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  • Review Article
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Coming full circle in diabetes mellitus: from complications to initiation

Nature Reviews Endocrinology volume 9, pages 113–123 (2013)Cite this article

Subjects

Abstract

Glycaemic control, reduction of blood pressure using agents that block the renin–angiotensin system and control of dyslipidaemia are the major strategies used in the clinical management of patients with diabetes mellitus. Each of these approaches interrupts a number of pathological pathways, which directly contributes to the vascular complications of diabetes mellitus, including renal disease, blindness, neuropathy and cardiovascular disease. However, research published over the past few years has indicated that many of the pathological pathways important in the development of the vascular complications of diabetes mellitus are equally relevant to the initiation of diabetes mellitus itself. These pathways include insulin signalling, generation of cellular energy, post-translational modifications and redox imbalances. This Review will examine how the development of diabetes mellitus has come full circle from initiation to complications and suggests that the development of diabetes mellitus and the progression to chronic complications both require the same mechanistic triggers.

Key Points

  • The development of diabetes mellitus and its associated vascular complications share common pathogenic pathways

  • Vascular damage is often the result of imbalances in glucose handling at many sites within the cardiovascular system

  • Dyslipidaemia and abnormalities in cellular energetics are frequently seen in both the development of diabetes mellitus and its associated vascular complications

  • Research programs should now investigate patterns of damage across the body in patients with diabetes mellitus

  • Grouping and characterization of patterns in the initiation of diabetes mellitus to enable comparison with patterns in vascular complications of diabetes mellitus might result in superior therapies

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Figure 1: Pathway leading to the dysfunction of cellular energy generation that results in diabetic complications.

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  1. Glycation and Diabetes Complications, Mater Medical Research Institute, Level 3, Aubigny Place, Raymond Terrace, South Brisbane, QLD 4101, Australia

    Brooke E. Harcourt, Sally A. Penfold & Josephine M. Forbes

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B. E. Harcourt and J. M. Forbes contributed to researching data for the article, discussion of content, writing the article and reviewing/editing the article before submission. S. A. Penfold contributed to researching data for the article and writing the article.

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Harcourt, B., Penfold, S. & Forbes, J. Coming full circle in diabetes mellitus: from complications to initiation. Nat Rev Endocrinol 9, 113–123 (2013). https://doi.org/10.1038/nrendo.2012.236

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