Islet Cell Regeneration: It's Not Over 'Til It's Over
As I continue to peruse this site and read the latest news about diabetes, I can't help but be optimistic about the latest treatment innovations and the progress of different research avenues. One of Ann Bartlett's research update bullets particularly caught my attention: "pancreatic islet cells living in established diabetics." As per my usual practice, I went directly to the original literature. The article "Residual Insulin production and Pancreatic (beta cell) turnover after 50 years of Diabetes: Joslin medals study" (published online ahead of the actual paper) in Diabetes by Keenan et al (senior author G.King) provided significant evidence-based data to support islet cell regeneration!
The study evaluated pancreatic beta cell function in people with type 1 diabetes over 50 years of age. The participants were 56.2+/- 5.8 years and 67.2 +/- 7.5 years. The insulin dose was 0.46 +/- 0.2 units. 94 percent were positive for the DR3/DR4 alleles and 29.5 percent were positive for IA2 and GAD 65 autoantibodies. The random c-peptide level (indicative of endogenous insulin secretion was >64.4 percent (minimal 0.03-0.2 nmol/L) or sustained range (>0.2 nmol/L). Post mortem examination of the pancreas from nine medallists revealed that ALL had endogenous insulin and beta cells (some positive for evidence of death (apoptosis), proliferation and insulinitis). In summary, the persistence and function of insulin producing cells strongly suggests the possibility of "steady -state turnover in which stimuli to enhance endogenous Beta cell survival could be a viable therapeutic approach in a significant number of people with type 1 diabetes even with a chronic duration of illness."
Why is this report of evidenced-based data so significant? Treatment of type 1 diabetes will most likely consist of multiple approaches targeting different modalities at different stages of the illness. Immunotherapy, if demonstrated to be safe with minimal side effects, is becoming a major player, particularly during the initial onset of T1DM. Indeed Phase 3 trials in the DEFEND 2 study are currently underway. The entrance criteria for this study includes diagnosis of type 1 diabetes within 10 weeks and ages 12-45. The DEFEND 2 Trial Phase 3 study drug is Otelixzumab, a monoclonal antibody that attacks killer T cells that destroy the pancreatic B islet cells. Several patients with relatively new onset T1DM in our Children's National Medical Center practice are in DEFEND 2 Phase 3 trials at other research institutions. Once these monoclonal antibodies (and there are several) are demonstrated to be safe and effective in early onset diabetes, you may be assured that the next step in these trials is to study the monoclonal antibodies in people with different durations of T1DM. Thus, the continual regeneration of pancreatic beta islet cells despite autoimmune destruction is a major asset to the armamentarium of future therapeutic regimens.
I still believe that the future therapy (maybe even the near future) of type 1 diabetes will be a trifecta. The first arm will aim towards prevention with a (yet to be discovered) vaccine in those individuals that have been demonstrated to be at high risk (through antibody testing in studies like TrialNet). The second arm will include treatment with insulin (multiple daily injections/insulin pump/ continuous blood glucose sensor/ artificial pancreas/ next big innovation etc.). The third arm will be developed to treat diabetes with medications such as immunotherapeutic agents to be employed at various stages of type 1 diabetes to save and preserve pancreatic islet cells and in effect, allow for their regeneration. The key will be to produce enough Beta cells to secrete just enough insulin to maintain insulin production-a perpetual honeymoon period of sorts! Therefore, the importance in maintaining daily glycemic control cannot be underestimated and behavioural tools to improve adherence will continue to be necessary until our research colleagues provide 2 out of my 3 potential arms of treatment.
Remember, as Yogi Berra once said, "It's not over, 'til it's over!"