The Clinical Impact of Islet Transplantation Fiorina, P.; Shapiro, A. M. J.; Ricordi, C. ...
American journal of transplantation,
October 2008, Letnik:
8, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Islet cell transplantation has recently emerged as one of the most promising therapeutic approaches to improving glycometabolic control in diabetic patients and, in many cases, achieving insulin ...independence. Unfortunately, many persistent flaws still prevent islet transplantation from becoming the gold standard treatment for type 1 diabetic patients. We review the state of the art of islet transplantation, outcomes, immunosuppression and—most important—the impact on patients' survival and long‐term diabetic complications and eventual alternative options. Finally, we review the many problems in the field and the challenges to islet survival after transplantation. The rate of insulin independence 1 year after islet cell transplantation has significantly improved in recent years (60% at 1 year posttransplantation compared with 15% previously). Recent data indicate that restoration of insulin secretion after islet cell transplantation is associated with an improvement in quality of life, with a reduction in hypoglycemic episodes and potentially with a reduction in long‐term diabetic complications. Once clinical islet transplantation has been successfully established, this treatment could even be offered to diabetic patients long before the onset of diabetic complications.
The authors review islet transplant outcomes and immunosuppression, and in particular the impact on patient survival and diabetic complications, as well as alternative options.
Inflammatory bowel disease (IBD) is defined as a relapsing and remitting condition characterized by chronic inflammation at different sites in the gastrointestinal tract. Crohn's disease (CD) and ...ulcerative colitis (UC) represents the two major forms of IBD. Even though IBD pathophysiology is still not fully understood, genetic factors, environmental factors, dysregulation of both innate and adaptive immune responses, alterations in gut microbiota composition, excessive consumption of saturated fats and cumulative antibiotic exposure have all been suggested to play a role in the development of this condition. Amongst the environmental factors, vitamin D deficiency has been suggested to participate in IBD pathophysiology. Indeed, vitamin D exerts several pleiotropic effects beyond its well-established regulation of bone and calcium homeostasis, including anti-infective, anti-inflammatory and immunomodulatory effects as well as maintenance of gastrointestinal barrier integrity and beneficial gut microbiota composition. In this narrative review, we discuss the role of vitamin D deficiency in IBD pathophysiology as well as the potential therapeutic use of vitamin D for the management of IBD.
The Collaborative Islet Transplant Registry (CITR) collects data on clinical islet isolations and transplants. This retrospective report analyzed 1017 islet isolation procedures performed for 537 ...recipients of allogeneic clinical islet transplantation in 1999–2010. This study describes changes in donor and islet isolation variables by era and factors associated with quantity and quality of final islet products. Donor body weight and BMI increased significantly over the period (p < 0.001). Islet yield measures have improved with time including islet equivalent (IEQ)/particle ratio and IEQs infused. The average dose of islets infused significantly increased in the era of 2007–2010 when compared to 1999–2002 (445.4 ± 156.8 vs. 421.3 ± 155.4 ×103 IEQ; p < 0.05). Islet purity and total number of β cells significantly improved over the study period (p < 0.01 and <0.05, respectively). Otherwise, the quality of clinical islets has remained consistently very high through this period, and differs substantially from nonclinical islets. In multivariate analysis of all recipient, donor and islet factors, and medical management factors, the only islet product characteristic that correlated with clinical outcomes was total IEQs infused. This analysis shows improvements in both quantity and some quality criteria of clinical islets produced over 1999–2010, and these parallel improvements in clinical outcomes over the same period.
Product criteria from clinical grade allogeneic human islets exhibit consistently superior‐quality characteristics and significantly increasing islet equivalent yield, paralleling improving success rates of islet transplantation for type I diabetes.
Early diagnosis of diabetes mellitus can significantly improve therapeutic strategies and overall health span. Identifying biomarkers as a tool for determining the risk of developing diabetes as well ...as a monitoring strategy for progression of the disease state would be useful in predicting potential complications while simultaneously improving our ability to prevent and treat diabetes. Extracellular vesicles (EV) have recently emerged as prominent mediators of intercellular communication and as a potential source for the discovery of novel biomarkers. A deeper understanding of the cargo molecules present in EVs obtained from type 1 diabetes mellitus (T1D) patients may aid in the identification of novel diagnostic and prognostic biomarkers, and can potentially lead to the discovery of new therapeutic targets.
The large, randomized, double-blind, placebo-controlled trial VITAL (Vitamin D and omega 3 trial) recently confirmed that vitamin D and omega-3 polyunsaturated fatty acid (PUFA) co-supplementation ...(VIDOM) can reduce the incidence of autoimmune diseases. Based on these relevant results, this commentary summarizes the molecular mechanisms behind the anti-inflammatory and immunomodulatory properties of vitamin D and omega-3 PUFAs. We also describe the potential bidirectional interplay between vitamin D metabolism and omega-3 PUFA metabolism that underlies the rationale for VIDOM co-supplementation and that may contribute to enhance the anti-inflammatory and immunomodulatory actions of vitamin D and omega-3 PUFAs when these compounds are administered in combination.
Previous studies in humans with type 1 diabetes mellitus (T1D) and in nonobese diabetic mice have investigated the beneficial immunomodulatory potential of aerobic physical activity. Performing high ...volume of aerobic exercise may favorably regulate autoimmunity in diabetes. We tested whether increased physical activity is a self-sufficient positive factor in T1D subjects. During a 3-month observational period, active (six males; 40.5 ± 6.1 years; BMI: 24.5 ± 2.1) and sedentary (four males, three females; 35.9 ± 8.9 years; BMI: 25.7 ± 3.8) T1D individuals on insulin pump therapy were studied for metabolic, inflammatory, and autoimmune parameters. At baseline and at the end of a 3-month period, glycosylated hemoglobin (HbA1c), autoantibodies (anti-GAD, anti-ZnT8, anti-IA2, and ICA) and proinflammatory cytokines (IL-6 and TNF-α) were evaluated. During the third month of the period, physically active T1D patients showed a significant reduction in the average glucose levels (-9%, p = 0.025, by CGM) compared to the first month values, and even their hyperglycemic episodes (>180 mg/dl) diminished significantly (-24.2%, p = 0.032 vs. first month). Moreover, active T1D subjects exhibited an improved body composition with respect to sedentary controls. No significant changes were detected as to the autoimmune and inflammatory profiles. This study confirms the beneficial role of physical exercise associated with insulin pump therapy in order to improve metabolic control in individuals with T1D. These preliminary positive observations need to be challenged in a prolonged interventional follow-up.
The aim of this study was to test whether an omental pouch can be used as an alternative site for islet implantation in diabetic monkeys. Here we report the successful engraftment of islets in ...diabetic cynomolgus monkeys when loaded on a synthetic biodegradable scaffold and placed in an omental pouch. One autologous and five allogeneic diabetic monkey transplants under the cover of steroid‐free immune suppression (SFIS) were undertaken. Fasting blood glucose (FBG) and C‐peptide (CP), exogenous insulin requirements (EIR), intravenous glucose tolerance test (IVGTT), A1C and histopathology were used to assess islet engraftment and survival. All animals achieved CP levels > 1.0 ng/mL following transplant, a 66–92% posttransplant decrease in EIR and reduced A1C. Following graft removal, CP became negative and histopathological analysis of the explanted grafts demonstrated well‐granulated and well‐vascularized, insulin‐positive islets, surrounded by T‐cell subsets and macrophages. Compared to intrahepatic allogeneic islet transplants (n = 20), there was a delayed engraftment for omental pouch recipients but similar levels of CP production were ultimately achieved, with a broad range of IEQ/kg transplanted in both sites. Our results suggest this extrahepatic transplantation site has potential as an alternative site for clinical islet cell transplantation.
Auto and allogeneic islets seeded on a synthetic biodegradable scaffold and transplanted in an omental pouch in nonhuman primates engrafted and survived for long periods of time, with sustained improvement in metabolic control.
A unifying thread over the wide spectrum of diabetes might be the triggering of innate immunological and inflammatory pathways leading to insulin resistance, beta-cell dysfunction and beta-cell ...destruction: the hybrid features of type 1 and type 2 diabetes. In fact, hyperglycemia can arise from a deficit in insulin action, insulin secretion, or both. Regularly exercising at moderate intensity has been shown to efficiently and positively impact upon physiological imbalances caused by several morbid conditions. Even in different immunological dysfunctions, physical exercise has been prescribed as a complementary therapeutic strategy. In fact, as suggested by our observations, there is a putative inverse relationship between autoimmunity markers (GAD, IA) and exercise-derived energy expenditure in type 1 pre-diabetic subjects. Exercise also has been shown to maintain muscle mitochondrial function and thus ability to maintain fuel metabolism and islet cell function. An additional benefit is the enhancement of antioxidant defense system and thus reducing oxidative stress. Therefore, the purpose of this review is to address the importance of physical exercise in a broad range of metabolic disorders that set out a common milieu in which type 1 and type 2 diabetes could be identified as one extensive syndrome.
PDF
