Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Institutional Barriers to the Successful Implementation of Telemedicine for Type 1 Diabetes Care.

The aim of this study was to describe rates of telemedicine use 18 months after the start of the coronavirus disease 2019 pandemic and to assess the institutional barriers to its implementation for type 1 diabetes care across centers of the T1D Exchange Quality Improvement Collaborative. Observational electronic health record data capturing telemedicine rates from 15 U.S. centers between September 2020 and September 2021 and a survey of 33 centers capturing telemedicine rates and key components of telemedicine were analyzed. A capacity score was developed and summed to a total capacity score and compared with overall telemedicine rates across centers. Telemedicine visits decreased by 17.4% from September 2020 to September 2021. Generally, it was observed that the lower the average telemedicine capacity score, the lower the rate of telemedicine visits. Despite a decline in the utilization of telemedicine 18 months after the start of the pandemic, visit rates were still 20% higher than in the pre-pandemic period. However, there is a need to improve structural components to ensure telemedicine capacity and robust telemedicine utilization.

Type 1 Diabetes and Cardiovascular Health.

Type 1 diabetes (T1D) is associated with an increased risk of cardiovascular disease (CVD). CVD occurs much earlier in people with T1D than in the general population, and several risk factors have been identified some of which are modifiable. Risk prediction models and imaging tests to detect early signs of CVD have not been extensively validated. Strategies to promote cardiovascular health (CVH) in T1D include identifying risk factors, early treatment to achieve CVH targets, and improving the education of health care providers and people with T1D.

Impact of GAD65 and IA2 autoantibodies on islet allograft survival.

Introduction: Islet transplantation (ITx) shows promise in treating T1D, but the role of islet autoantibodies on graft survival has not been clearly elucidated. We aimed to analyze the effect of GAD65 and IA2 autoantibody status on graft survival and attainment of insulin independence in subjects with T1D who underwent ITx. Method: We conducted a retrospective cohort study on 47 ITx recipients from 2000 to 2018. Islet infusion was performed via intrahepatic portal (n=44) or onto the omentum via laparoscopic approach (n=3). Immunosuppression involved anti-IL2 receptor antibody, anti-TNF, and dual combinations of sirolimus, tacrolimus, or mycophenolate mofetil (Edmonton-like) in 38 subjects (80.9%). T-cell depletion induction with Edmonton-like maintenance was used in 9 subjects (19%). GAD65 and IA2 autoantibodies were assessed pre-transplant and post-transplant (monthly) until graft failure, and categorized as persistently negative, persistently positive, or seroconverters. Graft survival was analyzed using U-Mann-Whitney test, and Quade's nonparametric ANCOVA adjusted for confounders. Kaplan-Meier and Log-Rank tests were employed to analyze attainment of insulin independence. P value <0.05 indicated statistical significance. Results: ITx recipients with persistent autoantibody negativity (n = 21) showed longer graft function (98 [61 - 182] months) than those with persistent autoantibody positivity (n = 18; 38 [13 - 163] months), even after adjusting for immunosuppressive induction protocol (P = 0.027). Seroconverters (n=8) had a median graft survival time of 73 (7.7 - 167) months, which did not significantly differ from the other 2 groups. Subjects with persistently single antibody positivity to GAD65 (n = 8) had shorter graft survival compared to negative islet autoantibody (GAD65/IA2) subjects (n = 21; P = 0.016). Time of graft survival did not differ in subjects with single antibody positivity to IA2. The proportion of insulin independence attainment was similar irrespective of autoantibody status. Conclusion: The persistence of islet autoantibodies, as markers of islet autoimmunity, may represent an underappreciated contributing factor to the failure of transplanted ß cells. Whether induction with T-cell depletion may lead to improved graft survival, independent of islet autoantibody status, could not be evaluated in our cohort. Larger prospective studies are needed to further address the role of islet autoantibody status on islet graft survival.

Comparison of Glycemic Control Between In-Person and Virtual Diabetes Consults in Hospitalized Patients With Diabetes.

BACKGROUND: There is limited evidence that the diabetes in-person consult in hospitalized patients can be replaced by a virtual consult. During COVID-19 pandemic, the diabetes in-person consult service at the University of Miami and Miami Veterans Affairs Healthcare System transitioned to a virtual model. The aim of this study was to assess the impact of telemedicine on glycemic control after this transition. METHODS: We retrospectively analyzed glucose metrics from in-person consults (In-person) during January 16 to March 14, 2020 and virtual consults during March 15 to May 14, 2020. Data from virtual consults were analyzed by separating patients infected with COVID-19, who were seen only virtually (Virtual-COVID-19-Pos), and patients who were not infected (Virtual-COVID-19-Neg), or by combining the two groups (Virtual-All). RESULTS: Patient-day-weighted blood glucose was not significantly different between In-person, Virtual-All, and Virtual-COVID-19-Neg, but Virtual-COVID-19-Pos had significantly higher mean ± SD blood glucose (mg/dL) compared with others (206.7 ± 49.6 In-person, 214.6 ± 56.2 Virtual-All, 206.5 ± 57.2 Virtual-COVID-19-Neg, 229.7 ± 51.6 Virtual-COVID-19-Pos; P = .015). A significantly less percentage of patients in this group also achieved a mean ± SD glucose target of 140 to 180 mg/dL (23.8 ± 22.5 In-person, 21.5 ± 20.5 Virtual-All, 25.3 ± 20.8 Virtual-COVID-19-Neg, and 14.4±18.1 Virtual-COVID-19-Pos, P = .024), but there was no significant difference between In-person, Virtual-All, and Virtual-COVID-19-Neg. The occurrence of hypoglycemia was not significantly different among groups. CONCLUSIONS: In-person and virtual consults delivered by a diabetes team at an academic institution were not associated with significant differences in glycemic control. These real-world data suggest that telemedicine could be used for in-patient diabetes management, although additional studies are needed to better assess clinical outcomes and safety.

Connecting From Afar: Implementation of Remote Data-Sharing for Patients With Type 1 Diabetes on Insulin Pump Therapy.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an effort to improve the remote collection of insulin pump data in an academic center in South Florida.

Patient Demographics and Clinical Outcomes Among Type 1 Diabetes Patients Using Continuous Glucose Monitors: Data From T1D Exchange Real-World Observational Study.

BACKGROUND: The benefits of Continuous Glucose Monitoring (CGM) on glycemic management have been demonstrated in numerous studies; however, widespread uptake remians limited. The aim of this study was to provide real-world evidence of patient attributes and clinical outcomes associated with CGM use across clinics in the U.S. based T1D Exchange Quality Improvement (T1DX-QI) Collaborative. METHOD: We examined electronic Health Record data from eight endocrinology clinics participating in the T1DX-QI Collaborative during the years 2017-2019. RESULTS: Among 11,469 type 1 diabetes patients, 48% were CGM users. CGM use varied by race/ethnicity with Non-Hispanic Whites having higher rates of CGM use (50%) compared to Non-Hispanic Blacks (18%) or Hispanics (38%). Patients with private insurance were more likely to use CGM (57.2%) than those with public insurance (33.3%) including Medicaid or Medicare. CGM users had lower median HbA1c (7.7%) compared to nonusers (8.4%). Rates of diabetic ketoacidosis (DKA) and severe hypoglycemia were significantly higher in nonusers compared to CGM users. CONCLUSION: In this real-world study of patients in the T1DX-QI Collaborative, CGM users had better glycemic control and lower rates of DKA and severe hypoglycemia (SH) events, compared to nonusers; however, there were significant sociodemographic disparities in CGM use. Quality improvement and advocacy measures to promote widespread and equitable CGM uptake have the potential to improve clinical outcomes.

Symptomatic diabetic autonomic neuropathy in type 1 diabetes (T1D): Findings from the T1D exchange.

AIMS: We aimed to evaluate the contemporary prevalence of and risk factors for symptomatic diabetic autonomic neuropathy (DAN) in participants with type 1 diabetes (T1D) enrolled in the T1D Exchange Clinic Registry. METHODS: DAN symptoms and severity were assessed with the Survey of Autonomic Symptoms (SAS) in adults with ≥5 years of T1D participating in the T1D Exchange from years 2010-2017. Associations of demographic, clinical, and laboratory factors with symptomatic DAN were assessed. RESULTS: Of the 4919 eligible T1D participants, 965 (20%) individuals completed the SAS questionnaire [mean age 40 ± 17 years, median diabetes duration 20 years (IQR: 13,34), 64% female, 90% non-Hispanic White, and 82% with private insurance]. DAN symptoms were present in 166 (17%) of responders with 72% experiencing moderate severity symptoms or worse. Symptomatic DAN participants had higher hemoglobin A1c (p = 0.03), longer duration (p = 0.004), were more likely to be female (p = 0.03), and more likely to have lower income (p = 0.03) versus no DAN symptoms. Symptomatic DAN was associated with diabetic peripheral neuropathy (p < 0.0001), smoking (p = 0.002), cardiovascular disease (p = 0.02), depression (p < 0.001), and opioid use (p = 0.004). CONCLUSIONS: DAN symptoms are common in T1D. Socioeconomic factors and psychological comorbidities may contribute to DAN symptoms and should be explored further.

Benefit of Continuous Glucose Monitoring in Reducing Hypoglycemia Is Sustained Through 12 Months of Use Among Older Adults with Type 1 Diabetes.

Objective: To evaluate glycemic outcomes in the Wireless Innovation for Seniors with Diabetes Mellitus (WISDM) randomized clinical trial (RCT) participants during an observational extension phase. Research Design and Methods: WISDM RCT was a 26-week RCT comparing continuous glucose monitoring (CGM) with blood glucose monitoring (BGM) in 203 adults aged ≥60 years with type 1 diabetes. Of the 198 participants who completed the RCT, 100 (98%) CGM group participants continued CGM (CGM-CGM cohort) and 94 (98%) BGM group participants initiated CGM (BGM-CGM cohort) for an additional 26 weeks. Results: CGM was used a median of >90% of the time at 52 weeks in both cohorts. In the CGM-CGM cohort, median time <70 mg/dL decreased from 5.0% at baseline to 2.6% at 26 weeks and remained stable with a median of 2.8% at 52 weeks (P < 0.001 baseline to 52 weeks). Participants spent more time in range 70-180 mg/dL (TIR) (mean 56% vs. 64%; P < 0.001) and had lower hemoglobin A1c (HbA1c) (mean 7.6% [59 mmol/mol] vs. 7.4% [57 mmol/mol]; P = 0.01) from baseline to 52 weeks. In BGM-CGM, from 26 to 52 weeks median time <70 mg/dL decreased from 3.9% to 1.9% (P < 0.001), TIR increased from 56% to 60% (P = 0.006) and HbA1c decreased from 7.5% (58 mmol/mol) to 7.3% (57 mmol/mol) (P = 0.025). In BGM-CGM, a severe hypoglycemic event was reported for nine participants while using BGM during the RCT and for two participants during the extension phase with CGM (P = 0.02). Conclusions: CGM use reduced hypoglycemia without increasing hyperglycemia in older adults with type 1 diabetes. These data provide further evidence for fully integrating CGM into clinical practice. Clinicaltrials.gov (NCT03240432).

Age and Hospitalization Risk in People With Type 1 Diabetes and COVID-19: Data From the T1D Exchange Surveillance Study.

CONTEXT: COVID-19 morbidity and mortality are increased in type 1 diabetes (T1D), but few data focus on age-based outcomes. OBJECTIVE: This work aimed to quantify the risk for COVID-19-related hospitalization and adverse outcomes by age in people with T1D. METHODS: For this observational, multisite, cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 56 clinical sites in the United States, data were collected from April 2020 to March 2021. The distribution of patient factors and outcomes across age groups (0-18, 19-40, and > 40 years) was examined. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between age, adverse outcomes, and hospitalization. The main outcome measure was hospitalization for COVID-19. RESULTS: A total of 767 patients were analyzed. Fifty-four percent (n = 415) were aged 0 to 18 years, 32% (n = 247) were aged 19 to 40 years, and 14% (n = 105) were older than 40 years. A total of 170 patients were hospitalized, and 5 patients died. Compared to the 0- to 18-years age group, those older than 40 years had an adjusted odds ratio of 4.2 (95% CI, 2.28-7.83) for hospitalization after adjustment for sex, glycated hemoglobin A1c, race, insurance type, and comorbidities. CONCLUSION: Age older than 40 years is a risk factor for patients with T1D and COVID-19, with children and younger adults experiencing milder disease and better prognosis. This indicates a need for age-tailored treatments, immunization, and clinical management of individuals affected by T1D.

Facilitators and Barriers to Smart Insulin Pen Use: A Mixed-Method Study of Multidisciplinary Stakeholders From Diabetes Teams in the United States.

This study sought to identify barriers and facilitators to successful smart insulin pen (SIP) use and gauge prescribing practices and integration into clinical practice by assessing provider and care team perspectives at participating endocrinology clinics within the T1D Exchange Quality Improvement Collaborative. The identified provider-related, patient-related, and clinic- and operational-level barriers and facilitators varied based on clinic knowledge, capacity, and resources. High-impact barriers included insurance coverage and prescribing processes; high-impact facilitators included improved diabetes clinic visit quality and use of SIPs as an alternative to insulin pump therapy. Findings indicated the need for provider and care team education and training on proper SIP features, use, and prescribing.

Adoption of Telemedicine for Type 1 Diabetes Care During the COVID-19 Pandemic.

Background: We describe the utilization of telemedicine visits (video or telephone) across the type 1 diabetes (T1D) Exchange Quality Improvement Collaborative (T1DX-QI) during the COVID-19 pandemic. Metrics, site-level survey results, and examples of interventions conducted to support telemedicine in T1D are shown. Materials and Methods: Thirteen clinics (11 pediatric, 2 adult) provided monthly telemedicine metrics between December 2019 and August 2020 and 21 clinics completed a survey about their telemedicine practices. Results: The proportion of telemedicine visits in T1DX-QI before the pandemic was <1%, rising to an average of 95.2% in April 2020 (range 52.3%-99.5%). Three sites initially used mostly telephone visits before converting to video visits. By August 2020, the proportion of telemedicine visits decreased to an average of 45% across T1DX-QI (range 10%-86.6%). The majority of clinics (62%) performed both video and telephone visits; Zoom was the most popular video platform used. Over 95% of clinics reported using CareLink™, Clarity®, Glooko™, and/or t:connect® to view device data, with only one center reporting automated data upload into the electronic medical record. The majority of centers had multidisciplinary teams participating in the video visits. All sites reported reimbursement for video visits, and 95% of sites reported coverage for telephone visits early on in the pandemic. Conclusions: There was rapid adoption of telemedicine in T1DX-QI during the COVID-19 pandemic. Future insurance reimbursement for telemedicine visits and the ideal ratio of telemedicine to in-person visits in T1D care remain to be determined.

Impact of bariatric surgery and weight loss medications in adults with type 1 diabetes in the T1D Exchange Clinic Registry.

AIM: To investigate the impact of bariatric surgery and weight loss medications in adults with type 1 diabetes. MATERIALS AND METHODS: Subjects enrolled in the T1D Exchange (T1DX) Clinic Registry age ≥ 18 years with a diabetes duration of ≥1 year were included in the analysis (n = 13,501). Data for participants (n = 37) with bariatric surgery after diabetes onset were assessed before and after surgery and also compared to a matched control group. Data for participants who reported the use of FDA-approved weight loss medications (n = 483) were assessed before starting, during use, and after stopping the medications and also compared to a matched control group. Variables of interest included BMI, HbA1c, blood pressure, lipid profile, rates of acute complications. Data were analyzed using linear mixed models. RESULTS: Bariatric surgery resulted in BMI reduction from 38.8 ±â€¯9.1 kg/m2 to 33.3 ±â€¯6.7 kg/m2 (P = 0.006) and HbA1c reduction from 8.8 ±â€¯1.3% (73 ±â€¯14.2 mmol/mol) to 8.1 ±â€¯1.1% (65 ±â€¯12.0 mmol/mol) (P = 0.05). Weight loss medications were not associated with weight loss or better glycemic control although stopping liraglutide favored weight gain. Both interventions were not associated with a significant change in blood pressure or lipid profile. There were no adverse events associated with the use of weight loss medications. CONCLUSIONS: Bariatric surgery is effective for weight loss and may improve glycemic control in selected patients. Weight loss medications are not associated with diabetes improvement. A trial with liraglutide may be attempted for weight control, but weight loss medications in general do not show a significant effect.

COVID-19 Hospitalization in Adults with Type 1 Diabetes: Results from the T1D Exchange Multicenter Surveillance Study.

CONTEXT: Diabetes mellitus is associated with increased COVID-19 morbidity and mortality, but there are few data focusing on outcomes in people with type 1 diabetes. OBJECTIVE: The objective of this study was to analyze characteristics of adults with type 1 diabetes for associations with COVID-19 hospitalization. DESIGN: An observational multisite cross-sectional study was performed. Diabetes care providers answered a 33-item questionnaire regarding demographics, symptoms, and diabetes- and COVID-19-related care and outcomes. Descriptive statistics were used to describe the study population, and multivariate logistic regression models were used to analyze the relationship between glycated hemoglobin (HbA1c), age, and comorbidities and hospitalization. SETTING: Cases were submitted from 52 US sites between March and August 2020. PATIENTS OR OTHER PARTICIPANTS: Adults over the age of 19 with type 1 diabetes and confirmed COVID-19 infection were included. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Hospitalization for COVID-19 infection. RESULTS: A total of 113 cases were analyzed. Fifty-eight patients were hospitalized, and 5 patients died. Patients who were hospitalized were more likely to be older, to identify as non-Hispanic Black, to use public insurance, or to have hypertension, and less likely to use continuous glucose monitoring or insulin pumps. Median HbA1c was 8.6% (70 mmol/mol) and was positively associated with hospitalization (odds ratio 1.42, 95% confidence interval 1.18-1.76), which persisted after adjustment for age, sex, race, and obesity. CONCLUSIONS: Baseline glycemic control and access to care are important modifiable risk factors which need to be addressed to optimize care of people with type 1 diabetes during the worldwide COVID-19 pandemic.

Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Continuous glucose monitoring (CGM) provides real-time assessment of glucose levels and may be beneficial in reducing hypoglycemia in older adults with type 1 diabetes. Objective: To determine whether CGM is effective in reducing hypoglycemia compared with standard blood glucose monitoring (BGM) in older adults with type 1 diabetes. Design, Setting, and Participants: Randomized clinical trial conducted at 22 endocrinology practices in the United States among 203 adults at least 60 years of age with type 1 diabetes. Interventions: Participants were randomly assigned in a 1:1 ratio to use CGM (n = 103) or standard BGM (n = 100). Main Outcomes and Measures: The primary outcome was CGM-measured percentage of time that sensor glucose values were less than 70 mg/dL during 6 months of follow-up. There were 31 prespecified secondary outcomes, including additional CGM metrics for hypoglycemia, hyperglycemia, and glucose control; hemoglobin A1c (HbA1c); and cognition and patient-reported outcomes, with adjustment for multiple comparisons to control for false-discovery rate. Results: Of the 203 participants (median age, 68 [interquartile range {IQR}, 65-71] years; median type 1 diabetes duration, 36 [IQR, 25-48] years; 52% female; 53% insulin pump use; mean HbA1c, 7.5% [SD, 0.9%]), 83% used CGM at least 6 days per week during month 6. Median time with glucose levels less than 70 mg/dL was 5.1% (73 minutes per day) at baseline and 2.7% (39 minutes per day) during follow-up in the CGM group vs 4.7% (68 minutes per day) and 4.9% (70 minutes per day), respectively, in the standard BGM group (adjusted treatment difference, -1.9% (-27 minutes per day); 95% CI, -2.8% to -1.1% [-40 to -16 minutes per day]; P <.001). Of the 31 prespecified secondary end points, there were statistically significant differences for all 9 CGM metrics, 6 of 7 HbA1c outcomes, and none of the 15 cognitive and patient-reported outcomes. Mean HbA1c decreased in the CGM group compared with the standard BGM group (adjusted group difference, -0.3%; 95% CI, -0.4% to -0.1%; P <.001). The most commonly reported adverse events using CGM and standard BGM, respectively, were severe hypoglycemia (1 and 10), fractures (5 and 1), falls (4 and 3), and emergency department visits (6 and 8). Conclusions and Relevance: Among adults aged 60 years or older with type 1 diabetes, continuous glucose monitoring compared with standard blood glucose monitoring resulted in a small but statistically significant improvement in hypoglycemia over 6 months. Further research is needed to understand the long-term clinical benefit. Trial Registration: ClinicalTrials.gov Identifier: NCT03240432.

Continuous Glucose Monitoring Profiles in Healthy Nondiabetic Participants: A Multicenter Prospective Study.

CONTEXT: Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. OBJECTIVE: To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. DESIGN: Multicenter, prospective study. SETTING: Twelve centers within the T1D Exchange Clinic Network. PATIENTS OR PARTICIPANTS: Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. INTERVENTION: Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. MAIN OUTCOME MEASURES: CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. RESULTS: A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d). CONCLUSION: By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies.

Marine-Lenhart Syndrome: Case Report, Diagnosis, and Management.

The coexistence of thyroid functioning nodules and Graves' disease is called Marine-Lenhart syndrome. This condition is estimated to occur in 0.8-2.7% of patients with Graves' disease with few cases reported in the literature. Criteria for the diagnosis are not well defined. Here, we present a case of hyperthyroidism characterized by the presence of stimulating TSH receptor antibodies and severe bilateral exophthalmos. A thyroid uptake and scan revealed an elevated 24-hour iodine-131 uptake and a discrete hot nodule in the upper pole of the right lobe which was also observed with a thyroid ultrasound. The patient was diagnosed with Marine-Lenhart syndrome complicated by thyroid eye disease and was treated with methimazole followed by thyroidectomy and orbital decompression. We review the existing literature and propose criteria for the diagnosis and treatment of this condition.

Lessons From Pancreas Transplantation in Type 1 Diabetes: Recurrence of Islet Autoimmunity.

Type 1 diabetes recurrence (T1DR) affecting pancreas transplants was first reported in recipients of living-related pancreas grafts from twins or HLA identical siblings; given HLA identity, recipients received no or minimal immunosuppression. This observation provided critical evidence that type 1 diabetes (T1D) is an autoimmune disease. However, T1DR is traditionally considered very rare in immunosuppressed recipients of pancreas grafts from organ donors, representing the majority of recipients, and immunological graft failures are ascribed to chronic rejection. We have been performing simultaneous pancreas-kidney (SPK) transplants for over 25 years and find that 6-8 % of our recipients develop T1DR, with symptoms usually becoming manifest on extended follow-up. T1DR is typically characterized by (1) variable degree of insulitis and loss of insulin staining, on pancreas transplant biopsy (with most often absent), minimal to moderate and rarely severe pancreas, and/or kidney transplant rejection; (2) the conversion of T1D-associated autoantibodies (to the autoantigens GAD65, IA-2, and ZnT8), preceding hyperglycemia by a variable length of time; and (3) the presence of autoreactive T cells in the peripheral blood, pancreas transplant, and/or peripancreatic transplant lymph nodes. There is no therapeutic regimen that so far has controlled the progression of islet autoimmunity, even when additional immunosuppression was added to the ongoing chronic regimens; we hope that further studies and, in particular, in-depth analysis of pancreas transplant biopsies with recurrent diabetes will help identify more effective therapeutic approaches.