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

Reviews in Endocrine & Metabolic Disorders
Jacob Bar-Tana

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 glycem...Continue Reading

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Citations

Aug 23, 2020·International Journal of Environmental Research and Public Health·Zarish NoreenSomiranjan Ghosh
Nov 27, 2020·Frontiers in Immunology·John V ForresterMirela Delibegovic
Jun 15, 2021·Journal of Developmental Origins of Health and Disease·Saúl Lira-AlbarránPaolo Rinaudo
Sep 21, 2021·Reviews in Endocrine & Metabolic Disorders·Wiktoria RatajczakCatriona Kelly

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Methods Mentioned

BETA
GTPase
ubiquitination

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