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Biologic therapeutics are currently not approved for the treatment of patients with type 1 and type 2 diabetes. However, promising results from recent randomized controlled studies suggest that biologic therapeutics have therapeutic potential. This article summarizes the causal steps of the pathogenesis of type 1 and type 2 diabetes which are targeted by biologic therapeutics and reviews the treatment results.

Interleukin-1 receptor antagonist (IL-1Ra) expression is reduced in islets of patients with type 2 diabetes. 70 patients with type 2 diabetes were randomized to treatment with anakinra (IL-1Ra) or placebo for 13 weeks. Following treatment glycated hemoglobin was 0.46 percent lower, C-peptide secretion was enhanced, and systemic IL-6 and C-reactive protein levels were reduced in the anakinra group compared to the placebo group. Insulin resistance remained unchanged. Blocking IL-1 activity improved glycemia and b-cell secretory function and reduced markers of systemic inflammation.

The 1999 WHO classification delineates immune mediated type 1 diabetes from other types of diabetes by the presence of auto-antibodies against beta-cell constituents. The GAD65 auto-antibody test is the method of first choice because it has the highest sensitivity, specificity and positive predictive value and is the most standardized and well-characterized type 1 diabetes related auto-antibody analysis. It is recommended that demonstration of GAD auto-antibodies leads to diagnosis, classification or re-classification of diabetes patients as immune mediated type 1 diabetes.

After introduction of recombinant human insulin, immunological reactions have become rare, but symptomatic immune reactions to insulin still occur. We present four insulin-treated diabetic patients who developed hypersensitivity to insulin or additives to insulin preparations. We show that symptomatic immunological reactions to insulin have not been eliminated by the introduction of recombinant human insulin. Furthermore it demonstrates the importance of skin-biopsy-verified diagnoses and the relevance of differentiation between different types of insulin allergy.

Rubella infection in utero is associated with a high risk of later development of type 1 diabetes. The mechanism is still unclear although the balance between the so-called Th1 and Th2 immune response seems to be important. Whether viral infections are involved in the pathogenesis of the common type of immune mediated type 1 diabetes is still unclear. Prospective serological investigations suggest a higher frequency of enteroviral infections in utero or in early childhood in children later developing type 1 diabetes. There is a need for confirmatory investigations of these observations especially with regard to demonstration of viral genome.