Impaired Awareness Of Hypoglycemia Research Articles

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.

Application of Closed-loop Theory in Deep Learning Training Guided by High-strength Intelligent Machinery

Artificial intelligence (AI) algorithms and continuous monitoring technologies have the potential to transform the way chronic illnesses are managed. We will also talk about the problems and potential that AI technology presents for CGM in individualised and preventive medicine. Furthermore, we assessed the AHCL system's usefulness in patients with impaired awareness of hypoglycemia (IAH) and those who correctly recognised hypoglycemia symptoms. The participants' ages varied from 37 to 15, and they had received diabetes medication for an average of 20 to 10 years. IAH was seen in 12 individuals (27%) with a Clarke's score of less than 3. Patients with IAH were older than those who did not have IAH. The baseline CGM readings and A1c were the same, but the estimated glomerular filtration rate (eGFR) was lower. Despite prior insulin treatment, the AHCL system resulted in an overall drop in A1c (from 6.9 0.5% to 6.7 0.6%, P 0.001). Only three patients (7%) received Clarke's three scores after six months on the AHCL system, resulting in a 20% absolute risk decrease for IAH (95% confidence interval: 7-32).

Associations Between Hypoglycemia Awareness Status and Symptoms of Hypoglycemia Among Adults with Type 1 or Insulin-Treated Type 2 Diabetes Using the Hypo-METRICS Smartphone Application.

Introduction: This study examined associations between hypoglycemia awareness status and hypoglycemia symptoms reported in real-time using the novel Hypoglycaemia-MEasurement, ThResholds and ImpaCtS (Hypo-METRICS) smartphone application (app) among adults with insulin-treated type 1 (T1D) or type 2 diabetes (T2D). Methods: Adults who experienced at least one hypoglycemic episode in the previous 3 months were recruited to the Hypo-METRICS study. They prospectively reported hypoglycemia episodes using the app for 10 weeks. Any of eight hypoglycemia symptoms were considered present if intensity was rated between "A little bit" to "Very much" and absent if rated "Not at all." Associations between hypoglycemia awareness (as defined by Gold score) and hypoglycemia symptoms were modeled using mixed-effects binary logistic regression, adjusting for glucose monitoring method and diabetes duration. Results: Of 531 participants (48% T1D, 52% T2D), 45% were women, 91% white, and 59% used Flash or continuous glucose monitoring. Impaired awareness of hypoglycemia (IAH) was associated with lower odds of reporting autonomic symptoms than normal awareness of hypoglycemia (NAH) (T1D odds ratio [OR] 0.43 [95% confidence interval {CI} 0.25-0.73], P = 0.002); T2D OR 0.51 [95% CI 0.26-0.99], P = 0.048), with no differences in neuroglycopenic symptoms. In T1D, relative to NAH, IAH was associated with higher odds of reporting autonomic symptoms at a glucose concentration <54 than >70 mg/dL (OR 2.18 [95% CI 1.21-3.94], P = 0.010). Conclusion: The Hypo-METRICS app is sensitive to differences in hypoglycemia symptoms according to hypoglycemia awareness in both diabetes types. Given its high ecological validity and low recall bias, the app may be a useful tool in research and clinical settings. The clinical trial registration number is NCT04304963.

Impact of impaired awareness of hypoglycemia on glucose decline during and after exercise in T1D: The T1DEXI Study.

To assess whether impaired awareness of hypoglycemia (IAH) affects exercise-associated hypoglycemia in adults with type 1 diabetes (T1D). We compared continuous glucose monitoring (CGM)-measured glucose during exercise and for 24-hours following exercise from 95 adults with T1D and IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event within the past year) to 95 'Aware' adults (Clarke score ≤2 and no severe hypoglycemic event within the past year) matched on sex, age, insulin delivery modality, and HbA1c. A total of 4,236 exercise sessions, and 1,794 exercise days and 839 sedentary days, defined as 24-hours following exercise or a day without exercise, respectively, were available for analysis. Participants with IAH exhibited a non-significant trend towards greater decline in glucose during exercise compared to 'Aware' (-21 ± 44 vs. -19 ± 43 mg/dL [-1.17 ± 2.44 vs. -1.05 ± 2.39 mmol/L], adjusted group difference of -4.2 [95% CI: -8.4 to 0.05] mg/dL [-0.23 95% CI: -0.47 to 0.003 mmol/L], P = 0.051). Individuals with IAH had higher proportion of days with hypoglycemic events <70 mg/dL[3.89 mmol/L] (≥15 minutes <70 mg/dL[<3.89 mmol/L]) both on exercise days (51% vs. 43%, P = 0.006) and sedentary days (48% vs. 30%, P = 0.001). The increased odds of experiencing a hypoglycemic event <70 mg/dL[<3.89 mmol/L] for individuals with IAH compared to 'Aware' did not differ significantly between exercise and sedentary days (interaction P = 0.36). Individuals with IAH have a higher underlying risk of hypoglycemia than 'Aware' individuals. Exercise does not appear to differentially increase risk for hypoglycemia during the activity, or in the subsequent 24-hours for IAH compared to Aware individuals with T1D.

Relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes using continuous glucose monitoring systems

AimsTo evaluate relationships of hypoglycemia awareness, hypoglycemia beliefs, and continuous glucose monitoring (CGM) glycemic profiles with anxiety and depression symptoms in adults with type 1 diabetes (T1D) who use CGM. MethodsA cross-sectional survey and data collections were completed with 196 T1D adults who used CGM (59% also used automated insulin delivery devices (AIDs)). We assessed hypoglycemia awareness (Gold instrument), hypoglycemia beliefs (Attitudes to Awareness of Hypoglycemia instrument), CGM glycemic profiles, demographics, and anxiety and depression symptoms (Hospital Anxiety and Depression Scale). Analysis included simple and multiple linear regression analyses. ResultsLower hypoglycemia awareness, weaker “hypoglycemia concerns minimized” beliefs, stronger “hyperglycemia avoidance prioritized” beliefs were independently associated with higher anxiety symptoms (P < 0.05), with similar trends in both subgroups using and not using AIDs. Lower hypoglycemia awareness were independently associated with greater depression symptoms (P < 0.05). In participants not using AIDs, more time in hypoglycemia was related to less anxiety and depression symptoms (P < 0.05). Being female and younger were independently associated with higher anxiety symptoms, while being younger was also independently associated with greater depression symptoms (P < 0.05). ConclusionOur findings revealed relationships of impaired hypoglycemia awareness, hypoglycemia beliefs, CGM-detected hypoglycemia with anxiety and depression symptoms in T1D adults who use CGMs.

Metabolomic associations of impaired awareness of hypoglycaemia in type 1 diabetes

This study investigates impaired awareness of hypoglycaemia (IAH), a complication of insulin therapy affecting 20–40% of individuals with type 1 diabetes. The exact pathophysiology is unclear, therefore we sought to identify metabolic signatures in IAH to elucidate potential pathophysiological pathways. Plasma samples from 578 individuals of the Dutch type 1 diabetes biomarker cohort, 67 with IAH and 108 without IAH (NAH) were analysed using the targeted metabolomics Biocrates AbsoluteIDQ p180 assay. Eleven metabolites were significantly associated with IAH. Genome-wide association studies of these 11 metabolites identified significant single nucleotide polymorphisms (SNPs) in C22:1-OH and phosphatidylcholine diacyl C36:6. After adjusting for the SNPs, 11 sphingomyelins and phosphatidylcholines were significantly higher in the IAH group in comparison to NAH. These metabolites are important components of the cell membrane and have been implicated to play a role in cell signalling in diabetes. These findings demonstrate the potential role of phosphatidylcholine and sphingomyelins in IAH.

Hypoglycemia Unawareness-A Review on Pathophysiology and Clinical Implications.

Hypoglycemia is a particular problem in people with diabetes while it can also occur in other clinical circumstances. Hypoglycemia unawareness describes a condition in which autonomic and neuroglycopenic symptoms of hypoglycemia decrease and hence are hardly perceivable. A failure to recognize hypoglycemia in time can lead to unconsciousness, seizure, and even death. The risk factors include intensive glycemic control, prior episodes of severe hypoglycemia, long duration of diabetes, alcohol consumption, exercise, renal failure, and sepsis. The pathophysiological mechanisms are manifold, but mainly concern altered brain glucose sensing, cerebral adaptations, and an impaired hormonal counterregulation with an attenuated release of glucagon, epinephrine, growth hormone, and other hormones, as well as impaired autonomous and neuroglycopenic symptoms. Physiologically, this counterregulatory response causes blood glucose levels to rise. The impaired hormonal counterregulatory response to recurrent hypoglycemia can lead to a vicious cycle of frequent and poorly recognized hypoglycemic episodes. There is a shift in glycemic threshold to trigger hormonal counterregulation, resulting in hypoglycemia-associated autonomic failure and leading to the clinical syndrome of hypoglycemia unawareness. This clinical syndrome represents a particularly great challenge in diabetes treatment and, thus, prevention of hypoglycemia is crucial in diabetes management. This mini-review provides an overview of hypoglycemia and the associated severe complication of impaired hypoglycemia awareness and its symptoms, pathophysiology, risk factors, consequences, as well as therapeutic strategies.

Burden of impaired awareness of hypoglycemia in people with diabetes undergoing hemodialysis

IntroductionImpaired awareness of hypoglycemia (IAH) refers to a diminished capacity to detect hypoglycemia. IAH can result in severe and even life-threatening outcomes for individuals with diabetes, especially those in advanced...

Severe Hypoglycemia and Impaired Awareness of Hypoglycemia Persist in People With Type 1 Diabetes Despite Use of Diabetes Technology: Results From a Cross-sectional Survey.

To determine how diabetes technologies, including continuous glucose monitoring (CGM) and automated insulin delivery (AID) systems, impact glycemic metrics, prevalence of severe hypoglycemic events (SHEs), and impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes in a real-world setting within the U.S. In this retrospective, observational study with cross-sectional elements, participants aged ≥18 years were enrolled from the T1D Exchange Registry/online community. Participants completed a one-time online survey describing glycemic metrics, SHEs, and IAH. The primary objective was to determine the proportions of participants who reported achieving glycemic targets (assessed according to self-reported hemoglobin A1c) and had SHEs and/or IAH. We performed additional subgroup analyses focusing on the impact of CGM and insulin delivery modality. A total of 2,074 individuals with type 1 diabetes were enrolled (mean ± SD age 43.0 ± 15.6 years and duration of type 1 diabetes 26.3 ± 15.3 years). The majority of participants (91.7%) were using CGM, with one-half (50.8%) incorporating AID. Despite high use of diabetes technologies, only 57.7% reported achieving glycemic targets (hemoglobin A1c <7%). SHEs and IAH still occurred, with ∼20% of respondents experiencing at least one SHE within the prior 12 months and 30.7% (95% CI 28.7, 32.7) reporting IAH, regardless of CGM or AID use. Despite use of advanced diabetes technologies, a high proportion of people with type 1 diabetes do not achieve glycemic targets and continue to experience SHEs and IAH, suggesting an ongoing need for improved treatment strategies.

Experimental pharmacological approaches to reverse impaired awareness of hypoglycemia-a review.

The colossal global burden of diabetes management is compounded by the serious complication of hypoglycemia. Protective physiologic hormonal and neurogenic counterregulatory responses to hypoglycemia are essential to preserve glucose homeostasis and avert serious morbidity. With recurrent exposure to hypoglycemic episodes over time, these counterregulatory responses to hypoglycemia can diminish, resulting in an impaired awareness of hypoglycemia (IAH). IAH is characterized by sudden neuroglycopenia rather than preceding cautionary autonomic symptoms. IAH increases the risk of subsequent sudden and severe hypoglycemic episodes in patients with diabetes. The postulated causative mechanisms behind IAH are complex and varied. It is therefore challenging to identify a single effective therapeutic strategy. In this review, we closely examine the efficacy and feasibility of a myriad of pharmaceutical interventions in preventing and treating IAH as described in clinical and preclinical studies. Pharmaceutical agents outlined include N-acetyl cysteine, GABA A receptor blockers, opioid receptor antagonists, AMP activated protein kinase agonists, potassium channel openers, dehydroepiandrosterone, metoclopramide, antiadrenergic agents, antidiabetic agents and glucagon.

Prevalence and associations of impaired awareness of hypoglycemia in a pediatric type 1 diabetes population – The Norwegian Childhood Diabetes Registry

AimsTo determine the prevalence and associations of impaired awareness of hypoglycemia (IAH) in pediatric type 1 diabetes. MethodsNationwide, population-based cross-sectional study with 51 % participation. Participants (n = 1329; 53 % males) aged 2–19 years (median 13.3) with type 1 diabetes ≥ 6 months (median 4.6 years) self-assessed hypoglycemia awareness with a validated questionnaire (‘Clarke’). Parents responded for children aged < 9 years (n = 235). We estimated associations between IAH and clinical data in the Norwegian Childhood Diabetes Registry. ResultsThe overall prevalence of IAH was 22 %, but gradually decreased from 53 % in preschoolers to 12 % in adolescents aged ≥ 16 years. IAH was associated (adjusted OR; 95 %CI) with episodes of severe hypoglycemia (6.0; 3.04, 11.8) and diabetic ketoacidosis (3.45; 1.37, 8.68) the preceding year, increased fear of hypoglycemia (highest quartile vs. lowest: 2.27; 1.51, 3.40), female sex (1.41; 1.05, 1.90), and HbA1c ≥ 8.5 % (69 mmol/mol) vs. 7.5–8.4 % (58–68 mmol/mol) (1.48; 1.01, 2.18), but not with disease duration, use of insulin pump or continuous glucose monitoring, or HbA1c < 7.5 % (58 mmol/mol). ConclusionsIAH is prevalent in pediatric diabetes and more likely reported in young children. IAH is associated with severe hypoglycemia and fear of hypoglycemia, but good metabolic control seems achievable without increased risk 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.

Cerebral blood flow in type II diabetes mellitus patients with impaired awareness of hypoglycemia: a cross-sectional study

Cerebral blood flow is maintained and regulated through various homeostatic mechanisms. It is maintained even during hypoglycemia in patients with type 1 diabetes mellitus, but appears to increase in those with impaired awareness of hypoglycemia. However, experiments are lacking to clarify these findings. Thus, this study was conducted to investigate whether cerebral blood flow increases in type 2 diabetes mellitus patients with impaired awareness of hypoglycemia by using Doppler sonography. This was a cross-sectional study conducted from July 2021 to June 2022 in the emergency department (ED) of Inje University Busan Paik Hospital, Busan, South Korea. Patients with type 2 diabetes with complaints of various symptoms of hypoglycemia (defined as blood glucose level &lt;60 mg/dL) were evaluated for this study after obtaining their informed consent. First, we assessed each patient’s awareness of hypoglycemia using the Gold method. Cerebral blood flow was then measured on Doppler sonography. The primary outcome was blood flow in both internal carotid arteries, and secondary outcomes included the diameter and time-averaged maximum velocity of both internal carotid arteries. A total of 132 patients were enrolled in the study, but 11 patients were excluded from analysis. Hypoglycemia was associated with increased cerebral blood flow in those with impaired awareness of hypoglycemia, but this association was not observed in other groups. The blood flow in the left internal carotid artery was significantly higher compared to the right side, perhaps due to the anatomical differences between the two arteries. The increased cerebral blood flow could be due to an adaptive response to hypoglycemia to enhance nutrient supply to the brain. However, given that this was a cross-sectional study, causality could not be determined. Thus, as in type 1 diabetes mellitus, hypoglycemia is associated with an increased cerebral blood flow in type 2 diabetes mellitus as well.

Validation of the hypoglycemia awareness questionnaire to assess hypoglycemia awareness in patients with type 2 diabetes treated with insulin

AimsGiven the implications of impaired hypoglycemia awareness in patients with type 2 diabetes (T2D), it is necessary to identify reliable and valid instruments for its measurement. The Hypoglycemia Awareness Questionnaire (HypoA-Q) measures impaired awareness, symptom severity, and symptom frequency. The present study evaluated the HypoA-Q validity for assessing awareness of hypoglycemia in patients with T2D treated with insulin. MethodsThe questionnaire was administered to 406 patients diagnosed with T2D on insulin treatment at four centers in Bogotá, Colombia. The internal structure of the questionnaire was analyzed using exploratory and confirmatory factor analyses, internal consistency and test–retest reliability were evaluated, and criterion validity was rated by assessing its correlation with the Clarke scale. ResultsFactor analysis identified an empirical structure of four domains that adequately represented the construct. Cronbach's alpha and McDonald's Omega coefficients yielded values between 0.75 and 0.79 for the impaired awareness scale. Lin and intraclass correlation coefficients were 0.86 and 0.85, respectively. The correlation between the impaired awareness subscale and Clarke scale was 0.654, and differences were found between patients with good and poor awareness of hypoglycemia. ConclusionsThe HypoA-Q is a valid and reliable tool for measuring the awareness of hypoglycemia in patients with T2D who are treated with insulin.

High intensity interval training as a novel treatment for impaired awareness of hypoglycaemia in people with type 1 diabetes (HIT4HYPOS): a randomised parallel-group study

Aims/hypothesisImpaired awareness of hypoglycaemia (IAH) in type 1 diabetes may develop through a process referred to as habituation. Consistent with this, a single bout of high intensity interval exercise as a novel stress stimulus improves counterregulatory responses (CRR) to next-day hypoglycaemia, referred to as dishabituation. This longitudinal pilot study investigated whether 4 weeks of high intensity interval training (HIIT) has sustained effects on counterregulatory and symptom responses to hypoglycaemia in adults with type 1 diabetes and IAH.MethodsHIT4HYPOS was a single-centre, randomised, parallel-group study. Participants were identified using the Scottish Diabetes Research Network (SDRN) and from diabetes outpatient clinics in NHS Tayside, UK. The study took place at the Clinical Research Centre, Ninewells Hospital and Medical School, Dundee, UK. Participants were aged 18–55 years with type 1 diabetes of at least 5 years’ duration and HbA1c levels <75 mmol/mol (<9%). They had IAH confirmed by a Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating [DAFNE] hypoglycaemia awareness rating of 2 or 3, and/or evidence of recurrent hypoglycaemia on flash glucose monitoring. Participants were randomly allocated using a web-based system to either 4 weeks of real-time continuous glucose monitoring (RT-CGM) or RT-CGM+HIIT. Participants and investigators were not masked to group assignment. The HIIT programme was performed for 20 min on a stationary exercise bike three times a week. Hyperinsulinaemic–hypoglycaemic (2.5 mmol/l) clamp studies with assessment of symptoms, hormones and cognitive function were performed at baseline and after 4 weeks of the study intervention. The predefined primary outcome was the difference in hypoglycaemia-induced adrenaline (epinephrine) responses from baseline following RT-CGM or RT-CGM+HIIT.ResultsEighteen participants (nine men and nine women) with type 1 diabetes (median [IQR] duration 27 [18.75–32] years) and IAH were included, with nine participants randomised to each group. Data from all study participants were included in the analysis. During the 4 week intervention there were no significant mean (SEM) differences between RT-CGM and RT-CGM+HIIT in exposure to level 1 (28 [7] vs 22 [4] episodes, p=0.45) or level 2 (9 [3] vs 4 [1] episodes, p=0.29) hypoglycaemia. The CGM-derived mean glucose level, SD of glucose and glucose management indicator (GMI) did not differ between groups. During the hyperinsulinaemic–hypoglycaemic clamp studies, mean (SEM) change from baseline was greater for the noradrenergic responses (RT-CGM vs RT-CGM+HIIT: −988 [447] vs 514 [732] pmol/l, p=0.02) but not the adrenergic responses (–298 [687] vs 1130 [747] pmol/l, p=0.11) in those participants who had undergone RT-CGM+HIIT. There was a benefit of RT-CGM+HIIT for mean (SEM) change from baseline in the glucagon CRR to hypoglycaemia (RT-CGM vs RT-CGM+HIIT: 1 [4] vs 16 [6] ng/l, p=0.01). Consistent with the hormone response, the mean (SEM) symptomatic response to hypoglycaemia (adjusted for baseline) was greater following RT-CGM+HIIT (RT-CGM vs RT-CGM+HIIT: −4 [2] vs 0 [2], p<0.05).Conclusions/interpretationIn this pilot clinical trial in people with type 1 diabetes and IAH, we found continuing benefits of HIIT for overall hormonal and symptomatic CRR to subsequent hypoglycaemia. Our findings also suggest that HIIT may improve the glucagon response to insulin-induced hypoglycaemia.Trial registrationISRCTN15373978.FundingSir George Alberti Fellowship from Diabetes UK (CMF) and the Juvenile Diabetes Research Foundation.Graphical