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Insulin Secretion Restored At Diagnosis of Type 1 With Tight Control

New study focuses on isolated islets of Langerhans.

Thirty years ago, a convergence of investigational observations lead to the now widely accepted notion that type 1 diabetes results from an autoimmune destruction of insulin-producing β-cells in subjects genetically predisposed to the disease. Believing in the concept of “informative failures” (a.k.a., wise people learn from their mistakes), this lecture reviews the knowledge base collected over this time period and, when combined with an analysis of those research experiences, sets forth a proposal for future investigations.

While the relative importance of reduced β-cell function versus reduced β-cell mass is currently debated in type 2 diabetes, T1D has been considered the classic example where diabetes results from reduced β-cell mass secondary to autoimmune attack. However, this view has recently been challenged.

So far, there were not many studies about the etiology of type 1 diabetes, and the understanding of the functionality of islet of Langerhans was limited. However, a new study published in Diabetes reported the ability of insulin secretion and the expression of insulin pathway genes in isolated islets of Langerhans. They obtained pancreatic tissue from recent onset type 1 diabetes patients and nondiabetic patients.

This study was the Diabetes Virus Detection (DiViD) study, which was to collect pancreatic tissue from living subjects shortly after diagnosing of type 1 diabetes. The outcomes were to exam the islet function and whole transcriptome sequencing of isolated islets of Langerhans.

For patients at onset of type 1 diabetes, all human transcripts were presented in the insulin pathway. In these group of patients, some of them had glucose-induced insulin secretion. Moreover, insulin release was obtained after some days in a nondiabetogenic environment in the lab. In type 1 diabetes patients, normally not all beta cells were functioning. Now this study indicated insulin secretion could be restored after removing them from the diabetogeinc millieu. Due to the small number of samples in this study, the researchers called for further studies to aim to restore beta cell function.

While the relative importance of reduced β-cell function versus reduced β-cell mass is currently debated in type 2 diabetes, T1D has been considered the classic example where diabetes results from reduced β-cell mass secondary to autoimmune attack. However, this view has recently been challenged.

In another study, published in Diabetes, Krogvold et al. compared residual glucose-dependent insulin secretion and whole-genome RNA sequencing of islet tissue from donors with and without diabetes. Islets were obtained from adult T1D subjects soon after the onset of the disease. Recent studies have shown that residual plasma C-peptide levels are present long after the onset of diabetes in patients with T1D. A third possibility is that the surviving β-cells, being in the minority, may simply represent the tail end of the normal distribution of islets originally residing in the pancreas. Finding residual C-peptide secretion is correlated with a more favorable long-term clinical outcome, including better metabolic control and a lower risk for micro- and macrovascular complications.

In five of six adult subjects with T1D, where islets could be successfully isolated from pancreatic tissue residual glucose-dependent insulin secretion could be observed in vitro, and culturing the T1D islets for 1–6 days under euglycemic conditions tended to improve overall secretory function and sometimes even restored first-phase insulin secretion. While there have been previous reports of β-cell function persisting in islets from T1D patients, these have been few and far between as human T1D islets are rarely isolated for study. In addition, previous studies resulted in generally discrepant data regarding the ability of culture to improve function. The current data set is more extensive than those of the few previous studies, and the relative rarity of this kind of research adds considerably to the significance of this work to the field, even if the data are understandably incomplete.

The question becomes, can euglycemia prevent the destruction of the remaining beta-cells?

Practice Pearls:

  • A DiViD study accessed the ability of insulin secretion and the expression of insulin pathway genes in isolated islets of Langerhans.
  • Researchers found out glucose-induced insulin secretion and insulin release were presented in patients at onset of type 1 Diabetes.
  • The researchers called for further studies to aim to restore beta cell function.

Publisher’s note: Keeping blood sugars normal at diagnosis of type 1 diabetes can extend the honeymoon period dramatically.

Krogvold L, Skog O, Sundstorm G, Edwin B, Bueane T, Hanssen K, Ludvigsson J, Grabherr M, Korsgren, O, Dahi K. Fucntion of Isolated Pancreatic Islets From Patients at Onset of Type 1 Diabetes: Insulin Secretion Can Be Restored After Some Days in a Nondiabetogenic Environment In Virto: Results form the DiViD Study. Diabetes. Volume 64(7), July 2015, p2506-2512