The Twin Cycle Hypothesis of type 2 diabetes aetiology: From concept to national NHS programme.

IF 2.6 4区医学 Q2 PHYSIOLOGY

Experimental Physiology Pub Date : 2025-02-03 DOI:10.1113/EP092009

Roy Taylor

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引用次数: 0

Abstract

The development of magnetic resonance methods for quantifying intra-organ metabolites has permitted advances in the understanding of fasting and post-prandial carbohydrate and lipid handling in people with and without type 2 diabetes. Insulin resistance in the liver was shown to be related to excess intra-organ fat and was able to be returned to normal by weight loss. The practical effect of having muscle insulin sensitivity in the lower part of the wide normal range resulted in the obligatory shunting of carbohydrates via de novo lipogenesis into saturated fat. These observations provided the basis for the Twin Cycle Hypothesis of the aetiology of type 2 diabetes. Subsequent studies on people with type 2 diabetes confirmed the postulated pathophysiological abnormalities and demonstrated their reversibility by dietary weight loss of 10-15 kg. Overall, the fundamental understanding of the mechanisms causing type 2 diabetes has bridged physiological and clinical perspectives. Large population-based randomised controlled trials confirmed the practical clinical application of the method of achieving substantial weight loss, and an NHS programme is now in place offering potential remission to people within 6 years of diagnosis.

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来源期刊

Experimental Physiology 医学-生理学

CiteScore

5.10

自引率

3.70%

发文量

262

审稿时长

1 months

期刊介绍： Experimental Physiology publishes research papers that report novel insights into homeostatic and adaptive responses in health, as well as those that further our understanding of pathophysiological mechanisms in disease. We encourage papers that embrace the journal’s orientation of translation and integration, including studies of the adaptive responses to exercise, acute and chronic environmental stressors, growth and aging, and diseases where integrative homeostatic mechanisms play a key role in the response to and evolution of the disease process. Examples of such diseases include hypertension, heart failure, hypoxic lung disease, endocrine and neurological disorders. We are also keen to publish research that has a translational aspect or clinical application. Comparative physiology work that can be applied to aid the understanding human physiology is also encouraged. Manuscripts that report the use of bioinformatic, genomic, molecular, proteomic and cellular techniques to provide novel insights into integrative physiological and pathophysiological mechanisms are welcomed.