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. 2022 Nov 1;17(11):e0275786. doi: 10.1371/journal.pone.0275786

Hypoglycemia prevention practice and associated factors among diabetes mellitus patients in Ethiopia: Systematic review and meta-analyssis

Tadele Lankrew Ayalew 1,*, Belete Gelaw Wale 2, Bitew Tefera Zewudie 3
Editor: José Luiz Fernandes Vieira4
PMCID: PMC9624414  PMID: 36318542

Abstract

Background

Hypoglycemia is an urgent, life-threatening condition that requires prompt recognition and treatment for diabetes mellitus patients to prevent organ and brain damage. Hypoglycemia is one of the most important complications of diabetes mellitus patients around the globe. Hypoglycemia may increase vascular events and even death, in addition to other possible detrimental effects. In spite of the absence of other risk factors, patients receiving intensive insulin therapy are more likely to experience hypoglycemia. To reduce the risk of hypoglycemia and calculate the combined prevalence of hypoglycemia prevention practices among diabetes mellitus patients, recognition of hypoglycemia is critical.

Objective

The main aim of this review was to evaluate the available data on Ethiopian diabetes mellitus patients’ practices for preventing hypoglycemia and related factors.

Methods and materials

This review was searched using PubMed, the Cochrane Library, Google, Google Scholar, and the Web of Sciences. Microsoft Excel was used to extract the data. All statistical analyses were done using STATA Version 14 software with a random-effects model. The funnel plot and heterogeneity of the studies were checked. Subgroup analysis was done with the study area and authors’ names.

Results

In this systematic review, 12 studies totaling 3,639 participants were included. The estimated overall practice for preventing hypoglycemia among diabetic patients in Ethiopia were 48.33% (95% CI (28.21%, 68.46%, I2 = 99.7%, p ≤ 0.001). According to the subgroup analysis based on region, the highest estimated prevalence of the prevention practice of hypoglycemia among diabetes patients in Addis Ababa was 90%, followed by SNNRP at 76.18% and in the Amhara region at 68.31% respectively. The least prevalent was observed in the Oromia region 6.10%. In this meta-analysis, diagnoses with type II diabetes (AOR = 2.53, 95%CI: 1.05, 4.04), duration (AOR = 5.49, 95%CI:3.27,7.70), taking insulin for a long time(AOR = 4.31,95%CI:2.60,6.02), having good prevention knowledge (AOR = 2.89, 95%CI: 1.15,4.23), and occupation (AOR = 4.17, 95%CI: 2.20, 6.15) were significantly associated with hypoglycemia prevention practice.

Conclusions

This systematic review revealed that diabetic patients in Ethiopia had poor hypoglycemia prevention practices. Being an employee, taking insulin for a long time, having a good prevention practice, and having a type of diabetes mellitus were strongly correlated with practicing hypoglycemia prevention. This review implied the subsequent need for educational interventions for an individualized patient.

Introduction

Hypoglycemia is an emergency life-threatening condition that requires prompt recognition and treatment to prevent organ and brain damage [1]. Hypoglycemia is one of the most significant complications experienced by people with diabetes mellitus worldwide [2]. Hypoglycemia is defined as an abnormally low plasma glucose concentration (70 mg/dl); however, signs and symptoms may not appear until plasma glucose concentration drops below 55 mg/dl which exposes the patient to potential harm [1, 3]. Hypoglycemia is an acute medical situation that occurs when blood sugar falls below the recommended level [4]. Along with other potential negative consequences, hypoglycemia may increase vascular events, including death [5]. Despite the absence of additional risk factors, patients receiving intensive insulin therapy are at increased risk of hypoglycemia. Depending on how severe or long-lasting it is, hypoglycemia can result in serious morbidity or even death [6]. Hypoglycemia is thought to be the cause of death for 2–4 percent of people with diabetes mellitus. It could explain the "dead-in-bed syndrome," which refers to the mysterious deaths of type 1 diabetics that happen at night [4, 7]. The signs of low blood sugar levels can change over time and vary from person to person [8]. A person with low blood sugar may experience trembling, sweating, hunger, and anxiety in the early stages. Walking difficulties, weakness, visual disturbances, strange behavior, personality changes, confusion, and unconsciousness or seizures may all be seen as the symptoms worsen [9].

The high cost of hospitalization, frequent use of ambulances, and frequent emergency room visits caused by hypoglycemia place a significant financial strain on the healthcare system. Despite being widely acknowledged by patients and their healthcare professionals, hypoglycemia is now understood to be a significant and potentially curable cause of morbidity, mortality, high costs, decreased productivity, and poor quality of life [10]. The biggest factor that makes it challenging for diabetic patients to maintain their blood sugar levels within a normal range is hypoglycemia. It had a detrimental effect on work productivity, health care resource use, and quality of life. Dietary control, taking medications as prescribed at the right times, engaging in regular physical activity, and self-monitoring blood glucose levels are all part of the prevention of hypoglycemia. Patients with diabetes should also wear identification bracelets or tags properly [11].

For both type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, hypoglycemia affects patient safety and glycemic control during insulin therapy (T2DM). Because of its effects on the heart, blood vessels, eyes, kidneys, and nerves, diabetes mellitus is a leading cause of morbidity and mortality worldwide [12]. The risk of hypoglycemia is a barrier to optimal treatment of type 1 diabetes (T1DM) and type 2 diabetes (T2DM), especially in the context of insulin therapy, making blood glucose control optimization challenging [13]. The short-and long-term complications include neurologic damage, trauma, cardiovascular events, and death [14, 15]. Identification and prevention of hypoglycemia can lower the burden of diabetes by preventing hypoglycemia complications because severe untreated hypoglycemia can result in a significant economic and personal burden [1, 6, 16]. For diabetic patients, hypoglycemia is a fact of life [17]. All patients who take insulin have had hypoglycemic episodes in about 90% of cases. Hypoglycemia has been linked to between 2–4% of deaths in this population, according to estimates. The only way to determine whether a person is experiencing low blood glucose is to check blood glucose levels [18, 19].

Effective methods for lowering the risk of hypoglycemia include patient education and self-monitoring of blood glucose (SMBG), dietary changes, and regular exercise, medication alterations, careful glucose monitoring by the patient, and attentive clinician follow-up [1, 20, 21]. Additionally, Ethiopian diabetes patients should practice hypoglycemia prevention because it makes people more likely to have better habits. In a different study carried out in Ethiopia, 63.2% of participants practiced effective hypoglycemia prevention techniques. They suggested patient education as a tactic for improving the practice of hypoglycemia prevention [4, 16, 22]. Despite the fact that many studies on hypoglycemia prevention methods and awareness have been published, no estimated pooled studies have been conducted on practices and related factors regarding hypoglycemia prevention among diabetes mellitus patients in Ethiopia. Therefore, the purpose of this review was to evaluate the combined prevalence of prevention practices and related variables among patients with diabetes mellitus in Ethiopia.

Methods and materials

Study design and search strategy

We searched studies of hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia by using Google Scholar, African Journal online and MEDLINE, Pub Med, and Cochran Library, and Ethiopian University Repository online. We check the database at (http://www.library.ucsf.edu) and the Cochrane library to ensure this had not been done before and to avoid duplication. We also checked whether there was any similar ongoing systemic review and meta-analysis in the PROSPERO database registration message on CRD [287162]; reassured that there had been no previous similar studies undertaken. Studies published from 2015 to February 2022 were included in this review. The reference lists already identified were screened to retrieve articles. Articles were searched using MESH terms on the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia. We strictly follow Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) protocols to estimate the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia.

Eligibility criteria

Inclusion criteria

Eligible articles for this systematic review and meta-analysis were studies that assessed the prevention practice of hypoglycemia and associated factors among diabetic patients in Ethiopia, and studies that assessed factors associated with the prevention practice of hypoglycemia. It included participants who are living in Ethiopia, cross-sectional study design; studies published in the English language for data analysis were included.

Exclusion criteria

Articles were excluded if they were: studies were done outside of Ethiopia, case reports, RCT, and reviews. An attempt was made to contact the corresponding authors using the email address or phone number as provided in the published articles.

Data extraction and quality assessment

The parameters used in the data extraction template included the author’s name, sample size, study region, study design, year of publication, OR, and 95% CI. We gathered pertinent data from accepted articles using the typical Microsoft Excel spreadsheet. The authors (BG, TL, and BT) carried out data extraction from the included articles independently. Disputes were settled through discussion and agreement with the other authors. After summarizing the relevant articles in the table and performing a critical analysis using the Joanna Brings Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MASTER), the studies that met the eligibility requirements were included. Joanna found studies, and their titles and abstracts were used to determine whether they should be included. Before choosing for the final review, each article was reviewed for quality. Studies with a quality assessment indicator score of seven or higher were deemed low risk (Table 1). Discussions with other reviewers helped resolve any disagreements that arose between them during the review process.

Table 1. Critical appraisal results of eligible studies in the systematic review and meta-analysis on the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia, 2022.

Authors Q1 Q2 Q3 Q4 Q5 Q6 Q7 Q8 Q9 Total
Esileman A. et al Y Y Y Y Y N Y Y Y 8
Gashayeneh G., et al Y N Y Y Y Y Y Y Y 8
Gebrewahd B., et al Y Y Y Y Y Y Y U Y 8
Girma N., et al Y Y Y Y Y Y Y Y Y 9
Yitagesu M., et al Y Y Y Y Y Y Y Y Y 9
Yohannes T., et al Y Y Y Y N Y Y Y Y 8
Alebachew F., et al Y Y Y Y Y Y U Y Y 8
Alemu G., et al Y Y Y Y Y Y Y U Y 8
Solomon M., et al Y N Y Y Y Y Y Y Y 8
Tefera K., et al Y Y Y Y Y Y Y Y Y 9
Temesgen F., et al Y Y Y Y Y Y Y Y Y 9
Tewodros Y., et al Y Y Y Y Y N Y Y Y 8
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Y = Yes, N = No, U = Unclear; JBI Critical Appraisal Checklist for Studies Reporting Prevalence Data: Q1 = was the sample frame appropriate to address the target population? Q2.Were study participants sampled appropriately. Q3. Was the sample size adequate? Q4. Were the study subjects and the setting described in detail? Q5.Was the data analysis conducted with sufficient coverage of the identified sample. Q6.Were the valid methods used for the identification of the condition. Q7.Was the condition measured in a standard, reliable way for all participants. Q8.Was there appropriate statistical analysis. Q9. Was the response rate adequate, and if not, was the low response rate managed appropriately?

Outcome variable

The first outcome of interest for this systematic review and meta-analysis was the hypoglycemia prevention practice among diabetic patients in Ethiopia. Moreover, the pooled hypoglycemia prevention practice and associated factors was computed. The second outcome variable is a factor associated with the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia and was computed by using the log and ratio. Eighteen studies were included in this review.

Data processing and analysis

We used standard Microsoft Excel spreadsheet data and STATA version 14 software for data extraction and analysis of extracted data, respectively. Random effect model meta-analysis was used to compute the pooled hypoglycemia prevention practice and associated factors in Ethiopia, because eighteen studies were included in the final analysis and some of the studies used different scales, the unstandardized and standard regression coefficients of the random effect analysis model were used. Publication bias was checked by funnel plot via visual assessment. Heterogeneity between studies was checked by using Cochrane Q-statistic and I2 tests. Subgroup analysis was computed to compare the hypoglycemia prevention practice and associated factors among diabetic patients within regions of Ethiopia. Point prevalence was presented in forest plot format with 95%CI.

Results

Identification of included studies

We found 159 articles through database searching (PubMed, Google scholar, African journal online, MEDLINE, and Cochrane library, and Ethiopian University repository online). Moreover, 151 articles reminded after removal of duplication. After reading the 151 abstracts and titles, 110 articles and 29 articles were excluded after reviewing the full articles and abstracts. Finally, 12 articles that fill the inclusion criteria were used to determine the pooled hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia (Fig 1).

Fig 1. PRISMA diagram of selecting and including studies for systematic review and meta-analysis for the prevention practice of hypoglycaemia and associated factors among diabetic patients in Ethiopia, 2022.

Fig 1

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Characteristics of searched studies

This systematic review and meta-analysis included 3,639 study participants from 12 studies that evaluated the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia. According to the regional distribution of the articles found through the search, three from Oromia, seven from Amhara, and one each from Tigray and Addis Ababa were included (Table 2).

Table 2. Characteristics of studies in a systematic review and meta-analysis on the prevalence of the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia, 2022.

Authors’ name Year Region study area Study period SD SS cases PP (%)
Esileman A. et al 2020 Amhara NORTH February-March 2019 CS 422 393 93.1
Gashayeneh G., et al 2019 Amhara East Gojjam Nov 2017 Jan 2018 CS 369 346 93.7
Gebrewahd B., et al 2020 Tigray Public Hospitals Mar-Apr 2018 CS 158 100 63.2
Girma N., et al 2015 Amhara South Gonder Jun-Oct 2012 CS 416 89 21.4
Yitagesu M., et al 2019 Oromia JUMC Apr-Jun 30, 2017 CS 410 47 22.90
Yohanss T., et al 2018 Addis Ababa TASH Mar-Apr, 2015 CS 412 224 54.4
Alebachew F., et al 2019 Amhara UOGRTH Feb-Mar 2017 CS 147 58 39.5
Alemu G., et al 2020 Amhara DMRH Feb-June 2020. CS 423 311 73.5
Solomon M., et al 2015 Amet al NORTH Jan and Feb 2013 CS 253 89 35.3
Tefera K., et al 2016 Oromia JUTH Feb14-Apr 9, 2014 CS 309 90 29.1
Temesgen F., et al 2018 Amhara DRH Jan1-Apr 30, 2017 CS 384 112 29.2
Tewodros Y., et al 2021 Oromia AMCH Mar1-30, 2020 CS 245 88 35.9
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NB = Hypoglycemia demarcation is <70 mg/dl; PP = prevalence percentage; SD = study design. SS = sample size

Hypoglycemia prevention practice among diabetic patients (systemic review and meta-analysis)

The estimated pooled prevalence hypoglycemia prevention practice among diabetic patients in Ethiopia was 48.33% (95%CI: 28.21, 68.46, I2 = 99.7%, P≤ 0.001) (Fig 2).

Fig 2. Forest plot of systematic review and meta-analysis on the prevalence of hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia, 2022.

Fig 2

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Subgroup analysis of hypoglycemia prevention practice among diabetic patients in Ethiopia

We have also performed subgroup analysis based on regions where the studies were carried out. The highest hypoglycemia prevention practice was observed in Addis Ababa with a prevalence of 90.00 (95% CI: 88.54, 91.50) followed by SNNRP 76.18(72.02, 80.34) and in the Amhara region 68.31(61.58, 75.05) respectively. The least prevalent was observed in the Oromia region 6.10% (95% CI: 3.09%, 9.05%), I2 = 98.70%) (Fig 3).

Fig 3. Subgroup analysis of systematic review and meta-analysis on the prevalence of the prevention practice of hypoglycemia and associated factors among diabetic patients in Ethiopia, 2021.

Fig 3

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Heterogeneity and publication bias

The I2 (variation in ES attributable to heterogeneity) test results revealed that there was considerable heterogeneity with I2 = 99.7%, at p-value ≤ 0.001. The funnel plot results revealed that a systematic distribution of the included studies through inspection, which implied there was no potential publication bias and (Egger’s test: b = 0.187, p = 0.442) (Fig 4).

Fig 4. Funnel plot (a), Egger test (b) of a systematic review and meta-analysis on the prevention practice of hypoglycemia and associated factors among diabetic patients in Ethiopia, 2021.

Fig 4

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Sensitive analysis of hypoglycemia prevention practice among diabetic patients in Ethiopia

We performed the test using a random effect, and the results showed that no single study influenced the overall pooled prevalence of hypoglycemia prevention practice in Ethiopia (Fig 5).

Fig 5. Sensitive analysis of a systematic review and meta-analysis on the prevention practice of hypoglycemia and associated factors among diabetic patients in Ethiopia, 2021.

Fig 5

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Factors associated with hypoglycemia prevention practice among diabetic patients

We have comprehensively reviewed and meta-analyzed the associated factors of the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia by using twelve relevant studies [1, 4, 16, 17, 23–30]. This study done in Ethiopia revealed the associated factors including the type of diabetes mellitus, duration of diabetes mellitus, taking of insulin therapy for a long time, good knowledge of hypoglycemia prevention practices, and occupation of the study participants in the prevention practice of hypoglycemia and associated factors among diabetic patients in Ethiopia. In this meta-analysis, diagnoses with type II diabetes mellitus were 2.53 times more likely to hypoglycemia prevention practice than persons who are diagnosed with type I diabetes mellitus (AOR = 2.53, 95%CI: 1.05, 4.04) (Fig 6). Study participants who have more than four-year duration have 5.49 times more likely to hypoglycemia prevention practice than a person who has less than four-year duration (AOR = 5.49, 95%CI:3.27,7.70) (Fig 7). Taking insulin therapy for a longer time is 4.31 times more likely to practice prevention of hypoglycemia more than taking insulin with less time (AOR = 4.31,95%CI:2.60,6.02) (Fig 8). In this review, patients who have good prevention knowledge were 2.89 times more likely to practice prevention of hypoglycemia among diabetes mellitus patients in Ethiopia than those who have not have good knowledge (AOR = 2.89, 95%CI: 1.15,4.23) (Fig 9). The other factor significantly associated with the prevention practice of hypoglycemia is being government employment is 4.17 times more likely to practice hypoglycemia prevention (AOR = 4.17, 95%CI: 2.20, 6.15) (Fig 10).

Fig 6. Forest plot on the association between type of diabetes mellitus and hypoglycemia prevention practice among diabetic patients in Ethiopia, 2022.

Fig 6

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Fig 7. Forest plot on the association between duration of diabetes milletus and hypoglycemia prevention practice among diabetic patients in Ethiopia, 2022.

Fig 7

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Fig 8. Forest plot on the association between insulin taking for long time and hypoglycemia prevention practice among diabetic patients in Ethiopia, 2022.

Fig 8

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Fig 9. Forest plot on the association between good prevention knowledge and hypoglycemia prevention practice among diabetic patients in Ethiopia, 2022.

Fig 9

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Fig 10. Forest plot on the association between occupation and hypoglycemia prevention practice among diabetic patients in Ethiopia, 2022.

Fig 10

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Discussion

In this review, the overall pooled prevalence of hypoglycemia prevention practice among diabetic patients in Ethiopia was 48.33%. This finding is lower when compared to the Ethiopian study’s, which had a 49.79% accuracy rate [31], in teaching hospitals of Ethiopia 93.1% [1], in Tigray 63.2% [16]. This variation could be the result of various study factors, including different study participants, a different participant sample size, various tools, and various study designs. The output of this review is higher than the study conducted South Gondar 21.4% [4], USA 19% [32], China 31.2% [33], in the United Kingdom 45% [34]. Study period, study area, sample size differences, sampling techniques, and information sources could all serve as possible defenses.

In this meta-analysis, diagnoses with type II diabetes mellitus were significantly associated with hypoglycemia prevention practice than persons who are diagnosed with type I diabetes mellitus. This study was supported by previous studies [12, 16, 33]. Study participants who have more than four-year duration have significantly associated with hypoglycemia prevention practice than a person who has less than four-year duration. This review is similar with study conducted previously [1, 16, 35]. Taking insulin therapy for a longer time is 4.31 times more likely to practice prevention of hypoglycemia more than taking insulin with less time. In this review, patients who have good prevention knowledge were 2.89 times more likely to practice prevention of hypoglycemia among diabetes mellitus patients in Ethiopia than those who have not have good knowledge. The other factor significantly associated with the prevention practice of hypoglycemia is being government employment is 4.17 times more likely to practice hypoglycemia prevention. This finding was supported by previous studies [4, 16, 35].

Strengths of this review

The strength of this review was it uses multiple databases to search articles (both manual and electronic search) for meta-analysis, abstraction of information uniformly using a predetermined format that helped to minimize error. This meta-analysis also included studies from different parts of the Ethiopian regions.

Limitations of this review

Bias may be there because the search was only in the English language. Primary studies of this review did not include all ten regions of Ethiopia, which may be difficult to conclude the findings for all regions in Ethiopia.

Conclusions

In conclusion, hypoglycemia prevention practice among diabetic patients were low as revealed by this review. This review found that factors such as the type of diabetes, the length of diabetes, the use of insulin therapy for a long time, knowledge of the prevention of hypoglycemia practices, and the study participants’ occupation were all significantly related to the prevention of hypoglycemia among diabetic patients in Ethiopia. This review demonstrates that hypoglycemia is surprisingly common in diabetics. Education campaigns should be incorporated on successfully spreading awareness of hypoglycemia and the best ways to prevent it in people with diabetes mellitus. In order to lower the risk of hypoglycemia, this emphasizes the need for educational interventions and the personalization of therapies.

Supporting information

S1 Dataset

(CSV)

Click here for additional data file. (779B, csv)
S1 Fig. PRISMA diagram of selecting and including studies for systematic review and meta-analysis for the prevention practice of hypoglycaemia and associated factors among diabetic patients in Ethiopia, 2021.

(DOCX)

Click here for additional data file. (50.3KB, docx)

Abbreviations

CDC

Centers for Disease Control and Prevention

WHO

World Health Organization

SNNPR

Southern Nation, Nationalities and Peoples’ of Region

Data Availability

All relevant data are within the paper and Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

José Luiz Fernandes Vieira

2 Aug 2022

PONE-D-22-00290Prevention practice of Hypoglycemia and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-AnalysisPLOS ONE

Dear Dr. Lankrek

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

ACADEMIC EDITOR: 

Dear dr. Lankrew

Based on several issue pointed out by the reviewers in the methodological section, I recommend a Major revision of your manuscript adressing the recomendations of the reviewers.

For Lab, Study and Registered Report Protocols: These article types are not expected to include results but may include pilot data. 

==============================

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We look forward to receiving your revised manuscript.

Kind regards,

José Luiz Fernandes Vieira

Academic Editor

PLOS ONE

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We will carefully review your manuscript upon resubmission, so please ensure that your revision is thorough."

Additional Editor Comments (if provided):

Dear Dr. Lankrew

Based in several issues highlighted by reviewers related to methodological issues. I reccomend a Major revision of your manuscript

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: General comments

This manuscript addresses an interesting and relevant topic, and it is very important to work for Ethiopia. However, this manuscript needs substantial correction

Title

Could be Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis

Abstracts

In the result section of the abstract please include the meta-regression analysis result of the pooled OR with its respective CI

The sentence is not clear needs revision“ by 93.13% and 73.52% in the Amhara region respectively.”

Methods

The presentation of the search key terms is not reproducible and clearly indicated. Authors need to indicate whether title-specific or topic-specific (title-abstract-keyword) search was done in the database as well as record the entire filter applied.

Authors are advised to present the results from each database individually on the PRISMA diagram.

The choice of the time frame need to be justify as well. It is advised that the study be update to at least February 2022.

The outcome (primary and secondary) you review is not clearly stated. So, add as one sub-section in the method section of your manuscript including how you measure the primary outcome

Results

Define cases and Prevalence in your table 2. What cares and prevalence of what?

Perform a meta-regression analysis for risk factors and present your results accordingly with appropriate data presentation methods.

Discussion

The discussion is inadequate as well and too superficial.

Strength and limitation

Two independent reviewers were used in data extraction and the assessment of the risk of bias". This is a common methodological requirement for systematic reviews (PRISMA), I do not foresee this as a particular strength following a usual requirement. Authors should remove this.

Conclusion

Your conclusion is not different from your result. The content and placement of your conclusion should make its function clear without the need for additional indication of the pooled prevalence.

Missing of some abbreviations

Language editing is required. Grammatical errors and typographical errors also need to correct throughout the manuscript. Authors can give the manuscript to colleagues (senior ones) to criticize and review before resubmission

Reviewer #2: This manuscript addresses an interesting and relevant topic,and it is very important to work for Ethiopia. We know that we have very limited data. Therefore, this manuscript helps to advance the paper in the country.

Comment to the authors

1. Grammar errors need to be corrected. The manuscript presented in an intelligible fashion and written in standard English.

2. Reduce the volume of the abstraction and introduction and write the story chronologically. Currently, it is haphazard.

3. On conclusion focus only with your findings

Questions to the authors

1. How did you assess pooled prevalence?

2. what type of study designs you include in this review?

3. which study tool was used to assess review outcome?

4. How you reduce the bias of this review?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

**********

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Attachment

Submitted filename: Comments to the Author by Kirubel Eshetu.docx

Click here for additional data file. (12.9KB, docx)
PLoS One. 2022 Nov 1;17(11):e0275786. doi: 10.1371/journal.pone.0275786.r002

Author response to Decision Letter 0

18 Aug 2022

Dear Editor of PLOS ONE

This point-by-point response letter complements the responses of authors to reviewers’ comments regarding our manuscript. We are pleased to resubmit the revised version of our paper entitled “Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis” Tadele Lankrew Ayalew1*, Belete Gelaw Wale2, Bitew Tefera Zewudie3 which has a submission manuscript/identification number of PONE-D-22-00290R1 given by the journal. It is well known that this manuscript has been reviewed by peer reviewers and sent back to the authors for further revision as per the Journal Requirements and resubmission. We are so eager and thankful to work with you.

We would like to take this opportunity to thank the reviewers for their views and constructive comments. The reviewers’ comments and recommendations were important to improve the quality of our manuscript. Therefore, we have organized our response letter based on reviewers’ comments and questions. (Title, Abstract, introduction, methods, results, discussion, and conclusion). Under each section, the reviewers’ comments are given followed by the authors’ responses. The authors’ responses are also shown by the track changes in the revised version of our manuscript. The responses for each of the reviewers’ comments are addressed in the following pages using the point-by-point response format.

Our responses are written in yellow background words (highlighted with yellow).

We look forward to hearing from you at a suitable time.

With regards

Tadele Lankrew Ayalew

(On the behalf of all authors)

Comments to the Authors

The authors of this systematic review and Meta-analysis study have presented valuable data to determine Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia. Consequently, there are specific critical issues that the reviewers would like the authors to address for further improvement in the quality of our manuscript.

Authors’ response: we are very delighted with the reviewer’s appreciation of our efforts; and we have just given our respective responses to each of the specific reviewers concerns as detailed below. Please find below our response to the comments. All changes made in the document are highlighted in yellow word background.

Journal requirements:

We follow PLOS ONE's style requirements, including those for file naming. Since no funding source for this review, we stated like “The authors received no specific funding for this work.”

For competing interests, because of the absence of conflict within authors, we stated, “The authors have declared that no competing interests exist."

We've checked your submission and before we can proceed, we need you to address the following issues:

1. Your article cannot proceed until you upload a copy of the completed PRISMA checklist as Supporting Information. We note that this manuscript is a systematic review or meta-analysis; our author guidelines, therefore, require that you use PRISMA guidance to help improve reporting quality of this type of study.

Thank you very much for your constructive comment. We have made corrections based on your suggestion. Please see the supporting information section.

2. Please, include a separate legend for each figure in your manuscript.

Thank you very much for your constructive comment. We have made corrections based on your suggestion. Please see line 373

3. We note that your Data Availability statement states the following: "No"

PLOS journals require that all data presented in the study be made publicly available at or before the time of acceptance. If there are legal or ethical restrictions on the data being made publicly available, such as IRB restrictions or patient confidentiality, authors must provide a way for fellow researchers to access the data.

Before we can proceed, please clarify the following:

1. Are there legal or ethical restrictions being placed upon the data? If so, please explain them in detail (e.g., data contain potentially identifying or sensitive patient information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., a Research Ethics Committee or Institutional Review Board, etc.).

2. If there are no legal or ethical restrictions, please upload the data as a Supporting Information file or to a recommended stable public repository. (https://journals.plos.org/plosone/s/recommended-repositories)

Thank you very much for your constructive comment. We have made correction based on your suggestion. Please see line 267

3. Please note that PLOS does not allow authors to be the sole contact for data inquiries. If the data is only available upon request, please provide contact information, such as an email address, for a non-author, institutional point of contact (such as an IRB or ethics committee contact) who can field data inquiries from fellow researchers. If the data contact is an individual, please provide their title and relationship to the data as well.

Thank you very much for your constructive comment. Please contact:

Tesfaye Yitna Chichiabellu (Assistant Professor of Maternity and RH Nursing, School of Nursing, Wolaita Sodo University, Ethiopia.

Head of Generic Nursing Department)

Email: yefaste2005@gmail.com/tesfaye.yitna@wsu.edu.et

Cell no: +251913864251/+251930749616

OR

Tilahun  Saol Tura (Assistant Professor of Maternity and Reproductive Health Nursing, Dean of Nursing School CHSM, Wolayta Sodo University, Ethiopia)

email:tilahunsaol@gmail.com/

tilahun.saol@wsu.edu.et

Phone Number +251913734117/+251962149708

Authors’ Responses to Reviewer's Questions

Reviewers' comments and Responses to Questions

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you for your constructive comments. Really, we appreciate and accepted all the comments you raised for us.

2. Has the statistical analysis been performed, appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Thank you for your valuable suggestion.

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you for your constructive comments. We have accepted all the comments you raised.

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Thank you for your constructive comments.

5.Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: General Comments

This manuscript addresses an interesting and relevant topic, and it is very important to work for Ethiopia. However, this manuscript needs substantial correction

Title

could be Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis

Thank you for your constructive comments. We have accepted your comments you raised. We have made correction based on your suggestion to the revised manuscript. In the revised manuscript, we have corrected like” Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis” ==>Please see on the title page.

Abstracts

In the result section of the abstract please include the meta-regression analysis result of the pooled OR with its respective CI

Thank you for your constructive comments. We have accepted your comments you raised. We have made corrections based on your suggestion to the revised manuscript. ==>Please, see the abstract section.

The sentence is not clear and needs revision“ by 93.13% and 73.52% in the Amhara region respectively.”

Thank you very much for your critical comments. We would like to say sorry for the unclear expression. We have accepted the comments you raised. We have made corrections in the revised manuscript. ==>Please, see the abstract section and thorough the revised manuscript.

Methods

The presentation of the search key terms is not reproducible and clearly indicated. Authors need to indicate whether title-specific or topic-specific (title-abstract-keyword) search was done in the database as well as record the entire filter applied.

Thank you for your constructive comments. We have accepted the comments you raised. We have made corrections based on your suggestion to the revised manuscript.

Authors are advised to present the results from each database individually on the PRISMA diagram.

Thank you for your constructive comments. We have accepted the comments you raised. We have made corrections based on your suggestion to the revised manuscript.

The choice of the time frame need to be justify as well. It is advised that the study be update to at least February 2022.

Thank you for your constructive comments. We have made correction based on your suggestion to the revised manuscript. ==>Please, see line 124.

The outcome (primary and secondary) you review is not clearly stated. So, add as one sub-section in the method section of your manuscript including how you measure the primary outcome

Thank you for your constructive comments. We would like to say sorry for the unclear expression. We had avoid based on your suggestion to the revised manuscript.

Results

Define cases and Prevalence in your table 2. What cases and prevalence of what?

Thank you for your constructive comments. We would like to say sorry for the unclear expression. Here our concern was that case showed that the frequency and describe in number, whereas prevalence showed that the percentage of the case.

Perform a meta-regression analysis for risk factors and present your results accordingly with appropriate data presentation methods.

Thank you for your constructive comments. We apologize for the missing of risk factors analysis. We have made correction based on your suggestion to the revised manuscript. ==>Please, see lines 205-221.

Discussion

The discussion is inadequate as well and too superficial.

Thank you very much for your critical review. After proofreading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript. ==>Please, see discussion section.

Strength and limitation

Two independent reviewers were used in data extraction and the assessment of the risk of bias". This is a common methodological requirement for systematic reviews (PRISMA), I do not foresee this as a particular strength following a usual requirement. Authors should remove this.

Thank you for your constructive comments. We apologize for the unclear expression. We removed based on your suggestion to the revised manuscript. ==>Please Strength and limitation section.

Conclusion

Your conclusion is not different from your result. The content and placement of your conclusion should make its function clear without the need for additional indication of the pooled prevalence.

Thank you very much for your critical review. After proof reading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript. ==>Please, see conclusion section.

Missing of some abbreviations

Language editing is required. Grammatical errors and typographical errors also need to correct throughout the manuscript. Authors can give the manuscript to colleagues (senior ones) to criticize and review before resubmission

Thank you very much for your critical review. After proof reading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript. Concerning grammatical errors and typographical errors, we had use online grammar checker and consulted to senior expert in English language.

Reviewer #2: This manuscript addresses an interesting and relevant topic,and it is very important to work for Ethiopia. We know that we have very limited data. Therefore, this manuscript helps to advance the paper in the country.

Comment to the authors

1. Grammar errors need to be corrected. The manuscript presented in an intelligible fashion and written in standard English.

Thank you very much for your critical review. After proof reading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript. Concerning grammatical errors and typographical errors, we used an online grammar checker and consulted to senior expert in the English language.

2. Reduce the volume of the abstraction and introduction and write the story chronologically. Currently, it is haphazard.

Thank you very much for your critical review. After proofreading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript.

3. On conclusion focus only with your findings

Thank you very much for your critical review. After proof reading, the appropriate correction was made to the revised manuscript based on the given comment throughout the manuscript.

Questions to the authors

1. How did you assess pooled prevalence?

Thank you very much. We used standard Microsoft Excel spreadsheet data and STATA version 14 software for data extraction and analysis of extracted data, respectively. Finally random effect model meta-analysis was used to compute the pooled prevalence.==>please see line 165

2. what type of study designs you include in this review?

Thank you very much for valuable questions. We had used cross-sectional study.

3. which study tool was used to assess review outcome?

Thank you very much. We used Joanna Brings Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MASTER) and We strictly follow Preferred Reporting Items for Systematic and Meta-Analysis (PRISMA) protocols to estimate the hypoglycemia prevention practice and associated factors among diabetic patients in Ethiopia. ==> Please, see line 145.

4. How you reduce the bias of this review?

Thank you very much for encouraging us. To reduce the bias of this review, first, we set the eligible criteria, and then the funnel plot and egger’s test were used. ==> Please, see line 210.

6.PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

It means PLOS now offers accepted authors the opportunity to publish the peer review history of their manuscript alongside the final article. The peer review history package includes the complete editorial decision letter for each revision, with reviews, and your responses to reviewer comments, including attachments.

Attachment

Submitted filename: Response to reviewers.pdf

Click here for additional data file. (527.7KB, pdf)

Decision Letter 1

José Luiz Fernandes Vieira

26 Sep 2022

Hypoglycemia prevention practice and Associated Factors among Diabetes Mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis

PONE-D-22-00290R1

Dear Dr. Tadele Lankrew

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

José Luiz Fernandes Vieira

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: The authors try to address all my comments, so it is accepted for publication from my point of view.

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Reviewer #1: No

Reviewer #2: No

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Acceptance letter

José Luiz Fernandes Vieira

19 Oct 2022

PONE-D-22-00290R1

Hypoglycemia prevention practice and Associated Factors among Diabetes mellitus Patients in Ethiopia: Systematic Review and Meta-Analysis

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on behalf of

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Associated Data

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    Supplementary Materials

    S1 Dataset

    (CSV)

    Click here for additional data file. (779B, csv)
    S1 Fig. PRISMA diagram of selecting and including studies for systematic review and meta-analysis for the prevention practice of hypoglycaemia and associated factors among diabetic patients in Ethiopia, 2021.

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    Attachment

    Submitted filename: Comments to the Author by Kirubel Eshetu.docx

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    Submitted filename: Response to reviewers.pdf

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