Background: The Clarke Questionnaire (CQ) determines the perception of hypoglycemia symptoms, and a score ?4 detects patients with Hypoglycemia unawareness (HU). Evidence regarding the association between Continuous Glucose Monitoring (CGM) metrics and the CQ score is limited.
Purpose: To describe the association between the CQ score and CGM metrics in patients diagnosed with diabetes treated with insulin at high risk of hypoglycemia.
Methodology: A cross-sectional study in adult patients with diabetes diagnostic, treated with insulin and a history of severe hypoglycemia or risk factors for hypoglycemia unawareness (HU). Firstly, Baseline demographic, clinical, and Clarke score data were recorded; secondly, a professional CGM was performed for six days. Finally, CGM metrics were compared for the groups with or without hypoglycemia unawareness, using different cut-off points (Clarke ? 4 and Clarke ? 3).
Results: 83 patients were included (median age 63 years old [IQR 53.5-70.5], DM2 63.9%, HbA1c 7.6±1.6%). The median of time in range (%TIR 70-180mg/dl) was 75% [RIC 63-92], time above range (%TAR>180mg/dl) was 15% [3-27], and the median time below range (%TBR< 70mg/dl) 3% (IQR 1-7). In patients with Clarke ?4 the %TIR was lower (Median 55[RIC 41-89] vs 77[RIC 68-92], p=0.05) at the expense of higher %TAR (Median 23[IQR 7-54] vs 15[IQR 3-16], p=0.15). No significant differences were found in %TBR<70mg/dl.
Conclusions: HU was associated with a lower %TIR between 70-180 mg/dL in a clinically and statistically significant way in patients using insulin with risk factors for hypoglycemia.
Martín-Timón I, Del Cañizo-Gómez FJ. Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes. 2015 jul. 10;6(7):912–926. https://doi.org/10.4239/wjd.v6.i7.912
Rubin NT, Seaquist ER, Eberly L, Kumar A, Mangia S, Öz G, et. al. Relationship Between Hypoglycemia Awareness Status on Clarke/Gold Methods and Counterregulatory Response to Hypoglycemia. J Endocr Soc. 2022 sep.;6(9):bvac107. https://doi.org/10.1210/jendso/bvac107
ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, et. al. 6. Glycemic Targets: Standards of Care in Diabetes-2023. Diabetes Care. 2023 jan. 1;46(Suppl 1):S97–S110. https://doi.org/10.2337/dc23-S006
Malone SK, Peleckis AJ, Grunin L, Yu G, Jang S, Weimer J, et. al. Characterizing Glycemic Control and Sleep in Adults with Long-Standing Type 1 Diabetes and Hypoglycemia Unawareness Initiating Hybrid Closed Loop Insulin Delivery. J Diabetes Res. 2021;2021:6611064. https://doi.org/10.1155/2021/6611064
Huang B, Jiang Q, Wu T, Shen Q, Wang W, Wang S, et. al. Hypoglycemia unawareness identified by continuous glucose monitoring system is frequent in outpatients with type 2 diabetes without receiving intensive therapeutic interventions. Diabetol Metab Syndr. 2022 nov.;14:180. https://doi.org/10.1186/s13098-022-00959-x
The International Hypoglycaemia Study Group. Hypoglycaemia, cardiovascular disease, and mortality in diabetes: epidemiology, pathogenesis, and management. Lancet Diabetes Endocrinol. 2019 may.;7(5):385–96. https://doi.org/10.1016/S2213-8587(18)30315-2
Rehni AK, Dave KR. Impact of Hypoglycemia on Brain Metabolism During Diabetes. Mol Neurobiol. 2018 dec.;55(12):9075–9088. https://doi.org/10.1007/s12035-018-1044-6
Vieira IH, Barros LM, Baptista CF, Melo M, Rodrigues DM, Paiva IM. Hypoglycemia unawareness in type 1 diabetes patients using intermittent continuous glucose monitoring: Identification of risk factors and glycemic patterns. Diabetes Metab Syndr. 2022 jun.;16(6):102525. https://doi.org/10.1016/j.dsx.2022.102525
van Meijel LA, de Vegt F, Abbink EJ, Rutters F, Schram MT, van der Klauw MM, et. al. High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes: The Dutch Diabetes Pearl Cohort. BMJ open diabetes Res care. 2020 feb;8:e000935. https://doi.org/10.1136/bmjdrc-2019-000935
Takagi S, Miura J, Takita M, Mochizuki S, Asanuma T, Hoshina S, et. al. Factors associated with hypoglycemia unawareness and severe hypoglycemia in type?1 diabetes mellitus patients. J Diabetes Investig. 2022 dec.;13(12):2018–2026. https://doi.org/10.1111/jdi.13886
Jansa M, Quirós C, Giménez M, Vidal M, Galindo M, Conget I. Psychometric analysis of the Spanish and Catalan versions of a questionnaire for hypoglycemia awareness. Med Clin (Barc). 2015 may 21;144(10):440–444. https://doi.org/10.1016/j.medcle.2015.12.012
Clarke WL, Cox DJ, Gonder-Frederick LA, Julian D, Schlundt D, Polonsky W. Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care. 1995 apr. 1;18(4):517–522. https://doi.org/10.2337/diacare.18.4.517
De Mesa U, Anonuevo-Cruz MC, Nicodemus NJ, Reyes NG. Development and Validation of a Questionnaire Evaluating Impaired Hypoglycemia Awareness among Adult Filipino Patients with Type 2 Diabetes Mellitus. J ASEAN Fed Endocr Soc. 2017;32(2):158–164. https://doi.org/10.15605/jafes.032.02.10
Gómez AM, Imitola A, Henao D, García-Jaramillo M, Giménez M, Viñals C, et. al. Factors associated with clinically significant hypoglycemia in patients with type 1 diabetes using sensor-augmented pump therapy with predictive low-glucose management: A multicentric study on iberoamerica. Diabetes Metab Syndr. 2021 jan.-feb.;15(1):267–272. https://doi.org/10.1016/j.dsx.2021.01.002
Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–383. https://doi.org/10.1016/0021-9681(87)90171-8
Amiel SA. The consequences of hypoglycaemia. Diabetologia. 2021 feb. 7;64(5):963–970. https://doi.org/10.1007/s00125-020-05366-3
Bergenstal RM, Beck RW, Close KL, Grunberger G, Sacks DB, Kowalski A, et. al. Glucose Management Indicator (GMI): A New Term for Estimating A1C From Continuous Glucose Monitoring. Diabetes Care. 2018 nov.;41(11):2275–2280. https://doi.org/10.2337/dc18-1581
Battelino T, Danne T, Bergenstal RM, Amiel SA, Beck R, Biester T, et. al. Clinical targets for continuous glucose monitoring data interpretation: Recommendations from the international consensus on time in range. Diabetes Care. 2019 aug.;42(8):1593–1603. https://doi.org/10.2337/dci19-0028
Lu J, Ma X, Zhou J, Zhang L, Mo Y, Ying L, et. al. Association of Time in Range, as Assessed by Continuous Glucose Monitoring, With Diabetic Retinopathy in Type 2 Diabetes. Diabetes Care. 2018 nov.;41(11):2370–2376. https://doi.org/10.2337/dc18-1131
Yang J, Yang X, Zhao D, Wang X, Wei W, Yuan H. Association of time in range, as assessed by continuous glucose monitoring, with painful diabetic polyneuropathy. J Diabetes Investig. 2021 may;12(5):828–836. https://doi.org/10.1111/jdi.13394
Lu J, Ma X, Shen Y, Wu Q, Wang R, Zhang L, et. al. Time in Range Is Associated with Carotid Intima-Media Thickness in Type 2 Diabetes. Diabetes Technol Ther. 2020 jan. 22;22(2):72–78. https://doi.org/10.1089/dia.2019.0251
Lu J, Wang C, Shen Y, Chen L, Zhang L, Cai J, et al. Time in Range in Relation to All-Cause and Cardiovascular Mortality in Patients With Type 2 Diabetes: A Prospective Cohort Study. Diabetes Care. 2021 feb;44(2):549–555. https://doi.org/10.2337/dc20-1862
Khunti K, Alsifri S, Aronson R, Cigrovski Berkovi? M, Enters-Weijnen C, Forsén T, et. al. Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes. Diabetes Res Clin Pract. 2017 aug.;130:121–129. https://doi.org/10.1016/j.diabres.2017.05.004
Silbert R, Salcido-Montenegro A, Rodriguez-Gutierrez R, Katabi A, McCoy RG. Hypoglycemia Among Patients with Type 2 Diabetes: Epidemiology, Risk Factors, and Prevention Strategies. Curr Diab Rep. 2018 jun 21;18(8):53. https://doi.org/10.1007/s11892-018-1018-0
Goldenberg RM, Aroda VR, Billings LK, Christiansen ASL, Meller Donatsky A, Parvaresh Rizi E, et al. Effect of insulin degludec versus insulin glargine U100 on time in range: SWITCH PRO, a crossover study of basal insulin-treated adults with type 2 diabetes and risk factors for hypoglycaemia. Diabetes Obes Metab. 2021 nov;23(11):2572–2581. https://doi.org/10.1111/dom.14504
Cheng A, Bailey TS, Mauricio D, Roussel R. Insulin glargine 300?U/mL and insulin degludec: A review of the current evidence comparing these two second-generation basal insulin analogues. Diabetes Metab Res Rev. 2020 apr.;36(7):e3329. https://doi.org/10.1002/dmrr.3329
Henao-Carrillo DC, Muñoz OM, Gómez AM, Rondón M, Colón C, Chica L, et al. Reduction of glycemic variability with Degludec insulin in patients with unstable diabetes. J Clin Transl Endocrinol. 2018 jun.;12:8–12. https://doi.org/10.1016/j.jcte.2018.03.003
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Copyright (c) 2023 Revista Colombiana de Endocrinología, Diabetes & Metabolismo