Impaired Awareness Of Hypoglycemia Research Articles

SUN-299 Flash Glucose Sensor Monitoring for Patients with Endogenous Hyperinsulinaemic Hypoglycaemia

Flash Glucose Sensor Monitoring for patients with endogenous hyperinsulinaemic hypoglycaemiaBackground:Flash glucose monitoring systems (FGS) have recently been introduced and measure interstitial glucose using an amperometric electrochemical sensor assay, and are increasingly used to provide a convenient means to monitor levels on a minute-by-minute basis over two weeks in ambulatory patients with diabetes. Although continuous glucose monitoring systems have been previously used in patients with insulinoma,(1) to our knowledge, FGS use has only been described once previously in an adult patient with an insulinoma.(2) Here, we describe use of this system in 6 patients with confirmed endogenous hyperinsulinaemic hypoglycaemia, especially for the critical nocturnal period.Methods and patients:FGS data obtained over each 2-week monitoring was reviewed in 6 patients seen between 2018 and 2019: 5 had a biochemically proven insulinoma and 1 had Hirata’s syndrome. In 4 patients, follow-up readings were obtained after adjustment of glucose-raising medication: two on octreotide, one on diazoxide and one on diazoxide and dexamethasone.Results:Median age was 63 years (range 37–83). In the 4 patients with more than one 2-week FGS assessment comparison between first and last readings demonstrated that the average duration of hypoglycaemia (<4mmol/L) 126, 171, 173 and 282 minutes improved to 46, 128, 30 and 0 minutes, respectively. The percentage of glucose readings below target (<4mmol/L) improved from 8%, 58%, 4%, and 47% to 1%, 39%, 0%, and 0%, respectively. The mean glucose was 5.9, 3.9, 7.8, and 4.4 mmol/L, which improved to 10.9, 5.0, 7.9, and 7.5 mmol/L respectively. The lowest average glucose was nocturnal (22:00-06:00) (5.8, 3.3, 6.5, and 4.1 mmol/L) which showed significant improvement after adjustment of medications (11.3, 4.2, 7.2, and 5.7 mmol/L). At least 2 of these 4 patients had well documented impaired awareness of hypoglycaemia based on diminished classical adrenergic symptoms. Among the two patients who had only one 2-week FGS assessment, one went on to have curative successful surgery and the second patient who had Hirata’s syndrome did not have significant detectable hypoglycaemia.Conclusion:FGS is a convenient tool that may be used to monitor and adjust therapy in patients with endogenous hyperinsulinism. In carefully selected patients, FGS may allow domiciliary glycaemic management avoiding the need for hospital admission for monitoring purposes.

Prevalencia de hipoglucemia grave en una cohorte de pacientes con diabetes tipo 1

IntroductionHypoglycemia is the major limiting factor in the glycemic management of type 1 diabetes. Severe hypoglycemia puts patients at risk of injury and death. Recurrent hypoglycemia leads to impaired awareness of hypoglycemia and this increases the risk of severe hypoglycemia. Recent studies have reported rates for severe hypoglycemia of 35% in type 1 diabetic patients. ObjectivesTo assess the prevalence of severe hypoglycemia in type 1 diabetes mellitus patients and to evaluate the relationship between this and impaired awareness of hypoglycemia according to the Clarke test. Patients and methodsThe following data were collected from a cohort of type 1 diabetic patients: age, gender, duration of type 1 diabetes, treatment (multiple daily insulin injection or continuous subcutaneous insulin infusion), glycemia self-control, HbA1c, episodes of severe hypoglycemia and impaired awareness of hypoglycemia. ResultsOf the participants, 39.8% had had at least one episode of severe hypoglycemia (in the previous 6 months), 11.4% with loss of consciousness (in the previous 12 months). According to the Clark test, 40.9% had impaired awareness of hypoglycemia. Older age and longer duration of diabetes were associated with a higher prevalence of severe hypoglycemia with unconsciousness; older age and a lower level of HbA1c were associated with impaired awareness of hypoglycemia. ConclusionsOur study allows us to confirm the high rate of severe hypoglycemia and impaired awareness of hypoglycemia in patients with type 1 diabetes.

Associations Between the Time in Hypoglycemia and Hypoglycemia Awareness Status in Type 1 Diabetes Patients Using Continuous Glucose Monitoring Systems.

Background: Continuous glucose monitoring (CGM) systems help reduce hypoglycemia in patients with type 1 diabetes (T1D). It remains unclear whether T1D patients with impaired awareness of hypoglycemia (IAH) continue to develop more hypoglycemia than those with normal hypoglycemia awareness (NA) despite CGM use. Materials and Methods: For this cross-sectional observational study, 99 T1D patients using real-time CGMs for ≥86% of time were recruited. Fifty and 49 patients were found to have NA and IAH (based on the Clarke questionnaire), respectively. Two-week CGM hypoglycemia data were collected. Results: IAH was associated with greater percentages of CGM values <70 and <54 mg/dL (P = 0.012, P = 0.004) compared to NA. Clarke scores correlated positively with the percentage of CGM values <70 and <54 mg/dL (P = 0.013, P = 0.004). IAH was also related to more events with glucose <70 and <54 mg/dL determined either with at ≥1 time point (P = 0.048, P = 0.003) or lasting ≥20 min (P = 0.016, P = 0.004). IAH patients presented with more day-time events with glucose <54 mg/dL (P = 0.015), nocturnal events with glucose levels <70 and <54 mg/dL (P = 0.009, P = 0.007) and longer day-time event duration with glucose levels <70 and <54 mg/dL (P < 0.001, P = 0.006), respectively. Conclusions: T1D patients with IAH continue to experience more hypoglycemia despite dedicated CGM use.

Characterization of pre-transplant psychosocial burden in an integrated national islet transplant program

ABSTRACT The psychological burden experienced by people with diabetes prior to islet transplantation is recognized but has not been studied comprehensively, especially in relation to glycemia. Therefore, we conducted a rigorous pre-operative psychosocial profile of UK islet transplant recipients, and compared groups with higher/lower HbA1 c to test the null hypothesis that pre-transplant hypoglycemia awareness and psychosocial burden would not be related to baseline HbA1 c in this high-risk cohort. Pre-transplant, recipients (n = 44) completed validated hypoglycemia awareness questionnaires and generic/diabetes-specific measures of psychological traits and states. Scores were compared in groups, dichotomized by HbA1 c (≤8% versus >8%). Participants were aged (mean±SD) 53 ± 10 years; 64% were women; with HbA1 c 8.3 ± 1.7%. Median rate of severe hypoglycemia over the preceding 12 months was 13 events/person-year and 90% had impaired awareness of hypoglycemia (Gold/Clarke score ≥4). Participants had elevated fear of hypoglycemia (HFS-II Worry), impaired diabetes-specific quality of life (DQoL) and low generic health status (SF-36; EQ-5D). One quarter reported scores indicating likely anxiety/depression (HAD). Dispositional optimism (LOT-R) and generalized self-efficacy (GSE) were within published ‘norms.’ Despite negative perceptions of diabetes (including low personal control), participants were confident that islet transplantation would help (BIPQ). Hypoglycemia awareness and psychosocial profile were comparable in lower (n = 24) and higher (n = 20) HbA1 c groups. Islet transplant candidates report sub-optimal generic psychological states (anxiety/depressive symptoms), health status and diabetes-specific psychological states (fear of hypoglycemia, diabetes-specific quality of life). While their generic psychological traits (optimism, self-efficacy) are comparable with the general population, they are highly optimistic about forthcoming transplant. HbA1 c is not a proxy measure of psychosocial burden, which requires the use of validated questionnaires to systematically identify those who may benefit most from psychological assessment and support.

Frequency of Hypoglycemia in Type 2 Diabetic Patients in Sample of Egyptian People in Clinic Based Study

Abstract Background Hypoglycemia is a true medical emergency which requires prompt recognition and treatment to prevent organ and brain damage. Hypoglycemia is not a disease in itself; it is a sign of a health problem; whose importance lies in its effects upon brain function. With increasing incidence of diabetes and with various modalities of intensive control of blood glucose levels, there is always a risk of a proportional increase in the incidence of hypoglycemia. Aim of The Work we measured the frequency of hypoglycemic attacks in type 2 diabetic patients (T2DM) in clinic based study and correlate the attacks of hypoglycemia with treatment regimens and duration of the diabetes mellitus (DM) Methods Copies of pre-tested questionnaire were administered directly to 1000 patients with T2DM at the study site. This questionnaire was previously published as a part of the Workgroup of the American Diabetes Association and The Endocrine Society (ADA) on 2013. After translating it into public traditional Egyptian Arabic language. Results Our main finding was that for people with T2DM the incidence of hypoglycemia was 36% (360 out of 1000 patients). 26.39% (95 out of 360 patients) on oral hypoglycemic drugs compared to 71.94% (259 from 360 patients) on insulin. hypoglycemia was 48.42% (46 out of 95 patients) in Diabetic patients having diabetes for more than five years and on oral hypoglycemic drugs, compared to 76.83% (199 out of 259 patients) in diabetic patients on insulin. there is a highly statistically significant difference between diabetic patients on insulin and long duration of diabetes (p &amp;lt; 0.001). Also show that there is a statistically significant difference between diabetic patients on oral hypoglycemic and long duration of diabetes p value 0.034. Prevalence of (IAH) impaired awareness of hypoglycemia is 49.94%&amp;unawareness 27.72% Conclusion Hypoglycemia is common in T2DM (36%). It is a significant complication of diabetes therapy and although mild hypoglycemia causes unpleasant symptoms and disrupts patients’ daily activities, severe hypoglycemia can result in coma, seizures, and death.

Hypoglycemia symptoms and awareness of hypoglycemia in type 1 diabetes mellitus: cross-cultural adaptation and validation of the Portuguese version of three questionnaires and evaluation of its risk factors

BackgroundTo adapt and validate the Clarke and Gold questionnaires and the Edinburgh Hypoglycemia Symptom Scale (EHSS) to Brazilian Portuguese and to determine the prevalence and risk factors associated with impaired awareness of hypoglycemia (IAH) in patients with type 1 diabetes mellitus (T1DM).MethodsThe process of translation, cultural adaptation, and validation of the questionnaires followed the recommendations of the International Society for Pharmacoeconomics and Outcomes Research (ISPOR)-Task Force for Translation and Cultural Adaptation. Patients with T1DM for a minimum of 12 months, aged 18 years or older, and with Brazilian nationality were selected to participate.ResultsA total of 123 patients were enrolled. The Clarke and Gold questionnaires as well as the EHSS exhibited adequate internal consistency, test–retest reliability, and convergent validity. The prevalence of IAH was 38.3% with the Clarke questionnaire and 25.2% with the Gold questionnaire. The prevalence increased with longer duration of diabetes, lower HbA1c, and lower eGFR.ConclusionsThe validation and cross-cultural adaptation of the proposed questionnaires to Brazilian Portuguese were adequate. In this sample of T1DM, the prevalence of IAH was high and associated with a longer duration of T1DM, lower HbA1C and lower eGFR.

High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes: The Dutch Diabetes Pearl Cohort

ObjectivePeople with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim...

A randomised controlled study of high intensity exercise as a dishabituating stimulus to improve hypoglycaemia awareness in people with type 1 diabetes: a proof-of-concept study

Aims/hypothesisApproximately 25% of people with type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia (IAH), the cause of which is unknown. We recently proposed that IAH develops through habituation, a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory hormonal responses to hypoglycaemia (referred to as dishabituation) in a rodent model of IAH following introduction of a novel stress stimulus (high intensity training [HIT]). In this proof-of-concept study we sought to further test this hypothesis by examining whether a single episode of HIT would amplify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had IAH (assessed by Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating (DAFNE) hypoglycaemia awareness rating 2 or 3). The primary outcome was the difference in adrenaline response to hypoglycaemia following both a single episode of HIT and rest.MethodsIn this randomised, crossover study 12 participants aged between 18 and 55 years with type 1 diabetes for ≥5 years and an HbA1c <75 mmol/mol (9%) were recruited. Individuals were randomised using computer generated block randomisation to start with one episode of HIT (4 × 30 s cycle sprints [2 min recovery] at 150% of maximum wattage achieved during dot{V}{mathrm{O}}_{2mathrm{peak}} assessment) or rest (control). The following day they underwent a 90 min hyperinsulinaemic–hypoglycaemic clamp study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing (four-choice reaction time and digit symbol substitution test). Each intervention and subsequent clamp study was separated by at least 2 weeks. The participants and investigators were not blinded to the intervention or measurements during the study. The investigators were blinded to the primary outcome and blood analysis results.ResultsAll participants (six male and six female, age 19–54 years, median [IQR] duration of type 1 diabetes 24.5 [17.3–29.0] years, mean [SEM] HbA1c 56 [3.67] mmol/mol; 7.3% [0.34%]) completed the study (both interventions and two clamps). In comparison with the rest study, a single episode of HIT led to a 29% increase in the adrenaline (epinephrine) response (mean [SEM]) (2286.5 [343.1] vs 2953.8 [384.9] pmol/l); a significant increase in total symptom scores (Edinburgh Hypoglycaemia Symptom Scale: 24.25 [2.960 vs 27.5 [3.9]; p<0.05), and a significant prolongation of four-choice reaction time (591.8 [22.5] vs 659.9 [39.86] ms; p<0.01] during equivalent hypoglycaemia induced the following day.Conclusions/interpretationThese findings are consistent with the hypothesis that IAH develops in people with type 1 diabetes as a habituated response and that introduction of a novel stressor can restore, at least partially, the adapted counterregulatory hormonal, symptomatic and cognitive responses to hypoglycaemia.Trial registrationISRCTN15236211.

A systematic review of the effect of prior hypoglycaemia on cognitive function in type 1 diabetes.

Background:The effect of prior hypoglycaemia on cognitive function in type 1 diabetes is an important unresolved clinical question. In this systematic review, we aimed to summarize the studies exploring the impact of prior hypoglycaemia on any aspect of cognitive function in type 1 diabetes.Methods:We used a multidatabase search platform Healthcare Database Advanced Search to search Medline, PubMed, EMBASE, EMCARE, CINAHL, PsycINFO, BNI, HMIC, and AMED from inception until 1 May 2019. We included studies on type 1 diabetes of any age. The outcome measure was any aspect of cognitive function.Results:The 62 studies identified were grouped as severe hypoglycaemia (SH) in childhood (⩽18 years) and adult-onset (>18 years) diabetes, nonsevere hypoglycaemia (NSH) and nocturnal hypoglycaemia (NH). SH in early childhood-onset diabetes, especially seizures and coma, was associated with poorer memory (verbal and visuospatial), as well as verbal intelligence. Among adult-onset diabetes, SH was associated with poorer cognitive performance in the older age (>55 years) group only. Early versus late exposure to SH had a significant association with cognitive dysfunction (CD). NSH and NH did not have any significant association with CD, while impaired awareness of hypoglycaemia was associated with poorer memory and cognitive-processing speeds.Conclusion:The effect of SH on cognitive function is age dependent. Exposure to SH in early childhood (<10 years) and older age groups (>55 years) was associated with a moderate effect on the decrease in cognitive function in type 1 diabetes [PROSPERO ID: CRD42019141321].

Assessing awareness of hypoglycemia in children and adolescents with type 1 diabetes: Evaluation of established questionnaires.

To evaluate the use of two questionnaires assessing awareness of hypoglycemia, in a pediatric type 1 diabetes (T1D) population. Prospective observational study with children (aged 9-18 years) and parents (for children aged 2-11 years) answering the Gold and Clarke questionnaires assessing awareness of hypoglycemia. Psychometric properties of the questionnaires were evaluated, and the most appropriate cut-off score to classify participants as having normal vs impaired awareness of hypoglycemia (IAH) was determined by ability to recognize subsequent hypoglycemia and hypoglycemia severity, documented in a 4-week blood glucose diary. Questionnaires were readministered at follow-up assessment approximately 1.5 years later. In total, 112 participants (51% male) with median (IQR) age 13.7 (11.1-15.8) years, T1D duration 4.7 (2.2-7.8) years, and HbA1c 62 (57-73) mmol/mol (7.8%) were included. Both questionnaires demonstrated acceptable psychometric properties. Using score ≥3 to classify IAH gave a prevalence of IAH of 41% (Gold) and 22% (Clarke). When classified using the Gold questionnaire, IAH participants had higher incidences of mild asymptomatic hypoglycemia, whereas with the Clarke questionnaire, they had higher incidences of clinically significant and severe hypoglycemia. Subgroup analyses confirmed these associations only in participants aged ≥9 years. Follow-up was completed in 90% of the participants, and a change of awareness status was observed in 22% to 36%. The Gold and Clarke questionnaires may be used to assess awareness of hypoglycemia in pediatric T1D in those ≥9 years of age, but the more detailed Clarke questionnaire has higher specificity and is superior in predicting risk of clinically significant hypoglycemia.

Glucose and Counterregulatory Responses to Exercise in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia Using Closed-Loop Insulin Delivery: A Randomized Crossover Study.

To evaluate exercise-related glucose and counterregulatory responses (CRR) in adults with type 1 diabetes with impaired awareness of hypoglycemia (IAH) using hybrid closed-loop (HCL) insulin delivery to maintain glucose homeostasis. Twelve participants undertook 45-min high-intensity intermittent exercise (HIIE) and moderate-intensity exercise (MIE) in random order. The primary outcome was continuous glucose monitoring (CGM) time in range (70-180 mg/dL) for 24-h post-exercise commencement. CGM time in range was similar for HIIE and MIE (median 79.5% [interquartile range 73.2, 87.6] vs. 76.1% [70.3, 83.9], P = 0.37), and time with levels <54mg/dL post-exercise commencement was 0%. HIIE induced greater increases in cortisol (P = 0.002), noradrenaline (P = 0.005), and lactate (P = 0.002), with no differences in adrenaline, dopamine, growth hormone, or glucagon responses. IAH adults using HCL undertaking HIIE and MIE exhibit heterogeneity in CRR. Novel findings were a preserved cortisol response and variable catecholamine responses to HIIE.

Effectiveness-implementation hybrid type 2 trial evaluating two psychoeducational programmes for severe hypoglycaemia in type 1 diabetes: implementation study protocol

IntroductionTwo of the most acute and feared complications in type 1 diabetes (T1D) are hypoglycaemia and severe hypoglycaemia (SH). While impaired awareness of hypoglycaemia (IAH) can lead to SH with...

Impaired awareness of hypoglycemia in children and adolescents with type 1 diabetes mellitus in north of Jordan

BackgroundHypoglycemia is a common complication of insulin therapy in patients with Type 1 Diabetes Mellitus (DM). Awareness of hypoglycemic symptoms helps patients to recognize hypoglycemia and initiate self-treatment. Impaired Awareness of Hypoglycemia (IAH) exposes patients to severe hypoglycemia, which could be associated with seizures and unconsciousness. This study aimed to assess IAH, frequency of hypoglycemia, severe hypoglycemia and intensity of hypoglycemic symptoms among children and adolescents with Type 1 DM in North of Jordan.MethodsData were collected from 94 children and adolescents with Type 1 DM. Clarke’s and Edinburgh surveys were used to assess IAH and individual symptoms of hypoglycemia, respectively. Frequency of hypoglycemia and other related information were obtained by self-reporting or from medical records.Results16.0% of participants were having IAH, 66.0% of participants reported recurrent hypoglycemia (>once/month) and 18.0% of participants developed ≥1 severe hypoglycemia during the previous year. IAH was not associated with age, gender, duration of DM, HbA1c, insulin regimen, adherence to insulin or development of severe hypoglycemia (p-values> 0.05). Instead, IAH was associated with frequency of hypoglycemia during the previous 6 months (p-value< 0.01). Hunger, tiredness, dizziness, drowsiness, inability to concentrate, trembling and weakness were the most common symptoms felt by participants when they develop hypoglycemia. Hunger was the only common symptom that was significantly higher in children compared to adolescent (p-value < 0.01).ConclusionsThis study has reported low prevalence of IAH in children and adolescents with Type 1 DM in North of Jordan. IAH was more common in subjects with more frequent hypoglycemia.

Hippocampal Neurochemical Profile and Glucose Transport Kinetics in Patients With Type 1 Diabetes.

Longstanding type 1 diabetes (T1D) may lead to alterations in hippocampal neurochemical profile. Upregulation of hippocampal glucose transport as a result of recurrent exposure to hypoglycemia may preserve cognitive function during future hypoglycemia in subjects with T1D and impaired awareness of hypoglycemia (IAH). The effect of T1D on hippocampal neurochemical profile and glucose transport is unknown. To test the hypothesis that hippocampal neurochemical composition is altered in T1D and glucose transport is upregulated in T1D with IAH. Hippocampal neurochemical profile was measured with single-voxel magnetic resonance spectroscopy at 3T during euglycemia in 18 healthy controls (HC), 10 T1D with IAH, and 12 T1D with normal awareness to hypoglycemia (NAH). Additionally, 12 HC, 8 T1D-IAH, and 6 T1D-NAH were scanned during hyperglycemia to assess hippocampal glucose transport with metabolic modeling. University medical center. Concentrations of hippocampal neurochemicals measured during euglycemia and ratios of maximal transport rate to cerebral metabolic rate of glucose (Tmax/CMRGlc), derived from magnetic resonance spectroscopy-measured hippocampal glucose as a function of plasma glucose. Comparison of hippocampal neurochemical profile revealed no group differences (HC, T1D, T1D-IAH, and T1D-NAH). The ratio Tmax/CMRGlc was not significantly different between the groups, T1D-IAH (1.58 ± 0.09) and HC (1.65 ± 0.07, P = 0.54), between T1D-NAH (1.50 ± 0.09) and HC (P = 0.19), and between T1D-IAH and T1D-NAH (P = 0.53). Subjects with T1D with sufficient exposure to recurrent hypoglycemia to create IAH did not have alteration of Tmax/CMRglc or neurochemical profile compared with participants with T1D-NAH or HC.

Impaired hypoglycemia awareness in children and adolescents with type 1 diabetes

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

116 - Impaired Awareness of Hypoglycemia Increases Severe Hypoglycemia Rates in T2DM (InHypo-DM Study)

Few investigations have quantified the real-world, population-based effect of impaired awareness of hypoglycemia (IAH) on severe hypoglycemia (SH) in type 2 diabetes mellitus (T2DM). The current evaluation aims to address this gap by leveraging the pragmatic value of participant-reported hypoglycemia data.

Predictors of Recurrent Severe Hypoglycemia in Adults With Type 1 Diabetes and Impaired Awareness of Hypoglycemia During the HypoCOMPaSS Study.

The HypoCOMPaSS study was designed to test the hypothesis that successful avoidance of biochemical hypoglycemia without compromising overall glycemic control would restore sufficient hypoglycemia awareness to prevent recurrent severe hypoglycemia in the majority of participants with established type 1 diabetes. Before starting the study, we planned to investigate associations between baseline characteristics and recurrent severe hypoglycemia over 2 years' follow-up. A total of 96 adults with type 1 diabetes and impaired awareness of hypoglycemia participated in a 24-week 2 × 2 factorial randomized controlled trial comparing insulin delivery and glucose monitoring modalities, with the goal of rigorous biochemical hypoglycemia avoidance. The analysis included 71 participants who had experienced severe hypoglycemia in the 12-month prestudy with confirmed absence (complete responder) or presence (incomplete responder) of severe hypoglycemia over 24 months' follow-up. There were 43 (61%) complete responders and 28 (39%) incomplete responders experiencing mean ± SD 1.5 ± 1.0 severe hypoglycemia events/person-year. At 24 months, incomplete responders spent no more time with glucose ≤3 mmol/L (1.4 ± 2.1% vs. 3.0 ± 4.8% for complete responders; P = 0.26), with lower total daily insulin dose (0.45 vs. 0.58 units/24 h; P = 0.01) and greater impairment of hypoglycemia awareness (Clarke score: 3.8 ± 2.2 vs. 2.0 ± 1.9; P = 0.01). Baseline severe hypoglycemia rate (16.9 ± 16.3 vs. 6.4 ± 10.8 events/person-year; P = 0.002) and fear of hypoglycemia were higher in incomplete responders. Peripheral neuropathy was more prevalent in incomplete responders (11 [39%] vs. 2 [4.7%]; P < 0.001) with a trend toward increased autonomic neuropathy. Recurrent severe hypoglycemia was associated with higher preintervention severe hypoglycemia rate, fear of hypoglycemia, and concomitant neuropathy.

Frequency and awareness of hypoglycemia in patients with Type 2 Diabetes treated with two or more insulin injections in primary care outpatient clinics

AimsTo assess the frequency of hypoglycemia events, patient characteristics and the prevalence of impaired awareness of hypoglycemia (IAH) in patients with Type 2 Diabetes (T2D) using two or more insulin injections in primary care. MethodsCross-sectional study performed at 9 Primary Care Centers including review of electronic medical records and an on-site visit to patients using >2 insulin injections with suboptimal control. Episodes of severe hypoglycemia (SH) in the last 12months were recorded. Non-severe hypoglycemia (NSH) was considered as self-monitoring blood glucose <70mg/dl. IAH was evaluated and HbA1c was obtained. Results157 subjects were included (age 68.4+10.7years, 82 women, T2D duration 18.3+8.7years). 57% used multiple daily injections. Total insulin was 66.9+43.4 units/day. The mean HbA1c was 9.2±1.4% (77±12mmol/mol) and only 13.4% had HbA1c <8% (64mmol/mol). The frequency of NSH was 0.74±1.37 episodes/week. Only one patient had a SH the last 12months. Around 10–12% of patients had IAH. In comparison with normal awareness, those with IAH had a longer duration of T2D (25.3±11.6 vs. 16.1±8.2 years, respectively, p<0.01). In the multiple linear regression analysis, only the IAH score and the total insulin dose independently determined the NSH number. ConclusionsNSH/SH in patients with T2D treated with two or more insulin injections in primary care settings seems to be relatively common. Although hypoglycemia awareness is predominantly preserved, the presence of IAH should not be ignored as it increases the risk of hypoglycemia and constitutes an additional barrier to recognize and address this burden in T2D.

Impaired Awareness of Hypoglycemia Disrupts Blood Flow to Brain Regions Involved in Arousal and Decision Making in Type 1 Diabetes

Impaired awareness of hypoglycemia (IAH) affects one-quarter of adults with type 1 diabetes and significantly increases the risk of severe hypoglycemia. Differences in regional brain responses to hypoglycemia may contribute to the susceptibility of this group to problematic hypoglycemia. This study investigated brain responses to hypoglycemia in hypoglycemia aware (HA) and IAH adults with type 1 diabetes, using three-dimensional pseudo-continuous arterial spin labeling (3D pCASL) functional MRI to measure changes in regional cerebral blood flow (CBF). Fifteen HA and 19 IAH individuals underwent 3D pCASL functional MRI during a two-step hyperinsulinemic glucose clamp. Symptom, hormone, global, and regional CBF responses to hypoglycemia (47 mg/dL [2.6 mmol/L]) were measured. In response to hypoglycemia, total symptom score did not change in those with IAH (P = 0.25) but rose in HA participants (P < 0.001). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were lower in the IAH group (P < 0.05). Hypoglycemia induced a rise in global CBF (HA P = 0.01, IAH P = 0.04) but was not different between groups (P = 0.99). IAH participants showed reduced regional CBF responses within the thalamus (P = 0.002), right lateral orbitofrontal cortex (OFC) (P = 0.002), and right dorsolateral prefrontal cortex (P = 0.036) and a lesser decrease of CBF in the left hippocampus (P = 0.023) compared with the HA group. Thalamic and right lateral OFC differences survived Bonferroni correction. Responses to hypoglycemia of brain regions involved in arousal, decision making, and reward are altered in IAH. Changes in these pathways may disrupt IAH individuals' ability to recognize hypoglycemia, impairing their capacity to manage hypoglycemia effectively and benefit fully from conventional therapeutic pathways to restore awareness.

Impaired Awareness of Hypoglycaemia in Insulin-treated Type 2 Diabetes Mellitus.

Patients with Type 2 Diabetes Mellitus (T2DM) may develop hypoglycemia as an adverse effect of insulin therapy. Hypoglycemia has dangerous consequences that result from neuroglycopenia and hypersecretion of counter-regulatory hormones. Patients who recognize early symptoms of hypoglycemia can initiate self-treatment and rectify the situation. Impaired Awareness of Hypoglycemia (IAH) predisposes patients to severe hypoglycemia and unconsciousness. To assess the prevalence of IAH, the intensity of hypoglycaemic symptoms, the frequency of severe hypoglycemia and factors associated with IAH in patients with insulin-treated T2DM. This is a cross-sectional study that used Clarke's and Gold's surveys to assess IAH and Edinburgh survey to assess the intensity of hypoglycemic symptoms in patients with insulin-treated T2DM (n= 388). The frequency of hypoglycemia and other data were collected by self-reporting or from medical records. The prevalence (95% confidence interval) of IAH was 17.01% (13.27%-20.75%) as determined by Clarke's method and 5.93% (3.58-8.28) by Gold's method (Odds= 3.25, p-value<0.00001). Drowsiness, hunger, sweating, tiredness, trembling and weakness, were the most intense hypoglycaemic symptoms, and 6.19% of participants reported at least one episode of severe hypoglycaemia within the past year. Regardless of classification method used, IAH is not dependent on age, gender, duration of T2DM or duration of insulin therapy (p-values>0.05). Instead, IAH is positively associated with frequency of hypoglycaemia during the previous six months (p-value<0.05) and development of severe hypoglycaemia within the past year (p-value <0.05). This study highlights large variability in IAH depending on the method used for assessment. Increased hypoglycaemia frequency may increase the prevalence of IAH and thus the development of severe hypoglycemia.