Normal Awareness Of Hypoglycemia Research Articles

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.

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.

Hypoglycemia Awareness Trajectories in Young People with Type 1 Diabetes Using Flash Glucose Monitoring

Aim. The trajectories of the hypoglycemia awareness status (HAS) have not yet been studied in children and adolescents with Type 1 diabetes (T1D). Methods. This 2-year follow-up study included children and adolescents with T1D aged 6‒20 years old and using flash glucose monitoring. The HAS of each participant was determined by the Gold score and assessed at three time points, along with clinical data. The trajectories based on HAS progression over time were identified, and a logistic regression analysis was performed to compare their characteristics. Results. Among the 255 participants, we identified four HAS trajectories (T1–T4). T1: normal awareness of hypoglycemia (NAH) maintained over time (n = 82, 29%); T2: NAH recovered during follow-up (n = 40, 18%); T3: impaired awareness of hypoglycemia (IAH) developed during follow-up (n = 28, 12.4%); T4: IAH maintained over time (n = 59, 21%). Sixteen participants (7%) displayed no identifiable trajectory. Participants belonging to the T3 group were younger. Following a specific trajectory defined the risk of developing future severe hypoglycemia. Conclusions. HAS changed in a significant proportion of pediatric people with T1D over time. Participants with a trajectory toward IAH were younger. Frequent HAS assessments may help to improve hypoglycemia risk management, especially in young children with T1D.

Decreased branched-chain amino acids and elevated fatty acids during antecedent hypoglycemia in type 1 diabetes

IntroductionHypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to...

689-P: Comparing the Rates of Sensor-Detected Hypoglycaemia and Patient-Reported Hypoglycaemia by Awareness of Hypoglycaemia Using Continuous Glucose Monitoring: The Hypo-METRICS Trial

Impaired awareness of hypoglycemia (IAH) is attributed to hypoglycemia exposure. Continuous glucose monitoring (CGM) detects more hypoglycemia particularly during sleep. We compared rates and duration of sensor detected hypoglycemia (SDH) and patient reported hypoglycemia (PRH) in people with type 1 diabetes (T1D) using CGM or flash monitoring.We recruited 92 participants with T1D using CGM/Flash reporting &amp;gt;1 hypoglycemic episode in the last month. Participants were defined as normal awareness of hypoglycemia (NAH) (Gold score &amp;lt;4; n=70) and IAH (Gold score &amp;gt;4; n=22) . All wore an additional blinded CGM and recorded episodes of PRH (symptomatic episodes that resolved on carbohydrate ingestion, or a measured glucose &amp;lt;72mg/dl) in real time on a smartphone app for weeks. Sleep status was obtained using an actigraphy monitor. Time in range (59.4 vs. 62.4%; p=0.18) and time &amp;lt; 70 mg/dl (4.6 vs. 6.0%; p=0.44) were not different between groups. Rates and duration of SDH &amp;lt; 70 mg/dl, &amp;lt; 55 mg/dl and &amp;lt; 40 mg/dl during sleep and awake were not different (table 1) . Rates of PRH were also not different (table 1) . While CGM has benefits, it cannot be used to define IAH. CGM allows people with IAH to self-detect hypoglycemia similar to those with NAH, providing a technology supported awareness. Disclosure P.Divilly: None. S.R.Heller: Advisory Panel; Eli Lilly and Company, Medtronic, Mylan N.V., Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker’s Bureau; Novo Nordisk A/S. M.Evans: Advisory Panel; Pila Pharma, Zucara Therapeutics, Other Relationship; Abbott Diabetes, Dexcom, Inc., Medtronic, Novo Nordisk, Research Support; AstraZeneca, Sanofi, Speaker’s Bureau; Lilly Diabetes. J.K.Mader: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Speaker’s Bureau; Abbott Diabetes, Eli Lilly and Company, Medtronic, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Servier Laboratories, Stock/Shareholder; decide Clinical Software GmbH. S.A.Amiel: Advisory Panel; Medtronic, Novo Nordisk, Other Relationship; Sanofi. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. A.Seibold: Employee; Abbott Diabetes, Stock/Shareholder; Abbott. G.Martine-edith: Other Relationship; Novo Nordisk. Z.Mahmoudi: Employee; Novo Nordisk A/S. N.Zaremba: None. U.Soeholm: Research Support; Novo Nordisk A/S. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. B.E.De galan: Research Support; Novo Nordisk. E.Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. Funding Innovative Medicines Initiative (777460)

688-P: Comparing Rates of Sensor-Detected Hypoglycaemia and Patient-Reported Hypoglycaemia by Method of Glucose Monitoring: The Hypo-METRICS Trial

Continuous glucose monitoring (CGM) allows greater detection of hypoglycemia. We compared rates and duration of sensor detected hypoglycemia (SDH) and patient reported hypoglycemia (PRH) in people with type 1 diabetes (T1D) and normal awareness of hypoglycemia (NAH) (Gold score &amp;gt;4) using either flash or capillary blood glucose (CGB) monitoring. We included 91 participants (70 CGM vs. 21 CBG) with T1D with &amp;gt;1 hypoglycemic episode in the last month. They used blinded CGM in addition to their usual glucose monitoring and recorded PRH (symptomatic event that resolved on carbohydrate ingestion, or a self-measured glucose &amp;lt;72 mg/dl) in real time on a smartphone app for weeks. Sleep status was obtained using wrist wore actigraphy. Median (IQR) time in range (TIR) , 59.4 (17.4) vs 60.1 (16.9) % p=.54 and time below range, 4.6 (5.3) vs. 3.6 (5.7) % p=0.39, were not different. There were no significant differences in rates or duration of SDH &amp;lt;70 mg/dl or &amp;lt;54 mg/dl (table 1) . Rates of PRH were higher in the CGM group while awake, 2.9 (2.6) vs. 1.9 (2.6) episodes/week p=.039, with no difference during sleep. Median duration of SDH &amp;lt; 40mg/dl while awake was longer, 20.1 (12.7) vs. 43.2 (7.0) minutes p=.0068. For a given TIR, people with T1DM have similar hypoglycemia exposure regardless of mode of monitoring. CGM enhances awareness of events and shortens events &amp;lt; 40mg/dl whilst awake. Disclosure P.Divilly: None. S.R.Heller: Advisory Panel; Eli Lilly and Company, Medtronic, Mylan N.V., Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker’s Bureau; Novo Nordisk A/S. M.Evans: Advisory Panel; Pila Pharma, Zucara Therapeutics, Other Relationship; Abbott Diabetes, Dexcom, Inc., Medtronic, Novo Nordisk, Research Support; AstraZeneca, Sanofi, Speaker’s Bureau; Lilly Diabetes. S.A.Amiel: Advisory Panel; Medtronic, Novo Nordisk, Other Relationship; Sanofi. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. A.Seibold: Employee; Abbott Diabetes, Stock/Shareholder; Abbott. G.Martine-edith: Other Relationship; Novo Nordisk. Z.Mahmoudi: Employee; Novo Nordisk A/S. N.Zaremba: None. U.Soeholm: Research Support; Novo Nordisk A/S. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. E.Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. Funding Innovative Medicines Initiative (777460)

Effect of lactate administration on cerebral blood flow during hypoglycemia in people with type 1 diabetes

IntroductionImpaired awareness of hypoglycemia, clinically reflected by the inability to timely detect hypoglycemia, affects approximately 25% of the people with type 1 diabetes. Both altered brain lactate handling and increased...

Impaired awareness of hypoglycaemia in women with type 1 diabetes in pregnancy: Hypoglycaemia fear, glycaemic and pregnancy outcomes.

AimsTo examine maternal fear of hypoglycaemia, glycaemia and pregnancy outcomes in women with impaired and normal awareness of hypoglycaemia.MethodsA pre‐planned sub‐study of 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed hypoglycaemia fear surveys (HFS‐II) at baseline. Logistic regression and Poisson regression analyses were used to obtain an adjusted estimate for the rate ratio relating awareness to the number of severe hypoglycaemic episodes, and for several neonatal outcomes in relation to the total HFS‐II score. The role of continuous glucose monitoring (CGM) use was examined.ResultsOverall, 30% of participants reported impaired awareness of hypoglycaemia (n = 64). Women with impaired awareness of hypoglycaemia had more episodes of severe hypoglycaemia (mean 0.44 vs. 0.08, p < 0.001) (12–34 weeks gestation) and scored higher on the HFS‐II scale (43.7 vs. 36.0, p 0.008), indicating more fear of hypoglycaemia. They spent more time below range (CGM <3.5 mmol/L) and exhibited more glycaemic variability at 12 weeks gestation. Higher overall HFS‐II scores were associated with a higher risk of maternal severe hypoglycaemia episodes (Rate Ratio 1.78, 95% CI 1.39–2.27). Women with impaired awareness of hypoglycaemia had less maternal weight gain but there were no differences in neonatal outcomes between women with impaired awareness of hypoglycaemia and normal hypoglycaemia awareness. Higher HFS‐II scores were associated with more nephropathy (Odds Ratio 1.91, 95% CI 1.06–3.4). CGM use after 12 weeks was not associated with the number of episodes of severe hypoglycaemia (RR 0.75, 95% CI 0.49–1.15; p = 0.18).ConclusionsIn pregnant women with type 1 diabetes, impaired awareness of hypoglycaemia is associated with more maternal severe hypoglycaemia episodes and more fear of hypoglycaemia. Having impaired awareness of hypoglycaemia and/or fear of hypoglycaemia should alert clinicians to this increased risk. Reassuringly, there was no increase in adverse neonatal outcomes.

P.140: Impact of Successful Pancreas Transplantation on Patient Reported Hypoglycemia Outcomes

Introduction: Poorly controlled Type 1 Diabetes (T1D) is associated with increased HbA1c, increased severe hypoglycemia, decreased hypoglycemia awareness and diabetic ketoacidosis. These comorbidities and decreased quality of life are indications for Pancreas Transplantation (PT). Limited data are available about patient reported outcomes (PROs) related to Hypoglycemia after PT. Therefore, we prospectively studied these PROs over a year after PT in patients with T1D. Methods: Ten PT recipients were enrolled within a month after PT and completed 3 visits (V1, V2 & V3 at 4 weeks, 4 months and 1 year). At each visit, participants completed Hypoglycemia Fear Survey-II (HFS-II) and Clarke hypoglycemia unawareness survey. HFS-II is a 33-item questionnaire to measure behavior and worry subscales related to fear of hypoglycemia in patients with T1D. Behavior subscale (HFS-B) describes behaviors individual would engage in to avoid hypoglycemia or its consequences. Worry subscale (HFS-W) describes concerns related to hypoglycemia. Clarke questionnaire evaluates awareness of hypoglycemia based on responses to 8 questions, identifying awareness (A) or reduced awareness (R). The Clarke R score ranges from 0 to 7 with ≤ 2 indicating normal A, 3 as undetermined A and score ≥4 suggesting impaired awareness of hypoglycemia (IAH). We analyzed insulin independent and partial graft function on insulin separately. Statistical analysis was done using a linear mixed effects model. Results: Patients were 46.3 ± 14.3 years old, 9 F, duration of T1D 27.8 ± 15.8 years with 29.4 ± 18.3 days interval from PT. Laboratory results were HbA1c (%) 6.3, 5.4 and 5.4, fasting plasma glucose (mg/dL) 88.6, 104.8 and 91 and C-peptide (ng/ml) 4.6, 3.1 and 2.4 on V1, 2 & 3 respectively. In insulin independent participants (n=8), HFS-B showed almost every participant reported taking some behavioral measures over last 6 months to avoid hypoglycemia at V1. On V2, five participants took some behavioral measures and on V3 only one to avoid hypoglycemia (Table). HFS-W showed almost every participant had some concerns about low blood sugar at V1, five on V2 and none on V3. Two participants who had partial graft function around V2 engaged in behavior to avoid hypoglycemia on V1, 2 & 3, with a subsequent decreased behavioral engagement (p 0.1197) and concern to avoid hypoglycemia (p 0.1391) compared to V1. Clarke scoring showed indeterminate awareness at V1, improved significantly (p 00.0146) and attained normal hypoglycemia awareness over the year on V2 and V3 respectively (Table). Two participants who had partial graft failure reported IAH on all 3 visits (V1: V2:V3=5.0: 4.0: 4.0, p 0.5000). Conclusion: PT recipients reported reduced Fear of hypoglycemia and improved hypoglycemia awareness over a period of 1 year, even in patients with partial graft function. More studies would enable better assessment of these PROs and improve the field.

48-OR: Changes in Global Cerebral Blood Flow in Response to Hypoglycemia in Type 1 Diabetes Do Not Influence Awareness Status

Changes in global cerebral blood flow (gCBF) have been suggested as a mechanism for mitigating the functional impact of hypoglycemia on the brain. The impact of type 1 diabetes (T1D) or hypoglycemia awareness status is not clear. We measured gCBF during progressive lowering of plasma glucose in people with and without T1D, and with retained or impaired awareness of hypoglycemia. Methods: Fifty-one participants (15 with no diabetes (ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 21 with T1D and impaired awareness of hypoglycemia (IAH)) underwent a two-step hyperinsulinemic hypoglycemic clamp. gCBF was estimated using pseudocontinuous arterial spin labelling magnetic resonance imaging at 6 timepoints: 2 euglycemic, two in the descent phase and two hypoglycemic. gCBF was extracted using a global grey matter mask in SPM12. Statistical analysis and thresholded linear models were performed in R. Results: The mean (+ SD) glucose values at the six timepoints were 95.8 (8.0), 95.5 (9.2), 55.0 (8.3), 50.8 (5.3), 45.7 (4.3) and 45.8 (4.0) mg/dL. Symptom responses to hypoglycemia were absent in IAH. There was a significant increase in CBF in response to hypoglycemia (3-way ANOVA p = 0.04). This was driven by responses in NAH (+7.3%, p &amp;lt; 0.05) and IAH (+10.6% p &amp;lt; 0.01) with no response in ND (+3.5% p = 0.16). The response was not linear, with glucose thresholds of 55.8 mg/dL in NAH and 54.0 mg/dL in IAH (pNAH vs IAH = 0.9) with no threshold in ND. Conclusion: In people with T1D, there is a non-linear relationship between falling glucose and rising gCBF which is not related to awareness status and is not seen in health. The threshold glucose between 54 and 56 mg/dL corresponds closely with level 2 hypoglycemia cut-offs used in current clinical practice. We propose that there is a failure of cerebral vascular autoregulation in response to hypoglycemia in T1D. gCBF responses to hypoglycemia in T1D are independent of symptomatic responses and not responsible for lack of hypoglycemia awareness. Disclosure P. Jacob: None. O. Odaly: None. S. A. Amiel: Advisory Panel; Self; Diabetes UK, Medtronic, Other Relationship; Self; Sanofi, Research Support; Self; Diabetes UK, European Union, JDRF. P. Choudhary: Advisory Panel; Self; Abbott Diabetes, Insulet Corporation, Lilly Diabetes, Medtronic, Sanofi-Aventis, Speaker’s Bureau; Self; Dexcom, Inc., Novo Nordisk. Funding JDRF (3-SRA-2017-484-S-B)

Structural Gray and White Matter Differences in Patients With Type 1 Diabetes and Impaired Awareness of Hypoglycemia.

Type 1 diabetes (T1D) is associated with an increased risk of cognitive decline, where severe hypoglycemia (SH) and impaired awareness of hypoglycemia (IAH) may play a role. While there is evidence of a possible association between IAH and brain damage, the potential brain changes remain poorly characterized by magnetic resonance imaging (MRI). To investigate whether there are structural brain differences in a group of T1D patients with IAH compared with normal awareness of hypoglycemia (NAH). General practice, population-based, cross-sectional study (July 2018 to July 2019). Endocrinology Department, Hospital Santa Creu i Sant Pau. A total of 40 T1D patients (20 each with IAH and NAH) matched for age, sex, T1D duration, and education level. Using different neuroimaging techniques, we compared whole-brain gray matter (GM) and white matter (WM) differences. We used voxel-based morphometry and cortical surface area analysis methods to assess GM differences, and fractional anisotropy (FA) to assess WM differences. Compared with patients with T1D-NAH, patients with T1D-IAH had reduced GM volumes and cortical surface areas, especially in frontal and parietal regions (P < 0.05 corrected), and also showed reduced FA values in major WM tracts. The observed MRI differences correlated with both SH frequency and IAH severity. MRI for patients with T1D show that IAH is associated with brain changes involving both GM and WM. Further research is needed to elucidate whether the observed differences are a consequence of increased SH episode frequency and increased IAH severity.

Increased cerebral FDG-PET uptake in type 1 diabetes patients with impaired awareness of hypoglycaemia.

Approximately 20% of type 1 diabetes (T1D) patients have an impaired awareness of hypoglyceamia (IAH). IAH represents a risk factor for severe and recurrent hypoglycaemic events, which can lead to brain damage. Because no effective treatments are currently available to prevent IAH in this population, characterising the set of brain alterations associated with IAH may reveal novel preclinical diagnostic or therapeutic strategies. Using state-of-the art neuroimaging techniques, we compared 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) uptake at rest between 10 T1D patients with IAH and nine patients with normal awareness of hypoglycaemia (NAH). T1D-IAH patients showed a pattern of increased FDG-PET uptake with respect to NAH patients (P<.05 corrected). Topographically, glucose metabolism was increased in the frontal and precuneus regions. Importantly, within the IAH group, this abnormal hypermetabolism correlated with IAH severity. This hypermetabolic state appeared to be unrelated to compensatory mechanisms as a result of reduced grey matter density or a neuroinflammatory state. We observed an abnormal increase in FDG-uptake in T1D patients with IAH in brain regions strongly related to cognition. Because this hypermetabolic state correlated with IAH severity, its biological characterisation could reveal new preventive or therapeutic strategies. A possible mechanism could be that glucose transport is increased in hypoglycaemia unawareness to compensate for recurrent hypoglycaemia, although this need to be confirmed in further research.

Real-time CGM Is Superior to Flash Glucose Monitoring for Glucose Control in Type 1 Diabetes: The CORRIDA Randomized Controlled Trial.

OBJECTIVEThe aim of this trial was to compare the efficacy of real-time and intermittently scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control.RESEARCH DESIGN AND METHODSIn this randomized study, adults with type 1 diabetes (T1D) and normal hypoglycemia awareness (Gold score <4) used rtCGM (Guardian Connect Mobile) or isCGM (FreeStyle Libre) during 4 days of physical activity (exercise phase) and in the subsequent 4 weeks at home (home phase). Primary end points were time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) and time in range (3.9–10.0 mmol/L [70–180 mg/dL]). The isCGM group wore an additional masked Enlite sensor (iPro2) for 6 days to check for bias between the different sensors used by the rtCGM and isCGM systems.RESULTSSixty adults with T1D (mean age 38 ± 13 years; A1C 62 ± 12 mmol/mol [7.8 ± 1.1%]) were randomized to rtCGM (n = 30) or isCGM (n = 30). All participants completed the study. Percentage of time in hypoglycemia (<3.9 mmol/L [<70 mg/dL]) was lower among rtCGM versus isCGM participants in the exercise phase (6.8 ± 5.5% vs. 11.4 ± 8.6%, respectively; P = 0.018) and during the home phase (5.3 ± 2.5% vs. 7.3 ± 4.4%, respectively; P = 0.035). Hypoglycemia differences were significant and most notable during the night. rtCGM participants spent more time in range (3.9–10 mmol/L [70–180 mg/dL]) than isCGM participants throughout both the exercise (78.5 ± 10.2% vs. 69.7 ± 16%, respectively; P = 0.0149) and home (75.6 ± 9.7% vs. 67.4 ± 17.8%, respectively; P = 0.0339) phases. The results were robust to the insignificant bias between rtCGM and isCGM sensors that masked CGM found in the isCGM arm.CONCLUSIONSrtCGM was superior to isCGM in reducing hypoglycemia and improving time in range in adults with T1D with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management.

Increased plasma neurofilament light chain levels in patients with type-1 diabetes with impaired awareness of hypoglycemia

IntroductionImpaired awareness of hypoglycemia (IAH) is a common complication in patients with type-1 diabetes (T1D). IAH is a major risk factor for severe hypoglycemic events, leading to adverse clinical consequences...

155-OR: ADA Presidents’ Select Abstract: Symptom Responses to Hypoglycemia Are Related to Connectivity Change between the Thalamus and Frontal Lobes

Neuroimaging studies highlight the importance of thalamic activation in response to hypoglycemia in people with and without type 1 diabetes (T1D). This activation is characteristically attenuated in impaired awareness of hypoglycaemia (IAH), a major risk factor for severe hypoglycemia. We investigated changes in connectivity of the thalamus with other brain regions during hypoglycemia. Methods: Fourteen people without diabetes (no diabetes, ND), 15 with T1D and normal awareness of hypoglycemia (NAH) and 22 with IAH, all right-handed, age, sex and gender matched, underwent a hyperinsulinemic glucose clamp during which we acquired blood oxygen level dependent fMRI at euglycemia (90mg/dL) and at onset of hypoglycemia (48mg/dL). Connectivity was studied using the CONN toolbox in SPM12. A thalamic seed was used in a seed-to-voxel analysis with and without the increase in symptoms at hypoglycemia as an explanatory regressor variable. Results: Symptom scores in response to hypoglycemia rose earliest and to the greatest levels in NAH (11.0 to 18.3, p= 0.029). The rise in symptom scores in ND was not significant at this timepoint (9.2 to 13.8, p= 0.057), whilst IAH showed no symptom change (10.5 to 9.8, p= 0.7). In ND, hypoglycemia increased thalamic connectivity with the right frontal pole (pFDR = 0.018). This did not occur in diabetes, either in NAH or IAH. The NAH group demonstrated a positive relationship between change in symptoms with change in connectivity of the thalamus and a left frontal pole region (pFDR = 0.035), whereas an overlapping area had a negative correlation in ND (pFDR = 0.001). There was no correlation in IAH. Conclusion: During hypoglycemia, those with T1D display aberrantly enhanced thalamic connectivity with brain regions responsible for complex behavior. Disruption of this network occurs in IAH and may be the mechanism for failure of perception of the onset of hypoglycemia and reduced hypoglycemia avoidance behaviors, increasing severe hypoglycemia risk. Disclosure P. Jacob: None. M. Nwokolo: Other Relationship; Self; Sanofi. O. ODaly: None. F.O. Zelaya: None. S.A. Amiel: Advisory Panel; Self; Medtronic, Novo Nordisk A/S, Roche Pharma. Other Relationship; Self; Diabetes UK. P. Choudhary: Advisory Panel; Self; Abbott, Eli Lilly and Company, Insulet Corporation, Medtronic. Research Support; Self; European Union, JDRF. Speaker’s Bureau; Self; Dexcom, Inc., Novartis AG, Novo Nordisk A/S, Sanofi-Aventis. Funding JDRF (3-SRA-2017-484-S-B)

194-OR: Impaired Awareness of Hypoglycemia and Maternal/Neonatal Outcomes in the CONCEPTT Trial

Background: Patients with diabetes and impaired awareness of hypoglycemia (IAH) are at increased risk of severe hypoglycemia (SH). IAH is increased during pregnancy. To date, maternal and neonatal outcomes of pregnant women with hypoglycemia unawareness or SH has not been well described. Aim: To examine maternal and neonatal outcomes in women with IAH compared to women with normal awareness of hypoglycemia (NAH). Methods: We included 214 pregnant women with type 1 diabetes who participated in the CONCEPTT trial. Participants completed Hypoglycemia Fear Surveys (HFS-II) at baseline and study completion. Post-hoc analysis of data was conducted using logical regression analysis to estimate the odds of occurrence of events by IAH versus NAH. The role of continuous glucose monitoring (CGM) use on outcomes was also examined. Results: Overall, 30% of participants reported IAH (n=64). Women with IAH had more episodes of SH during pregnancy (mean 0.44 vs. 0.08, p&amp;lt;0.001). Women with IAH scored significantly higher on the HFS-II worry scale (25.9 vs. 20.1, p 0.0036), indicating more fear of hypoglycemia at baseline. They also spent more time below range (&amp;lt;63 mg/dl) at 12 weeks gestation. Higher overall HFS-II scores were associated with a higher risk of maternal SH episodes (RR 1.78, 95% CI 1.39-2.27) and a lower incidence of neonatal hypoglycemia (OR 0.597, 95% CI 0.385-0.893). There were no other differences in obstetric/neonatal outcomes between women with IAH and NAH. Higher HFS-II scores were associated with more diabetes-related complications, such as nephropathy (OR 1.907, 95% CI 1.06-3.4), independent of duration of diabetes. Finally, CGM did not affect incidence of SH (RR 0.54, 95% CI 0.12 - 2.16). Conclusion: In pregnant women with type 1 diabetes, IAH is associated with more maternal SH episodes and more fear of hypoglycemia. Fear of hypoglycemia was associated with reduced neonatal hypoglycemia as well as more maternal diabetes-related complications. Disclosure J. Bahrami: None. G. Tomlinson: None. H.R. Murphy: Advisory Panel; Self; Medtronic. D. Feig: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic. Funding JDRF; Canadian Clinical Trial Network

852-P: Is Real-Time CGM Superior to Flash Glucose Monitoring? Results of the Type 1 Diabetes CORRIDA Randomized Control Trial

Background: The trial aim was to compare the efficacy of real-time and intermittently-scanned continuous glucose monitoring (rtCGM and isCGM, respectively) in maintaining optimal glycemic control. Methods: In this randomized study, adults with T1D and normal hypoglycemia awareness (GOLD score Results: Sixty adults with T1D (age 38±13 years, HbA1c 7.8±1.1% [62±12 mmol/mol]) were randomized to rtCGM (n=30) or isCGM (n=30). All participants completed the study. Time in hypoglycemia ( Conclusion: rtCGM was superior to isCGM in preventing hypoglycemia and improving time in range in T1D adults with normal hypoglycemia awareness, demonstrating the value of rtCGM alarms during exercise and in daily diabetes self-management. Disclosure J. Soupal: Advisory Panel; Self; Abbott. Consultant; Self; Medtronic, Roche Diabetes Care. Speaker’s Bureau; Self; Dexcom, Inc. A. Haskova: None. G. Grunberger: Research Support; Self; Medtronic. L. Petruzelkova: None. C. Parkin: Consultant; Self; Abbott, CeQur Corporation, Dexcom, Inc., DreaMed Diabetes, Novo Nordisk Inc., Onduo, Roche Diabetes Care, Valeritas, Inc. J. Skrha: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Eli Lilly and Company, Merck Sharp & Dohme Corp. L. Radovnicka: None. E. Horova: None. M. Prazny: Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Roche Diabetes Care. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk A/S, Sanofi, Teva Pharmaceutical Industries Ltd. Funding 15-26705A (Program RVO-VFN00064165)

157-OR: People with Type 1 Diabetes and Impaired Awareness of Hypoglycemia Have a Delayed Reaction to Perform a Glucose Scan during Hypoglycemia: A Prospective Observational Study

Background: Considering that people with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) have a delayed perception of hypoglycemia, the question arises if they perform scans later in case of hypoglycemia compared to those with normal hypoglycemia awareness (non-IAH). We assessed if the time until performing a scan after reaching hypoglycemia while using a flash glucose monitoring (Flash GM) system is different in people with T1D and IAH compared to people with T1D and non-IAH. Material and Methods: 92 people with T1D (age of 42±14 years, BMI 25.1±4.0 kg/m2, HbA1c 57±9 mmol/mol (7.3±0.8%), 73 MDI/19 CSII) using a Flash GM system for 3 months were included. Flash GM data were downloaded and assessed for time until scan after reaching hypoglycemia level 1 (&amp;lt;70 mg/dL) and level 2 (&amp;lt;54 mg/dL) and compared for T1D with IAH versus non-IAH via unpaired t-test or Mann-Whitney-U test (p&amp;lt;0.05). IAH was routinely assessed by means of Gold, Clarke and Pedersen-Bjergaard Score. Results: Significant differences were only found for the delay between reaching hypoglycemia and scan between IAH and non-IAH for both Gold Score (hypoglycemia level 1: IAH 78 min [51-105] vs. non-IAH 63 min [42-89], p=0.03; nighttime hypoglycemia level 2: IAH 140 min [107-227] vs. non-IAH 96 min [41-155], p=0.004) and Pedersen-Bjergaard Score (hypoglycemia level 1: IAH 76 min [52-97] vs. non-IAH 54 min [38-71], p=0.01; nighttime hypoglycemia level 1: IAH 132 min [79-209] vs. non-IAH 89 min [59-143], p=0.01; nighttime hypoglycemia level 2: IAH 134 min [66-212] vs. non-IAH 80 min [37-131], p=0.002). Conclusion: These preliminary data suggest that the time until scan after reaching hypoglycemia may serve as an objective assessment tool for IAH in people with T1D. Disclosure O. Moser: Other Relationship; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi. H. Ziko: None. H. Elsayed: None. D.A. Hochfellner: None. T. Poettler: None. A. Mueller: None. M.L. Eckstein: Research Support; Self; Dexcom, Inc., Novo Nordisk A/S, Sanofi-Aventis. L. Knoll: None. H. Sourij: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Sanofi. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis.

913-P: Higher Glucose Thresholds for Hypoglycemia Alarms on Continuous Glucose Monitoring Systems (CGMs) Are Associated with Less Time in Hypoglycemia in Patients with Impaired Awareness of Hypoglycemia

A cross-sectional observational cohort analysis was conducted to assess whether higher hypoglycemia alarm thresholds on CGMs are associated with less hypoglycemia for both patients with normal (NAH) and impaired (IAH) awareness of hypoglycemia. Two-week CGM alarm/glucose data from 39 and 42 type 1 diabetes (T1D) patients with NAH and IAH (determined by the Clarke questionnaire) who have used CGMs for &amp;gt;3 months and had an active CGM usage time of ≥86% were included in the analysis. IAH patients with higher hypoglycemia alarm thresholds (i.e., alarm thresholds set &amp;gt;73 mg/dL vs. &amp;lt;73 mg/dL) spent 57.8% and 75.6% less time with glucose &amp;lt;70 and &amp;lt;54 mg/dL, respectively, while no significant differences were found between higher/lower alarm thresholds in the NAH groups. (Figure 1a, 1b) Fewer day and night-time numbers of hypoglycemic episodes (defined as ≥1 glucose value &amp;lt;70 and &amp;lt;54 mg/dL; Figure 1c, 1d) and shorter duration of episodes with glucose &amp;lt;54 mg/dL (Figure 1e, 1f) contributed to the reduced time spent in hypoglycemia in the IAH patients with higher alarm thresholds. The current analysis suggests that higher CGM hypoglycemia alarm thresholds are associated with less time spent in hypoglycemia in T1D patients with IAH, but not those with NAH. Disclosure Y. Lin: None. D. Groat: None. O. Chan: None. R. Pop-Busui: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Consultant; Self; Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk Inc. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. M. Varner: None. S. Fisher: None. Funding National Institute for Diabetes and Digestive and Kidney Diseases/Washington University School of Medicine (2P30DK020579); University of Utah Diabetes and Metabolism Research Center; National Institute for Diabetes and Digestive and Kidney Diseases (5T32DK091317); National Center for Advancing Translational Sciences (1ULTR002538)

Awareness of hypoglycemia and spectral analysis of heart rate variability in type 1 diabetes

AimsTo investigate the relationship of unawareness of hypoglycemia with spectral analysis of heart rate variability (HRV) and clinical variables in type 1 diabetes (T1D) individuals. MethodsParticipants with type 1 diabetes mellitus (type 1 diabetes) were prospectively assessed for hypoglycemia awareness using the Pedersen-Bjergaard method and were classified as normal hypoglycemia awareness, impaired hypoglycemia awareness and hypoglycemia unawareness. Indices of HRV in frequency domain were evaluated and Ewing tests were used for the diagnosis of cardiovascular autonomic neuropathy (CAN). ResultsNinety-eight participants with T1D (mean age 26 years, average diabetes duration 13 years, and mean HbA1c 8.4%) were included in this study. The prevalence of hypoglycemia unawareness was 28%. No significant difference was observed on the prevalence of CAN among groups of different hypoglycemia awareness (p = 0.740). On regression analyses, abnormal results of HRV in frequency domain were not associated with unawareness of hypoglycemia. On univariable regression analysis, age, diabetes duration and estimated creatinine clearance were associated with unawareness of hypoglycemia. ConclusionCAN as assessed by Ewing tests and spectral analysis of HRV is not associated with unawareness of hypoglycemia. There is association of age, diabetes duration and renal deficit with unawareness of hypoglycemia.