Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

BACKGROUND: Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. METHODS: Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. RESULTS: Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. CONCLUSIONS: Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. CLINICAL TRIAL REGISTRATION: ACTRN12617000520336.

The diabetes management experiences questionnaire: Psychometric validation among adults with type 1 diabetes.

AIMS: To examine the psychometric properties of the Diabetes Management Experiences Questionnaire (DME-Q). Adapted from the validated Glucose Monitoring Experiences Questionnaire, the DME-Q captures satisfaction with diabetes management irrespective of treatment modalities. METHODS: The DME-Q was completed by adults with type 1 diabetes as part of a randomized controlled trial comparing hybrid closed loop (HCL) to standard therapy. Most psychometric properties were examined with pre-randomization data (n = 149); responsiveness was examined using baseline and 26-week follow-up data (n = 120). RESULTS: Pre-randomization, participants' mean age was 44 ± 12 years, 52% were women. HbA1c was 61 ± 11 mmol/mol (7.8 ± 1.0%), diabetes duration was 24 ± 12 years and 47% used an insulin pump prior to the trial. A forced three-factor analysis revealed three expected domains, that is, 'Convenience', 'Effectiveness' and 'Intrusiveness', and a forced one-factor solution was also satisfactory. Internal consistency reliability was strong for the three subscales ( α range = 0.74-0.84) and 'Total satisfaction' ( α = 0.85). Convergent validity was demonstrated with moderate correlations between DME-Q 'Total satisfaction' and diabetes distress (PAID: rs = -0.57) and treatment satisfaction (DTSQ; rs = 0.58). Divergent validity was demonstrated with a weak correlation with prospective/retrospective memory (PRMQ: rs = -0.16 and - 0.13 respectively). Responsiveness was demonstrated, as participants randomized to HCL had higher 'Effectiveness' and 'Total satisfaction' scores than those randomized to standard therapy. CONCLUSIONS: The 22-item DME-Q is a brief, acceptable, reliable measure with satisfactory structural and construct validity, which is responsive to intervention. The DME-Q is likely to be useful for evaluation of new pharmaceutical agents and technologies in research and clinical settings.

Glycaemic outcomes in Australasian children and adults with type 1 diabetes: failure to meet targets across the age spectrum.

BACKGROUND: The goal of therapy in type 1 diabetes (T1D) is to achieve optimal glycaemic targets and reduce complications. Robust data representing glycaemic outcomes across the lifespan are lacking in Australasia. AIMS: To examine contemporary glycaemic outcomes and rate of use of diabetes technologies in Australasian people with T1D. METHODS: Cross-sectional analysis of de-identified data from 18 diabetes centres maintained in the Australasian Diabetes Data Network registry during 2019. Glycaemia was measured using glycated haemoglobin (HbA1c). The proportion of people with T1D achieving the international HbA1c target of <53 mmol/mol (7%) was calculated. Rates of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were determined. RESULTS: A total of 7988 individuals with T1D with 30 575 visits were recorded in the registry. The median (interquartile range) age was 15.3 (10.0) years and diabetes duration was 5.7 (9.4) years with 49% on multiple daily injections (MDI) and 36% on CSII. The mean HbA1c for the whole cohort was 66 mmol/mol (8.2%). HbA1c increased with age, from 60 mmol/mol (7.6%) in children <10 years, increasing during adolescence and peaking at 73 mmol/mol (8.8%) in the 20-25 years age group. The HbA1c target of <53 mmol/mol (7%) was met in 18% of children and 13% of adults. HbA1c was lower on CSII as compared with those on MDI (P < 0.0001). CONCLUSIONS: Only a minority of children and adults achieve the recommended glycaemic goals despite access to specialist care in major diabetes centres. There is a need to identify factors that improve glycaemic outcomes.

Nationally Subsidized Continuous Glucose Monitoring: A Cost-effectiveness Analysis.

OBJECTIVE: The Continuous Glucose Monitoring (CGM) Initiative recently introduced universal subsidized CGM funding for people with type 1 diabetes under 21 years of age in Australia. We thus aimed to evaluate the cost-effectiveness of this CGM Initiative based on national implementation data and project the economic impact of extending the subsidy to all age-groups. RESEARCH DESIGN AND METHODS: We used a patient-level Markov model to simulate disease progression for young people with type 1 diabetes and compared government-subsidized access to CGM with the previous user-funded system. Three years of real-world clinical input data were sourced from analysis of the Australasian Diabetes Data Network and National Diabetes Services Scheme registries. Costs were considered from the Australian health care system's perspective. An annual discount rate of 5% was applied to future costs and outcomes. Uncertainty was evaluated with probabilistic and deterministic sensitivity analyses. RESULTS: Government-subsidized CGM funding for young people with type 1 diabetes compared with a completely user-funded model resulted in an incremental cost-effectiveness ratio (ICER) of AUD 39,518 per quality-adjusted life-year (QALY) gained. Most simulations (85%) were below the commonly accepted willingness-to-pay threshold of AUD 50,000 per QALY gained in Australia. Sensitivity analyses indicated that base-case results were robust, though strongly impacted by the cost of CGM devices. Extending the CGM Initiative throughout adulthood resulted in an ICER of AUD 34,890 per QALY gained. CONCLUSIONS: Providing subsidized access to CGM for people with type 1 diabetes was found to be cost-effective compared with a completely user-funded model in Australia.

Driving with Type 1 Diabetes: Real-World Evidence to Support Starting Glucose Level and Frequency of Monitoring During Journeys.

There is limited evidence supporting the recommendation that drivers with insulin-treated diabetes need to start journeys with glucose >90 mg/dL. Glucose levels of drivers with type 1 diabetes were monitored for 3 weeks using masked continuous glucose monitoring (CGM). Eighteen drivers (median [IQR] age 40 [35, 51] years; 11 men) undertook 475 trips (duration 15 [13, 21] min). Hypoglycemia did not occur in any trip starting with glucose >90 mg/dL (92%; n = 436). Thirteen drivers recorded at least one trip (total n = 39) starting with glucose <90 mg/dL. Among these, driving glucose was <70 mg/dL in five drivers (38%) during 10 trips (26%). Among five drivers (28%), a ≥ 36 mg/dL drop was observed within 20 min of starting their journey. Journey duration was positively associated with maximum glucose change. These findings support current guidelines to start driving with glucose >90 mg/dL, and to be aware that glucose levels may change significantly within 20 min. A CGM-based, in-vehicle display could provide glucose information and alerts that are compatible with safe driving. Clinical Trial Registration number: ACTRN12617000520336.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Long-term HbA1c in 7,961 Children and Young Adults in the Australasian Diabetes Data Network.

OBJECTIVE: The relationship between diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes and long-term glycemic control varies between studies. We aimed, firstly, to characterize the association of DKA and its severity with long-term HbA1c in a large contemporary cohort, and secondly, to identify other independent determinants of long-term HbA1c. RESEARCH DESIGN AND METHODS: Participants were 7,961 children and young adults diagnosed with type 1 diabetes by age 30 years from 2000 to 2019 and followed prospectively in the Australasian Diabetes Data Network (ADDN) until 31 December 2020. Linear mixed-effect models related variables to HbA1c. RESULTS: DKA at diagnosis was present in 2,647 participants (33.2%). Over a median 5.6 (interquartile range 3.2, 9.4) years of follow-up, participants with severe, but not moderate or mild, DKA at diagnosis had a higher mean HbA1c (+0.23%, 95% CI 0.11,0.28; [+2.5 mmol/mol, 95% CI 1.4,3.6]; P < 0.001) compared with those without DKA. Use of continuous subcutaneous insulin infusion (CSII) was independently associated with a lower HbA1c (-0.28%, 95% CI -0.31, -0.25; [-3.1 mmol/mol, 95% CI -3.4, -2.8]; P < 0.001) than multiple daily injections, and CSII use interacted with severe DKA to lower predicted HbA1c. Indigenous status was associated with higher HbA1c (+1.37%, 95% CI 1.15, 1.59; [+15.0 mmol/mol, 95% CI 12.6, 17.4]; P < 0.001), as was residing in postcodes of lower socioeconomic status (most vs. least disadvantaged quintile +0.43%, 95% CI 0.34, 0.52; [+4.7 mmol/mol, 95% CI 3.4, 5.6]; P < 0.001). CONCLUSIONS: Severe, but not mild or moderate, DKA at diagnosis was associated with a marginally higher HbA1c over time, an effect that was modified by use of CSII. Indigenous status and lower socioeconomic status were independently associated with higher long-term HbA1c.

Benchmarking care outcomes for young adults with type 1 diabetes in Australia after transition to adult care.

AIM: To determine advantages conferred by a youth-specific transition clinic model for young adults with type 1 diabetes (T1D) at Westmead Hospital (WH) as compared with Australian registry data. METHODS: Prospectively collected data included age, diabetes duration, visit frequency, post code, BMI, mode of insulin delivery, continuous glucose monitoring, HbA1c, albumin creatinine ratio, BP, retinopathy and diabetic ketoacidosis (DKA) for all WH T1D clinic attendees aged 16-25 between January 2017 and June 2018 (n = 269). Results were compared with data collected during the same time period from 2 separate Australian data registries, one longitudinal (Australasian Diabetes Data Network, ADDN) and one a spot survey (the Australian National Diabetes Audit, ANDA). RESULTS: Across the three cohorts, HbA1c was similar (respectively, WH, ADDN, ANDA; 8.7%[72mmol/mol], 8.7%[72mmol/mol], 8.5%[69mmol/mol]) and HbA1c was significantly higher in young adults <21 years (8.7-8.9%[73-75mmol/mol]) as compared with ≥21 years (8.5%[69mmol/mol], p < .002). In the WH cohort, median interval between visits was shorter than in ADDN (4.5 vs. 9.0 months) and DKA was lower (respectively, 3.6 and 9.2/100 patient years; p < .001). CONCLUSIONS: While suboptimal HbA1c was recorded in all centres, the WH model of care saw increased attendance and reduced admissions with DKA as compared with other Australian adult centres.

Australian experience with total pancreatectomy with islet autotransplantation to treat chronic pancreatitis.

BACKGROUND: This study aimed to describe the clinical outcomes of total pancreatectomy with islet autotransplantation (TP-IAT) in Australia. METHODS: Individuals selected for TP-IAT surgery according to the Minnesota Criteria (Appendix) without evidence of diabetes were evaluated including time to transplantation from pancreatectomy, islet numbers infused and post-transplantation HbA1c, C-peptide, total daily insulin and analgesic requirement. RESULTS: Sixteen individuals underwent TP-IAT from Australia and New Zealand between 2010 and 2020. Two recipients are deceased. The median islet equivalents/kg infused was 4244 (interquartile range (IQR) 2290-7300). The median C-peptide 1 month post-TP-IAT was 384 (IQR 210-579) pmol/L and at median 29.5 (IQR 14.5-46.5) months from transplant was 395 (IQR 139-862) pmol/L. Insulin independence was achieved in eight of 15 (53.3%) surviving recipients. A higher islet equivalents transplanted was most strongly associated with the likelihood of insulin independence (P < 0.05). Of the 15 surviving recipients, 14 demonstrated substantial reduction in analgesic requirement. CONCLUSION: The TP-IAT programme in Australia has been a successful new therapy for the management of individuals with chronic pancreatitis including hereditary forms refractory to medical treatment to improve pain management with 50% insulin independence rates.

Less Nocturnal Hypoglycemia but Equivalent Time in Range Among Adults with Type 1 Diabetes Using Insulin Pumps Versus Multiple Daily Injections.

Background: This prerandomization analysis from the Australian HCL-Adult trial (registration number: ACTRN12617000520336) compared masked continuous glucose monitoring (CGM) metrics among adults using insulin pumps versus multiple daily injections (MDIs), who were all self-monitoring blood glucose (SMBG). Methods: Adults with type 1 diabetes, using an insulin pump or MDIs without real-time CGM (and entering a trial of closed-loop technology), were eligible. MDI users were given an insulin dosage calculator. All participants received diabetes and carbohydrate-counting education, then wore masked CGM sensors for 3 weeks. Ethics Approval: HREC-D 088/16 Results: Adults using MDIs (n = 61) versus pump (n = 59) did not differ by age, sex, diabetes duration, insulin total daily dose, or HbA1c at baseline. After education, median (interquartile range) CGM time in range (TIR) 70-180 mg/dL (3.9-10.0 mmol/L) was 54% (47, 62) for those using MDIs and 56% (48, 66) for those using pump (P = 0.40). All CGM metrics were equivalent for 24 h/day for MDI and pump users. Overnight, those using MDIs (vs. pump) spent more time with glucose <54 mg/dL (<3.0 mmol/L): 1.4% (0.1, 5.1) versus 0.5% (0.0, 2.0), respectively (P = 0.012). They also had more CGM hypoglycemia episodes (121 vs. 54, respectively; incidence rate ratio [95% confidence interval] 2.48 [1.51, 4.06]; P < 0.001). Conclusions: Adults with type 1 diabetes using pumps versus MDIs in conjunction with SMBG experienced less nocturnal hypoglycemia, measured by masked CGM, after equivalent diabetes and dietary education in conjunction with insulin dosage calculator provision to all. However, both groups had equivalent TIR. This observation may reflect advantages afforded by flexibility in basal insulin delivery provided by pumps.

Cardiac Autonomic Neuropathy Is Not Reversed by Euglycemia Following Islet Transplantation.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a significant cause of morbidity and mortality for people with type 1 (T1D) and type 2 (T2D) diabetes. Heart rate variability (HRV) has been shown to be a marker of CAN with 24-hour Holter monitoring being a robust modality to assess HRV. METHODS: To investigate the impact of hypoglycemia on CAN and its potential reversibility with islet transplantation, we compared HRV assessment by 24-hour Holter monitor on a total of 109 subjects from 5 cohorts: (1) T1D with recurrent severe hypoglycemia and on waiting list for islet transplant, (2) T1D following islet cell transplantation (ICT), (3) T2D without hypoglycemia, (4) individuals with prediabetes, and (5) controls without diabetes. SD of the normal-normal interval, square root of the mean squared differences of successive normal-normal intervals (rMSSD) and total spectral power were analyzed. RESULTS: There was no significant difference in HRV parameters between T1D subjects and T1D post ICT suggesting CAN is not reversible at a median of 4 years postislet transplant. There was a significant difference in controls and T1D in rMSSD and between controls and T2D in total power. The differential effect on rMSSD in T1D and T2D suggests potential greater impact of hypoglycemia on rMSSD. CONCLUSIONS: Achieving euglycemia after ICT may not reverse CAN once established with no significant difference in HRV parameters at a median of 4 years postislet transplant. Differential effects of T1D as compared with T2D on CAN were identified.

Determinants of Cardiovascular Risk in 7000 Youth With Type 1 Diabetes in the Australasian Diabetes Data Network.

CONTEXT: Cardiovascular disease occurs prematurely in type 1 diabetes. The additional risk of overweight is not well characterized. OBJECTIVE: The primary aim was to measure the impact of body mass index (BMI) in youth with type 1 diabetes on cardiovascular risk factors. The secondary aim was to identify other determinants of cardiovascular risk. DESIGN: Observational longitudinal study of 7061 youth with type 1 diabetes followed for median 7.3 (interquartile range [IQR] 4-11) years over 41 (IQR 29-56) visits until March 2019. SETTING: 15 tertiary care diabetes centers in the Australasian Diabetes Data Network.Participants were aged 2 to 25 years at baseline, with at least 2 measurements of BMI and blood pressure. MAIN OUTCOME MEASURE: Standardized systolic and diastolic blood pressure scores and non-high-density lipoprotein (HDL) cholesterol were co-primary outcomes. Urinary albumin/creatinine ratio was the secondary outcome. RESULTS: BMI z-score related independently to standardized blood pressure z- scores and non-HDL cholesterol. An increase in 1 BMI z-score related to an average increase in systolic/diastolic blood pressure of 3.8/1.4 mmHg and an increase in non-HDL cholesterol (coefficient + 0.16 mmol/L, 95% confidence interval [CI], 0.13-0.18; P < 0.001) and in low-density lipoprotein (LDL) cholesterol. Females had higher blood pressure z-scores, higher non-HDL and LDL cholesterol, and higher urinary albumin/creatinine than males. Indigenous youth had markedly higher urinary albumin/creatinine (coefficient + 2.15 mg/mmol, 95% CI, 1.27-3.03; P < 0.001) and higher non-HDL cholesterol than non-Indigenous youth. Continuous subcutaneous insulin infusion was associated independently with lower non-HDL cholesterol and lower urinary albumin/creatinine. CONCLUSIONS: BMI had a modest independent effect on cardiovascular risk. Females and Indigenous Australians in particular had a more adverse risk profile.

Six Months of Hybrid Closed-Loop Versus Manual Insulin Delivery With Fingerprick Blood Glucose Monitoring in Adults With Type 1 Diabetes: A Randomized, Controlled Trial.

OBJECTIVE: To investigate glycemic and psychosocial outcomes with hybrid closed-loop (HCL) versus user-determined insulin dosing with multiple daily injections (MDI) or insulin pump (i.e., standard therapy for most adults with type 1 diabetes). RESEARCH DESIGN AND METHODS: Adults with type 1 diabetes using MDI or insulin pump without continuous glucose monitoring (CGM) were randomized to 26 weeks of HCL (Medtronic 670G) or continuation of current therapy. The primary outcome was masked CGM time in range (TIR; 70-180 mg/dL) during the final 3 weeks. RESULTS: Participants were randomized to HCL (n = 61) or control (n = 59). Baseline mean (SD) age was 44.2 (11.7) years, HbA1c was 7.4% (0.9%) (57 [10] mmol/mol), 53% were women, and 51% used MDI. HCL TIR increased from (baseline) 55% (13%) to (26 weeks) 70% (10%) with the control group unchanged: (baseline) 55% (12%) and (26 weeks) 55% (13%) (difference 15% [95% CI 11, 19]; P < 0.0001). For HCL, HbA1c was lower (median [95% CI] difference -0.4% [-0.6, -0.2]; -4 mmol/mol [-7, -2]; P < 0.0001) and diabetes-specific positive well-being was higher (difference 1.2 [95% CI 0.4, 1.9]; P < 0.0048) without a deterioration in diabetes distress, perceived sleep quality, or cognition. Seventeen (9 device-related) versus 13 serious adverse events occurred in the HCL and control groups, respectively. CONCLUSIONS: In adults with type 1 diabetes, 26 weeks of HCL improved TIR, HbA1c, and their sense of satisfaction from managing their diabetes compared with those continuing with user-determined insulin dosing and self-monitoring of blood glucose. For most people living with type 1 diabetes globally, this trial demonstrates that HCL is feasible, acceptable, and advantageous.

Effect of 6 months of hybrid closed-loop insulin delivery in adults with type 1 diabetes: a randomised controlled trial protocol.

INTRODUCTION: Manual determination of insulin dosing largely fails to optimise glucose control in type 1 diabetes. Automated insulin delivery via closed-loop systems has improved glucose control in short-term studies. The objective of the present study is to determine the effectiveness of 6 months' closed-loop compared with manually determined insulin dosing on time-in-target glucose range in adults with type 1 diabetes. METHODS AND ANALYSIS: This open-label, seven-centre, randomised controlled parallel group clinical trial will compare home-based hybrid closed-loop versus standard diabetes therapy in Australia. Adults aged ≥25 years with type 1 diabetes using intensive insulin therapy (via multiple daily injections or insulin pump, total enrolment target n=120) will undertake a run-in period including diabetes and carbohydrate-counting education, clinical optimisation and baseline data collection. Participants will then be randomised 1:1 either to 26 weeks of MiniMed 670G hybrid closed-loop system therapy (Medtronic, Northridge, CA, USA) or continuation of their current diabetes therapy. The hybrid closed-loop system delivers insulin automatically to address basal requirements and correct to target glucose level, while bolus doses for meals require user initiation and carbohydrate estimation. Analysis will be intention to treat, with the primary outcome time in continuous glucose monitoring (CGM) target range (3.9-10.0 mmol/L) during the final 3 weeks of intervention. Secondary outcomes include: other CGM parameters, HbA1c, severe hypoglycaemia, psychosocial well-being, sleep, cognition, electrocardiography, costs, quality of life, biomarkers of vascular health and hybrid closed-loop system performance. Semistructured interviews will assess the expectations and experiences of a subgroup of hybrid closed-loop users. ETHICS AND DISSEMINATION: The study has Human Research Ethics Committee approval. The study will be conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Results will be disseminated at scientific conferences and via peer-reviewed publications. TRIAL REGISTRATION NUMBER: ACTRN12617000520336; Pre-results.

Access to a youth-specific service for young adults with type 1 diabetes mellitus is associated with decreased hospital length of stay for diabetic ketoacidosis.

BACKGROUND: Management of type 1 diabetes mellitus in youth with diabetes (YWD) is complex, and glycaemic control often deteriorates during this challenging period. We hypothesise that attendance at a youth-specific diabetes clinic reduces hospital admission rates and length of stay (LOS) for diabetic ketoacidosis (DKA). AIMS: To assess the impact of a youth-specific diabetes service for YWD on DKA admissions in two adjacent local health districts. METHODS: A retrospective cohort analysis of admissions for DKA in YWD aged 15-25 years, presenting to four hospitals in Western Sydney in 2011 was performed. Number of admissions, LOS and DKA severity were assessed. Cost was analysed as a function of LOS. Groups were divided by attendance at a youth-specific diabetes service and no record of attendance. RESULTS: There were 55 DKA admissions from 39 patients (median age 20.0 years); the majority of admissions (82%) was YWD not supported by a youth-specific diabetes service. Median LOS was significantly longer in the unsupported group (3.0 vs 1.5 days, P = 0.028). Median pH at presentation in the unsupported group was significantly lower, 7.11 versus 7.23 (P = 0.05). The admission rate was four times greater for those not supported by youth-specific diabetes services, 5.5% compared with 1.6% (P = 0.001). The estimated cost saved by youth-specific services was over $250,000 pa. CONCLUSIONS: Lack of access to supported care for YWD during transition from paediatric to adult care has an adverse impact on subsequent DKA admission rates and LOS.

Long-term effects of islet transplantation.

PURPOSE OF REVIEW: Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. RECENT FINDINGS: Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. SUMMARY: Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.