At Last...Type 1 Diabetes Can Be Prevented (But Only in Rats)!

Abstract & Commentary

By Jeff Unger, MD, Director, Metabolic Studies, Catalina Research Institute, Chino, CA. Dr. Unger reports no financial relationships relevant to this field of study.

Synopsis: The author reviewed the strategies of predicting and preventing type 1 diabetes across the different stages of development of the disorder. Not only can risk for type 1 diabetes be predicted, but the approximate age of diabetes onset in children can be ascertained. Although diabetes can be prevented in animal models, clinical trials in humans have demonstrated only the ability to delay loss of insulin secretion. To date, no clinical trial has resulted in complete reversal and restoration of pancreatic beta-cell function in human subjects.

Source: Eisenbarth GS. Prevention of type 1A diabetes mellitus. Endocr Pract 2012;18:745-749.

Type 1 diabetes (T1D) is a chronic progressive autoimmune disorder affecting more than 500,000 Americans. The pathogenetic stages of T1D begin with genetic susceptibility, followed by a triggering of autoimmunity marked by the appearance of islet autoantibodies (autoantibodies to insulin, glutamic acid decarboxylates, insulinoma-associated antigen, and the islet zinc transporter), followed by progressive beta-cell death (apoptosis) and overt hyperglycemia. The initial and primary antigenic target in humans is endogenous insulin. The levels of insulin autoantibody appearance correlate with the rate of progression toward hyperglycemia. Interestingly, some patients who have had T1D for more than 50 years demonstrate histologic evidence within some islets of complete destruction, whereas other islets appear to be normal.1 Pathologic examinations of pancreases from islet autoantibody-positive cadaver donors have shown both insulinitis and areas of psuedoatrophic islets consistent with a chronic-progressive autoimmune beta-cell destructive process.2

The results of clinical trials that have been designed to address each of the phases of autoimmune pathogenesis in T1D are listed in Table 1 (see Table 1).

Table 1 Clinical Trials Designed to Prevent T1D*

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In summary, no effective and safe antigen-specific immunologic therapy exists for reversing type 1 diabetes in high-risk patients. Newly diagnosed patients with T1D should be made aware of screening and intervention studies such as T1D TrialNet through the National Institutes of Health (http://www.diabetestrialnet.org). Ultimately, preventive therapies for T1D will require combinations of interventions to fully mitigate one’s dysregulated immunity.

References

1. Keenan HA, et al. Residual insulin production and pancreatic b-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes 2010;59:2846-2853.

2. In’t Veld P, et al. Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 2007;56:2400-2404.