Twin cycle hypothesis in the pathogenesis of type 2 diabetes may explain relapse following remission of type 2 diabetes

The twin cycle hypothesis proposed that type 2 diabetes occurs due to accumulation of fat in the liver, which induces insulin resistance, and hyperinsulinaemia – leading to a self-reinforcing cycle, by which insulin stimulates fat production, which spills into the pancreas and causes type 2 diabetes. Based on this, recent experimental and clinical studies have shown that Very low Calorie diet can induce remission of type 2 diabetes. However data from DIRECT suggest that a proportion of patients experienced relapse. A further study published in Cell Metabolism have investigated the mechanism of ‘relapse’ by quantifying liver and pancreas fat at 12 and 24 months. The study showed that those who relapse appears to re-accumulate liver and intra-pancreatic fat, which supports the twin cycle hypothesis. This study was the first to report the underlying physiological changes during a full cycle of disease reversal and re-emergence, and could form a basis for future study to induce long-term diabetes remission following dietary intervention.

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