Risk factors contributing to hypoglycemia among diabetes mellitus patients: a systematic review and meta-analysis 10.55131/jphd/2025/230223
Article Sidebar
Main Article Content
Abstract
Hypoglycemia is a dangerous, life-threatening condition affecting various populations, specifically diabetes mellitus (DM) patients. The condition has been reported to be influenced by several factors, such as gender, age, and body mass index (BMI). However, previous studies exploring these factors have yielded varying results, indicating the need for further investigations. This study aimed to identify factors contributing to hypoglycemia among DM patients through a systematic review and meta-analysis. The study procedures were carried out using PRISMA 2020 statement review reporting standards. In addition, a literature search was performed on four databases, including Pubmed, Scopus, Google Scholar, and Crossref, using Publish or Perish version 8 software. After the search, a total of 12 original articles were obtained based on the eligibility criteria. The results showed that eight factors significantly contributed to incidence of hypoglycemia, including elderly (OR 11.05; CI95%: 9.20-13.27), insulin use (OR 5.60; CI95%: 4.66-6.74), uncontrolled blood glucose (OR 4.07; CI95%: 3.41-4.85), have history of hypoglycemia (OR 3.52; CI95%: 2.27-5.45), overweight/obese (OR 2.63; CI95%: 1.89-3.64), sulfonylurea use (OR 1.98; CI95%: 1.37-2.85), longer DM duration (OR 1.29; CI95%: 1.20-1.38), and male gender (OR 1.31; CI95%: 1.21-1.42). Based on the results, the eight influential factors could be categorized into three domains, including medication-related hypoglycemia, non-modifiable medical conditions, and lifestyle-related hypoglycemia.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Nakhleh A, Shehadeh N. Hypoglycemia in Diabetes: An Update on Pathophysiology, Treatment, and Prevention. World J Diabetes. 2021;12(1):2036–2049. doi: 10.4239/wjd.v12.i12.2036
Foster NC, Beck RW, Miller KM, Clements MA, Rickels MR, DiMeglio LA, et al. State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016–2018. Diabetes Technol Ther. 2019;21(1): 66–72. doi: 10.1089/dia.2018.0384
ADVANCE Collaborative Group; Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, et al. Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes. NEJM. 2008;358(1): 2560–72. doi: 10.1056/NEJMoa 0802987
Lipska KJ, Yao X, Herrin J, McCoy RG, Ross JS, Steinman MA, et al. Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006–2013. Diabetes Care. 2017;40:468–75. doi: 10.2337/ dc16-0985
Lo CK, Mertz D, Loeb M. Newcastle-Ottawa Scale: Comparing Reviewers’ to Authors’ Assessments. BMC Med Res Methodol. 2014;1:14-45. doi: 10.1186/1471-2288-14-45
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. PLoS Med. 2021; 18(3):e1003583. doi: 10.1371/journal. pmed.1003583
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. BMJ (Clinical research ed.). 2021;372:n71. doi: 10.1136/bmj.n71
Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews. Int J Surg. 2021; 88:105906. doi: 10.1016/j.ijsu.2021. 105906
Miller CD, Phillips LS, Ziemer DC, Gallina DL, Cook CB, El-Kebbi IM. Hypoglycemia in Patients With Type 2 Diabetes Mellitus Arch Intern Med. 2001;161(13):1653-9. doi: 10.1001/ archinte.161.13.1653
Maynard GA, Huynh MP, Renvall M. Iatrogenic Inpatient Hypoglycemia: Risk Factors, Treatment, and Prevention. Diabetes Spectr. 2008; 21:241–247.
Quilliam BJ, Simeone JC, Ozbay AB. Risk Factors for Hypoglycemia-Related Hospitalization in Patients With Type 2 Diabetes: A Nested Case–Control Study. Clin Ther 2011;33(11): 1781–91. doi: 10.1016/j.clinthera. 2011.09.020
Davis TM, Brown SG, Jacobs IG, Bulsara M, Bruce DG, Davis WA. Determinants of Severe Hypoglycemia Complicating Type 2 Diabetes: The Fremantle Diabetes Study. J Clin Endocrinol Metab. 2010;95(5):2240–47. doi: 10.1210/jc.2009-2828
Bramlage P, Gitt AK, Binz C, Krekler M, Deeg E, Tschöpe D. Oral Antidiabetic Treatment in Type-2 Diabetes in the Elderly: Balancing the Need for Glucose Control and the Risk of Hypoglycemia. Cardiovasc Diabetol. 2012;11:122. doi: 10.1186/ 1475-2840-11-122
Kong AP, Yang X, Luk A, Ma RC, So WY, Ozaki R, et al. Severe Hypoglycemia Identifies Vulnerable Patients With Type 2 Diabetes at Risk for Premature Death and All-Site Cancer: The Hong Kong Diabetes Registry. Diabetes Care. 2014;37(4): 1024–31. doi: 10.2337/dc13-2507
Akirov A, Amitai O, Masri-Iraqi H, Diker-Cohen T, Shochat T, Eizenberg Y, et al. Predictors of Hypoglycemia in Hospitalized Patients with Diabetes Mellitus. IEM. 2018;13(3):343–350. doi: 10.1007/s11739-018-1787-0
Li TC, Li CI, Liu CS, Lin WY, Lin CH, Yang SY, et al. Development and Validation of Prediction Models for the Risks of Diabetes-Related Hospitalization and in-Hospital Mortality in Patients with Type 2 Diabetes. Metabolism. 2018;85:38–47. doi: 10.1016/j.metabol.2018. 02.003
Yunir E, Nugraha ARA, Rosana M, Kurniawan J, Iswati E, Sarumpaet A, et al. Risk Factors of Severe Hypoglycemia among Patients with Type 2 Diabetes Mellitus in Outpatient Clinic of Tertiary Hospital in Indonesia. Sci Rep. 2023;13(1):16259. doi: 10.1038/s41598-023-43459-2
Pratiwi C, Rumende M, Kshanti IAM, Soewondo P. Risk Factors for Inpatient Hypoglycemia in a Tertiary Care Hospital in Indonesia. J ASEAN Fed Endocr Soc. 2022;37(2):28–33. doi: 10.15605/jafes.037.02.06
Bakar A, Qomariah SN, Santoso CH, Gustomi MP, Syaful Y, Fatmawa L. Factors the Incidence of Hypoglycemia in Diabetes Mellitus Patients: A Pilot Study in the Emergency Room. Enferm Clin. 2020; 30:46–49.
AlKhaldi YM, AlKhaldi AY, AlQahtani AS, Al-Shahrani BS, Meshawi EA, Albishri BM. Incidence of hypoglycemia and its risk factors among diabetics during Ramadan in Abha city, Aseer Region, KSA. J Family Med Prim Care. 2019;8(9): 2793-2798. doi: 10.4103/jfmpc. jfmpc_250_19
Heianza Y, Hara S, Arase Y, Saito K, Fujiwara K, Tsuji H, et al. HbA1c 5·7-6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study. Lancet. 2011; 378(9786):147-55. doi: 10.1016/ S0140-6736(11)60472-8
Yeboah J, Bertoni AG, Herrington DM, Post WS, Burke GL. Impaired Fasting Glucose and the Risk of Incident Diabetes Mellitus and Cardiovascular Events in an Adult Population. J Am Coll Cardiol. 2011; 58(2):140–46. doi: 10.1016/j.jacc. 2011.03.025
Richter B, Hemmingsen B, Metzendorf MI, Takwoingi Y. Intermediate Hyperglycaemia as a Predictor for the Development of Type 2 Diabetes: Prognostic Factor Exemplar Review. CDSR. 2017.1: 012661.
Thrasher J. Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies. Am J Med. 2017;130(6S):S4–S17. doi: 10.1016/j.amjmed.2017.04.004
West MP. Acute Care Setting. In Acute Care Handbook for Physical Therapists. Elsevier. 2014;1:1–9.
Jaya MKA, Endarti D, Kartika IGAA, Veryanti PR, Swastini DA. The Role Of Medication Reminder Technology As An Enhancement Of Patient Compliance. Int J Pharm Res. 2020; 12(1):418-427. doi: 10.31838/ijpr/ 2020.SP1.052
World Health Organization. The Top 10 Causes of Death [Internet]. [Cited 2023 November 22]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death.
Lu CL, Hsu PC, Shen HN, Chang YH, Chen HF, Li CY. Association Between History of Severe Hypoglycemia and Risk of Falls in Younger and Older Patients With Diabetes. Medicine (Baltimore). 2015;94(33):e1339. doi: 10.1097/MD.0000000000001339
McCoy RG, Van Houten HK, Ziegenfuss JY, Shah ND, Wermers RA, Smith SA. Increased Mortality of Patients With Diabetes Reporting Severe Hypoglycemia. Diabetes Care. 2012;35(9):1897–1901. doi: 10.2337/ dc11-2054
Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, et al. Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society. Diabetes Care. 2013;36(5):1384–95. doi: 10.2337/ dc12-2480
Pratley RE, Kanapka LG, Rickels MR, Ahmann A, Aleppo G, Beck R, et al. Effect of Continuous Glucose Monitoring on Hypoglycemia in Older Adults With Type 1 Diabetes. JAMA. 2020;323(23):2397-2406. doi: 10.1001/jama.2020.6928
International Hypoglycaemia Study Group. Minimizing Hypoglycemia in Diabetes. Diabetes Care. 2015;38(8):1583-91. doi: 10.2337/ dc15-0279.
Farland MZ, Byrd DC, McFarland MS, Thomas J, Franks AS, George CM, et al. Pharmacist-Physician Collaboration for Diabetes Care: The Diabetes Initiative Program. Ann Pharmacother. 2013;47(6):781–789. doi: 10.1345/aph.1S079
Pristianty L, Abdullah I, Rhamadan PZ, Hermansyah A. Assessment of Doctor-Pharmacist Collaboration in the Treatment of Diabetes Mellitus Patients at Airlangga University Hospital Surabaya from the Pharmacist’s Perspective. Pharm Educ. 2022;22:974–79.
Cowart K, Patel V, Bianco J, Martinez A, Castro J. Pharmacist-Physician Collaborative Practice to Improve Diabetes Care at Tampa General Medical Group. Clin Diabetes. 2022;40(2):240–244. doi: 10.2337/ cd21-0080
Ikeda Y, Kubo T, Oda E, Abe M, Tokita S. Incidence rate and patient characteristics of severe hypoglycemia in treated type 2 diabetes mellitus patients in Japan: Retrospective Diagnosis Procedure Combination database analysis. J Diabetes Investig. 2018;9(4):925–936. doi: 10.1111/ jdi.12778
Min JY, Griffin MR, Hung AM, Grijalva CG, Greevy RA, Liu X, et al. Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes. J Gen Intern Med. 2016;31(6):638–646. doi: 10.1007/s11606-016-3633-2
Vos RC, van Avendonk MJ, Jansen H, Goudswaard AN, van den Donk M, Gorter K, et al. Insulin monotherapy compared with the addition of oral glucose-lowering agents to insulin for people with type 2 diabetes already on insulin therapy and inadequate glycaemic control. Cochrane Database Syst Rev. 2016;9(9): CD006992. doi: 10.1002/14651858. CD006992.pub2
Fu H, Xie W, Curtis B, Schuster D. Identifying factors associated with hypoglycemia-related hospitalizations among elderly patients with T2DM in the US: a novel approach using influential variable analysis. Curr Med Res Opin. 2014;30(9):1787–1793. doi: 10.1185/03007995.2014.922944
Mogensen UM, Andersson C, Fosbøl EL, Schramm TK, Vaag A, Scheller NM, et al. Sulfonylurea in combination with insulin is associated with increased mortality compared with a combination of insulin and metformin in a retrospective Danish nationwide study. Diabetologia. 2015;58(1):50–58. doi: 10.1007/ s00125-014-3372-z
von Elm E, Altman DG, Egger M, Pocock SJ, Gøtzsche PC, Vandenbroucke JP; STROBE Initiative. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Ann Intern Med. 2007; 147(8):573-7. doi: 10.7326/0003-4819-147-8-200710160-00010
Laelasari E, Sauriasari R, Banun A. Cost-Effectiveness Analysis of Insulin, Sulfonylurea, and Sulfonylurea–Metformin in Type 2 Diabetes Mellitus. Asian J Pharm Clin Res. 2017;10(5):50–53.
Sola D, Rossi L, Schianca GP, Maffioli P, Bigliocca M, Mella R, et al. Sulfonylureas and their use in clinical practice. Arch Med Sci. 2015;11(4): 840-8. doi: 10.5114/aoms.2015.53304
Laires P, Kurtyka K, Witt EA, Qiu Y, Yu S, Iglay K. Factors associated with physicians' decision to discontinue or down-titrate sulfonylureas for type 2 diabetes patients. Expert Rev Pharmacoecon Outcomes Res. 2019; 19(1):71-79. doi: 10.1080/14737167. 2018.1510774
Filion KB, Douros A, Azoulay L, Yin H, Yu OH, Suissa S. Sulfonylureas as initial treatment for type 2 diabetes and the risk of adverse cardiovascular events: A population-based cohort study. Br J Clin Pharmacol. 2019 Oct; 85(10):2378-2389. doi: 10.1111/bcp. 14056
Ratzki-Leewing A, Harris SB, Mequanint S, Reichert SM, Belle Brown J, Black JE, et al. Real-world crude incidence of hypoglycemia in adults with diabetes: Results of the InHypo-DM Study, Canada. BMJ Open Diabetes Res Care. 2018;6(1): e000503. doi: 10.1136/bmjdrc-2017-000503
O’Brien BC, Harris IB, Beckman TJ, Reed DA, Cook DA. Standards for Reporting Qualitative Research. Acad Med. 2014;89(9):1245-1251. doi: 10.1097/ACM.0000000000000388
Kimura Y, Kimura N, Akazawa M. Nutrition‐related risk and severe hypoglycemia in older adult outpatients with and without diabetes. Clin Case Reports. 2022;10(1): e05317. doi: 10.1002/ccr3.5317.
Alwafi H, Alsharif AA, Wei L, Langan D, Naser AY, Mongkhon P, et al. Incidence and prevalence of hypoglycemia in type 1 and type 2 diabetes individuals: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2020;170:108522. doi: 10.1016/j.diabres.2020.108522
Frier BM. Hypoglycemia in diabetes mellitus: epidemiology and clinical implications. Nat Rev Endocrinol. 2014;10(12):711-722. doi: 10.1038/ nrendo.2014.170
Iwahori T, Snoek F, Nagai Y, Spaepen E, Mitchell BD, Peyrot M. Conversations and Reactions Around Severe Hypoglycemia (CRASH): Japan Results From a Global Survey of People with T1DM or Insulin-Treated T2DM and Caregivers. Diabetes Ther. 2022;13(3):517-533. doi: 10.1007/ s13300-022-01211-5
