Aim: To examine how hypoglycemia while asleep impacts self-reported daily functioning among adults with type 1 diabetes (T1D) . Methods: On 70 consecutive mornings, 250 people with T1D wearing a continuous glucose monitor reported sleep quality, mood, and alertness via the Hypo-METRICS smartphone app. Each night was categorized based on presence (+) or absence (-) of person-reported hypoglycemia (PRH) and sensor-detected hypoglycemia (SDH) into one of four types (see Figure 1, Type A-D) . Multilevel regression assessed associations between hypoglycemia and daily functioning (unstandardized coefficients (β) on original 0-scale) , adjusted for baseline demographic, clinical and psychological factors. Results: In the first 54 adults (52% women, age[M±SD]: 45±15 years) , nighttime PRH (Type C & D, Figure 1) was associated with reduced subjective sleep quality (C: β=-0.67; D: β=-0.58) , mood (C: β=-0.43; D: β=-0.58) and alertness (C: β=-0.34, p=0.015; D: β=-0.46) (all p<0.0unless specified) compared to nights without hypoglycemia (Type A) . Nights with SDH only (Type B) showed no significant reductions in sleep, mood or alertness (p>0.05) . Conclusion: These novel data show the potentially pivotal role of the subjective experience of hypoglycemia for sleep quality, mood and alertness. Disclosure U.Soeholm: Research Support; Novo Nordisk A/S. 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. E.J.Abbink: None. P.M.Baumann: 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. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. 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. D.Pollard: Other Relationship; Novo Nordisk. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. S.A.Amiel: Advisory Panel; Medtronic, Novo Nordisk, Other Relationship; Sanofi. M.M.Broadley: None. C.Hendrieckx: None. J.Speight: Advisory Panel; Insulet Corporation, Research Support; Novo Nordisk, Sanofi. P.Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. F.Pouwer: Research Support; Eli Lilly and Company, Novo Nordisk, Sanofi. N.Zaremba: None. P.Divilly: None. G.Martine-edith: Other Relationship; Novo Nordisk. G.Nefs: None. Z.Mahmoudi: Employee; Novo Nordisk A/S. J.K.Mader: Advisory Panel; Abbott Diabetes, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Merck Sharp & 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 & Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis Deutschland GmbH, Servier Laboratories, Stock/Shareholder; decide Clinical Software GmbH. M.Cigler: None. Funding This work was supported by the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement 777460
Acute hypoglycemia impacts negatively on cognitive function. However, it remains unclear which specific domains of cognitive function are affected, and the extent to which level of hypoglycemia modifies this relationship. We conducted a systematic review and meta-analysis to investigate the impact of controlled hyperinsulinaemic hypoglycemia on cognitive function in adults with type 1 diabetes, following PRISMA guidelines. Experimental studies comparing cognitive function task performance during euglycemia and hypoglycemia were eligible for inclusion. Preliminary analyses were conducted on 38 studies, involving 54 cognitive task outcomes across three domains of cognitive function of varying complexity: attention/information processing speed (simplest) , working memory, and complex reasoning (most complex) . Three-level meta-analyses of the standardized mean differences (SMD) in performance during euglycemia and hypoglycemia, moderated by hypoglycemia level (Mdn=2.51; range=1.98-3.5 mmol/l) were conducted for each domain, with study and task as random effects to allow inclusion of multiple effect sizes per study. Hypoglycemia significantly impaired performance on all domains, with large effect sizes for attention/information processing speed (SMD=-1.17, 95% CI:-1.60 to -0.74) and working memory (SMD=-0.84, CI:-1.to -0.63) , and a medium effect size for complex reasoning (SMD=-0.61, CI:-0.99 to -0.23) . The degree of hypoglycemia significantly moderated this relationship for working memory only, such that for every 1mmol/l decrease in glucose level, performance was reduced by SMD=0.84 (CI:0.2 to 1.49) . These findings suggest that the impact of hypoglycemia on cognitive function is related to the cognitive domain complexity, with more impaired performance on simpler relative to more complex tasks. Further, degree of hypoglycemia may be differentially related to performance depending on the domain of cognitive function. Disclosure M.M.Broadley: None. C.Hendrieckx: None. R.J.Mccrimmon: Advisory Panel; Novo Nordisk, Sanofi, Research Support; Diabetes UK, European Union, MedImmune. G.Nefs: None. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi. C.E.Verhulst: None. J.Speight: Advisory Panel; Insulet Corporation, Research Support; Novo Nordisk, Sanofi. F.Pouwer: Research Support; Eli Lilly and Company, Novo Nordisk, Sanofi. The hypo-resolve consortium: n/a. H.Chatwin: None. U.Soeholm: Research Support; Novo Nordisk A/S. J.Axelsen: None. 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. B.E.De galan: Research Support; Novo Nordisk. T.W.Fabricius: 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. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)
Consensus defines nocturnal hypoglycemia as occurring between 00:00 and 06:00 hrs. However, this may introduce bias, as for many, these hours only partially match real sleeping hours. Therefore, we compared rates of hypoglycemia while asleep (defined by Fitbit Charge 4) to rates of conventionally-defined nocturnal hypoglycemia. Hypo-METRICS study participants wore a Fitbit charge 4 and blinded FreeStyle Libre glucose monitor for up to 70 days. Every hypoglycemia episode (≤70mg/dL or ≤54mg/dL for ≥15 min) was classified as ‘asleep’ or ‘awake’ based on Fitbit sleep intervals and ‘nocturnal’ (00:00-06:00 hrs) or ‘day-time’. We compared weekly sensor-detected hypoglycemia (SDH) rates whilst asleep to nocturnal SDH rates using a paired sample Wilcoxon test. We included 542 participants (269 with type 1 diabetes, median (IQR) age 56 (44-66) years, HbA1c 7.3%(6.7-7.9), with 69 (65-70) nights with sleep data/participant). Sleep duration was 6.1 (5.2-6.8) hours. Median weekly rates of SDH while asleep were higher than rates of nocturnal SDH both ≤70mg/dL (1.3 (0.6-2.5) vs 0.9 (0.4-1.8), p<0.001) and ≤54mg/dL (0.4 (0.2-0.9) vs 0.3 (0.1-0.7), p<0.001). Stratifying by type of diabetes did not change the direction or magnitude of the differences in SDH rates. Using clock time to estimate nocturnal hypoglycemia underestimates hypoglycemia whilst asleep by up to a third. Using activity trackers such as Fitbit to identify sleep offers a novel way to estimate hypoglycemia whilst asleep to better reflect lived experience of nocturnal hypoglycemia. Disclosure G.Martine-edith: Other Relationship; Novo Nordisk A/S. R.J.Mccrimmon: Advisory Panel; Sanofi, Speaker's Bureau; Novo Nordisk A/S. E.Renard: Consultant; Abbott Diabetes, Dexcom, Inc., AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Insulet Corporation, MannKind Corporation, Novo Nordisk, Sanofi, Roche Diabetes Care. S.R.Heller: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Other Relationship; Eli Lilly and Company, Research Support; Dexcom, Inc., Speaker's Bureau; Novo Nordisk, Medtronic. M.Evans: Advisory Panel; Zucara Therapeutics, Pila Pharma, Dexcom, Inc., Other Relationship; Novo Nordisk, AstraZeneca, Abbott Diabetes, Speaker's Bureau; Eli Lilly and Company. J.K.Mader: Advisory Panel; Novo Nordisk A/S, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Medtronic, Becton, Dickinson and Company, Pharmasense, embecta, Research Support; A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Dexcom, Inc., Profusa, Inc., Speaker's Bureau; Novo Nordisk A/S, A. Menarini Diagnostics, Abbott Diabetes, Roche Diabetes Care, Eli Lilly and Company, Sanofi, Boehringer Ingelheim Inc., Becton, Dickinson and Company, Ypsomed AG, Viatris Inc., Servier Laboratories, Medtrust, Stock/Shareholder; Decide Clinical Software GmbH. S.A.Amiel: Advisory Panel; Medtronic, Other Relationship; Sanofi, Novo Nordisk. P.Choudhary: Advisory Panel; Medtronic, Novo Nordisk, Dexcom, Inc., MannKind Corporation, Insulet Corporation, Research Support; Abbott Diabetes, Speaker's Bureau; Sanofi, Lilly. Hypo-resolve consortium: n/a. P.Divilly: None. N.Zaremba: None. U.Soeholm: Employee; Novo Nordisk A/S. A.Kingsnorth: None. Z.Mahmoudi: Employee; Novo Nordisk. M.Gomes: Employee; Novo Nordisk A/S. B.E.De galan: Research Support; Novo Nordisk. U.Pedersen-bjergaard: Advisory Panel; Novo Nordisk A/S, Sanofi, Vertex Pharmaceuticals Incorporated. Funding Innovative Medicines Initiative 2 Joint Undertaking (777460)
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