Identifying Biomarkers of Subclinical Diabetes

  1. Rohit N. Kulkarni
  1. Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Boston, Massachusetts
  1. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  1. Corresponding author: Rohit N. Kulkarni, rohit.kulkarni{at}

The epidemic of type 2 diabetes and the ever-increasing economic burden on society is a constant reminder of the continuing need for better therapeutic approaches to delay and/or prevent the onset of overt diabetes. Although tremendous scientific advances in our understanding of the signaling pathways and metabolism of individual tissues that are considered central to the pathophysiology of diabetes have occurred over the last several decades, efforts to reliably detect the subclinical stages early in the pathological process have remained elusive (1).

Studies aimed at detecting early stages in any disease are key for defining successful therapy, and in the case of type 2 diabetes, it is especially critical given the morbidity and mortality arising from uncontrolled hyperglycemia and multiorgan complications associated with this disease. The initial promise of the “omics” approach that evolved rapidly over the last decade has yet to deliver a cheap, widely-used biomarker that can reliably predict the development of overt diabetes. This may be related in part to the polygenic nature of the disease itself, the variable time of onset, and the progressive and unpredictable multiorgan pathophysiology that continues to challenge scientists. Given these variables, investigators have focused on finding a marker that can be linked to a consistent feature that characterizes overt diabetes such as hyperinsulinemia (e.g., proinsulin) to predict the ensuing uncontrolled hyperglycemia. However, few studies have been successful in identifying a marker of β-cell failure.

Renner and colleagues have taken advantage of the finding that patients with type 2 …

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