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Reviews in Endocrine and Metabolic Disorders
Published in: Reviews in Endocrine and Metabolic Disorders 4/2020

Open Access 01-12-2020 | Insulins

Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm

Author: Jacob Bar-Tana

Published in: Reviews in Endocrine and Metabolic Disorders | Issue 4/2020

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Abstract

The current paradigm of type 2 diabetes (T2D) is gluco-centric, being exclusively categorized by glycemic characteristics. The gluco-centric paradigm views hyperglycemia as the primary target, being driven by resistance to insulin combined with progressive beta cells failure, and considers glycemic control its ultimate treatment goal. Most importantly, the gluco-centric paradigm considers the non-glycemic diseases associated with T2D, e.g., obesity, dyslipidemia, hypertension, macrovascular disease, microvascular disease and fatty liver as ‘risk factors’ and/or ‘outcomes’ and/or ‘comorbidities’, rather than primary inherent disease aspects of T2D. That is in spite of their high prevalence (60–90%) and major role in profiling T2D morbidity and mortality. Moreover, the gluco-centric paradigm fails to realize that the non-glycemic diseases of T2D are driven by insulin and, except for glycemic control, response to insulin in T2D is essentially the rule rather than the exception. Failure of the gluco-centric paradigm to offer an exhaustive unifying view of the glycemic and non-glycemic diseases of T2D may have contributed to T2D being still an unmet need. An mTORC1-centric paradigm maintains that hyperactive mTORC1 drives the glycemic and non-glycemic disease aspects of T2D. Hyperactive mTORC1 is proposed to act as double-edged agent, namely, to interfere with glycemic control by disrupting the insulin receptor-Akt transduction pathway, while concomitantly driving the non-glycemic diseases of T2D. The mTORC1-centric paradigm may offer a novel perspective for T2D in terms of pathogenesis, clinical focus and treatment strategy.
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Metadata
Title
Type 2 diabetes – unmet need, unresolved pathogenesis, mTORC1-centric paradigm
Author
Jacob Bar-Tana
Publication date
01-12-2020
Publisher
Springer US
Published in
Reviews in Endocrine and Metabolic Disorders / Issue 4/2020
Print ISSN: 1389-9155
Electronic ISSN: 1573-2606
DOI
https://doi.org/10.1007/s11154-020-09545-w

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