The pathogenesis of non-insulin-dependent diabetes. An update

Ralph A Defronzo, E. Ferrannini

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Insulin secretion in response to glucose is frequently, but not invariably, deficient in individuals with fasting hyperglycemia. Basal insulin secretion, however, is normal and milder degrees of glucose intolerance can be associated with a normal or supernormal insulin response to glucose. Insulin resistance is almost uniformly present in subjects with any degree of clinically detectable glucose intolerance. This insulin resistance is located both in the liver and in the peripheral tissues, principally the muscle. Hepatic resistance is present in the form of inappropriately high glucose production in the fasting state and deficient glucose uptake following glucose ingestion. Peripheral resistance manifests itself as reduced glucose uptake (mostly by muscle) after exposure to endogenous or exogenous insulin and reduced clearance of plasma glucose in the fasting state. Decreased binding of insulin to its cellular receptors is commonly found in patients with both chemical and overt diabetes. Insulin binding, however, may be normal in diabetics with severe insulin resistance. A significant postreceptor defect in glucose metabolism appears to be present in subjects with marked fasting hyperglycemia. A general conceptual framework for the pathogenesis of non-insulin-dependent diabetes mellitus is presented in which a defect (a) in the secretory activity of the β-cell, (b) in the interaction between the gastrointestinal tract and the liver, or (c) at the cellular level is in turn considered as the possible initiating event. Each pathogenetic sequence is discussed in the context of the available evidence and is tentatively associated with a clinical subset of patients. A regular program of physical activity is very likely to improve glucose tolerance through an enhancement of insulin sensitivity. Newer sulfonylureas are promising measures to improve insulin resistance. The effects of dietary manipulations on insulin sensitivity need to be further assessed.

Original languageEnglish (US)
Pages (from-to)125-140
Number of pages16
JournalMedicine
Volume61
Issue number3
StatePublished - 1982
Externally publishedYes

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Glucose
Insulin Resistance
Insulin
Fasting
Glucose Intolerance
Hyperglycemia
Liver
Muscles
Vascular Resistance
Type 2 Diabetes Mellitus
Gastrointestinal Tract
Eating
Exercise

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The pathogenesis of non-insulin-dependent diabetes. An update. / Defronzo, Ralph A; Ferrannini, E.

In: Medicine, Vol. 61, No. 3, 1982, p. 125-140.

Research output: Contribution to journalArticle

Defronzo, RA & Ferrannini, E 1982, 'The pathogenesis of non-insulin-dependent diabetes. An update', Medicine, vol. 61, no. 3, pp. 125-140.
Defronzo, Ralph A ; Ferrannini, E. / The pathogenesis of non-insulin-dependent diabetes. An update. In: Medicine. 1982 ; Vol. 61, No. 3. pp. 125-140.
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