland GmbH
StatePublished - 2018

Publication series

NameEndocrinology (Switzerland)
ISSN (Print)2510-1927
ISSN (Electronic)2510-1935


  • Beta cell failure
  • Insulin resistance
  • Liver, muscle, adipocyte
  • Ominous octet
  • Pathophysiology of T2DM

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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