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Residual insulin secretion seen in individuals with longstanding type 1 diabetes

By Bianca Nogrady
Around one-third of individuals with long-standing type 1 diabetes have some residual insulin secretion and most retain at least some insulin-positive pancreatic beta cells, research suggests.

A longitudinal US study of 1019 individuals with type 1 diabetes and a documented history of at least 50 years of insulin dependence has found that 32.4% of study participants still had detectable C-peptide levels greater 0.05 ng/mL.

According to the findings, published in the Journal of Clinical Investigation, 5.8% of the 516 individuals who underwent a mixed-meal tolerance test responded with a doubling of baseline C-peptide levels, and over a median of four years of follow up, 12.2% of participants showed an increase in C-peptide levels.

Postmortem study of the pancreases of 68 participants showed all of them still had some insulin-positive pancreatic beta cells, and 14 had pancreatic lobes with multiple islets containing many insulin-positive cells.

Researchers also saw changes in the presence or absence of autoantibodies that are a hallmark of type 1 diabetes. Of the 77 individuals who tested positive for autoantibodies at their first study visit, 26% had converted to antibody-negative status on their second visit. Similarly, among the 103 individuals who were antibody-negative at their first visit, 16.5% had converted to antibody-positive at the second visit.

The study also looked at the genetic signatures for diabetes, and found that 7.9% of individuals carried monogenic diabetes variants.

Commenting on the study, Professor Jerry Greenfield, Head of Endocrinology at St Vincent’s Hospital in Sydney, said the finding of residual insulin secretion, even after such a long duration of disease, challenged current wisdom about the nature of type 1 diabetes.

‘Presumed thinking until now has been that insulin secretion decreases over time due to beta-cell failure and that individuals with type 1 diabetes for many decades have very little in the way of residual insulin secretion,’ he told Endocrinology Today.

He also noted the finding of pathogenic mutations in some individuals suggested that some may have been misclassified as having type 1 diabetes when in fact they had mature-onset diabetes of the young; a monogenic, inherited form of diabetes that often presents in adolescents or young adults.
J Clin Invest 2019; https://doi.org/10.1172/JCI127397.