Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have been in progress, yet this surgical procedure still remains the treatment of choice for diabetic patients with end-stage renal failure. Many improvements have been made in the surgical techniques and immunosuppressive regimens, both of which have contributed to an increasing number of indications for pancreas transplantation. This operation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure and lifelong immunosuppression. The various indications, categories, and outcomes of patients having a pancreas transplant are discussed, particularly with reference to the effect on long-term diabetic complications.

Background: Success in management of diabetes mellitus (DM) is defined as improvement of blood glucose concentrations and clinical signs. However, the psychological and social impact of DM and its daily treatment regimen on quality of life (QoL) of both animal and owner is uncertain. Hypothesis/Objectives: To design, validate, and apply a diabetic pet and owner‐centered, individualized measure of impact of DM (DIAQoL‐pet). Animals/Subjects: Two hundred and twenty‐one owners of insulin‐treated diabetic cats were recruited to complete the DIAQoL‐pet. Methods: Discussions and pilot surveys with clinicians and owners of diabetic cats led to the design of 29 specific DM‐associated QoL questions. Owners of diabetic cats completed the finalized survey. Each item was scored according to impact frequency and perceived importance. An item‐weighted impact score (IWIS) for each item was calculated, as was an average‐weighted impact score (AWIS) by averaging all IWISs. Principal component analysis and Cronbach's α calculation assessed the measure's reliability. Two overview questions measured overall QoL and diabetes‐dependent QoL. Results: The DIAQoL‐pet showed high reliability (Cronbach α 0.83). The AWIS was −1.76 ± 2.4 (mean ± SD). Areas reported as most negatively impacting QoL included: “boarding difficulties” (IWIS ± SD: −4.67 ± 5.3), “owner wanting more control” (−4.34 ± 4.7), “difficulties leaving cat with friends or family” (−4.21 ± 4.7), “worry” (−4.10 ± 3.9), “worry hypo” (−3.67 ± 3.5), “social life” (−3.48 ± 3.9), “costs” (−3.04 ± 3.8), and “work life” (−3.03 ± 3.7). Forty‐one percent of owners believed their cat's life would be “a little better” without DM. Conclusions and Clinical Importance: The DIAQoL‐pet proved robust and identified specific areas most negatively impacting on diabetic cats and their owners' QoL. This tool warrants further investigation for use in clinical or research settings.

β-cell replacement therapy, available currently as pancreas or islet transplantation, has developed without a clear definition of graft functional and clinical outcomes. The International Pancreas & Islet Transplant Association (IPITA) and European Pancreas & Islet Transplantation Association (EPITA) held a workshop to develop consensus for an IPITA/EPITA Statement on the definition of function and failure of current and future forms of β-cell replacement therapy. There was consensus that β-cell replacement therapy could be considered as a treatment for β-cell failure, regardless of etiology and without requiring undetectable C-peptide, accompanied by glycemic instability with either problematic hypoglycemia or hyperglycemia. Glycemic control should be assessed at a minimum by glycated hemoglobin (HbA ) and the occurrence of severe hypoglycemia. Optimal β-cell graft function is defined by near-normal glycemic control [HbA ≤ 6.5% (48 mmol/mol)] without severe hypoglycemia or requirement for insulin or other antihyperglycemic therapy, and with an increase over pretransplant measurement of C-peptide. Good β-cell graft function requires HbA < 7.0% (53 mmol/mol) without severe hypoglycemia and with a significant (>50%) reduction in insulin requirements and restoration of clinically significant C-peptide production. Marginal β-cell graft function is defined by failure to achieve HbA < 7.0% (53 mmol/mol), the occurrence of any severe hypoglycemia, or less than 50% reduction in insulin requirements when there is restoration of clinically significant C-peptide production documented by improvement in hypoglycemia awareness/severity, or glycemic variability/lability. A failed β-cell graft is defined by the absence of any evidence for clinically significant C-peptide production. Optimal and good functional outcomes are considered successful clinical outcomes.

Studies in animal models of type 2 diabetes have shown that glucagon-like peptide 1 (GLP-1) receptor agonists prevent β-cell loss. Whether GLP-1 mediates β-cell survival via the key lysosomal-mediated process of autophagy is unknown. In this study, we report that treatment of INS-1E β-cells and primary islets with glucolipotoxicity (0.5 mmol/L palmitate and 25 mmol/L glucose) increases LC3 II, a marker of autophagy. Further analysis indicates a blockage in autophagic flux associated with lysosomal dysfunction. Accumulation of defective lysosomes leads to lysosomal membrane permeabilization and release of cathepsin D, which contributes to cell death. Our data further demonstrated defects in autophagic flux and lysosomal staining in human samples of type 2 diabetes. Cotreatment with the GLP-1 receptor agonist exendin-4 reversed the lysosomal dysfunction, relieving the impairment in autophagic flux and further stimulated autophagy. Small interfering RNA knockdown showed the restoration of autophagic flux is also essential for the protective effects of exendin-4. Collectively, our data highlight lysosomal dysfunction as a critical mediator of β-cell loss and shows that exendin-4 improves cell survival via restoration of lysosomal function and autophagic flux. Modulation of autophagy/lysosomal homeostasis may thus define a novel therapeutic strategy for type 2 diabetes, with the GLP-1 signaling pathway as a potential focus.