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. 2011 Jan;60(1):1-8.
doi: 10.2337/db10-1114.

Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man

Jay S Skyler  1 , Camillo Ricordi
Affiliations

Stopping type 1 diabetes: attempts to prevent or cure type 1 diabetes in man

Jay S Skyler et al. Diabetes. 2011 Jan.
No abstract available

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Figures

FIG. 1.
FIG. 1.
Progression of the type 1 diabetes disease process. This is a cellular autoimmune process occurring in individuals with a genetic predisposition to the disease, presumably triggered by some environmental factor. Humoral antibodies indicate that the disease process is underway, and there is then progressive impairment of β-cell function manifested by progressive deterioration of glucose metabolism. The time frame is variable, so the x-axis is dimensionless. IAA, insulin autoantibody; ICA, islet cell antibody; IVGTT, intravenous glucose tolerance test; OGTT, oral glucose tolerance test.
FIG. 2.
FIG. 2.
Potential time points for intervention to alter the type 1 diabetes disease process. Intervention may be attempted in the genetically at-risk to try to abrogate autoimmunity, in those with antibodies signifying that the disease process is underway, or in those with varying degrees of metabolic abnormalities, including at the time of clinical onset of type 1 diabetes.
FIG. 3.
FIG. 3.
Progressive decline of β-cell function (measured by C-peptide) is evident even in studies that are successful. These include intervention with the anti-CD3 monoclonal antibodies teplizumab (A) (21) and otelixizumab (B) (22), the anti-CD20 monoclonal antibody rituximab (C) (23), and a GAD vaccine with aluminum (Alum) adjuvant (D) (24). AUC, area under the curve.
FIG. 4.
FIG. 4.
Potential scheme for combination therapy to interdict the type 1 diabetes disease process. Such a combination might include an anti-inflammatory therapy (e.g., anti–interleukin-1β [anti-IL1β] or anti-tumor necrosis factor [anti-TNF]), an immunomodulatory therapy (e.g., anti-CD3, anti-CD20, or co-stimulatory blockade), followed by initiation of antigen-specific therapy (e.g., GAD and/or oral insulin), with stimulation of protective immunity (e.g., with granulocyte colony stimulation factor [GCSF]) or provision of protective immunity by infusion of T-regulatory (T-reg) cells, and with stimulation of β-cells (e.g., with glucagon-like peptide 1 [GLP-1], exenatide, or human proislet peptide-2B [HIP-2B]). The time frame needs to be determined, so the x-axis is dimensionless.
FIG. 5.
FIG. 5.
The scale of various approaches to immunoisolation (37). Macro-scale encapsulation devices include intravascular, which are perfused with blood, or extravascular devices. Micro-scale devices are typically microcapsules (as illustrated). Nano-scale encapsulation commonly employs the coating of the islet spheroid with polymeric layers, such as conformal coating.
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