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Acta Diabetologica

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18-05-2023 | Insulins | Review Article

Prevalence and contributing factors of impaired awareness of hypoglycemia in patients with type 2 diabetes: a meta-analysis

Authors: Xiang-Ning Li, Yin-Shi Kan, Hong-Yuan Liu, Juan Pang, Yu-Ying He, Lin Liu, Yan Zou, Ning Zhang, Yu Zhang

Published in: Acta Diabetologica | Issue 9/2023

Abstract

Aims

To conduct a systematic review to summarize the definition, measurement tools, prevalence, and contributing factors of impaired awareness of hypoglycemia (IAH) in type 2 diabetes mellitus (T2DM).

Methods

A reproducible search strategy was used to identify factors affecting IAH in T2DM in PubMed, MEDLINE, EMBASE, Cochrane, PsycINFO, and CINAHL from inception until 2022. Literature screening, quality evaluation, and information extraction were performed independently by 2 investigators. A meta-analysis of prevalence was performed using Stata 17.0.

Results

The pooled prevalence of IAH in patients with T2DM was 22% (95%CI:14–29%). Measurement tools included the Gold score, Clarke’s questionnaire, and the Pedersen-Bjergaard scale. IAH in T2DM was associated with sociodemographic factors (age, BMI, ethnicity, marital status, education level, and type of pharmacy patients visited), clinical disease factors (disease duration, HbAlc, complications, insulin therapy regimen, sulfonylureas use, and the frequency and severity of hypoglycemia), and behavior and lifestyle (smoking and medication adherence).

Conclusion

The study found a high prevalence of IAH in T2DM, with an increased risk of severe hypoglycemia, suggesting that medical workers should take targeted measures to address sociodemographic factors, clinical disease, and behavior and lifestyle to reduce IAH in T2DM and thus reduce hypoglycemia in patients.

IDF Diabetes Atlas | Tenth Edition. https://diabetesatlas.org/. Accessed 14 Feb 2022

Balijepalli C, Druyts E, Siliman G et al (2017) Hypoglycemia: a review of definitions used in clinical trials evaluating antihyperglycemic drugs for diabetes. Clin Epidemiol 9:291–296. https://doi.org/10.2147/CLEP.S129268CrossRefPubMedPubMedCentral

Dolan C, Glynn R, Lawlor B (2020) A systematic review and delphi study to ascertain common risk factors for type 2 diabetes mellitus and dementia and brain-related complications of diabetes in adults. Can J Diabetes 44:628–635. https://doi.org/10.1016/j.jcjd.2020.01.004CrossRefPubMed

Graveling AJ, Frier BM (2010) Impaired awareness of hypoglycaemia: a review. Diabetes Metab 36(Suppl 3):S64-74. https://doi.org/10.1016/S1262-3636(10)70470-5CrossRefPubMed

Gerich JE, Mokan M, Veneman T et al (1991) Hypoglycemia unawareness. Endocr Rev 12:356–371. https://doi.org/10.1210/edrv-12-4-356CrossRefPubMed

Gold AE, MacLeod KM, Frier BM (1994) Frequency of severe hypoglycemia in patients with type I diabetes with impaired awareness of hypoglycemia. Diabetes Care 17:697–703. https://doi.org/10.2337/diacare.17.7.697CrossRefPubMed

Cryer PE (2015) Hypoglycemia-associated autonomic failure in diabetes: maladaptive, adaptive, or both? Diabetes 64:2322–2323. https://doi.org/10.2337/db15-0331CrossRefPubMedPubMedCentral

Stantonyonge N, Sampedro F, Méndez J et al (2021) Structural gray and white matter differences in patients with type 1 diabetes and impaired awareness of hypoglycemia. J Clin Endocrinol Metab 106:450–458. https://doi.org/10.1210/clinem/dgaa832CrossRefPubMed

Alkhatatbeh MJ, Abdalqader NA, Alqudah MAY (2019) Impaired awareness of hypoglycaemia in insulin-treated type 2 diabetes mellitus. Curr Diabetes Rev 15:407–413. https://doi.org/10.2174/1573399814666180806144937CrossRefPubMed

10.

Farrell CM, McCrimmon RJ (2021) Clinical approaches to treat impaired awareness of hypoglycaemia. Ther Adv Endocrinol Metab 12:20420188211000250. https://doi.org/10.1177/20420188211000248CrossRefPubMedPubMedCentral

11.

Lamounier RN, Geloneze B, Leite SO et al (2018) Hypoglycemia incidence and awareness among insulin-treated patients with diabetes: the HAT study in Brazil. Diabetol Metab Syndr 10:83. https://doi.org/10.1186/s13098-018-0379-5CrossRefPubMedPubMedCentral

12.

Rondags SMPA, de Wit M, van Tulder MW et al (2015) HypoAware-a brief and partly web-based psycho-educational group intervention for adults with type 1 and insulin-treated type 2 diabetes and problematic hypoglycaemia: design of a cost-effectiveness randomised controlled trial. BMC Endocr Disord 15:43. https://doi.org/10.1186/s12902-015-0035-0CrossRefPubMedPubMedCentral

13.

van Meijel LA, de Vegt F, Abbink EJ et al (2020) 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 8:e000935. https://doi.org/10.1136/bmjdrc-2019-000935CrossRefPubMedPubMedCentral

14.

Schopman JE, Geddes J, Frier BM (2010) Prevalence of impaired awareness of hypoglycaemia and frequency of hypoglycaemia in insulin-treated type 2 diabetes. Diabetes Res Clin Pract 87:64–68. https://doi.org/10.1016/j.diabres.2009.10.013CrossRefPubMed

15.

Cabré C, Colungo C, Vinagre I et al (2020) Frequency and awareness of hypoglycemia in patients with Type 2 Diabetes treated with two or more insulin injections in primary care outpatient clinics. Prim Care Diabetes 14:168–172. https://doi.org/10.1016/j.pcd.2019.08.001CrossRefPubMed

16.

Zhu L, Ang LC, Tan WB et al (2017) A study to evaluate the prevalence of impaired awareness of hypoglycaemia in adults with type 2 diabetes in outpatient clinic in a tertiary care centre in Singapore. Ther Adv Endocrinol Metab 8:69–74. https://doi.org/10.1177/2042018817707422CrossRefPubMedPubMedCentral

17.

Gomez-Peralta F, Fornos Pérez JA, Molinero A et al (2021) Adherence to antidiabetic treatment and impaired hypoglycemia awareness in type 2 diabetes mellitus assessed in Spanish community pharmacies: the ADHIFAC study. BMJ Open Diabetes Res Care 9:e002148. https://doi.org/10.1136/bmjdrc-2021-002148CrossRefPubMedPubMedCentral

18.

Dømgaard M, Bagger M, Rhee NA et al (2015) Individual and societal consequences of hypoglycemia: A cross-sectional survey. Postgrad Med 127:438–445. https://doi.org/10.1080/00325481.2015.1045815CrossRefPubMed

19.

van Beers CAJ, de Wit M, Kleijer SJ et al (2017) Continuous glucose monitoring in patients with type 1 diabetes and impaired awareness of hypoglycemia: also effective in patients with psychological distress? Diabetes Technol Ther 19:595–599. https://doi.org/10.1089/dia.2017.0141CrossRefPubMed

20.

Shen Z, Xu J, Yin W et al (2022) Common Sense Model program on illness perceptions in patients with impaired awareness of hypoglycemia. Contemp Nurse. https://doi.org/10.1080/10376178.2022.2071311CrossRefPubMed

21.

Przezak A, Bielka W, Molęda P (2022) Fear of hypoglycemia—An underestimated problem. Brain Behav 12:e2633. https://doi.org/10.1002/brb3.2633CrossRefPubMedPubMedCentral

22.

Anderbro T, Gonder-Frederick L, Bolinder J et al (2015) Fear of hypoglycemia: relationship to hypoglycemic risk and psychological factors. Acta Diabetol 52:581–589. https://doi.org/10.1007/s00592-014-0694-8CrossRefPubMed

23.

Fidler C, Elmelund Christensen T, Gillard S (2011) Hypoglycemia: an overview of fear of hypoglycemia, quality-of-life, and impact on costs. J Med Econ 14:646–655. https://doi.org/10.3111/13696998.2011.610852CrossRefPubMed

24.

Berlin I, Sachon CI, Grimaldi A (2005) Identification of factors associated with impaired hypoglycaemia awareness in patients with type 1 and type 2 diabetes mellitus. Diabetes Metab 31:246–251. https://doi.org/10.1016/s1262-3636(07)70191-xCrossRefPubMed

25.

Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 6:e1000097. https://doi.org/10.1371/journal.pmed.1000097CrossRefPubMedPubMedCentral

26.

The Joanna Briggs Institute Critical Appraisal tools. https://www.academia.edu/49208033/The_Joanna_Briggs_Institute_Critical_Appraisal_tools_for_use_in_JBI_Systematic_Reviews_Checklist_for_Analytical_Cross_Sectional_Studies. Accessed 31 Oct 2022

27.

He J, Chen X, Wang Y et al (2021) The experiences of pregnant women with gestational diabetes mellitus: a systematic review of qualitative evidence. Rev Endocr Metab Disord 22:777–787. https://doi.org/10.1007/s11154-020-09610-4CrossRefPubMed

28.

Liberali R, Del Castanhel F, Kupek E, de Assis MAA (2021) Latent Class Analysis of Lifestyle Risk Factors and Association with Overweight and/or Obesity in Children and Adolescents: Systematic Review. Child Obes Print 17:2–15. https://doi.org/10.1089/chi.2020.0115CrossRef

29.

Cryer PE (1990) Human insulin and hypoglycemia unawareness. Diabetes Care 13:536–538. https://doi.org/10.2337/diacare.13.5.536CrossRefPubMed

30.

Clarke WL, Cox DJ, Gonder-Frederick LA et al (1995) Reduced awareness of hypoglycemia in adults with IDDM. A prospective study of hypoglycemic frequency and associated symptoms. Diabetes Care 18:517–522. https://doi.org/10.2337/diacare.18.4.517CrossRefPubMed

31.

Pedersen-Bjergaard U, Pramming S, Thorsteinsson B (2003) Recall of severe hypoglycaemia and self-estimated state of awareness in type 1 diabetes. Diabetes Metab Res Rev 19:232–240. https://doi.org/10.1002/dmrr.377CrossRefPubMed

32.

Martín-Timón I, del Cañizo-Gómez FJ (2015) Mechanisms of hypoglycemia unawareness and implications in diabetic patients. World J Diabetes 6:912–926. https://doi.org/10.4239/wjd.v6.i7.912CrossRefPubMedPubMedCentral

33.

Long C, Dungan K (2020) Hypoglycemia awareness and burden among hospitalized patients at high risk for hypoglycemia. J Diabetes Complications 34:107521. https://doi.org/10.1016/j.jdiacomp.2019.107521CrossRefPubMed

34.

Besen DB, Surucu HA, Koşar C (2016) Self-reported frequency, severity of, and awareness of hypoglycemia in type 2 diabetes patients in Turkey. PeerJ. https://doi.org/10.7717/peerj.2700CrossRef

35.

Amin A, Lau L, Crawford S et al (2015) Prospective assessment of hypoglycemia symptoms in children and adults with type 1 diabetes. Can J Diabetes 39(Suppl 4):26–31. https://doi.org/10.1016/j.jcjd.2015.09.086CrossRefPubMed

36.

Seaquist ER, Anderson J, Childs B et al (2013) Hypoglycemia and diabetes: a report of a workgroup of the american diabetes association and the endocrine society. J Clin Endocrinol Metab 98:1845–1859. https://doi.org/10.1210/jc.2012-4127CrossRefPubMed

37.

Bremer JP, Jauch-Chara K, Hallschmid M et al (2009) Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care 32:1513–1517. https://doi.org/10.2337/dc09-0114CrossRefPubMedPubMedCentral

38.

Cheng PC, Hsu SR, Tu ST et al (2018) Body mass index influences the plasma glucose concentration during iatrogenic hypoglycemia in people with type 2 diabetes mellitus: a cross-sectional study. PeerJ 6:e4348. https://doi.org/10.7717/peerj.4348CrossRefPubMedPubMedCentral

39.

Amiel SA, Choudhary P, Jacob P et al (2019) Hypoglycaemia awareness restoration programme for people with type 1 diabetes and problematic hypoglycaemia persisting despite optimised self-care (HARPdoc): protocol for a group randomised controlled trial of a novel intervention addressing cognitions. BMJ Open 9:e030356. https://doi.org/10.1136/bmjopen-2019-030356CrossRefPubMedPubMedCentral

40.

Nicolucci A, Prosperini G, Buzzetti R et al (2018) A multistep approach for the stratification of the risk of severe hypoglycemia in patients with type 2 diabetes. Minerva Endocrinol 43:501–510. https://doi.org/10.23736/S0391-1977.18.02850-XCrossRefPubMed

41.

Hsu P-F, Sung S-H, Cheng H-M et al (2013) Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study. Diabetes Care 36:894–900. https://doi.org/10.2337/dc12-0916CrossRefPubMedPubMedCentral

42.

Khunti K, Davies M, Majeed A et al (2015) Hypoglycemia and risk of cardiovascular disease and all-cause mortality in insulin-treated people with type 1 and type 2 diabetes: a cohort study. Diabetes Care 38:316–322. https://doi.org/10.2337/dc14-0920CrossRefPubMed

43.

Afroz A, Chowdhury HA, Shahjahan M et al (2016) Association of good glycemic control and cost of diabetes care: experience from a tertiary care hospital in Bangladesh. Diabetes Res Clin Pract 120:142–148. https://doi.org/10.1016/j.diabres.2016.07.030CrossRefPubMed

44.

Wang R, Ye H, Zhao Y et al (2022) Effect of sacubitril/valsartan and ACEI/ARB on glycaemia and the development of diabetes: a systematic review and meta-analysis of randomised controlled trials. BMC Med 20:487. https://doi.org/10.1186/s12916-022-02682-wCrossRefPubMedPubMedCentral

45.

Tian B, Deng Y, Cai Y et al (2022) Efficacy and safety of combination therapy with sodium-glucose cotransporter 2 inhibitors and renin-angiotensin system blockers in patients with type 2 diabetes: a systematic review and meta-analysis. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 37:720–729. https://doi.org/10.1093/ndt/gfab048CrossRef

46.

Almigbal TH (2021) Association between knowledge of hypoglycemia and likelihood of experiencing hypoglycemia among patients with insulin-treated diabetes mellitus. Diabetes Metab Syndr Obes Targets Ther 14:3821–3829. https://doi.org/10.2147/DMSO.S327368CrossRef

47.

Silbert R, Salcido-Montenegro A, Rodriguez-Gutierrez R et al (2018) Hypoglycemia among patients with type 2 diabetes: epidemiology, risk factors, and prevention strategies. Curr Diab Rep 18:53. https://doi.org/10.1007/s11892-018-1018-0CrossRefPubMedPubMedCentral

48.

Nicolucci A, Pintaudi B, Rossi MC et al (2015) The social burden of hypoglycemia in the elderly. Acta Diabetol 52:677–685. https://doi.org/10.1007/s00592-015-0717-0CrossRefPubMed

49.

Cryer PE, Haymond MW, Santiago JV, Shah SD (1976) Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med 295:573–577. https://doi.org/10.1056/NEJM197609092951101CrossRefPubMed

50.

Patel S, Abreu M, Tumyan A et al (2019) Effect of medication adherence on clinical outcomes in type 2 diabetes: analysis of the SIMPLE study. BMJ Open Diabetes Res Care 7:e000761. https://doi.org/10.1136/bmjdrc-2019-000761CrossRefPubMedPubMedCentral

51.

Meng J, Casciano R, Lee Y-C et al (2017) Effect of Diabetes Treatment-Related Attributes on Costs to Type 2 Diabetes Patients in a Real-World Population. J Manag Care Spec Pharm 23:446–452. https://doi.org/10.18553/jmcp.2017.23.4.446CrossRefPubMed

Title: Prevalence and contributing factors of impaired awareness of hypoglycemia in patients with type 2 diabetes: a meta-analysis
Authors: Xiang-Ning Li
Yin-Shi Kan
Hong-Yuan Liu
Juan Pang
Yu-Ying He
Lin Liu
Yan Zou
Ning Zhang
Yu Zhang
Publication date: 18-05-2023
Publisher: Springer Milan
Keywords: Insulins
Hypoglycemia
Diabetes
Insulins
Type 2 Diabetes
Published in: Acta Diabetologica / Issue 9/2023
Print ISSN: 0940-5429
Electronic ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-023-02102-2

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