Preoperative and Postoperative Predictors of Insulin Independence From Total Pancreatectomy and Islet Autotransplantation.

OBJECTIVE: This study examined the preoperative and postoperative variables associated with 1 year and long-term insulin independence following total pancreatectomy and islet autotransplantation (TPIAT). METHODS: 46 TPIAT patients from 2010 to 2022 in a single hospital system were retrospectively analyzed. Pre- and postoperative variables were compared between short-term (1 year) and long-term (last follow-up after year 1) insulin-independent versus -dependent patients. RESULTS: Nine (20%) and seven (15%) patients achieved short- and long-term insulin independence, respectively. The patients were followed up for a median of 2.8 years (interquartile range [IQR] 1.0, 4.7). Short-term insulin independence was associated with higher median transplanted islet equivalents (IEQ) per kg (6981 vs 4493, P = .02), lower units of basal insulin on discharge (7 vs 12, P = .009), and lower rates of discharge with an insulin regimen (67% vs 100%, P = .006). Odds of short-term insulin independence increased by 80% for every 1000 increase in IEQ per kg (OR 1.80, CI 1.18-3.12, P = .005) and decreased by 32% for every additional basal unit of insulin on discharge (OR 0.68, CI 0.42-0.91, P = .003) on average. Long-term insulin independence was also associated with transplanted IEQ per kg. No patient on antihyperglycemic medication before surgery achieved insulin independence. CONCLUSION: Short- and long-term insulin independence after TPIAT is associated with higher transplanted IEQ per kg and immediate postoperative variables that can be used to inform the discussions clinicians have with their patients regarding glycemic prognosis following TPIAT.

Redesigning Diabetes Care for Treatment Inertia: A Population Health Model.

In the past 2 decades, health care has witnessed technological and pharmacological advancements leading to innovations in diabetes management. Despite these advances, published guidelines, and treatment algorithms, most people with diabetes remain above glycemic targets. Thus, the authors designed a novel care model aimed at improving several causative factors, including therapeutic inertia, limited access to endocrinology and cardiovascular specialists, time constraints, and complexity in incorporating clinical practice guidelines. The model involves collaboration between the diabetes specialty team and primary care providers (PCPs). The intervention reviewed uncontrolled diabetes data and the patient's electronic medical record (EMR) and sent personalized, evidence-based recommendations to the provider using the task function in the EMR. Other services (eg, diabetes education) were utilized to optimize patient care to achieve optimal glycemic targets and address cardiometabolic risk. The overall mean hemoglobin A1c (HbA1c) decreased pre-post intervention by almost 1%, and 52.1% (347 of 666) of the cohort had ≥-0.5% change in HbA1c post-intervention. All pathways exhibited a decrease in HbA1c. Team-based approaches to managing diabetes patient care were the most effective. The interventions effectively utilized the resources across the health system without placing additional load or burden on primary care or diabetes specialty care teams. In the future, the authors hope to address the limitations of the current gap caused by increasing diabetes numbers, decreasing availability of PCPs and endocrinologists, and fee-for-service models using the innovative specialty consultant-primary care connection and knowledge exchange offered by this novel model, which can only be sustained with payer's support.

Novel Application of Microdosing Glucagon for Hypoglycemia After Total Pancreatectomy and Autologous Islet Transplant.

Total pancreatectomy and autologous islet transplantation (TPAIT) is a procedure to ameliorate dysglycemia associated with post-pancreatectomy. Patients who undergo TPAIT are at risk of developing hypoglycemia postoperatively. The current literature suggests that hypoglycemia may be due to a glucagon-deficiency state. To date, there is minimal literature available that explores treatment options to minimize hypoglycemia in these patients. In this case, a 29-year-old female patient was administered a microdosing glucagon protocol post TPAIT and experienced improvements in hypoglycemia. We describe the dosing regimen of the protocol and provide continuous glucose monitoring data to support our findings. This case adds to the limited evidence on effective treatment options for these rare patients. To our knowledge, this is the first application of a microdosing glucagon protocol to treat hypoglycemia associated with TPAIT.

Statin Intolerance: A Review and Update.

OBJECTIVE: To review the evidence of existing literature on the management of statin intolerance. METHODS: We searched for literature pertaining to statin intolerance and treatments in PubMed. We reviewed articles published between 2005 and 2022. RESULTS: Statin-associated myalgia is the most common adverse effect of statin therapy and the most common reason for statin discontinuation. The risk factors for statin intolerance include unexplained muscle pain with other lipid-lowering therapy, unexplained cramps, a history of increased creatine kinase levels, a family history of muscle symptoms, and a family history of muscle symptoms with lipid therapy. Vitamin D repletion and coenzyme Q supplementation may help alleviate the musculoskeletal effects of statins. Trials of different types of statins and different dosing regimens are recommended to improve tolerability. The use of statins in individuals who perform regular exercise requires closer attention to muscular symptoms and creatine kinase levels; however, it does not preclude the use of statins. CONCLUSION: Management of the adverse effects of statin therapy and improving statin tolerability are key to achieving optimum cardiovascular benefits. Identifying statin-associated adverse effects and managing them appropriately can reduce unnecessary statin discontinuation and subsequently provide longer cardiovascular protection.

Rekindling Hope for Remission: Current Impact of Diabetes for Our World's Future Health and Economy.

The individual and societal burdens of living with a chronic disease are a global issue. Diabetes directly increases health care costs to manage the disease and the associated complications and indirectly increases the economic burden through long-term complications that hinder the productivity of humans worldwide. Thus, it is crucial to have accurate information on diabetes-related costs and the geographic and global economic impact when planning interventions and future strategies. Health care systems must work with government agencies to plan national-level pre diabetes and diabetes strategies and policies. Public health services must focus on diabetes screening prevention and remission.

What Is a Honeymoon in Type 1, Can It Go into Remission?

Type 1 diabetes is a chronic autoimmune disorder that results in destruction of insulin-producing cells in the pancreas. The autoimmune process is thought to be waxing and waning resulting in variable endogenous insulin secretion ability. An example of this is the honeymoon phase or partial remission phase of type 1 diabetes, during which optimal control of blood glucoses can be maintained with significantly reduced exogenous insulin, and occasionally exogenous insulin can be temporarily discontinued altogether. Understanding this phase is important because even fairly small amounts of endogenous insulin secretion is associated with reduced risk of severe hypoglycemia and microvascular complications.

Islet Cell Therapy and Stem Cell Therapy for Type 1 Diabetes: There Will Always Be a Hope.

To date, people living with type 1 diabetes depend on external subcutaneous insulin while waiting for a cure, or a feasible method to preserve, replace, and generate fully functioning ß cells that secrete appropriate insulin in response to glucose. Current work includes evaluating renewable sources of ß cells, transplantation methods without immunosuppressives, and methods to preserve ß-cell function. Such methods include ß-cell encapsulation, scaffolding, immune modulation, gene editing, and disease-modifying therapies. The purpose of this article is to review the progress and describe ß-cell therapies over the past 5 years.

Follow-Up of Patients After Total Pancreatectomy and Islet Cell Autotransplantation at Off-Site Islet Isolation Facility.

CONTEXT: Total pancreatectomy with islet autotransplantation (TPIAT) is a definitive management for intractable pain in patients with chronic pancreatitis (CP). Islet autotransplantation (IAT) allows for the preservation of beta cells to prevent complications of long-term diabetes. OBJECTIVE: Our study follows TPIAT recipients for up to 12 years to determine the efficacy of the procedure completed with an off-site islet isolation facility. METHODS: Patient demographics, mixed meal tolerance test measures, glycosylated hemoglobin, insulin requirements, and homeostatic model assessment for insulin resistance values were collected prior to surgery and at the most recent follow-up assessment. RESULTS: Forty-four patients (median age, 46.0 years; range, 20-78 years) underwent TPIAT for CP. At an overall median follow-up time of 845.5 days (range, 195-4470 days) 8 patients were insulin independent and 36 patients were insulin dependent. At the most recent follow-up time point, islet yield per kilogram was the strongest indicator of insulin independence. Homeostatic model assessment for insulin resistance values were comparable between insulin independent and dependent cohorts. CONCLUSIONS: Our long-term follow-up data suggest that IAT can effectively reduce insulin requirements and improve postoperative glycemic control.

Lipoprotein(a) and Atherosclerotic Cardiovascular Disease, the Impact of Available Lipid-Lowering Medications on Lipoprotein(a): An Update on New Therapies.

OBJECTIVE: To review evidence of existing and new pharmacological therapies for lowering lipoprotein(a) (Lp[a]) concentrations and their impact on clinically relevant outcomes. METHODS: We searched for literature pertaining to Lp(a) and pharmacological treatments in PubMed. We reviewed articles published between 1963 and 2020. RESULTS: We found that statins significantly increased Lp(a) concentrations. Therapies that demonstrated varying degrees of Lp(a) reduction included ezetimibe, niacin, proprotein convertase subtilisin/kexin type 9 inhibitors, lipoprotein apheresis, fibrates, aspirin, hormone replacement therapy, antisense oligonucleotide therapy, and small interfering RNA therapy. There was limited data from large observational studies and post hoc analyses showing the potential benefits of these therapies in improving cardiovascular outcomes. CONCLUSION: There are multiple lipid-lowering agents currently being used to treat hyperlipidemia that also have a Lp(a)-lowering effect. Two RNA therapies specifically targeted to lower Lp(a) are being investigated in phase 3 clinical trials and, thus far, have shown promising results. However, evidence is lacking to determine the clinical relevance of reducing Lp(a). At present, there is a need for large-scale, randomized, controlled trials to evaluate cardiovascular outcomes associated with lowering Lp(a).

Long-term efficacy and safety of osilodrostat in Cushing's disease: final results from a Phase II study with an optional extension phase (LINC 2).

BACKGROUND: Many patients with Cushing's disease (CD) require long-term medical therapy to control their hypercortisolism. In the core phase of a Phase II study (LINC 2; NCT01331239), osilodrostat normalized mean urinary free cortisol (mUFC) in 78.9% of patients with CD. Here, we report long-term efficacy and safety data for osilodrostat following completion of an optional extension to LINC 2. METHODS: Adult patients with CD were enrolled in a 22-week prospective Phase II study. Patients with mUFC ≤ upper limit of normal (ULN) or receiving clinical benefit at week 22 could enter the optional extension. The proportion of complete (mUFC ≤ ULN) or partial (mUFC > ULN but ≥ 50% decrease from baseline) mUFC responders was assessed over time. RESULTS: Sixteen of 19 enrolled patients entered the extension. Median (range) osilodrostat exposure from baseline to study end was 5.4 years (0.04-6.7); median (range) average dose was 10.6 mg/day (1.1-47.9). Overall response rate (complete and partial mUFC responders) was consistently ≥ 50%. Sustained control of most cardiovascular-related parameters was observed during the extension. The long-term safety profile was consistent with that reported during the core phase. Testosterone levels (females) decreased towards baseline levels during long-term follow-up, with no new or worsening cases of hirsutism during the extension. CONCLUSIONS: In the longest prospective study of a steroidogenesis inhibitor to date, osilodrostat provided sustained reductions in mUFC for up to 6.7 years of treatment, with no new safety signals emerging during the extension. These findings support osilodrostat as an effective long-term treatment for patients with CD.

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort.

OBJECTIVE: To determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation. METHODS: We used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively. RESULTS: The sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates. CONCLUSION: There is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.

Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes.

BACKGROUND: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting. METHODS: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed. RESULTS: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group. CONCLUSIONS: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Lessons Learned From a Patient-Centered, Team-Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program.

Background The care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited. Methods and Results We conceptualized and initiated a patient-centered, team-based intervention called Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow-up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow-up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (-10.8%), total cholesterol (-7.9%), low-density lipoprotein cholesterol (-13.5%), systolic blood pressure (-4.0%), and body mass index (-2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium-glucose cotransporter 2 inhibitor or glucagon-like peptide-1 receptor agonist at baseline, 81% were prescribed evidence-based therapy with sodium-glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon-like peptide-1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3-month follow-up period. Conclusions A team-based, patient-centered approach to high-risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence-based therapies and improved control of multiple cardiovascular risk factors.

Management of Mild-to-Moderate Hypertriglyceridemia.

OBJECTIVE: Hypertriglyceridemia (HTG) is highly prevalent globally, and its prevalence is rising, with a worldwide increase in the incidence of obesity and diabetes. This review examines its current management and future therapies. METHODS: For this review, HTG is defined as mild-to-moderate elevation in the levels of triglyceride (TG): a fasting or nonfasting TG level of ≥150 mg/dL and <500 mg/dL. We reviewed scientific studies published over the last 30 years and current professional society recommendations regarding the evaluation and treatment of HTG. RESULTS: Genetics, lifestyle, and other environmental factors impact TG levels. In adults with mild-to-moderate HTG, clinicians should routinely assess and treat secondary treatable causes (diet, physical activity, obesity, metabolic syndrome, and reduction or cessation of medications that elevate TG levels). Because atherosclerotic cardiovascular disease risk is the primary clinical concern, statins are usually the first-line treatment. Patients with TG levels between ≥150 mg/dL and <500 mg/dL whose low-density lipoprotein cholesterol is treated adequately with statins (at "maximally tolerated" doses, per some statements) and have either prior cardiovascular disease or diabetes mellitus along with at least 2 additional cardiovascular disease risk factors should be considered for added icosapent ethyl treatment to further reduce their cardiovascular disease risk. Fibrates, niacin, and other approved agents or agents under development are also reviewed in detail. CONCLUSION: The treatment paradigm for mild-to-moderate HTG is changing on the basis of data from recent clinical trials. Recent trials suggest that the addition of icosapent ethyl to background statin therapy may further reduce atherosclerotic cardiovascular disease risk in patients with moderate HTG, although a particular TG goal has not been identified.

Bioenergetics of Islet Preparations in a Pilot Clinical Trial of Peri-Transplant Hydroxychloroquine for Autologous Islet Transplantation.

The inflammatory response is an obstacle to success in both allogeneic and autologous islet transplantation. In autologous islet transplantation (AIT), however, the recipient is also the donor, permitting pretreatment of donor/recipient for a controlled duration prior to transplantation. We sought to exploit this feature of (AIT) by pretreating donor/recipients with chronic pancreatitis undergoing total pancreatectomy and autologous islet transplantation (TPAIT) to test the hypothesis that peri-transplant treatment with the FDA-approved anti-inflammatory hydroxychloroquine (HCQ) improves graft function. In this randomized placebo-controlled pilot clinical study, patients (n = 6) were treated with oral HCQ for 30 days prior to and 90 days after TPAIT. In vivo islet function was assessed via Mixed Meal Tolerance Testing before HCQ treatment, 6- and 12-months after surgery. In vitro islet bioenergetics were assessed at the time of transplantation via extracellular flux analysis of islet preparation samples from the clinical trial cohort and six additional patients (n = 12). Our study shows that HCQ did not alter clinical endpoints, but HCQ-treated patients showed greater spare respiratory capacity (SRC) compared to samples from control patients (P=0.028). Glycolytic metabolism of islet preparations directly correlated with stimulated C-peptide secretion both before and after TPAIT (P=0.01, R2=0.489 and P=0.03, R2=0.674, respectively), and predicted in vivo islet function better than mitochondrial metabolism of islet preps or islet equivalents infused. Overnight culture of islet preparations altered bioenergetic function, significantly decreasing SRC and maximal respiration (P<0.001). In conclusion, while HCQ did not alter clinical outcomes, it was associated with significantly increased SRC in islet preparations. Bioenergetic analyses of islet preparations suggests that culture should be avoided and that glycolysis may be a more sensitive indicator of in vivo islet function than current metrics, including islet oxygen consumption and islet equivalents infused.

Elevated hCG can be a benign finding in perimenopausal and postmenopausal women.

In a perimenopausal or postmenopausal woman, an elevation in human chorionic gonadotropin (hCG) can raise the concern of malignancy or even pregnancy, but it can also be a benign physiologic finding due to production in the pituitary gland in this patient population. Diagnosing the underlying cause of hCG elevation can be challenging, especially if a pituitary source is not considered. Pituitary hCG production remains largely underrecognized and can lead to unnecessary testing, harmful therapy such as chemotherapy, or delay in receiving appropriate care for other unrelated diseases. It is therefore important to establish guidelines to aid medical evaluation.

The Association of Smoking and Alcohol Abuse on Anxiety and Depression in Patients With Recurrent Acute or Chronic Pancreatitis Undergoing Total Pancreatectomy and Islet Autotransplantation: A Report From the Prospective Observational Study of TPIAT Cohort.

OBJECTIVES: Smoking and alcohol use are risk factors for acute and chronic pancreatitis, and their role on anxiety, depression, and opioid use in patients who undergo total pancreatectomy and islet autotransplantation (TPIAT) is unknown. METHODS: We included adults enrolled in the Prospective Observational Study of TPIAT (POST). Measured variables included smoking (never, former, current) and alcohol abuse or dependency history (yes vs no). Using univariable and multivariable analyses, we investigated the association of smoking and alcohol dependency history with anxiety and depression, opioid use, and postsurgical outcomes. RESULTS: Of 195 adults studied, 25 were current smokers and 77 former smokers, whereas 18 had a history of alcohol dependency (of whom 10 were current smokers). A diagnosis of anxiety was associated with current smoking (P = 0.005), and depression was associated with history of alcohol abuse/dependency (P = 0.0001). However, active symptoms of anxiety and depression at the time of TPIAT were not associated with smoking or alcohol status. Opioid use in the past 14 days was associated with being a former smoker (P = 0.005). CONCLUSIONS: Active smoking and alcohol abuse history were associated with a diagnosis of anxiety and depression, respectively; however, at the time of TPIAT, symptom scores suggested that they were being addressed.

Evaluation of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome.

PURPOSE: To evaluate the performance of FKBP5 as a cortisol activity biomarker in patients with ACTH-dependent Cushing syndrome (CS). METHODS: This was a prospective, multicenter, nonrandomized, noninterventional study of a cortisol activity biomarker in adult patients (≥18 years) with documented ACTH-dependent, endogenous CS. The impact of surgery on FKBP5 mRNA expression levels in these patients and the difference in expression levels between these patients and healthy controls were evaluated. Cortisol and biomarker samples were collected before and immediately after surgery. A custom NanoString assay was used to quantify FKBP5 mRNA expression levels. The same method was used to analyze healthy volunteer samples collected from a different study. RESULTS: Surgery was considered successful in 14/24 patients (58.3%) and changes from baseline in serum cortisol were -92.6% (P = 0.0005) and -43.8% (not significant) in patients with successful and unsuccessful surgeries, respectively. A strong positive correlation between FKBP5 and cortisol levels was observed (before surgery: r = 0.72, P = 0.0002; after surgery: r = 0.85, P < 0.0001). After successful surgery, FKBP5 expression levels were similar to those of healthy subjects. In patients without surgical success, FKBP5 levels remained unchanged from baseline and distinct from healthy subjects (P = 0.0025). CONCLUSIONS: Our findings confirm that FKBP5 levels are higher in the presence of excess cortisol exposure in patients with CS and decrease to normal baseline levels after successful surgery. These findings suggest that FKBP5 can serve as a measure of biological cortisol activity and set the stage for the development of an FKBP5 mRNA expression assay as a biomarker of cortisol activity.

Circulating miRNA in Patients Undergoing Total Pancreatectomy and Islet Autotransplantation.

Circulating microRNAs (miRNAs) can be biomarkers for diagnosis and progression of several pathophysiological conditions. In a cohort undergoing total pancreatectomy with islet autotransplantation (TPIAT) from the multicenter Prospective Observational Study of TPIAT (POST), we investigated associations between a panel of circulating miRNAs (hsa-miR-375, hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-216a-5p, hsa-miR-320d, hsa-miR-200c, hsa-miR-125b, hsa-miR-7-5p, hsa-miR-221-3p, hsa-miR-122-5p) and patient, disease and islet-isolation characteristics. Plasma samples (n = 139) were collected before TPIAT and miRNA levels were measured by RTPCR. Disease duration, prior surgery, and pre-surgical diabetes were not associated with circulating miRNAs. Levels of hsa-miR-29b-3p (P = 0.03), hsa-miR-148a-3p (P = 0.04) and hsa-miR-221-3p (P = 0.01) were lower in those with genetic risk factors. Levels of hsa-miR-148a-3p (P = 0.04) and hsa-miR-7-5p (P = 0.04) were elevated in toxic/metabolic disease. Participants with exocrine insufficiency had lower hsa-miR-29b-3p, hsa-miR-148a-3p, hsa-miR-320d, hsa-miR-221-3p (P < 0.01) and hsa-miR-375, hsa-miR-200c-3p, and hsa-miR-125b-5p (P < 0.05). Four miRNAs were associated with fasting C-peptide before TPIAT (hsa-miR-29b-3p, r = 0.18; hsa-miR-148a-3p, r = 0.21; hsa-miR-320d, r = 0.19; and hsa-miR-221-3p, r = 0.21; all P < 0.05), while hsa-miR-29b-3p was inversely associated with post-isolation islet equivalents/kg and islet number/kg (r = -0.20, P = 0.02). Also, hsa-miR-200c (r = 0.18, P = 0.03) and hsa-miR-221-3p (r = 0.19, P = 0.03) were associated with islet graft tissue volume. Further investigation is needed to determine the predictive potential of these miRNAs for assessing islet autotransplant outcomes.