Background The Network for Pancreatic Organ donors with Diabetes was established to recover and characterize pancreata and related organs from cadaveric organ donors with various risk levels for type 1 diabetes (T1D). These biospecimens are available to investigators for collaborative studies aimed at addressing questions related to TID natural history and pathogenesis. Research design and methods Organ donors included T1D patients (new-onset to long-term), non-diabetic autoantibody positive subjects, non-diabetic controls, and individuals with disorders relevant to β-cell function. Pancreas recovery and transport met transplant-grade criteria. Additional samples recovered included serum, whole blood, spleen, and pancreatic and non-pancreatic lymph nodes. Biospecimens were processed for cryopreserved cells, fixed paraffin and fresh frozen blocks, and snap frozen samples. T1D autoantibodies, c-peptide levels, and high-resolution HLA genotyping for risk alleles were also determined. Results Over 160 donors have been enrolled (ages of 1 day to > 90 years). Standard operating procedures were established along with a quality management system. Donor demographics, laboratory assays, and histopathological characterizations were shared through an open online informatics system. Biospecimens were distributed to more than 60 investigators. Conclusions The nPOD program provides access to high quality biospecimens without cost to investigators. Collaborations and open data sharing are emphasized to maximize research potential of each donor. Based on initial successes, the nPOD program is expanding to recover additional organs relevant to T1D pathogenesis and complications from European countries (PanFin network).

A new synthetic procedure developed recently in our laboratories has made possible the synthesis of variety of new complexes of CuCN with diamines. Synthesis was effected by adding the ligand to a solution of CuCN in aqueous sodium thiosulfate. This procedure also provides an alternative pathway to a novel diamine complex reported by us previously, (CuCN)(3)(HMTA)(2) (1) (where HMTA = hexamethylenetetramine). The other diamine ligands used were 1,4-diazabicyclo[2.2.2]octane (dabco), 1,4-dimethylpiperazine (dmpip), piperazine (pip), 1,4-butanediamine (butda), N,N,N',N'-tetramethylethylenediamine (tetmen), and N-phenylpiperazine (phpip). Complex2, Cu(2)(CN)(3)(dabco-H), crystallizes in the hexagonal space group P6(3) with unit cell dimensions a = 8.174(3) Å, c = 8.083(4) Å, and Z = 2. Complex 3, (CuCN)(2)(dmpip), crystallizes in the monoclinic space group C2/m with unit cell dimensions a = 8.812(3) Å, b = 9.631(2) Å, c = 7.266(3) Å, beta = 113.40(3) degrees, and Z = 2. Complex 4, (CuCN)(2)(pip), crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 9.439(3) Å, b = 10.561(2) Å, c = 8.870(3) Å, beta = 98.32(3) degrees, and Z = 4. Complex 5, Cu(2)(CN)(3)(pip-H), crystallizes in the monoclinic space group C2/c with unit cell dimensions a = 20.573(9) Å, b = 8.354(2) Å, c = 15.989(6) Å, beta = 133.70(3) degrees, and Z = 8. Complex 6, (CuCN)(2)(butda), crystallizes in the monoclinic space group P2(1)/c with unit cell dimensions a = 10.456(2) Å, b = 5.550(1) Å, c = 8.669(3) Å, beta = 106.80(2) degrees, and Z = 2. Complex 7, (CuCN)(2)(tetmen), crystallizes in the orthorhombic space group Cmc2(1) with unit cell dimensions a = 11.889(4) Å, b = 33.380(8) Å, c = 9.012(3) Å, and Z = 12. Complex 8, (CuCN)(phpip), crystallizes in the monoclinic space group P2(1)/cwith unit cell dimensions a = 17.8819(3) Å, b = 6.9190(1) Å, c = 8.6972(1) Å, beta = 96.720(1) degrees, and Z = 4.

SummaryLike many other complex human disorders of unknown aetiology, autoimmune-mediated type 1 diabetes may ultimately be controlled via a therapeutic approach that combines multiple agents, each with differing modes of action. The numerous advantages of such a strategy include the ability to minimize toxicities and realize synergies to enhance and prolong efficacy. The recognition that combinations might offer far-reaching benefits, at a time when few single agents have yet proved themselves in well-powered trials, represents a significant challenge to our ability to conceive and implement rational treatment designs. As a first step in this process, the Immune Tolerance Network, in collaboration with the Juvenile Diabetes Research Foundation, convened a Type 1 Diabetes Combination Therapy Assessment Group, the recommendations of which are discussed in this Perspective paper.

No abstract