Abstract
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Type 2 diabetes is characterized by multiple pathophysiologic abnormalities which collectively have been referred to as the Ominous Octet:
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Muscle insulin resistance → reduced glucose uptake
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Hepatic insulin resistance → excessive glucose production
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Adipocyte insulin resistance → accelerated lipolysis and elevated circulating levels of FFA and insulin-resistance provoking adipocytokines
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Progressive β-cell failure and apoptosis
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Increased alpha cell secretion of glucagon and increased hepatic sensitivity to glucagon
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Reduced incretin effect due to beta cell resistance to GLP-1 and GIP
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Increased renal glucose production
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Elevated renal tubular glucose reabsorption
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Brain insulin resistance and altered neurotransmitter dysfunction leading to impaired appetite suppression and weight gain.
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Insulin resistance in muscle and liver are the earliest detectable abnormalities in the natural history of type 2 diabetes.
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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.
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DeFronzo, R.A. (2018). Pathogenesis of Type 2 Diabetes Mellitus. In: Bonora, E., DeFronzo, R. (eds) Diabetes Epidemiology, Genetics, Pathogenesis, Diagnosis, Prevention, and Treatment . Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-45015-5_8
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