Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 16 (2), 118-127

Insulin Resistance and Insulin Hypersecretion in the Metabolic Syndrome and Type 2 Diabetes: Time for a Conceptual Framework Shift

Affiliations
Review

Insulin Resistance and Insulin Hypersecretion in the Metabolic Syndrome and Type 2 Diabetes: Time for a Conceptual Framework Shift

Christopher J Nolan et al. Diab Vasc Dis Res.

Abstract

While few dispute the existence of the metabolic syndrome as a clustering of factors indicative of poor metabolic health, its utility above that of its individual components in the clinical care of individual patients is questioned. This is likely a consequence of the failure of clinicians and scientists to agree on a unifying mechanism to explain the metabolic syndrome. Insulin resistance has most commonly been proposed for this role and is generally considered to be a root causative factor for not only metabolic syndrome but also for its associated conditions of non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), obesity-related type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). An alternative view, for which evidence is mounting, is that hyper-responsiveness of islet β-cells to a hostile environment, such as westernised lifestyle, is primary and that the resulting hyperinsulinaemia drives the other components of the metabolic syndrome. Importantly, within this new conceptual framework, insulin resistance, while always a biomarker and state of poor metabolic health, is not considered to be harmful, but a protective adaptive response of critical tissues including the myocardium against insulin-induced metabolic stress. This major shift in how metabolic syndrome can be considered puts insulin hypersecretion into position as the unifying mechanism. If shown to be correct, this new conceptual framework has major implications for the future prevention and management of the metabolic syndrome, including its associated conditions of NAFLD, PCOS, obesity-related T2D and ASCVD.

Keywords: Cardiovascular diseases; insulin hypersecretion; insulin resistance; insulin-mediated metabolic stress; metabolic syndrome; non-alcoholic fatty liver disease; polycystic ovary syndrome; type 2 diabetes.

Similar articles

See all similar articles

Cited by 8 articles

See all "Cited by" articles

Publication types

MeSH terms

Grant support

LinkOut - more resources

Feedback