Impaired Awareness Of Hypoglycemia Research Articles

Prevalence and risk factors for impaired awareness of hypoglycaemia: A registry-based study of 10,202 adults with type 1 diabetes in Norway.

The aim of this study is to determine the prevalence of impaired awareness of hypoglycaemia (IAH) and examine risk factors for IAH in adults with type 1 diabetes. We conducted a population-based registry study of 10,202 adults (≥18 years) with type 1 diabetes using data from the Norwegian Diabetes Register for Adults. The registry used the 1-item Gold scale, measuring hypoglycaemia symptom awareness. We calculated the overall prevalence of IAH (Gold score ≥4) (95% CI) and prevalence for subgroups based on demographic and clinical variables. We estimated IAH prevalence based on continuous scales of age, diabetes duration and HbA1c using predicted probabilities from generalised additive logistic regression models. Finally, we quantified the associations of selected variables on IAH prevalence using log-binomial regression models. Overall, 18.0% reported IAH (95% CI 17.2, 18.7). The prevalence increased linearly with the participants' age, whereas the associations of diabetes duration and HbA1c with IAH were non-linear with higher prevalence in both lower and higher tails of their distributions. Multiple severe hypoglycaemic events, female sex, age ≥ 65 years, diabetes duration ≤4 years or ≥ 30 years, multiple DKA events and CGM use were associated with higher risk for IAH. HbA1c 65-74 mmol/mol (8.1-8.9%) was associated with lower risk for IAH. In this nationwide study, the IAH prevalence was 18.0%. Multiple hypoglycaemic events, female sex and diabetes duration were identified as important risk factors for IAH. Study findings highlight the complexity of self-reported hypoglycaemia symptom awareness and emphasise the importance of routinely addressing symptom awareness in diabetes follow-up.

Interoceptive Awareness Is Associated With Impaired Awareness of Hypoglycemia in Adults With Type 1 Diabetes.

To assess the association between impaired awareness of hypoglycemia (IAH) and interoceptive awareness in type 1 diabetes. A total of 154 adults with type 1 diabetes completed IAH surveys and the Multidimensional Assessment of Interoceptive Awareness, Version 2 (MAIA-2). Logistic regression was performed for assessment of associations between IAH and MAIA-2, accounting for covariates. Significant relationships were observed between IAH and two MAIA-2 scales. Each 1-point increase on the Not-Worrying subscale was associated with 87% increased odds of IAH (odds ratio 1.87, CI 1.01-3.46) and on the Attention Regulation subscale was associated with 72% decreased odds of IAH (0.28, 0.12-0.66). Compared with scoring >90th percentile for Attention Regulation, scoring <10th percentile and scoring in the 10th-90th percentiles were associated with 71-fold (71.26, 3.42-1482.10) and 12-fold (12.73, 1.19-135.57) increased odds of IAH, respectively. Less worry about and reduced ability to sustain and control attention to body sensations were associated with significantly increased odds of IAH.

Abstract 4112589: Typology of Self-Care in Adults with Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Introduction: Individuals with type 1 diabetes (T1D) complicated by impaired awareness of hypoglycemia (IAH) are at significantly increased risk for severe hypoglycemia: a marker of high risk of CVD. Tailoring interventions to promote hypoglycemia avoidance is difficult due to self-care heterogeneity among those with T1D. Aims: Map self-care heterogeneity among adults with T1D into behavioral phenotypes and identify common barriers to hypoglycemia avoidance within each phenotype. Methods: An explanatory sequential mixed methods study was performed in 200 adults with T1D. Participants reported personal, clinical, and social determinants of health, hypoglycemia awareness, and self-care of diabetes (Self-Care of Diabetes Inventory, scored 0-100, adequate ≥70) . Cluster analysis was performed to identify self-care clusters. Then, directed content analysis was applied to individual, semi-structured interviews performed in a subsample from each cluster with IAH ( n =20). Findings were integrated to develop a typology of self-care and identify barriers to hypoglycemia avoidance within each phenotype. Results: Three self-care phenotypes were identified. Experts ( n =70; mean age: 45±17 years; 24% Black; T1D duration: 25±16 years; HbA 1c : 7.36±1.67%; IAH: 20%) performed all aspects of self-care adequately (Maintenance: 84.9±8.8; Monitoring: 85.1±8.8; Management: 72.5±10). Yet, Experts with IAH reported purposefully delaying treatment of hypoglycemia due to lack of concern. Those with Inconsistent self-care ( n = 112; mean age 37±14 years; 20% Black: T1D duration: 21±13 years; HbA 1c : 7.26±1.16%; IAH: 30%) performed only self-care maintenance adequately (Maintenance: 78.6±8.9; Monitoring: 65.6±9.8; Management: 56.8±10.1). Those with Inconsistent self-care and IAH reported passive self-care monitoring that inhibited effective hypoglycemic management. Novices ( n = 18; mean age 27±7 years; 50% Black: T1D duration: 16±8 years; HbA 1c : 8.97±2.80%; IAH: 28%) reported difficulty performing all aspects of self-care (Maintenance: 51.9±7.7, Monitoring: 56.9±12.9, Management: 44.5±6.3) due to economic and psychosocial barriers. Conclusions: Self-care heterogeneity mapped onto three phenotypes that can be used to better understand patient barriers to hypoglycemia avoidance and hypoglycemia awareness restoration. This typology provides a framework for investigating how best to tailor IAH treatment considerate of self-care.

Characterising impaired awareness of hypoglycaemia and associated risks through HypoA-Q: findings from a T1D Exchange cohort.

We aimed to: (1) externally validate the five-item Hypoglycaemia Awareness Questionnaire (HypoA-Q) impaired awareness subscale (HypoA-Q IA); (2) examine how impaired awareness of hypoglycaemia (IAH) relates to the risk of severe hypoglycaemia and level 2 hypoglycaemia; and (3) identify factors associated with IAH. Nationwide survey of T1D Exchange registrants was conducted to collect data on demographics, 6 month severe-hypoglycaemia history, hypoglycaemia awareness status (via HypoA-Q IA, the Gold instrument and the Clarke instrument) and continuous glucose monitor (CGM) measures. The Clarke hypoglycaemia awareness factor (Clarke-HAF) was calculated to exclude severe-hypoglycaemia history items. Analyses included Cronbach's α, Spearman correlations and logistic regression. Valid survey responses were collected from N=1580 adults with type 1 diabetes (median age, 44 years; 52% female participants; median HbA1c, 48 mmol/mol [6.5%]). Of these, 94% of participants were using CGMs and 69% were using hybrid closed-loop (HCL) systems; 30% had at least one severe-hypoglycaemia episode in the past 6 months. The HypoA-Q IA had satisfactory internal reliability (α=0.79) and construct validity. Higher HypoA-Q IA scores were independently associated with greater risk of severe hypoglycaemia (p<0.001), performing comparably to the Gold instrument and the Clarke-HAF instrument. HypoA-Q IA-determined IAH was independently associated with 88% higher odds of developing severe hypoglycaemia (p<0.001) and twofold higher odds for spending ≥1% of time in level 2 hypoglycaemia (p=0.011). Higher age and longer diabetes duration were associated with higher IAH risk (p<0.001). CGM and HCL use was associated with lower IAH risk (p<0.001). The HypoA-Q IA is a brief, valid and reliable tool for assessing IAH in today's technology-oriented era. IAH was independently associated with severe hypoglycaemia and level 2 hypoglycaemia in a cohort with high prevalence of advanced diabetes technology use and HbA1c within the recommended range. CGM and HCL use was related to lower IAH risk.

Residual C-peptide is associated with new and persistent impaired awareness of hypoglycaemia in type 1 diabetes

AimsTo describe the change in impaired awareness of hypoglycaemia (IAH) over time and to identify factors associated with this change in the Dutch Type 1 Diabetes biomarkers cohort (NCT04977635). MethodsA prospective cohort of type 1 diabetes patients, with C-peptide <300 pmol/L, who had completed the Clarke questionnaire, to determine IAH status, at baseline and after 2 years. Changes in awareness status were defined and compares as follows: unchanged normal awareness (NAH) versus unchanged IAH, new IAH versus reversal of IAH. Multivariate logistic regression models were fitted using forward and backward stepwise selection using a 0.10 P-value cut-off, and stepwise backward selection using AIC criteria. ResultsA total of 431 out of 611 participants were included. The baseline prevalence of IAH was 17 % and 20 % after 2 years. The incidence proportion of new IAH and reversal of IAH were, 9.5 % and 31 %, respectively. For every 2.7-fold increase in C-peptide, the odds of IAH decrease by 58 %. A 1-unit increase in BMI over the 2-year follow-up period is associated with a 5.27-fold increase in the odds of reversing IAH. ConclusionsHigher C-peptide levels are protective against new IAH, and an increase in BMI over time is associated with the reversal of IAH.

Impaired Awareness of Hypoglycemia and its Risk Factors among Diabetic Patients in Jazan, Saudi Arabia: A Cross-Sectional Study.

Impaired awareness of hypoglycemia (IAH) is related to a three- to sixfold increase in the risk of severe hypoglycemia in adults with type 1 diabetes mellitus (T1D). This study aimed to assess the prevalence of IAH and its risk factors and determine the frequency of hypoglycemic symptoms. This study aimed to assess the prevalence of IAH and its risk factors and determine the frequency of hypoglycemic symptoms. A cross-sectional study was conducted among T1D patients attending Jazan Endocrine and Diabetes Center in Jazan province, Saudi Arabia. A total of 151 patients participated, using the interview-based Clarke questionnaire, a validated eight-item questionnaire to evaluate IAH. Scoring four or more answers as reduced awareness categorizes the participant as having IAH. The prevalence of IAH was 25.2% among the T1D patients. IAH was significantly associated with body mass index (BMI; p = 0.034), occupation (p = 0.014), and blood glucose monitoring methods (p = 0.027). Shaking and sweating were the most commonly reported symptoms of hypoglycemia. A BMI of <25 kg/m2 was higher linked to hunger and speech difficulty compared to a BMI of ≥25 kg/m2 (p < 0.05). Changing the insulin injection site was associated with confusion, odd behavior, and speech difficulty (p < 0.05). Monitoring blood glucose four times daily was associated with sweating, odd behavior, and incoordination (p = 0.024) compared to monitoring less than four times daily (p < 0.05). A hemoglobin A1c (HbA1c) reading of ≥7 was linked to odd behavior compared to an HbA1c reading of <7 (p = 0.032). Patients committed to insulin injections were more likely to experience palpitations than non-committed patients (p = 0.038). Each one-unit increase in age, monitoring blood glucose, and income was associated with a decrease in the odds of IAH (OR of Age = 0.89, 95% CI: 0.83-0.95) (OR of income = 0.10, 95% CI: 0.01-0.55). Moreover, individuals with a Body Mass Index (BMI) greater than or equal to 25 (OR = 2.99, 95% CI: 1.13-8.25), employed individuals (OR = 18.2, 95% CI: 3.75-105), and diabetes duration of more than ten years (OR = 3.96, 95% CI: 1.31- 13.2) exhibited an increase in the higher risk of IAH. IAH was prevalent among T1D patients attending Jazan Endocrine and Diabetes Center. The main associated factors included BMI, blood glucose monitoring method, and occupation. Future research should investigate the underlying causes of the observed associations and explore strategies to enhance the awareness of hypoglycemia.

HIT4HYPOS Continuous Glucose Monitoring Data Analysis: The Effects of High-Intensity Interval Training on Hypoglycemia in People With Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Aims: To assess the impact of high-intensity interval training (HIIT) on hypoglycemia frequency and duration in people with type 1 diabetes (T1D) with impaired awareness of hypoglycemia (IAH). Methods: Post hoc analysis of four weeks of continuous glucose monitoring (CGM) data from HIT4HYPOS; a parallel-group study comparing HIIT + CGM versus no exercise + CGM in 18 participants with T1D and IAH. Results: When compared with those participating individuals not exercising, HIIT did not increase total hypoglycemia frequency, THypo(L1) 1.44 [1.00-2.77]% versus 2.53 [1.46-4.23]%; P = .335, THypo(L2) 0.25 [0.09-0.37]% versus 0.45 [0.20-0.78]%; P = .146, HIIT + CGM versus CGM, respectively, rate ( EventPerWeekHypo 5.30 [3.35-8.27] #/week vs 7.45 [3.54-10.81] #/week, P = .340) or duration ( DurationHypo 33.33 [27.60-39.10] minutes vs 39.56 [31.00-48.38] minutes; P = .219, HIIT + CGM vs CGM, respectively). There was a reduction in nocturnal hypoglycemia in those who carried out HIIT, THypo(L1) 0.50 [0.13-0.97]% versus 2.45 [0.77-4.74]%; P = .076; THypo(L2) 0.00 [0.00-0.03]% versus 0.49 [0.13-0.74]%; P = .006, HIIT + CGM versus CGM, respectively. Conclusions/interpretation: Based on CGM data collected from a real-world study of four weeks of HIIT versus no exercise in individuals with T1D and IAH, we conclude that HIIT does not increase hypoglycemia, and in fact reduces exposure to nocturnal hypoglycemia.

Association between impaired awareness of hypoglycaemia and psychological outcomes in people living with insulin-treated type 2 diabetes

Association between impaired awareness of hypoglycaemia and psychological outcomes in people living with insulin-treated type 2 diabetes

Impaired Hypoglycemia Awareness in Children and Adolescents with Type 1 Diabetes and its Association with Diabetic Autonomic Neuropathy

Abstract Background In general, hypoglycemia is more frequent among the young explaining the higher frequency of impaired awareness of hypoglycemia (IAH) among children andadolescents. Thus the aim of the current study was to assess the frequency of IAH among anEgyptian cohort of children and adolescents with type 1 diabetes and identify the possible association between impaired awareness of hypoglycemia and autonomic neuropathy. Patients and Methods A crosssectional study recruiting 100 patients with type 1 diabetesfor at least 6 months duration and aged less than 18 years old recruited from the Pediatric and Adolescent Diabetes Unit (PADU). Patients with other form of diabetes, cardiac disease,thyroid disease, anemia, other chronic disease, patients with intellectual disabilities or patients taking any medications were excluded from the study. The Gold and Clarke questionnaires were used to assess hypoglycemia awareness among the studied cohort.Cardiac autonomic neuropathy (CAN) was assessed using 15 minutes Holterelectrocardiography (ECG). Results Among the studied cohort, 42% showed IAH using theClarke’s and Gold's Questionnaires. When assessing CAN, 46% of the studied cohort showedresting tachycardia and patients with resting tachycardia showed significantly longer diseaseduration.There were no normative heart rate variability parameters values for the Egyptian children that can be used as a reference for diagnosis of cardiac autonomic neuropathy. So weused sex and age matched control group to find specific cutoff values for heart rate variabilityparameters to diagnose CAN. The results showed that the prevalence of CAN among studiedpatients was 88% and there were no significant correlation between CAN and both questionnaires score. 55.7% of CAN patients were aware while 44.3% were unaware. Thus,there were no association between impaired awareness of hypoglycemia and CAN. Theresults showed that there was significant positive correlation between cardiac autonomicneuropathy (CAN) and diabetic duration more than 5 years. Conclusion Although there were no association between impaired awareness of hypoglycemia and cardiac autonomic neuropathy, it is important to screen for CAN in patients with IAH, especially that CAN isusually asymptomatic among children with type 1 diabetes.

A single-site feasibility randomised controlled trial comparing 'my hypo compass' short pyscho-educational intervention with standard care alone in individuals with type 1 diabetes and impaired awareness of hypoglycaemia.

The HypoCOMPaSS multi-centre trial achieved improvement in hypoglycaemia awareness and 20-fold reduction in severe hypoglycaemia (SH) in a cohort with long-standing type 1 diabetes (T1D). All participants received 'my hypo compass' (MHC) brief structured psycho-educational intervention in addition to optimisation of insulin delivery/glucose monitoring. In this 24-week, prospective, single-centre feasibility RCT, we piloted MHC as a sole intervention in comparison to standard clinical care alone (CON). Participants with T1D and impaired hypoglycaemia awareness (IAH) (Clarke score ≥4) were recruited. MHC comprised a group/individual 1-2 h face-to-face session followed by a telephone call and second face-to-face session at 4 weeks. Outcome measures at 24 weeks were compared with baseline. Fifty-two individuals provided consent for screening with 39 fulfilling eligibility criteria. Fifteen withdrew before any study intervention. Twenty-four adults with (mean ± SD) T1D duration 41.0 ± 15.1 years commenced/completed the study (100% visit attendance); 12 randomised to MHC and 12 to CON. All had IAH at baseline and at 24 weeks. Annualised SH rate following MHC was 3.8 ± 19.0 (24 weeks) versus 12.6 ± 3.5 (Baseline) and in CON group 2.0 ± 19.0 (24 weeks) versus 4.6 ± 11.5 (Baseline). 'Immediate Action' for and 'Worry' about hyperglycaemia measured by the Hyperglycaemia Avoidance Scale appeared lower following MHC. Participants attended all study visits and reflected positively on the MHC intervention. Feasibility of MHC implementation without additional intervention has been demonstrated. MHC education was associated with positive changes in attitudes and behaviours with the potential to reduce SH risk. MHC provides a validated, simple, well-received programme to fulfil the educational component within RCTs targeting problematic hypoglycaemia and as part of holistic clinical care.

Long-Term Sulfonylurea Use and Impaired Awareness of Hypoglycemia Among Patients With Type 2 Diabetes in Taiwan.

We undertook a study to investigate the relationship between duration of medication use and prevalence of impaired awareness of hypoglycemia (IAH) among patients with insulin-treated or sulfonylurea-treated type 2 diabetes in Taiwan. A total of 898 patients (41.0% insulin users, 65.1% sulfonylurea users; mean [SD] age = 59.9 [12.3] years, 50.7% female) were enrolled in pharmacies, clinics, and health bureaus of Tainan City, Taiwan. Presence of IAH was determined with Chinese versions of the Gold questionnaire (Gold-TW) and Clarke questionnaire (Clarke-TW). Sociodemographics, disease and treatment histories, diabetes-related medical care, and health status were collected. We used multiple logistic regression models to assess the relationship between duration of medication use and IAH. Overall IAH prevalence was 41.0% (Gold-TW) and 28.2% (Clarke-TW) among insulin users, and 65.3% (Gold-TW) and 51.3% (Clarke-TW) among sulfonylurea users. Prevalence increased with the duration of sulfonylurea use, whereas it decreased with the duration of insulin use. After controlling for potential confounders, 5 or more years of sulfonylurea use was significantly associated with 3.50-fold (95% CI, 2.39-5.13) and 3.06-fold (95% CI, 2.11-4.44) increases in the odds of IAH based on the Gold-TW and Clarke-TW criteria, respectively. On the other hand, regular blood glucose testing and retinal examinations were associated with reduced odds in both insulin users and sulfonylurea users. The prevalence of IAH was high among patients using sulfonylureas long term, but the odds of this complication were attenuated for those who received regular diabetes-related medical care. Our study suggests that long-term sulfonylurea use and irregular follow-up increase risk for IAH. Further prospective studies are needed to confirm the observed associations.Annals Early Access article.

Alternative therapeutic strategies in diabetes management

Diabetes is a heterogeneous metabolic disease characterized by elevated blood glucose levels resulting from the destruction or malfunction of pancreatic β cells, insulin resistance in peripheral tissues, or both, and results in a non-sufficient production of insulin. To adjust blood glucose levels, diabetic patients need exogenous insulin administration together with medical nutrition therapy and physical activity. With the aim of improving insulin availability in diabetic patients as well as ameliorating diabetes comorbidities, different strategies have been investigated. The first approaches included enhancing endogenous β cell activity or transplanting new islets. The protocol for this kind of intervention has recently been optimized, leading to standardized procedures. It is indicated for diabetic patients with severe hypoglycemia, complicated by impaired hypoglycemia awareness or exacerbated glycemic lability. Transplantation has been associated with improvement in all comorbidities associated with diabetes, quality of life, and survival. However, different trials are ongoing to further improve the beneficial effects of transplantation. Furthermore, to overcome some limitations associated with the availability of islets/pancreas, alternative therapeutic strategies are under evaluation, such as the use of mesenchymal stem cells (MSCs) or induced pluripotent stem cells for transplantation. The cotransplantation of MSCs with islets has been successful, thus providing protection against proinflammatory cytokines and hypoxia through different mechanisms, including exosome release. The use of induced pluripotent stem cells is recent and requires further investigation. The advantages of MSC implantation have also included the improvement of diabetes-related comorbidities, such as wound healing. Despite the number of advantages of the direct injection of MSCs, new strategies involving biomaterials and scaffolds have been developed to improve the efficacy of mesenchymal cell delivery with promising results. In conclusion, this paper offered an overview of new alternative strategies for diabetes management while highlighting some limitations that will need to be overcome by future approaches.

A cross-sectional questionnaire study: Impaired awareness of hypoglycaemia remains prevalent in adults with type 1 diabetes and is associated with the risk of severe hypoglycaemia.

Impaired awareness of hypoglycaemia (IAH) is a risk factor for severe hypoglycaemia (SH) in type 1 diabetes (T1D). Much of the IAH prevalence data comes from older studies where participants did not have the benefit of the latest insulins and technologies. This study surveyed the prevalence of IAH and SH in a tertiary adult clinic population and investigated the associated factors. Adults (≥18 years) attending a tertiary T1D clinic completed a questionnaire, including a Gold and Clarke score. Background information was collected from health records. 189 people (56.1% female) with T1D (median [IQR] disease duration 19.3 [11.5, 29.1] years and age of 41.0 [29.0, 52.0] years) participated. 17.5% had IAH and 16.0% reported ≥1 episode of SH in the previous 12 months. Those with IAH were more likely to report SH (37.5% versus 11.7%, p = 0.001) a greater number of SH episodes per person (median [IQR] 0 [0,2] versus 0 [0,0] P<0.001) and be female (72.7% versus 52.6%, p = 0.036). Socio-economic deprivation was associated with IAH (p = 0.032) and SH (p = 0.005). Use of technology was the same between IAH vs aware groups, however, participants reporting SH were more likely to use multiple daily injections (p = 0.026). Higher detectable C-peptide concentrations were associated with a reduced risk of SH (p = 0.04). Insulin pump and continuous glucose monitor use was comparable in IAH versus aware groups. Despite this, IAH remains a risk factor for SH and is prevalent in females and in older people. Socioeconomic deprivation was associated with IAH and SH, making this an important population to target for interventions.

177-OR: Time Below Range (TBR) and Its Link to Impaired Awareness of Hypoglycemia (IAH) and Severe Hypoglycemia (SH)—Evidence from the Association of British Clinical Diabetologists (ABCD) Study

177-OR: Time Below Range (TBR) and Its Link to Impaired Awareness of Hypoglycemia (IAH) and Severe Hypoglycemia (SH)—Evidence from the Association of British Clinical Diabetologists (ABCD) Study

Association between recent exposure to continuous glucose monitoring-recorded hypoglycaemia and counterregulatory and symptom responses to subsequent controlled hypoglycaemia in people with type 1 diabetes.

Experimental hypoglycaemia blunts the counterregulatory hormone and symptom responses to a subsequent episode of hypoglycaemia. In this study, we aimed to assess the associations between antecedent exposure and continuous glucose monitoring (CGM)-recorded hypoglycaemia during a 1-week period and the counterregulatory responses to subsequent experimental hypoglycaemia in people with type 1 diabetes. Forty-two people with type 1 diabetes (20 females, mean ± SD glycated haemoglobin 7.8% ± 1.0%, diabetes duration median (interquartile range) 22.0 (10.5-34.9) years, 29 CGM users, and 19 with impaired awareness of hypoglycaemia) wore an open intermittently scanned CGM for 1 week to detect hypoglycaemic exposure before a standardized hyperinsulinaemic-hypoglycaemic [2.8 ± 0.1 mmol/L (50.2 ± 2.3 mg/dl)] glucose clamp. Symptom responses and counterregulatory hormones were measured during the clamp. The study is part of the HypoRESOLVE project. CGM-recorded hypoglycaemia in the week before the clamp was negatively associated with adrenaline response [β -0.09, 95% CI (-0.16, -0.02) nmol/L, p = .014], after adjusting for CGM use, awareness of hypoglycaemia, glycated haemoglobin and total daily insulin dose. This was driven by level 2 hypoglycaemia [<3.0 mmol/L (54 mg/dl)] [β -0.21, 95% CI (-0.41, -0.01) nmol/L, p = .034]. CGM-recorded hypoglycaemia was negatively associated with total, autonomic, and neuroglycopenic symptom responses, but these associations were lost after adjusting for potential confounders. Recent exposure to CGM-detected hypoglycaemia was independently associated with an attenuated adrenaline response to experimental hypoglycaemia in people with type 1 diabetes.

Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial.

Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

Impaired Awareness of Hypoglycemia in Older Adults With Type 1 Diabetes: A Post Hoc Analysis of the WISDM Study.

Up to one-third of older adults with type 1 diabetes experience impaired awareness of hypoglycemia (IAH), yet the factors associated with IAH remain underexplored in older adults. This post hoc analysis evaluated the clinical and glycemic correlates of IAH in adults ≥60 years old with type 1 diabetes in the WISDM study. IAH and normal awareness of hypoglycemia (NAH) were defined by a Clarke score of ≥4 or <4, respectively. Demographic, clinical, and glycemic metrics were compared in those with IAH and NAH at baseline and in whom IAH did or did not improve over 26 weeks, using descriptive statistics and a multiple logistic regression variable selection procedure. Of the 199 participants (age 68.1 ± 5.7 years, 52% female), 30.6% had IAH. At baseline, participants with IAH had a longer diabetes duration and greater daytime hypoglycemia and glycemic variability, and more participants had nondetectable C-peptide levels than those with NAH. Logistic regression associated longer diabetes duration (odds ratio [OR] 1.03, 95% CI 1.01-1.05; P = 0.008) and greater daytime hypoglycemia (OR 1.31, 95% CI, 1.15-1.51; P < 0.0001) with a greater odds of IAH. A similar modeling procedure identified less daytime hypoglycemia (OR per additional percentage point 0.55, 95% CI 0.32-0.94; P = 0.029) and shorter diabetes duration (OR per additional year 0.96, 95% CI 0.91-1.004; P = 0.07) as predictors of restored awareness at 26 weeks, although the effect size for diabetes duration was not statistically significant. In older adults with type 1 diabetes, longer diabetes duration and greater daytime hypoglycemia are drivers of IAH. Dedicated research can personalize IAH management.

Psychometric validation of the hyperglycaemia avoidance scale UK (HAS-UK).

Hyperglycaemia aversion in type 1 diabetes can be associated with severe hypoglycaemia and impaired awareness of hypoglycaemia but is not routinely assessed clinically. This study aimed to undertake the first psychometric validation of the UK version of the Hyperglycaemia Avoidance Scale (HAS-UK). The HAS-UK was completed by adults with type 1 diabetes in three separate research studies. Psychometric properties were evaluated, using exploratory factor analysis, internal consistency, and convergent validity. Of the 431 participants who completed the HAS-UK in the three studies, mean age was 49.5 years, and 58.0% were women. Mean duration of diabetes was 29 years, with 192 (44.5%) using multiple daily injections and 229 (53.1%) using an insulin pump. Five participants were excluded from analyses due to incomplete HAS-UK responses. Exploratory factor analysis revealed a 3-factor solution, with acceptable internal consistency for 'worry' and 'blood glucose decisions' factors. HAS-UK total score was higher in those using insulin pumps versus multiple daily injections, and 'blood glucose decisions' score was higher in those using a continuous blood glucose sensor versus a meter. The HAS-UK is a reliable measure with acceptable structural validity and is likely to be useful for evaluating hyperglycaemia aversion in people with type 1 diabetes. Future research would benefit from investigating further psychometric properties including test-retest reliability, sensitivity to change, and clinical significance of scores.

Mitigating Severe Hypoglycemia in Users of Advanced Diabetes Technologies: Impaired Awareness of Hypoglycemia and Unhelpful Hypoglycemia Beliefs as Targets for Interventions.

Objective: A subgroup analysis of the Hypoglycemia Awareness Restoration Programme for people with type 1 diabetes and problematic hypoglycemia persisting despite optimized care (HARPdoc) trial was conducted to explore the impact of Blood Glucose Awareness Training (BGAT, a hypoglycemia awareness training program) and the HARPdoc (a psychoeducation addressing unhelpful hypoglycemia beliefs) in reducing severe hypoglycemia (SH) in individuals using advanced diabetes technologies (ADTs). Methods: Data from trial participants who utilized ADTs, including continuous glucose monitors or automated insulin delivery systems, were extracted. Generalized linear mixed-effects models with Poisson distribution or linear mixed-effects models were used to evaluate SH incidence, and Gold questionnaire, Attitudes to Awareness of Hypoglycemia (A2A), Problem Areas in Diabetes (PAID), Hospital Anxiety and Depress Scale (HADS)-anxiety, and HADS-depression scores as measures of hypoglycemia awareness, unhelpful hypoglycemia beliefs, diabetes distress, and anxiety and depression symptoms, respectively. Results: In the 45 participants using ADTs, the BGAT and HARPdoc interventions both reduced SH incidence by more than 50% (P < 0.0001) and yielded improvements in hypoglycemia awareness (P < 0.05). HARPdoc outperformed BGAT in reducing SH at month 24 (P = 0.01). HARPdoc also mitigated unhelpful hypoglycemia beliefs (P < 0.0001), diabetes distress (P < 0.05), and anxiety symptoms (P < 0.05); BGAT demonstrated no significant impacts in these respects. Neither HARPdoc nor BGAT had significant effects on depression symptoms. Conclusion: Psychoeducation (BGAT and HARPdoc) was effective in reducing SH in people using ADTs. HARPdoc may also provide greater long-term SH reduction and improves psychological well-being in this patient group.

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

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. 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. 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. 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. ACTRN12617000520336.