Impaired Awareness Of Hypoglycemia Research Articles

Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study

BackgroundHypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D.MethodsThis cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected.ResultsThe prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13–5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22–0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37–0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups.ConclusionWe identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia.Trial registrationUniversity hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020.

Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice.

Transplantation of allogeneic pancreatic donor islets has successfully been performed in selected patients with difficult-to-control insulin-dependent diabetes and impaired awareness of hypoglycemia (IAH). However, the required systemic immunosuppression associated with this procedure prevents this cell replacement therapy from more widespread adoption in larger patient populations. We report the editing of primary human islet cells to the hypoimmune HLA class I- and class II-negative and CD47-overexpressing phenotype and their reaggregation into human HIP pseudoislets (p-islets). Human HIP p-islets were shown to survive, engraft, and ameliorate diabetes in immunocompetent, allogeneic, diabetic humanized mice. HIP p-islet cells were further shown to avoid autoimmune killing in autologous, diabetic humanized autoimmune mice. The survival and endocrine function of HIP p-islet cells were not impaired by contamination of unedited or partially edited cells within the p-islets. HIP p-islet cells were eliminated quickly and reliably in this model using a CD47-targeting antibody, thus providing a safety strategy in case HIP cells exert toxicity in a future clinical setting. Transplantation of human HIP p-islets for which no immunosuppression is required has the potential to lead to wider adoption of this therapy and help more diabetes patients with IAH and history of severe hypoglycemic events to achieve insulin independence.

Switching to an advanced hybrid closed-loop system in real-world practice improves hypoglycemia awareness and metabolic control in adults with type 1 diabetes, particularly in those with impaired perception of hypoglycemia symptoms

AimsTo evaluate the efficacy of an advance closed-loop (AHCL) system in restoring awareness of hypoglycemia in patients with type 1 diabetes (T1D). MethodsWe conducted a prospective study including 46 subjects with T1D flash glucose monitoring (FGM) or continuous glucose monitoring (CGM) switching to a Minimed 780G® system. Patients were classified in three groups according to the therapy used before switching to Minimed® 780G: multiple dose insulin (MDI) therapy + FGM (n = 6), continuous subcutaneous insulin infusion + FGM (n = 21), and sensor-augmented pump with predictive low-glucose suspend (n = 19). FGM/CGM data were analyzed at baseline, after 2 and 6 months on AHCL. Clarke’s score of hypoglycemia awareness was compared at baseline and 6 months recordings. We also compared the efficacy of the AHCL system in improving A1c among patients with appropriate perception of symptoms of hypoglycemia compared to those presenting with impaired awareness of hypoglycemia (IAH). ResultsParticipants had a mean age of 37 ± 15 and a diabetes duration of 20 ± 10 years. At baseline, 12 patients (27%) showed IAH as defined by a Clarke’s score ≥ 3. Patients with IAH were older and had lower estimated glomerular filtration rate (eGFR) compared with those who did not have IAH; with no differences in baseline CGM metrics or A1c. An overall decrease in A1c was observed after 6 months on AHCL system (from 6.9 ± 0.5% to 6.7 ± 0.6%, P < 0.001), regardless of prior insulin therapy. The improvement in metabolic control was greater in patients with IAH, showing a reduction in A1c from 6.9 ± 0.5 to 6.4 ± 0.4% vs 6.9 ± 0.5 to 6.8 ± 0.6% (P = 0.003), showing a parallel increase in total daily boluses of insulin and automatic bolus correction administered by the AHCL system. In patients with IAH Clarke’s score decreased from 3.6 ± 0.8 at baseline to 1.9 ± 1.6 after 6 months (P < 0.001). After 6 months on AHCL system, only 3 patients (7%) presented with a Clarke’s score ≥ 3, resulting in an absolute risk reduction of 20% (95% confidence interval: 7–32) of having IAH. ConclusionsSwitching from any type of insulin administration to AHCL system improves restoration of hypoglycemia awareness and metabolic control in patients with T1D, particularly in adults with impaired perception of hypoglycemia symptoms. Trial RegistrationClinicalTrial.gov ID NCT04900636.

Automated Insulin Delivery for Hypoglycemia Avoidance and Glucose Counterregulation in Long-Standing Type 1 Diabetes with Hypoglycemia Unawareness.

Objective: Automated insulin delivery (AID) may benefit individuals with long-standing type 1 diabetes where frequent exposure to hypoglycemia impairs counterregulatory responses. This study assessed the effect of 18 months AID on hypoglycemia avoidance and glucose counterregulatory responses to insulin-induced hypoglycemia in long-standing type 1 diabetes complicated by impaired awareness of hypoglycemia. Methods: Ten participants mean ± standard deviation age 49 ± 16 and diabetes duration 34 ± 16 years were initiated on AID. Continuous glucose monitoring was paired with actigraphy to assess awake- and sleep-associated hypoglycemia exposure every 3 months. Hyperinsulinemic hypoglycemic clamp experiments were performed at baseline, 6, and 18 months postintervention. Hypoglycemia exposure was reduced by 3 months, especially during sleep, with effects sustained through 18 months (P ≤ 0.001) together with reduced glucose variability (P < 0.01). Results: Hypoglycemia awareness and severity scores improved (P < 0.01) with severe hypoglycemia events reduced from median (interquartile range) 3 (3-10) at baseline to 0 (0-1) events/person·year postintervention (P = 0.005). During the hypoglycemic clamp experiments, no change was seen in the endogenous glucose production (EGP) response, however, peripheral glucose utilization during hypoglycemia was reduced following intervention [pre: 4.6 ± 0.4, 6 months: 3.8 ± 0.5, 18 months: 3.4 ± 0.3 mg/(kg·min), P < 0.05]. There were increases over time in pancreatic polypeptide (Pre:62 ± 29, 6 months:127 ± 44, 18 months:176 ± 58 pmol/L, P < 0.01), epinephrine (Pre: 199 ± 53, 6 months: 332 ± 91, 18 months: 386 ± 95 pg/mL, P = 0.001), and autonomic symptom (Pre: 6 ± 2, 6 months: 6 ± 2, 18 months: 10 ± 2, P < 0.05) responses. Conclusions: AID led to a sustained reduction of hypoglycemia exposure. EGP in response to insulin-induced hypoglycemia remained defective, however, partial recovery of glucose counterregulation was evidenced by a reduction in peripheral glucose utilization likely mediated by increased epinephrine secretion and, together with improved autonomic symptoms, may contribute to the observed clinical reduction in hypoglycemia.

Awareness Level of Hypoglycemia Among Diabetes Mellitus Type 2 Patients in Al Qassim Region.

Background Hypoglycemia has a major impact on patient health and glycemic management during insulin therapy for both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). It is the rate-limiting complication in diabetes management that prevents stringent glucose control. Objectives To assess the knowledge and awareness about hypoglycemia as a complication of T2D in adults in Al Qassim, Saudi Arabia. Methods This is a cross-sectional study done among type 2 diabetes patients in Al-Qassim, Kingdom of Saudi Arabia, from January to June 2022. A previously validated online questionnaire was disseminated through social media to gather information from respondents. Participants were chosen via a simple random sampling technique. Data analysis was completed using SPSS (version 23; IBM Corp., Armonk, NY). Results Overall, 213 respondents were included in our study. The majority of them were females (70.9%). The participants' average age was 35.9 + 13.0 years. Our results revealed that the average awareness score of the study population was found to be 3.6 ± 1.1 (by using the Clarke method) and 3.7 ± 2.1 (by using the Gold method). Moreover, we found that impaired awareness of hypoglycemia's prevalence by Clarke's questionnaire was 52.1% and 53.5%by using the Gold questionnaire. In addition, almost half of the respondents reported weakness as a symptom of hypoglycemia over the last six months and unconsciousness over the last 12 months. Hypertension was the most commonly reported chronic disease by our participants. Lastly, factors such as age, gender, educational level, geographic distribution, and history of chronic illness did not show any significant association with impaired awareness of the prevalence of hypoglycemia. Conclusion According to our research, we concluded that patients with type 2 diabetes mellitus in the region of Al-Qassim, Saudi Arabia, had insufficient knowledge about hypoglycemia as a complication of T2D. Moreover, the impaired awareness of hypoglycemia in diabetic patients was found to be high. Hence, there is a need for interventional programs to raise public awareness.

New insights into the currently available questionnaire for assessing impaired awareness of hypoglycaemia (IAH) among insulin-treated type 2 diabetes- A key risk factor for hypoglycaemia

BackgroundGold and Clarke questionnaire are originally developed to assess impaired awareness of hypoglycaemia (IAH) in type 1 diabetes. Present study examined the similarities and differences between the two questionnaires when administered to insulin-treated type 2 diabetes patients. MethodsA total of 153 insulin-treated type 2 diabetes patients with mean age of 61.0±9.4 years and mean HbA1c of 8.4±1.5% completed questionnaire in diabetes outpatient clinics of tertiary-care hospital. Factor analysis was conducted to examine the psychometric properties of Clarke questionnaire. Spearman's correlation was used to examine convergent validity of Clarke questionnaire with Gold method. ResultsBifactorial structure for Clarke questionnaire was identified, namely Awareness of Hypoglycaemia (Factor 1) and Experience of Hypoglycaemia (Factor 2). Clarke Factor 1 correlated strongly with Gold scores (rs=0.77, p<0.001), and yielded 22.9% prevalence of IAH using cut-off score of ≥2.5, which is comparable to Gold method of 19.6%. ConclusionsGold single-item questionnaire assesses hypoglycaemia awareness only while Clarke questionnaire assesses both hypoglycaemia awareness and severe hypoglycaemia events. There is a high degree of convergence between Gold and Clarke in hypoglycaemia awareness assessment among insulin-treated type 2 diabetes. Hence, these two questionnaires are similar but not interchangeable due to bifactorial nature of Clarke questionnaire.

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

Real-World Diabetes Technology: Overcoming Barriers and Disparities.

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference 22‐25 February 2023 I Berlin &amp; Online

The Official Journal of ATTD Advanced Technologies &amp; Treatments for Diabetes Conference 22‐25 February 2023 I Berlin &amp; Online

Fall in prevalence of impaired awareness of hypoglycaemia in individuals with type 1 diabetes.

Impaired awareness of hypoglycaemia (IAH) has been reported to affect up to a third of people with type 1 diabetes. Whether the increased use of sensor technology has changed its prevalence remains unknown. The aim of this study was to investigate the current prevalence of IAH and its change over time in a cohort of individuals with type 1 diabetes. IAH was assessed using the modified Clarke questionnaire in adults with type 1 diabetes. Participants were recruited from the diabetes outpatient clinic from February 2020 through April 2021. The scores were compared to similar data collected during previous assessments in 2006, 2010 and 2016 respectively. A total of 488 individuals (51.2% male) with a mean (±SD) age of 51.3 ± 15.9 years, median [Q1-Q3] diabetes duration of 30 [16-40] years and mean HbA1c of 60 ± 12 mmol/mol (7.7 ± 1.1%) were included. Sensors were used by 85% of the study population. IAH was present among 78 (16.0%) participants, whereas 86 (17.6%) participants had a history of severe hypoglycaemia. By comparison, the prevalence of IAH equalled 32.5% in 2006, 32.3% in 2010 and 30.1% in 2016 (p for trend <0.001), while the proportion of individuals reporting severe hypoglycaemia equalled 21.2%, 46.7% and 49.8% respectively (p for trend 0.010). Comparing sequential assessments over time, the proportion of individuals with persistent IAH decreased from 74.0% and 63.6% between 2006 and 2016 to 32.5% in 2020. Among individuals with type 1 diabetes and high use of sensor technology, the current prevalence of IAH was 16%, about 50% lower as compared to previous years.

Epidemiological, Social and Economic Burden of Severe Hypoglycaemia in Patients with Diabetes Mellitus in Portugal: A Structured Literature Review.

The aim of this review was to identify and review studies reporting on the epidemiological, social and economic impact associated with severe hypoglycaemia (SH) in people with diabetes mellitus (DM) in Portugal. A structured literature search was carried out in PubMed and Embase using a predefined selection criterion. Studies published in either Portuguese or English, between January 2010 and February 2021 were deemed eligible for inclusion. Twelve studies including adults (aged ≥ 18years) with type 1 and/or type 2 diabetes mellitus (T1DM/T2DM) were eligible for inclusion. Epidemiological estimates varied according to the setting and type of data source used. The proportion of patients who experienced ≥ 1 SH episode (SHE) in the previous 6-12months varied from 3.1% in adults with T2DM to 36.8% in adults with T1DM. In adults with T2DM the prevalence in a community-based study was highest in the insulin and secretagogue combination treated group (9.1%), while in an emergency department setting prevalence was highest in the insulin-based therapy group and the oral hypoglycaemic agent without secretagogues group (32.0% and 20.0%, respectively). The prevalence of SH in other studies in patients with DM ranged from 0.1% (emergency department) to 18.1% (hospital ward). Patients treated with secretagogues had the highest rates of hospitalisations. In patients with T1DM, the annual rate of SHE was higher in those with impaired hypoglycaemia awareness than in those with intact awareness. Mean total cost (direct and indirect) per SHE ranged from €1493.00 in patients with T2DM treated in an emergency setting to €2608.51 in patients with T1DM who were hospitalised. Hypoglycaemic events, especially SHE, have a significant effect on the life of persons living with DM and their caregivers. Studies show that the prevalence of this acute complication of diabetes is not negligible. In addition to the negative impact on the quality of life, the burden of SHE in Portugal translates into a significant impact on the global health expenditure.

Diabetes education and counseling in adult patients with diabetes (Update 2023)

Diabetes education and self-management play acritical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and subsequent treatment modification as well as the ability of patients to integrate diabetes into their daily life and to appropriately adapt diabetes to their life style situation. Diabetes education has to be made accessible for all persons with the disease. In order to be able to provide astructured and validated education program, adequate personnel as well as space, organizational and financial prerequisites are required. Besides an increase in knowledge about the disease it has been shown that astructured diabetes education is able to improve diabetes outcome as measured by parameters, such as blood glucose, HbA1c, lipids, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes into everyday life, stress physical activity besides healthy eating as important components of life style therapy and use interactive methods in order to increase the acceptance of personal responsibility. Specific situations (e.g. impaired hypoglycemia awareness, illness, travel), the occurrence of diabetic complications and the use of technical devices such as glucose sensor systems and insulin pumps require additional educational measures supported by adequate electronic tools (diabetes apps and diabetes web portals). New data demonstrate the effect of telemedicine and internet-based services for diabetes prevention and management.

Impaired awareness of hypoglycaemia

Impaired awareness of hypoglycaemia

Changes in attitudes to awareness of hypoglycaemia during a hypoglycaemia awareness restoration programme are associated with avoidance of further severe hypoglycaemia episodes within 24 months: the A2A in HypoCOMPaSS study

Aims/hypothesisThe aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months).MethodsThis analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring.ResultsThe age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier ‘hyperglycaemia avoidance prioritised’ (η2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in ‘asymptomatic hypoglycaemia normalised’ from baseline (η2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for ‘asymptomatic hypoglycaemia normalised’, reduced change in ‘asymptomatic hypoglycaemia normalised’ scores at 24 weeks, and lower baseline ‘hypoglycaemia concern minimised’ scores (all p<0.05).Conclusions/interpretationParticipation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with ‘hyperglycaemia avoidance prioritised’ most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition ‘asymptomatic hypoglycaemia normalised’. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes.Clinical trials registrationwww.isrctn.org: ISRCTN52164803 and https://eudract.ema.europa.eu: EudraCT2009-015396-27.Graphical abstract

Impaired Awareness of Hypoglycemia in Type 1 Diabetes: A Report of An NIDDK Workshop in October 2021.

Hypoglycemia remains a limiting factor in the optimal treatment of type 1 diabetes. Repeated episodes of hypoglycemia result in impaired awareness of subsequent hypoglycemic events, inducing a vicious feed-forward cycle and increasing the risk of morbidity and mortality. Why this occurs and how to manage the problem in clinical practice remain uncertain. To address the obstacles and barriers that have hindered progress in this clinically important area, the National Institute of Diabetes and Digestive and Kidney Diseases convened a workshop on 14-15 October 2021. This perspective offers a summary of this outstanding meeting, which brought clinical and basic scientists from the fields of diabetes, neuroscience, psychology, psychiatry, and imaging together, on how to best advance the field of impaired awareness of hypoglycemia and hypoglycemia in general in patients with diabetes.

Glucose profiles of older adults with type 1 diabetes using sensor-augmented pump therapy in Australia: pre-randomisation results from the ORACL study

Older adults with type 1 diabetes are recommended modified glucose targets. However, data on the effects of diabetes technology in older age are scarce. We assessed older adults established on sensor-augmented insulin pump therapy during clinical trial run-in and compared their continuous glucose monitoring (CGM) profiles with consensus recommendations. We aimed to provide insight into the applicability of currently recommended CGM-based targets while accounting for current Diabetes UK guidelines. In this analysis, adults aged 60 years or older with type 1 diabetes with a duration of at least 10 years and entering the Older Adult Closed Loop (ORACL) trial were studied. The trial was done at two tertiary hospitals in Australia. Individuals who were independent with diabetes self-management, as well as those receiving caregiver assistance for their diabetes management, were eligible for inclusion. Participants underwent baseline clinical assessment, which included medical history and examination, testing for frailty, functional ability, cognitive functioning, psychosocial wellbeing, and subjective sleep quality; fasting venous blood samples were collected for C-peptide, glucose, and glycated haemoglobin A1c measurement. Sensor-augmented pumps, carbohydrate-counting education, and diabetes education were provided to participants by diabetes nurse educators, dietitians, and endocrinologists experienced in type 1 diabetes clinical care. CGM data were subsequently collected for 2 weeks during sensor-augmented pump therapy. The ORACL trial is registered with the Australian New Zealand Clinical Trial Registry, ACTRN12619000515190. Our analysis included all 30 participants who completed the ORACL trial run-in-19 (63%) women and 11 (37%) men (mean age 67 years [SD 5], median diabetes duration 38 years [IQR 20-47], and insulin total daily dose 0·55 units [0·41-0·66] per kg bodyweight). Ten (33%) of 30 participants had impaired hypoglycaemia awareness and six (20%) were pre-frail; none were frail. The median CGM time in range 3·9-10·0 mmol/L was 71% (IQR 64-79). The time spent with glucose above 10·0 mmol/L was 27% (18-35) and above 13·9 mmol/L was 3·9% (2·4-10·2). The time with glucose below 3·9 mmol/L was 2·0% (1·2-3·1) and the time below 3·0 mmol/L was 0·2% (0·1-0·4). Only two (7%) of 30 participants met all CGM-based consensus recommendations modified for older adults. Time in hypoglycaemia was lower among the 16 participants with predictive low-glucose alerts enabled than among the 14 participants not using predictive low-glucose alerts (median difference -1·1 percentage points [95% CI -2·0 to -0·1]; p=0·038). This difference was even greater overnight (-2·3 percentage points [-3·2 to -1·0]; p=0·0018). One serious adverse event occurred (elective cardiac stent). Using sensor-augmented pumps after multidisciplinary education, this group of older adults without frailty achieved a time in range far exceeding minimum consensus recommendations. However, the current stringent hypoglycaemia recommendations for all older adults were not met. Predictive low alerts could reduce hypoglycaemia, particularly overnight. Investigation into the effectiveness of CGM-based targets that consider frailty, functional status, and diabetes therapies for older adults is warranted. JDRF and Diabetes Australia.

Long-term Outcomes With Islet-Alone and Islet-After-Kidney Transplantation for Type 1 Diabetes in the Clinical Islet Transplantation Consortium: The CIT-08 Study.

To determine long-term outcomes for islet-alone and islet-after-kidney transplantation in adults with type 1 diabetes complicated by impaired awareness of hypoglycemia. This was a prospective interventional and observational cohort study of islet-alone (n = 48) and islet-after-kidney (n = 24) transplant recipients followed for up to 8 years after intraportal infusion of one or more purified human pancreatic islet products under standardized immunosuppression. Outcomes included duration of islet graft survival (stimulated C-peptide ≥0.3 ng/mL), on-target glycemic control (HbA1c <7.0%), freedom from severe hypoglycemia, and insulin independence. Of the 48 islet-alone and 24 islet-after-kidney transplantation recipients, 26 and 8 completed long-term follow-up with islet graft function, 15 and 7 withdrew from follow-up with islet graft function, and 7 and 9 experienced islet graft failure, respectively. Actuarial islet graft survival at median and final follow-up was 84% and 56% for islet-alone and 69% and 49% for islet-after-kidney (P = 0.007) with 77% and 49% of islet-alone and 57% and 35% of islet-after-kidney transplantation recipients maintaining posttransplant HbA1c <7.0% (P = 0.0017); freedom from severe hypoglycemia was maintained at >90% in both cohorts. Insulin independence was achieved by 74% of islet-alone and islet-after-kidney transplantation recipients, with more than one-half maintaining insulin independence during long-term follow-up. Kidney function remained stable during long-term follow-up in both cohorts, and rates of sensitization against HLA were low. Severe adverse events occurred at 0.31 per patient-year for islet-alone and 0.43 per patient-year for islet-after-kidney transplantation. Islet transplantation results in durable islet graft survival permitting achievement of glycemic targets in the absence of severe hypoglycemia for most appropriately indicated recipients having impaired awareness of hypoglycemia, with acceptable safety of added immunosuppression for both islet-alone and islet-after-kidney transplantation.

Time in range following flash glucose monitoring: Relationship with glycaemic control, diabetes-related distress and resource utilisation in the Association of British Clinical Diabetologists national audit.

The aim of this study was to understand the relationship between time in range (TIR) achieved using the isCGM with changes in glycaemic control, diabetes-related distress (DRD) and resource utilisation in people living with diabetes. Clinicians from 106 National Health System (NHS) UK hospitals submitted isCGM user baseline and follow-up data in a web-based tool held within the UK NHS network. Linear regression analysis was used to identify the relationship between follow-up glucose TIR (3.9-10 mmol/L) categories (TIR% 50-70 and TIR% >70) with change in haemoglobin A1c (HbA1c), DRD and Gold score (measure of hypoglycaemia unawareness, where a score ≥4 suggests impaired awareness of hypoglycaemia). Of 16,427 participants, 1241 had TIR follow-up data available. In this cohort, the mean TIR was 44.8% (±22.5). With the use of isCGM, at 7.9months mean follow-up, improvements were observed in HbA1c (-6.9 [13.5]mmol/mol, p < 0.001), Gold score (-0.35 [1.5], p < 0.001) and Diabetes Distress Screening (-0.73 [1.23], p < 0.001). In the regression analysis restricted to people living with type 1 diabetes, TIR% 50-70 was associated with a -8.9 mmol/mol (±0.6, p < 0.001) reduction in HbA1c; TIR% >70 with a -14 mmol/mol (±0.8, p < 0.001) reduction in HbA1c. Incremental improvement in TIR% was also associated with significant improvements in Gold score and DRD. TIR% >70 was associated with no hospital admissions due to hypoglycaemia, hyperglycaemia/diabetic ketoacidosis, and a 60% reduction in the paramedic callouts and 77% reduction in the incidence of severe hypoglycaemia. In a large cohort of UK isCGM users, we demonstrate a significant association of higher TIR% with improvement in HbA1c, hypoglycaemia awareness, DRD and resource utilisation.

Symptoms of Anxiety and Depression Are Independently Associated With Impaired Awareness of Hypoglycemia in Type 1 Diabetes.

We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes. In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics. Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19-6.04] and 2.46 [1.46-4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P < 0.001). The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH.

Evaluation of Clinical Metrics for Identifying Defective Physiologic Responses to Hypoglycemia in Long-Standing Type 1 Diabetes.

Repeated hypoglycemia exposure leads to impaired awareness of hypoglycemia (IAH) and the development of defective counterregulatory responses. To date, only pancreas or islet transplantation has demonstrated normalization of hypoglycemia awareness and the endogenous glucose production (EGP) response to defend against insulin-induced hypoglycemia in long-standing type 1 diabetes (T1D). This study aims to validate clinical metrics of IAH (Clarke score), hypoglycemia severity (HYPO score), glycemic lability (lability index), and continuous glucose monitoring (CGM) as predictors of absent autonomic symptom (AS) recognition and defective glucose counterregulation during insulin-induced hypoglycemia, thus enabling early identification of individuals with compromised physiologic defense against clinically significant hypoglycemia. Forty-three subjects with mean ± standard deviation age 43 ± 13 years and T1D duration 28 ± 13 years, including 32 with IAH and 11 with hypoglycemia awareness (Aware), and 12 nondiabetic control subjects, underwent single-blinded randomized-paired hyperinsulinemic-euglycemic and hypoglycemic clamp experiments. Receiver operating characteristic (ROC) curves and sensitivity analyses were performed to assess metric prediction of absent AS recognition and defective EGP responses to hypoglycemia. Clarke score and CGM measures of hypoglycemia exposure demonstrated good ability to predict absent AS recognition (area under the curve ≥0.80). A composite threshold of IAH-Clarke ≥4 with ROC curve-derived thresholds for CGM measures of hypoglycemia exposure showed high specificity and predictive value in identifying an absent AS response during the hypoglycemic clamp. Metrics demonstrated poor ability to predict defective glucose counterregulation by the EGP response, which was impaired even in the Aware group. Screening for IAH alongside assessment of CGM data can increase the specificity for identifying individuals with absent hypoglycemia symptom recognition who may benefit from further intervention.