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Drug Development for Diabetes Mellitus: Beyond Hemoglobin A1c

  • Fernando BrilEmail author
  • Marta Iruarrizaga-Lejarreta
  • Cristina Alonso
Chapter

Abstract

Improved understanding of the complex pathophysiology of type 2 diabetes provides a logical basis for target identification and the development of novel glucose-lowering agents. While the major driver of type 2 diabetes is obesity, if β-cells of the pancreatic islets are able to compensate for the obesity-associated insulin resistance by increasing insulin secretion, plasma glucose levels are initially preserved. Once β-cells are unable to maintain this high rate of insulin secretion, hyperglycemia develops. Despite being a relatively late manifestation in the course of insulin resistance, hyperglycemia remains the most important measurements used for the diagnosis and follow-up of patients with type 2 diabetes and to assess treatment response. Ideal biomarkers should be able to detect the early stages of the disease, when insulin resistance is present, but before the development of clinically significant hyperglycemia. We describe biomarkers related to hyperglycemia and their utility in drug development, as well as biomarkers of insulin resistance, which have the potential to identify early abnormalities in patients with type 2 diabetes and to detect nondiabetic subjects at risk of developing type 2 diabetes. Type 1 diabetes is characterized by severe insulin deficiency that necessitates life-long insulin replacement therapy. We consider the expanding role of continuous glucose monitoring in patients with diabetes. This technology is providing new insights into glucose variability, and it is being increasingly used to inform daily treatment decisions. Moreover, continuous glucose monitoring is also being used to inform the development of novel insulins and other classes of glucose-lowering medications.

Keywords

Blood-based biomarkers Hemoglobin A1c Hyperglycemia Insulin resistance Type 2 Diabetes Continuous glucose monitoring 

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Fernando Bril
    • 1
    • 2
    Email author
  • Marta Iruarrizaga-Lejarreta
    • 3
  • Cristina Alonso
    • 3
  1. 1.Division of Endocrinology, Diabetes and MetabolismUniversity of FloridaGainesvilleUSA
  2. 2.Malcom Randall Veterans Affairs Medical CenterGainesvilleUSA
  3. 3.OWL Metabolomics, Parque Tecnológico de BizkaiaDerioSpain

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