Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and its treatment impact patients' physical health as well as emotional and social wellbeing. This study aimed to assess health-related quality of life (HRQoL) and associated factors among patients with T2DM at a tertiary care hospital in Ethiopia.
METHODS: A face-to-face cross-sectional survey was conducted among patients with T2DM at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia. We collected data using a validated Amharic version of the 5-level EuroQoL-5 dimensions (EQ-5D-5L) questionnaire. Descriptive statistics were used to present patient characteristics. Kruskal-Wallis and Mann-Whitney U tests were performed to explore differences in the median scores of EQ-5D-5L utility and visual analog scale (EQ-VAS). Multivariable Tobit regression models were used to identify predictors of HRQoL. Utility scores were calculated using disutility weights of the Ethiopian general population. Statistical significance was determined at p < 0.05.
RESULTS: A total of 360 patients with T2DM participated. Mean (SD) age was 64.43(10.61) years. Reported health problems were mostly in the pain/discomfort (67.3%) dimension followed by mobility (60.5%), whereas the usual activities domain (34.1%) was the least health problem being reported. The median (IQR) EQ-5D-5L utility and EQ-VAS scores were 0.95 (0.88-0.96) and 80 (75.0-85.0), respectively. In multivariable Tobit regression models older age, having poor glycemic control, longer duration of diabetes, insulin usage, obesity, and having diabetes-related complications were significant negative predictors of HRQoL.
CONCLUSIONS: Overall, patients with T2DM had lower HRQoL than the general population, which was attributed to being older age, longer duration of diabetes, insulin use, obesity, inadequate glycemic control, and diabetes-related complications. The utility index we generated can be used in future economic evaluations to inform decisions about alternative interventions and resource allocation.

Introduction

Type 2 diabetes mellitus (T2DM) is a growing public health challenge associated with significant health, social, and economic burden on patients, families, and healthcare systems [1, 2]. According to the International Diabetes Federation (IDF), an estimated 19.4 million adults aged 20–79 years were living with diabetes in the IDF Africa region in 2019, representing a regional prevalence of 3.9% [1]. In Ethiopia, the number of people with diabetes exceeds 2.57 million (5.2%), making it one of the highest prevalence countries in Sub-Saharan Africa [1, 2]. The global epidemic of diabetes is linked to an increasing rate of an aging population, urbanization, unhealthy eating habits, sedentary lifestyle as well as lack of physical activities [3].

HRQoL is a patient-reported outcome measure that evaluates the extent to how diseases, disability, and treatment affects the health status of patients [4]. It encompasses physical, functional, psychosocial, and emotional functioning domains of quality of life [5, 6]. It can provide information about a person’s overall health status because it considers both physical and mental health, and their respective impact on HRQoL [7]. Thus, healthcare providers and researchers use self-reported HRQoL measures to evaluate the burden of disease and its treatments in addition to clinical outcomes in patients with diabetes [8, 9]. Moreover, HRQoL is a relevant input to conduct economic evaluations and identify cost-effective interventions that lead to efficient utilization of scarce resources [10].

Demographic factors are an independent determinants of HRQoL in patients with diabetes, particularly aging is strongly negatively associated with HRQoL [10, 11]. In addition, poor glycemic control and diabetes-related complications can lead to a reduction in HRQoL in patients with diabetes [7, 12, 13]. To augment these, many studies demonstrated that patients with diabetes have poor HRQoL compared to people without diabetes [14-17]. Furthermore, studies indicated that duration of diabetes, insulin use which might be associated with pain of multiple injections, are linked with poor HRQoL [9, 18, 19]. Moreover, the presence of comorbidities among patients with T2DM has been linked to a lower HRQoL [12, 20–23].

Several generic and disease-specific tools have been developed for measuring the HRQoL of patients with diabetes [24-27]. The EQ-5D-5L questionnaire is a generic, preference-based multi-attribute utility HRQoL measure validated for use in clinical and economic evaluations. It has the benefit of being able to convert health states into a single summary score called utility. The EQ-5D-5L is being used in many countries for health technology assessment (HTA) such as the National Institute for Health and Care Excellence (NICE) and other European countries’ economic evaluations, which inform resource allocation decisions in many jurisdictions [18, 19, 28, 29].

There are no previous studies on HRQoL of patients with T2DM using EQ-5D-5L in Ethiopia; however, a few studies have explored patients’ views on the impact of the disease and its treatments using the Short-Form 36 item health survey (SF-36), and the World Health Organization Quality of Life (WHOQOL-BREF) instrument. These studies demonstrate that general health, environmental, psychological, physical, bodily pain and vitality were the most affected dimensions of the HRQoL. Additionally, the findings illustrate that diabetes-related complications, old age, obesity, duration of diabetes, insulin and oral anti-diabetic medication use were the major predictors that require comprehensive intervention strategies to enhance the HRQoL of patients with diabetes. Furthermore, the findings showed that HRQoL remains the most disregarded component in routine clinical practice in Ethiopia [19, 30–32]. Hence, this study aimed to evaluate the HRQoL and associated factors among patients with T2DM at a tertiary teaching hospital in Ethiopia.

Methods

Study design and setting

We conducted a face-to-face cross-sectional survey from January to June 2019 among patients with T2DM at an outpatient diabetes clinic of Tikur Anbessa Specialized Hospital (TASH) in Addis Ababa, Ethiopia. The hospital is the largest and oldest tertiary care hospital in Ethiopia. It has 800 beds and serves over half a million patients per year (330 outpatients and 200,000 inpatients, with an average length of stay of 9.3 days). Of these, 6,000 patients attend the diabetic clinic annually.

Instruments

We used a validated Amharic version of the EQ-5D-5L questionnaire developed by the EuroQol Research Foundation [33, 34] (S1 File). The instrument comprises a short descriptive system questionnaire and EQ-VAS. The first part of the EQ-5D-5L involves the patient self-reported component: patients report about their health status in the descriptive system that comprises five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Under each dimension, there are five levels: no problems, slight problems, moderate problems, severe problems, and extreme problems; which represent the severity of problems for the specific dimension. Participants were asked to choose a level that reflects their current health state for each dimension. The second part of the instrument is the EQ-VAS, an instrument used for subjective assessment of one’s current state of health from the patient’s perspective [34]. Using this method, each patient self-rated their health status on a vertical scale that ranges from zero (the worst health state) to 100 (the best health state). We also collected sociodemographic (age, gender, marital status, level of education, employment status, average monthly household income, and social history) and clinical data (duration of diabetes diagnosis, previous hospitalization due to diabetes, antidiabetic medications, comorbidities, presence of diabetes-related complications and number of medications).

Sample size determination, recruitment, and data collection procedure

The sample size was determined using the simple proportion population formula [35], considering a Z-value of 1.96 with a 95% level of confidence and 5% margin of error. To obtain the largest sample size possible, the proportion (P) for sample size estimate was set at 50% of patients with T2DM who rated their overall perceived HRQoL as good. Moreover, sample size adjustment was made since the target populations were less than 10,000. The sample size was calculated to be 360 [35]. We were unable to employ a systematic random sampling strategy due to the limited time available for the investigation and the small number of patients with T2DM. Instead, study participants were recruited consecutively until we reached the required sample size. Patients were eligible if they were 18 years of age or older and diagnosed with T2DM at least six months before data collection. We excluded patients with gestational diabetes, type 1 diabetes mellitus, and those who had a cognitive/mental problem as per the clinical chart. Data were collected by final-year pharmacy students. All data collectors were trained to ensure uniformity and reduce inter-observer bias in data collection. The purpose and procedure of the study were explained to all study participants before data collection. During the data collection process, data collectors clarified queries raised about the questionnaire by the patients. Information about the health status and sociodemographic characteristics such as gender, age, marital status, occupation, level of education, alcohol, smoking status, lifestyle modifications, and average monthly household income, were collected through face-to-face interviews. Information about the duration of T2DM, history of previous hospitalization, current antidiabetic medications, diabetes-related complications, comorbidities, fasting blood sugar (FBS) level (mg/dl), hemoglobin A1c (HbA1c, %), and the number of medications used were obtained from patients’ medical records.

Ethics

The study was approved by the Ethics Review Board of the School of Pharmacy, Addis Ababa University, Ethiopia (Protocol#: ERB/SOP/75/04/2019). Written informed consent was obtained from all study participants who were able to read and write before data collection. We obtained verbal informed consent for illiterate participants. Most of our illiterate participants had no accompanying family members or relatives; thus, obtaining proxy written consent was not practical. Personal identifiers were not collected, and data were reported in aggregate. The data were stored in password-protected computers, and access to data was restricted to the research team.

Statistical analysis

Descriptive statistics were used to present the demographic and clinical characteristics of the study participants. Differences in the proportions of reported problems with patients’ characteristics were tested using the χ2 test. As the EQ-5D-5L utility and EQ-VAS scores were non-normally distributed (Kolmogorov–Smirnov test, p< 0.05), we presented median (IQR) scores. The Kruskal-Wallis and Mann-Whitney U tests were used to determine differences in the EQ-5D-5L utility and EQ-VAS scores of participants. To explore the potential predictors of HRQoL, multivariable Tobit regression models were employed. Candidate independent variables were chosen based on previous studies [10, 36] and clinical significance. Patients’ EQ-5D-5L utility scores were computed using disutility coefficients obtained from the Ethiopian general population [37]. Statistical significance was determined at p < 0.05. All statistical analyses were performed using STATA Version 14.

Results

Socio-demographic characteristics of the patients

A total of 360 patients with T2DM were interviewed, but data from eight patients were excluded due to incomplete information. Hence, 352 patients were included in the final analyses. The mean (SD) age of the patients was 64.43 (10.61) years, and the majority (70.7%) were 65 years or older. More than half (55.7%) of the patients were female; 249 (70.7%) were married, 110 (31.3%) were illiterate (i.e., they could not read and/or write), and 95 (27.1%) had a household monthly income of less than US$ 14.84 (Table 1).

Table 1

Sociodemographic characteristics of the patients with T2DM (N = 352).

Variables	N (%)
Gender
Male	156 (44.3)
Female	196 (55.7)
Age categories (in years), Mean (SD)	64.43 (10.6)
< 60	144 (40.9)
≥ 65	208 (59.1)
Marital status
Married	249 (70.7)
Unmarried	103 (29.3)
Educational status
Illiterate	110 (31.3)
Primary school	102 (29.1)
Secondary and above	139 (39.6)
Occupational status
Employed	130 (36.9)
Non-employed	222 (63.1)
Average monthly household income (ETB)
< 14.84 US$	95 (27.1)
≥ 14.84 US$	256 (72.9)

* US$ 1 = 40.43 Ethiopian Birr (ETB).

Clinical characteristics of patients

Approximately half (48.1%) of the patients had T2DM for more than 10 years, and a quarter (24.1%) of them had a history of hospital admission due to diabetes. Most (89%) patients reported adopting lifestyle modifications. The majority of patients (77.3%) had one or more comorbidities, with hypertension accounting for the largest proportion (43.8%). More than three-fourth (75.9%) of patients were taking oral antidiabetic agents. The majority (91.2%) of patients had poor glycemic control (FBS ≥126 mg/dl), with an average fasting blood sugar level of 164.11(39.26) mg/dl and an average glycated hemoglobin A1c (HbA1c) value of 7.39%. Most (83%) patients had normal body weight, 191 (54.4%) had diabetes-related complications, and 54 (15.4%) were taking more than five medications (Table 2).

Table 2

Clinical characteristics of patients with T2DM (N = 352).

Variables	N (%)
Time since DM diagnosis
< 5 years	73 (20.7)
6–10 years	109 (31.1)
> 10 years	169 (48.1)
History of hospitalization due to DM
Never	267 (75.9)
One or more	85 (24.1)
Adoption of lifestyle modification
Yes	327 (93.1)
No	24 (6.80)
Types of lifestyle modification
Dietary	216 (66.1)
Physical activity	75 (22.9)
Dietary and physical activity	36 (11.0)
Smoking status
Yes	31 (8.80)
No	321 (91.2)
Alcohol habits
Yes	157 (44.6)
No	195 (55.4)
Comorbidities
Yes	272 (77.3)
No	80 (22.7)
Types of comorbidities
HTN*	119 (43.8)
HTN + HF*	83 (30.5)
Asthma	15 (5.5)
HTN + asthma	19 (7.0)
HTN + RVI*	16 (5.9)
Others	20 (7.3)
Antidiabetic medications
Oral	261 (75.9)
Insulin only	38 (11.0)
Oral + Insulin	45 (13.1)
FBS level, mean (SD)	164.1 (39.3)
HbA1c, mean (%)	7.39 (0.476)
Body mass index (BMI), Kg/m2
Normal body weight	292 (83.0)
Obese	60 (17.0)
Presence of diabetes-related complication
Yes	191 (54.4)
No	160 (45.6)
Number of complications
< 2 complications	163 (85.3)
≥ 2 complications	28 (14.7)
Number of medications used
< 5	297 (84.6)
≥ 5	54 (15.4)

*HTN = Hypertension, HF = Heart failure, RVI = HIV/AIDS, FBS = Fasting blood sugar level.

Distribution of EQ-5D-5L dimensions

Patients’ self-reported health status for the five dimensions of EQ-5D-5L is presented in Fig 1. The most frequent health problems were reported for the “pain/discomfort dimension” (67.3%, all levels) followed by “mobility” (60.5%, all levels), while the least was in “usual activities” (34.1%, all levels). The distribution of responses with “no problem” or a “perfect health state” (11111) was reported by 28 (8%) patients in the EQ-5D-5L descriptive dimension, while only 3.7% reported the “best health state” (100) in the EQ-VAS. A significantly higher proportion of any problems reported in EQ-5D-5L descriptive dimensions were observed across patients’ characteristics such as gender, marital status, older age, comorbidities, types of antidiabetic medications as well as polypharmacy (S1 Table).

Fig 1

Percentage distribution of self-reported health problems among patients with T2DM.

EQ-5D-5L index and EQ-VAS scores

Overall, the median (IQR) EQ-5D-5L utility and EQ-VAS scores were 0.95 (0.88–0.96) and 80 (75.0–85.0), respectively. The distribution of the EQ-5D-5L utility and EQ-VAS scores were skewed towards 1 and 100, respectively (Fig 2). The median EQ-5D-5L utility scores of patients aged 45 years or younger and those with higher household income (> US$ 14.48) were significantly higher than their counterparts. On the other hand, patients who were living with diabetes for a longer duration and taking more than 5 medications had significantly lower EQ-5D-5L index score compared with patients living for a short period of time and patients taking fewer than 5 antidiabetic medications, respectively. The median EQ-VAS in men was significantly higher in comparison to women (83 versus 75; p = 0.038). In the Kruskal-Wallis analyses, lower median EQ-5D-5L utility scores were reported in those who were on insulin (0.88), those taking a combination of glibenclamide and insulin (0.44) than metformin alone (0.96) (p < 0.05). Besides, the difference between the median scores of the EQ-5D-5L utility and EQ-VAS scores with controlled and uncontrolled HbA1c was significant (p < 0.05) (Table 3).

Fig 2

Distribution of the EQ-5D-5L utility and EQ-VAS scores of patients with T2DM.

Table 3

Median (IQR) differences of EQ-5D-5L utility and EQ-VAS scores with patient demographic and clinical characteristics.

Variables	EQ-5D-5L index median (IQR) score	p-value	EQ-VAS median (IQR) score	p-value
Overall scores	0.95 (0.88–0.96)		80 (75.0–85.0)
Gender
Male	0.95 (0.76–0.97)	0.198	83.0 (70.0–90.0)	0.038
Female	0.88 (0.79–0.96)		75.0 (70.0–85.0)
Age category
< 45	0.96 (0.90–0.98)	0.004	80.7 (70.0–95.0)	0.017
45–64	0.95 (0.91–0.96)		80.0 (70.0–90.0)
≥ 65	0.94 (0.75–0.96)		75.0 (70.0–85.0)
Marital status
Married	0.95 (0.69–0.96)	0.708	80.0 (60.0–90.0)	0.529
unmarried	0.94 (0.89–0.97)		80.0 (70.0–85.0)
Educational status
Illiterate	0.86 (0.90–0.96)	0.013	75.0 (60.0–85.0)	0.070
Primary school	0.88 (0.93–0.96)		80.0 (70.0–85.0)
Secondary school and higher	0.95 (0.75–0.96)		80.0 (70.0–90.0)
Employment status
Employed	0.96 (0.88–0.97)	0.011	80.0 (75.0–90.0)	0.004
Unemployed	0.94 (0.79–0.96)		75.0 (70.0–85.0)
Average household income
< 14.84 US$	0.91 (0.78–0.96)	0.039	80.0 (70.0–85.0)	0.684
≥ 14.84 US$	0.95 (0.90–0.96)		75.0 (70.0–85.0)
Duration of DM
< 5 years	0.96 (0.91–0.97)	0.002	87.5 (75.0–95.0)	0.001
5–10 years	0.95 (0.91–0.97)		80.0 (70.0–90.0)
> 10 years	0.93 (0.75–0.96)		75.0 (70.0–85.0)
Hospitalization due to DM
Never	0.95 (0.88–0.96)	0.258	80.0 (70.0–85.0)	0.340
One or more	0.94 (0.72–0.96)		75.0 (60.0–90.0)
Adoption of lifestyle modification
Yes	0.95 (0.88–0.96)	0.986	80.0 (70.0–85.0)	0.203
No	0.96 (0.94–0.96)		75.0 (70.0–80.0)
Comorbidities
Yes	0.94 (0.77–0.96)	0.021	75.0 (70.0–85.0)	0.237
No	0.95 (0.90–0.97)		80.0 (70.0–90.0)
Antidiabetic medications
Oral	0.95 (0.91–0.96)	0.001	80.0 (70.0–85.0)	0.002
Insulin	0.74 (0.42–0.95)		70.0 (53.7–85.0)
Oral + Insulin	0.95 (0.67–0.97)		80.0 (70.0–90.0)
Number of medications
< 5	0.95 (0.89–0.96)	0.020	80.0 (70.0–90.0)	0.289
≥ 5	0.93 (0.79–0.96)		75.0 (70.0–85.0)
FBS level
< 126 mg/dl	0.95 (0.90–0.96)	0.009	80.0 (70.0–85.0)	0.186
≥ 126 mg/dl	0.93 (0.78–0.95)		75.0 (70.0–85.0)
HbA1c
< 6.4%	0.71 (0.71–0.72)	0.022	50.0 (0.00)	0.006
≥ 6.4%	0.95 (0.89–0.96)		80.0 (70.0–85.0)
Body mass index
Normal	0.95 (0.91–0.96)	0.001	80.0 (70.0–85.0)	0.001
Obese	0.89 (0.72–0.95)		75.0 (60.0–80.0)
Presence of complication
Yes	0.94 (0.88–0.97)	0.001	70.0 (65.0–80.0)	0.001
No	0.96 (0.88–0.97)		80.0 (70.0–90.0)

Predictors of health-related quality of life

In the multivariable Tobit regression model, having diabetes-related complications (β = -0.029; 95% CI = -0.047; -0.011; p-value < 0.05), insulin usage (β = -0.173, 95% CI = -0.227; -0.119, p-value < 0.05), being obese (β = -0.071, 95% CI = -0.116; -0.025, p-value < 0.05), and longer duration since diabetes diagnosis (β = -0.003, 95% CI = -0.005; -0.001, p-value < 0.05) were significant negative predictors of the EQ-5D-5L utility score. Likewise, older age, higher FBS values, and having one or more comorbidities were negatively associated with EQ-5D-5L utility. Whereas higher HbA1c (β = -4.29, p-value < 0.05) and smoking (β = -5.12, 95% CI = -9.53; -0.721, p-value < 0.05) were significantly negatively associated with the EQ-VAS score. Marital status, occupation, average household income, education level, and polypharmacy were not significantly associated with either the EQ-5D-5L utility or EQ-VAS score. The Tobit regression results are presented in Table 4.

Table 4

Predictors of HRQoL in patients with Type-2 diabetes mellitus.

Variables	EQ-5D-5L utility score		EQ-VAS score
	β-Coeff. [95% CI]	p-value	β-Coeff. [95% CI]	p-value
Gender, Female (ref = Male)	0.018 [-0.016; 0.053]	0.686	0.455 [-2.42; 3.33]	0.756
Level of education (ref = Illiterate)
Primary	-0.029 [-0.074;0.016]	0.294	-0.71 [-4.35;2.92]	0.699
Secondary and higher	-0.033 [-0.075;0.010]	0.282	0.293 [-3.15;3.73]	0.867
Household income (ref = ≤ US$14.84)
> US$14.84	0.035 [-0.003;0.073]	0.053	-1.67 [-4.83;1.49]	0.758
Age (Ref = < 65 years)
≥ 65 years	-0.055 [-0.091; -0.018]	0.036 *	-2.30 [-5.31;0.691]	0.143
Smoking (ref = Non-smoker)
Smoker	-0.006 [-0.057;0.045]	0.202	-5.12 [-9.53; -0.721]	0.022 *
FBS (mg/dl)	-0.001 [-0.001; -0.004]	0.043 *	-0.029 [0.065;0.007]	0.503
HbA1c (%)	-0.003 [-0.039;0.034]	0.604	-3.86 [-6.79; -0.935]	0.012 *
Years since T2DM diagnosis	-0.003 [-0.005; -0.001]	0.001 *	-0.313 [0.484;0.142]	0.001 *
Comorbidity (ref = No)
Yes	-0.043 [-0.083; -0.003]	0.582	-1.74 [-4.97; 1.50]	0.338
Antidiabetic medications (Ref = Oral)
Insulin only	-0.173 [-0.227; -0.119]	0.002 *	-7.24 [-11.8; -2.71]	0.002 *
Insulin + Oral medications	-0.045 [-0.095;0.005]	0.360	1.45 [-2.81;5.71]	0.504
BMI (ref = Normal)
Obese	-0.071 [-0.116; -0.025]	0.001 *	-8.09 [-11.82; -4.35]	0.001 *
Complication (ref = No)
Yes	-0.029 [-0.047; -0.011]	0.001 *	-3.19 [-4.66; -1.72]	0.001 *
Number of medication (Ref = < 5)
> 5 medications	0.015 [-0.032;0.028]	0.884	1.87 [-2.23; 5.98]	0.490

* p ≤ 0.05;

FBS = Fasting blood sugar level; HbA1c = Glycosylated hemoglobin; DM = Diabetes Mellitus; MTF = Metformin; BMI = Body mass index; β-Coeff = Beta coefficient; CI = Confidence interval; SE = Standard error & Ref = Reference.

Discussion

This study aimed to assess the HRQoL and its determinants among patients with T2DM at a tertiary care hospital in Ethiopia, using the EQ-5D-5L instrument. Overall, patients with T2DM reported problems with all descriptive dimensions ranging from 34.1% to 67.3%. We found that the mean health preference-based utility score for patients with T2DM was 0.87, which is lower than the utility score of 0.92 for the general Ethiopian population [37]. Consistent with previous studies [7, 10, 14], duration of diabetes, uncontrolled blood sugar level, insulin usage, obesity, and diabetes-related complications were negatively associated with HRQoL.

Notably, only 8% of patients reported a perfect health state (11111), and approximately 4% reported having the best imaginable health (100%), which is lower than the general population, demonstrating the significant impact of T2DM on patients’ HRQoL. Similar to studies conducted in other countries [21, 37, 38], we found that pain/discomfort was the most affected dimension (67.3%) followed by mobility (60.5%). In a Chinese study, however, most of the patients reported problems in pain/discomfort and anxiety/depression [39]. Indeed, these discrepancies among studies could be due to differences in socioeconomic characteristics, duration of diabetes, comorbidities, diabetes-related complications, and health care system-related factors [12, 40]. In line with the previous studies’ findings [11, 41], patients with frequent insulin injections and uncontrolled blood sugar levels reported more problems with EQ-5D-5L dimensions. We also found that most participants were physically inactive and should be encouraged to exercise to improve their health status. In this study, usual activities were the least reported problem (34.1%) which is comparable to Iranian patients (32.9%) [42], but lower than in Indonesian patients (48%) [36]. This may indicate that the majority of patients with T2DM are capable of doing daily routine activities such as work and study, and family or leisure activities.

When comparing our findings with previous studies, the mean EQ-5D-5L utility score (0.87) was approximately similar with studies from Iran (0.89) [23], Korea (0.87) [43], Finland (0.85) [44], and Japan (0.86) [45], but higher than reported in an Indonesian study (0.77) [11], and lower than a Chinese study’s findings (0.939) [14]. The mean EQ-VAS score was computed to be 76.34 while previous studies reported 56.8 to 80.06% [14, 23, 42, 45, 46]. The differences in socioeconomic characteristics, health system, and patient characteristics, as well as the value set, we used might have contributed to these variations.

Our study showed that patients’ HRQoL can be affected by sociodemographic characteristics. The EQ-5D-5L utility score decreased from 0.97 in relatively younger patients with T2DM to 0.85 in older patients, which is consistent with previous studies [9, 47]. This could be explained by the progressive increment of different types of comorbidities and diabetes-related complications in the older populations [17, 48]. Consistent with previous studies [20, 23, 41], educational status was correlated with a higher EQ-5D-5L utility score. Patients with better education might have a better understanding of their disease, treatment regimens, and diabetes-related complications. As a result, they could become more diligent about their illness and medication adherence that ultimately enhances their HRQoL [20]. Conversely, poor glycemic control had a negative correlation with EQ-5D-5L utility and EQ-VAS scores; similar findings were reported elsewhere [10, 18]. Javanbakht et al. reported that diabetes-related complications such as nephropathy and retinopathy were associated with reduced EQ-5D-5L utility and EQ-VAS scores [43], where the EQ-VAS decrease with the magnitude of 20 in patients who had both complications as compared to no complication, suggesting that having both diabetes-related complications are associated with a marked reduction in HRQoL. Poorly controlled diabetes might increase the risk of disease progression that leads to reduced HRQoL [10, 18].

In Tobit regression models, longer duration of diabetes, uncontrolled blood sugar level, insulin usage, obesity, and presence of diabetic-related complications were negatively associated with EQ-5D-5L utility and EQ-VAS scores [17, 42, 48]. Similarly, Redekop et al. and Nguyen et al. studies also found insulin therapy, presence of complications, and obesity were associated with lower HRQoL [22, 28]. As demonstrated by Tran et al. interventions focused on controlling blood glucose levels, diabetes-related complications, and comorbidities may help to improve HRQoL in patients with diabetes. Similar to our findings, a Vietnamese study demonstrated that having comorbidity reduced the patient’s utility [28]. Furthermore, insulin therapy associated decrement in HRQoL might also be explained by the pain of multiple injections. Thus, management protocols for patients with T2DM and clinicians should pay attention to adequately controlling blood glucose levels, diabetes-related complications, normalized body weight, managing comorbidities as well as achieving optimal glycemic control in patients with T2DM to improve HRQoL.

Our study has some limitations. Since this is a cross-sectional study, causality cannot be established between HRQoL and its predictors. As our study was carried out at a single hospital, where the majority of the patients had medical comorbidities and diabetes-related complications, our findings may not represent the health status of diabetes patients across Ethiopia. Third, the current study was conducted over a short time frame and possible changes in the disutility of health problems over time remained unclear. We, therefore recommend longitudinal studies to assess whether differences exist. Despite these limitations, our study generated utility values based on a value set specific for the Ethiopia population, avoiding potential bias given preference-based measures of HRQoL are likely to vary across different populations. Our findings can be used by practitioners and policymakers in designing and implementing strategies aimed at improving diabetes care. Moreover, the study findings can be used as a benchmark to continuously monitor treatment or intervention impact on patients with T2DM. The generic preference-based measures including EQ-5D-5L are the most widely used instruments for assessing health status around the world [33]. However, because they are less sensitive, it is also recommended that disease-specific instruments are included to capture essential aspects of health that are specific to the condition. Ethiopia does not have HTA guidelines, and the choice of preference-based measures remains unclear. This can make it difficult for the ministry to make consistent decisions, given that different preference-based measures yield systematically different values. In many countries, the EQ-5D-5L is the preferred generic preference-based measure for evaluations of health technology [49, 50]. EQ-5D-5L is popular because it is simple to administer, allows for comparisons across interventions and between conditions, and the data reflect the mean value for the population of interest (usually based on values from members of the general population) [18, 29]. Hence, the utility values we generated using EQ-5D-5L could be used to conduct future cost-utility analysis and prioritize interventions, programs, and policies targeting improving health outcomes of Ethiopian patients with diabetes.

Conclusions

Our study showed that patients with T2DM had a lower EQ-5D-5L utility than the general population. Patients with T2DM frequently reported problems with pain/discomfort and mobility. Being older, a longer duration of diabetes, insulin use, obesity, inadequate glycemic control, and diabetes-related complications were significant negative predictors of HRQoL. Hence, interventions to improve HRQoL should focus on achieving adequate glycemic control, promoting exercise to reduce obesity, reducing pain/discomfort, and reducing diabetes-related complications. The health preference-based utility value generated in this study could be used to monitor clinical outcomes and conduct economic evaluations of different healthcare interventions in patients with T2DM.

All raw data (STATA software).

(DTA)

Click here for additional data file.

English and Amharic version of EQ-5D-5L questionnaires.

(DOCX)

Click here for additional data file.

Percentage of self-reported health problems among patients with T2DM using EQ-5D-5L descriptive systems.

(DOCX)

Click here for additional data file.

23 Jul 2021

PONE-D-21-20037

Health-related quality of life of patients with type 2 diabetes mellitus​ at a tertiary care hospital in Ethiopia

PLOS ONE

Dear Dr. Gebremariam,

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.

I have received the reports from our advisors on your manuscript which you submitted to PLOS ONE.

Based on the comments received, I feel that your manuscript could be reconsidered for publication should you be prepared to incorporate major revisions.

When preparing your revised manuscript, you are asked to carefully consider the reviewer comments below and submit a list of responses to the comments.

Editor Comments: The paper should be checked by a professional speaker of English before complete acceptance.

Please submit your revised manuscript by Sep 04 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see:  http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at  https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Muhammad Sajid Hamid Akash

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety. All PLOS journals require that the minimal data set be made fully available. For more information about our data policy, please see http://journals.plos.org/plosone/s/data-availability.

"Upon re-submitting your revised manuscript, please upload your study’s minimal underlying data set as either Supporting Information files or to a stable, public repository and include the relevant URLs, DOIs, or accession numbers within your revised cover letter. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. Any potentially identifying patient information must be fully anonymized.

Important: If there are ethical or legal restrictions to sharing your data publicly, please explain these restrictions in detail. Please see our guidelines for more information on what we consider unacceptable restrictions to publicly sharing data: http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. Note that it is not acceptable for the authors to be the sole named individuals responsible for ensuring data access.

We will update your Data Availability statement to reflect the information you provide in your cover letter.

3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

4. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 3 in your text; if accepted, production will need this reference to link the reader to the Table.

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.

6. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

[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: No

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: No

**********

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: Thank you for the invitation to review this manuscript which reports the results of a survey on health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia. This is much needed and long overdue work, and I commend the authors for conducting this work. The manuscript reads well and has several methodological strengths including the use of a validated Amharic version of EQ-5D-5L instrument, which can be regarded as a good source of evidence for conducting economic evaluations.

My only comment is around the sampling strategy. The authors mentioned that a total of 360 T2DM patients were interviewed. While the recruitment strategy is clear, the sampling techniques and assumptions behind the number “360” is not clear. I also recommend explaining “consecutive sampling method” in a bit more detail here.

Result, analysis, and discussion are well executed and well written.

Reviewer #2: Thank you for the opportunity to review this interesting paper. The study measured health related quality of life and identified associated factors among people with diabetes at a tertiary care hospital in Ethiopia. The study found a median (IQR) EQ-5D-5L utility and EQ-VAS scores of 0.95 (0.88-0.96) and 80 (75.0-85.0), respectively. The two dimensions of EQ-5D-5L for which the most health problems were reported were pain/discomfort (67.3%) and mobility (60.5%). Poor glycemic control, longer duration of diabetes, insulin usage, and being obese had significant negative association with HRQoL.

A very important strength of the study is the use of Ethiopian value sets which makes the findings very suitable for future economic evaluations in the country and other similar settings. However, the authors may want to consider the following points in their revision of the manuscript.

Major comments:

• The methods section provides no information on how sample size was determined and sampling was undertaken. This is important to comment on the appropriateness of inferences even at hospital level.

• While the use of generic instrument in the study is great, there are still benefits of using disease specific tools especially in countries such as Ethiopia where cost utility studies are rare. It would be interesting to consider this perspective in the discussion.

• The introduction is excellent in terms of discussing the factors affecting HRQoL of patients with diabetes. However, it would be great to have a succinct summary of previous HRQoL studies among patients with diabetes in Ethiopia instead of saying “However, there is a paucity of data on diabetic patient’s HRQoL in Ethiopia” even without any reference citation.

Minor comments:

• I am not sure if this is a personal preference but using phrases such as “people with diabetes” or “patients with diabetes” feels much better than “diabetic patients”

• The study hospital has been referred to as “tertiary care hospital” and Specialized Hospital at different parts in the paper. It would be to use one of these consistently throughout.

• In the conclusion of the abstract: I would include one or a couple of the main factor/s instead of leaving it as “several factors”

• According to Table 1, 32% of the respondents were illiterate? Can you please define what “illiterate” mean in this study? And how was the consent signing done for these respondents?

• Table 2 it would be better to present the order of “Yes” and “No” consistently

• Language issues: Although the paper’s message is not compromised due to language issues, there are some grammar issues and typo here and there. Therefore, a careful reading and editing is encouraged. The following are some examples I picked:

o “All data collectors had the training to ensure uniformity and reduce inter-observer bias in data collection.” Should be “All data collectors had a training to ensure uniformity and reduce inter-observer bias in data collection.”

o Page 7 line 160: “More than half (55.7%) of the patients were female; 249 (70.7%)…” should be “More than half (55.7%) of the patients were females; 249 (70.7%)…”. In addition, n(%) reporting has not been consistently followed.

o In Table 1, average monthly household income (ETB), average row there is some erroneously pasted number (2314.87 (2921.9))

o Page 8 line 168: “using lifestyle modifications”… adopting lifestyle modifications and…” The majority (76.4%) had one or more comorbidities”… The majority of patients (76.4%) had one or more comorbidities

o Page 10, line 192: The following sentence needs to state the comparators “On the other hand, patients who were living with diabetes for a longer duration and taking more than 5 medications had significantly lower EQ-5D-5L index and EQ-VAS scores compared to their counterparts with X and Y, respectively

o In Table 2, “Lifestyle modification use” can be more informative if paraphrased as “adoption of lifestyle modification” or similar. Similarly, in the same table, “obesity” should be written as “obese” and “> 2 complication” as “> 2 complications”

o Page 9 line 179: “The most frequent health problems were the pain/discomfort dimension” should be paraphrased as “The most frequent health problems were reported for the “pain/discomfort dimension”

o On page 10 line 189: The distribution of the EQ-5D-5L utility and EQ-VAS scores was were skewed => were skewed…

o Page 16 line 262: “Conversely, glycemic control had a negative correlation with EQ-5D-5L utility and EQ-VAS scores and similar findings were reported elsewhere” is not clear. Was it to mean poorer/weaker glycemic control had a negative correlation with…?

o Page 16 line 267: “suggesting that developing both complications are responsible for a remarkable decline…”

o Page 16 line 274: “I as noted by Tran…”…“The negative association between insulin usaged and…”

**********

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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Befikadu L. Wubishet

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

17 Sep 2021

Point-by -point response

Dear Muhammad Sajid Hamid Akash

Academic Editor,

We are pleased to resubmit the revised version of PONE-D-21-20037 ‘‘Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia’’ for publication. We appreciate the constructive criticisms of the reviewers and the academic editor. We have addressed their concerns and suggestions as outlined below. All changes in the manuscript are indicated by track changes and detailed explanation as to why the changes are required has been provided here in the point-by-point response.

We hope that these revisions improve the manuscript, and you will consider it worthy for publication.

Sincerely,

Girma Tekle Gebremariam, Corresponding Author

School of Pharmacy, Addis Ababa University

Zambia Street, Addis Ababa, Ethiopia

Email: girma.tekle@aau.edu.et

Response to reviewers' comments and questions

Academic editor comments and suggestions

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Thank you. The manuscript has been revised according to PLOS ONE format.

2. In your Data Availability statement, you have not specified where the minimal data set underlying the results described in your manuscript can be found. PLOS defines a study's minimal data set as the underlying data used to reach the conclusions drawn in the manuscript and any additional data required to replicate the reported study findings in their entirety.

Thank you for pointing out this. We have mentioned in the manuscripts that ‘‘The raw dataset is available as supporting information.’’ (Please see line 354).

3. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Thank you. The ethics statement has been removed from the last section of the manuscript (Please see line 356).

4. We note you have included a table to which you do not refer in the text of your manuscript. Please ensure that you refer to Table 3 in your text; if accepted, production will need this reference to link the reader to the Table.

Thank you. Table 3 has been cited in the text (please see line 232).

5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly.

Thank you. Captions for all supporting information have been included as ‘‘S2 Table: Percentage of self-reported health problems among patients with T2DM using EQ-5D-5L descriptive systems (please see line 519).’’

6. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Thank you for your suggestion. We have revised all the reference list and citations. We have also added some additional references (reference # 29-32, 35, 49).

Reviewer #1:

Thank you for the invitation to review this manuscript which reports the results of a survey on health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia. This is much needed and long overdue work, and I commend the authors for conducting this work. The manuscript reads well and has several methodological strengths including the use of a validated Amharic version of EQ-5D-5L instrument, which can be regarded as a good source of evidence for conducting economic evaluations.

My only comment is around the sampling strategy. The authors mentioned that a total of 360 T2DM patients were interviewed. While the recruitment strategy is clear, the sampling techniques and assumptions behind the number “360” is not clear. I also recommend explaining “consecutive sampling method” in a bit more detail here.

Response: Thank you for your feedback! In the revised manuscript, we have provided more detailed information on sample size determination and sampling procedure (please see line 133 to 141). In short, we used single proportion with sample size correction formula to determine sample size and consecutive sampling was used to recruit study participants. Consecutive sampling involves recruiting all the people who meet the inclusion criteria and are conveniently available, as part of the sample. It is akin to convenience sampling. In our study, we recruited all eligible T2DM patients consecutively until we reached our pre-determined sample size. We have provided the detail information about sample size determination and the sampling procedure as follows.

Reviewer #2

Thank you for the opportunity to review this interesting paper. The study measured health related quality of life and identified associated factors among people with diabetes at a tertiary care hospital in Ethiopia. The study found a median (IQR) EQ-5D-5L utility and EQ-VAS scores of 0.95 (0.88-0.96) and 80 (75.0-85.0), respectively. The two dimensions of EQ-5D-5L for which the most health problems were reported were pain/discomfort (67.3%) and mobility (60.5%). Poor glycaemic control, longer duration of diabetes, insulin usage, and being obese had significant negative association with HRQoL. A very important strength of the study is the use of Ethiopian value sets which makes the findings very suitable for future economic evaluations in the country and other similar settings. However, the authors may want to consider the following points in their revision of the manuscript.

Thank you!

Major comments

1. The methods section provides no information on how sample size was determined and sampling was undertaken. This is important to comment on the appropriateness of inferences even at hospital level.

Response: Thank you for your feedback! In the revised manuscript, we have provided more detailed information on sample size determination and sampling procedure (please see line 133 to 141). In short, we used single proportion with sample size correction formula to determine sample size and consecutive sampling was used to recruit study participants. Consecutive sampling involves recruiting all the people who meet the inclusion criteria and are conveniently available, as part of the sample. It is akin to convenience sampling. In our study, we recruited all eligible T2DM patients consecutively until we reached our pre-determined sample size. We have provided the detail information about sample size determination and the sampling procedure as follows.

2. While the use of generic instrument in the study is great, there are still benefits of using disease specific tools especially in countries such as Ethiopia where cost utility studies are rare. It would be interesting to consider this perspective in the discussion.

Response: Thanks for your suggestion. In the last paragraph of the discussion, we added a detail description (please see line 327 to 338). In short, the generic preference-based measures including EQ-5D-5L are the most widely used instruments for assessing health status around the world. However, because they are less sensitive, it is also recommended that disease-specific instruments are included so as to capture essential aspects of health that are specific to the condition. Ethiopia does not have HTA guidelines, and the choice of preference-based measures remains unclear. This can make it difficult for the ministry to make consistent decisions, given that different preference-based measures yield systematically different values. In many countries, the EQ-5D-5L is the preferred generic preference-based measure for evaluations of health technology. EQ-5D-5L is popular because it is simple to administer, allows for comparisons across interventions and between conditions, and the data reflects the mean value for the population of interest.

3. The introduction is excellent in terms of discussing the factors affecting HRQoL of patients with diabetes. However, it would be great to have a succinct summary of previous HRQoL studies among patients with diabetes in Ethiopia instead of saying “However, there is a paucity of data on diabetic patient’s HRQoL in Ethiopia” even without any reference citation.

Thank you for your suggestion, In the last paragraph of the introduction, we added briefly the summary of different findings in Ethiopian among patients with diabetes (please see line 93 to 103). In short, there are no previous studies on HRQoL of patients with T2DM using EQ-5D-5L in Ethiopia; however, a few studies have explored patients' views on the impact of the disease and its treatments. These studies demonstrated that general health, environmental, psychological, physical, bodily pain and vitality were the most affected dimensions of the HRQoL. Additionally, the findings illustrate that diabetes-related complications, old age, obesity, duration of diabetes, insulin and oral anti-diabetic medication use were the major predictors that require comprehensive intervention strategies to enhance the HRQoL of patients with diabetes. Furthermore, the findings showed that HRQoL remains the most disregarded component in routine clinical practice in Ethiopia.

Minor comments

I am not sure if this is a personal preference but using phrases such as “people with diabetes” or “patients with diabetes” feels much better than “diabetic patients”

Thank you for your suggestion. We have used consistently “patients with diabetes”

study hospital has been referred to as “tertiary care hospital” and Specialized Hospital at different parts in the paper. It would be to use one of these consistently throughout.

Thank you for your suggestion. We amended the document and now consistently use the term ‘tertiary care hospitals.’

In the conclusion of the abstract: I would include one or a couple of the main factor/s instead of leaving it as “several factors”

Thank you for your suggestion. The major predictors are mentioned in the conclusion part of the abstract section (please see line 52 to 53). In short, we mentioned the major predictors, being older age, longer duration of diabetes, insulin use, obesity, inadequate glycaemic control, and diabetes-related complications.

According to Table 1, 32% of the respondents were illiterate? Can you please define what “illiterate” mean in this study? And how was the consent signing done for these respondents?

Thank you for the feedback. We obtained written consent for those who can read and write but we found it impractical to do the same for the illiterate (who can’t read and/or write) as they are unable to read an informed consent form and understand the risks and benefits of their participation. Besides, most of our illiterate participants had also no accompanying family members so obtaining written proxy consent was not practical. To clarify this, we added some statements in the ‘ethics’ section and reads as follow:” Written informed consent was obtained from all study participants who were able to read and write before data collection. We obtained verbal informed consent for illiterate participants. Most of our illiterate participants had no accompanying family members or relatives; thus, obtaining proxy written consent was not practical (Please see line.

Table 2 it would be better to present the order of “Yes” and “No” consistently

Thank you. suggestion accepted. We changed and used consistently ‘Yes’ and ‘No’’ (Please see Table 2).

Language issues: Although the paper’s message is not compromised due to language issues, there are some grammar issues and typo here and there. Therefore, a careful reading and editing is encouraged. The following are some examples I picked:

�  “All data collectors had the training to ensure uniformity and reduce inter-observer bias in data collection.” Should be “All data collectors had a training to ensure uniformity and reduce inter-observer bias in data collection.”

Thank you. We revised the manuscript to fix issues related to language.

�  Page 7 line 160: “More than half (55.7%) of the patients were female; 249 (70.7%) …” should be “More than half (55.7%) of the patients were females; 249 (70.7%) …”. In addition, n (%) reporting has not been consistently followed……

Thank you. Suggestion accepted

�  In Table 1, average monthly household income (ETB), average row there is some erroneously pasted number (2314.87 (2921.9))

Thank you for pointing out this. Certainly, it is not an error, however our intention to put this number is to know the mean monthly household income. We deleted the number 2314.87 (2921.9) in Table 1 if it confusing to readers.

�  Page 8 line 168: “using lifestyle modifications” … adopting lifestyle modifications and…” The majority (76.4%) had one or more comorbidities” … The majority of patients (76.4%) had one or more comorbidities

Thank you. Suggestion accepted (Please see line 193).

�  Page 10, line 195: The following sentence needs to state the comparators “On the other hand, patients who were living with diabetes for a longer duration and taking more than 5 medications had significantly lower EQ-5D-5L index and EQ-VAS scores compared to their counterparts with X and Y, respectively.

Thank you. Suggestion accepted (Please see line 222-223) ‘On the other hand, patients who were living with diabetes for a longer duration and taking more than 5 medications had significantly lower EQ-5D-5L index and EQ-VAS scores compared to with patients living for a short period of time and patients taking fewer than 5 antidiabetic medications, respectively.’’

�  In Table 2, “Lifestyle modification use” can be more informative if paraphrased as “adoption of lifestyle modification” or similar. Similarly, in the same table, “obesity” should be written as “obese” and “> 2 complication” as “> 2 complications”

Thank you. All suggestions accepted and please see Table 2.

�  Page 9 line 182: “The most frequent health problems were the pain/discomfort dimension” should be paraphrased as “The most frequent health problems were reported for the “pain/discomfort dimension”

Thank you for your suggestion. The sentence rephrased as “The most frequent health problems were reported for the “pain/discomfort dimension” (Please see line 205-206).

�  On page 10 line 193: The distribution of the EQ-5D-5L utility and EQ-VAS scores was were skewed => were skewed

Thank you. Suggestion accepted

�  Page 16 line 262: “Conversely, glycaemic control had a negative correlation with EQ-5D-5L utility and EQ-VAS scores and similar findings were reported elsewhere” is not clear. Was it to mean poorer/weaker glycaemic control had a negative correlation with…?

Thank you for your suggestion. The negative correlation refers poor glycaemic control and we amended accordingly to make it with poor glycaemic control (please see line 292).

�  Page 16 line 267: “suggesting that developing both complications are responsible for a remarkable decline…”

Thank you. Suggestion accepted

�  Page 16 line 274: “I as noted by Tran…” … “The negative association between insulin usaged and…”

Thank you. Suggestion accepted

Thank you both reviewers!

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

7 Feb 2022

Health-related quality of life of patients with type 2 diabetes mellitus​ at a tertiary care hospital in Ethiopia

PONE-D-21-20037R1

Dear Dr. Gebremariam,

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,

Vijayaprakash Suppiah, PhD

Academic Editor

PLOS ONE

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?

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: No

Reviewer #2: Yes

**********

5. 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

**********

6. 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: thank you for revising the manuscript "Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia" The comments have now been addressed satisfactorily.

Reviewer #2: Thank you for revising the paper. All the suggestions I had on the first draft have been addressed and I don't have any more suggestions for change.

**********

7. 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.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: Yes: Befikadu Wubishet

10 Feb 2022

PONE-D-21-20037R1

Health-related quality of life of patients with type 2 diabetes mellitus at a tertiary care hospital in Ethiopia

Dear Dr. Gebremariam:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Vijayaprakash Suppiah

Academic Editor

PLOS ONE