Treatment outcomes of diabetic ketoacidosis among diabetes patients in Ethiopia. Hospital-based study.

BACKGROUND: There was limited data on treatment outcomes among patients with diabetic ketoacidosis (DKA) in Ethiopia.
OBJECTIVE: The aim of the study was to determine the treatment outcomes of DKA patients attending Debre Tabor General Hospital.
METHOD: A retrospective study was conducted at Debre Tabor General Hospital and data were collected from June 1 to June 30 of 2018. Participants included in the study were all diabetic patients with DKA admitted from August 2010 to May 31, 2018. The primary outcomes were the treatment outcomes of DKA including (in-hospital glycemic control, the length of hospital stay and in-hospital mortality). The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS) version 22. Descriptive statistics was presented in the form of means with standard deviation and binary regression was conducted to determine factors that affect length of hospital stay among DKA patients. RESULT: 387 patients were included in the study. The mean age of patients was 33.30± 14.96 years. The most common precipitating factor of DKA was new onset diabetes mellitus 150(38.8%). The mean length of hospital stay was 4.64(±2.802) days. The mean plasma glucose at admission and discharge was 443.63(±103.33) and 172.94 (±80.60) mg/dL, respectively. The majority 370 (95.60%) of patients improved and discharged whereas 17 (4.40%) patients died in the hospital. Patients with mild and moderate DKA showed short hospital stay; AOR: 0.16 [0.03-0.78] and AOR:0.17[0.03-0.96] compared with severe DKA. Diabetic ketoacidosis precipitated by infection were nearly five times more likely to have long hospital stay than DKA precipitated by other causes; AOR: 4.59 [1.08-19.42]. In addition, serum glucose fluctuation during hospitalization increased the likelihood of long hospital stay, AOR: 2.15[1.76-2.63].
CONCLUSIONS: New onset type 1 diabetes was the major precipitating factor for DKA. Admitted DKA patients remained in hospital for a duration of approximately five days. About five out of hundred DKA patients ended up with death in the hospital. Infection, serum glucose fluctuations and severity of DKA were determinants of long hospital stay. Early prevention of precipitating factors and adequate management of DAK are warranted to reduce length of hospital stay and mortality.

Introduction

Diabetes mellitus (DM) represents a group of metabolic disorders characterized by increased blood glucose concentration. The international diabetes federation estimated that 463 million adults were diagnosed for DM in 2019 [1-4]. Diabetic ketoacidosis (DKA) is an acute life-threatening complication of DM. Multiple pathophysiologic factors have been postulated for the pathophysiology of DKA including oxidative stress and pro-inflammatory cytokines (i.e., tumor necrosis factor-alpha (TNF-α)) that might lead to inadequate insulin secretion or utilization in the body [5-10]. The clinical characteristics of DKA include polyuria, polydipsia, weight loss, vomiting, dehydration, fatigue, mental status change, Kussmaul respirations, tachycardia, and hypotension [11, 12]. A diagnosis of DKA is made when patients are presented with blood pH level of less than 7.30, and bicarbonate level below 18 meq/L along with certain level of mental status impairment [11, 13–15].

Diabetic ketoacidosis is associated with high mortality rates in the developing world [16, 17]. The poor management of DKA can lead to debilitating and potentially fatal complication including cerebral edema and severe hypoglycemia. Mortality of DKA has been reported to be less than 5% in treatment experienced centers of the Americas, Europe and Asia [18, 19]. In Africa, the mortality of DKA is unacceptably high with a reported death rate of 26 to 29% in studies from Kenya, Tanzania, and Ghana [8]. In Ethiopia, mortality from DKA was found be high [20]. A retrospective study conducted at Shashemene Referral Hospital reported that DKA contributed 12% in-hospital mortality [21]. Another study conducted in Hiwot Fana Specialized University Hospital indicated that about 11% of patients with diagnosis of DKA died in hospital [22].

In order to reduce mortality different countries have been undertaking different strategies and prevention measures including diabetes self-management education, increasing the pathophysiology of DKA and adoption of DKA treatment guidelines [19]. However, these strategies have not been appropriately implemented in Ethiopia. In addition, the cost and lack of medication supplies, presence of comorbid conditions, inappropriate insulin storage, medication non-adherence, electrolyte disturbance and smoking habits complicated the prevention and treatment of DKA in Ethiopia [21, 23, 24]. There was limited data on treatment outcomes including hospital stay, glycemic control during hospitalization and in-hospital mortality related to DKA in north Ethiopia. The present study will determine the treatment outcomes of DKA among patients attending general hospital in North Ethiopia. The study findings will be relevant to improve the management of DKA, to minimise in-hospital mortality and to reduce length of hospital stay among DKA patients.

Methods

Study setting and period

This study was conducted at Debre Tabor General Hospital (DTGH) from 1 June 2018 to 30 June 2018. Debre Tabor General Hospital is a government hospital located in Debre Tabor Town, North Ethiopia. The hospital provides twice weekly outpatient services for chronic illness patients including DM, Asthma and Cardiovascular disorders. Outpatient follow-up of DM patients and in-patient management of DKA have been undertaken in the hospital. Insulin administration and fluid resuscitation are the major emergency management of DKA along with treatment of the precipitating factors. The emergency unit of the general hospital delivers the acute management of DKA followed by in-patient service until the patient status indicate improvement in terms of functional and clinical parameters.

Study design and population

A hospital based retrospective study was conducted on DKA patients presented to DTGH. All DKA patients who were admitted to inpatient ward from August 1, 2010, to May 31, 2018, were included in the study.

Inclusion and exclusion criteria

Inclusion criteria

Participants included in the study were all adult (age≥18 years old) diabetic patients with DKA.

Exclusion criteria

Pregnant and breastfeeding women were excluded from the study.

Sample size determination and sampling technique

Patients who fulfilled the inclusion criteria were selected using Convenience sampling technique.

Study variables

Dependent variables

Length of hospital stay, glycemic control and in-hospital mortality.

Independent variables

Age, gender, residence, family history of DM, types of DM, severity of DKA, blood glucose level, blood pressure, respiratory rate, pulse rate, co-morbidities, and precipitating factors.

Data collection methods

Medical record of patients with DKA admitted to the hospital was traced from patient logbook and drawn from card room. The data were collected by trained data collectors using structured pretested data extraction tool. Data was collected on demographics, presenting symptoms, precipitating causes of DKA, vital signs, biochemical profiles (admission blood glucose, admission urine ketone, urine glucose), length of hospitalization and in-hospital mortality.

Data quality control technique

Data collectors were trained intensively on the contents of the questionnaire, data collection methods and ethical concerns. In order to ensure its quality, the questionnaire was pretested in 5% of DM subjects who were attending DTGH. The findings of the pretest were not included in the final analysis. The necessary amendment was done on the final version of the questionnaire during the process of the pretest. Expert consultation was sought after developing the questionnaire for validation. Supervision and checking was made by the supervisor to ensure the completeness and consistency of the collected data. All collected data were examined for completeness and consistency during data management, storage, and analysis

Data analysis

All the statistical data was carried out using Statistical Package for Social Sciences (SPSS), version 22 (SPSS Inc., Cary, NC, USA) [25]. Descriptive statistics was calculated for categorical variables. Bivariate analysis was done and variables with a P–value <0.2 were considered statically significant and analyzed using multivariate logistic regression. Binary logistic regression was done to determine factors that affect length of hospital stay. Variables with p–value of less than 0.05 with 95% confidence interval were considered statistically significant. Hosmer–Lemeshow goodness- of -fit test was done to check model fitness.

Hyperglycemia is defined as random plasma glucose >200 mg/dL and

Hypoglycemia is defined as a blood glucose level ≤70 mg/Dl [26, 27].

Euglycemia is defined as serum glucose level between 100 and 200mg/dL [11].

Long-hospital stay was defined as hospital stay for more than seven days [28].

Short-hospital stay was defined as the patient stayed in the hospital for ≤ 7 days [29].

Treatment outcomes defined as a composite of level of glycemic control, the length of hospital stay and in-hospital mortality of DKA.

Good glycemic control: Proportion of patients having plasma glucose <250 mg/dL within 6 hours of therapy

Poor glycemic control: Proportion of patients having plasma glucose >250 mg/dL after 6 hours of therapy.

Mild DKA is defined as (arterial pH, 7.25–7.30 and serum bicarbonate, 15–18 mEq/L).

Moderate DKA is defined as (arterial pH, 7.00 to < 7.25 and serum bicarbonate, 10 to < 15 mEq/L).

Severe DKA is defined as (arterial pH, < 7.00and serum bicarbonate, < 10 mEq/L) [11, 18].

Rebound Ketonuria: It is defined as the increase in ketone level once it is controlled with insulin management and fluid resuscitation

Results

Sociodemographic characteristics of DKA patients

A total of 387 patients were included in the study. Out of them, 305 (78.8%) and 82(21.2%) patients had T1DM and T2DM, respectively. The mean age of the patients was 33.30± 14.96 (range 15–64 years). More than half of the patients were urban residents. Family history of diabetes was reported in 50 (12.9%) of patients. The mean duration of DM was 26.21 (±39.62) months (Table 1).

Table 1

Sociodemographic and disease status of DKA patients admitted at DTGH from August 2010 to May 31, 2018(n = 387).

Characteristics	Frequency (%)
Age
Overall (Mean ±SD)	33.29 (±14.96)
15–24	135(34.9)
25–34	95(24.5)
35–44	76(19.6)
45–54	44(11.4)
55–64	37(9.6)
Sex
Male	143(37.00)
Female	244(63.00)
Residence
Urban	264(68.20)
Rural	123(31.80)
Family history of diabetes
Yes	50(12.90)
No	53(13.70)
Unknown	284(73.40)
Types of DM
Newly diagnosed T1DM	146(37.70)
Newly diagnosed T2DM	21(5.40)
Known T1DM	159(41.10)
Known T2DM	61(15.80)
Duration of DM (mean± SD)	26.22(±39.67)

Clinical characteristics of DKA patients

Polyuria and polydipsia (97.9%) were the most frequent clinical manifestations of DKA patients followed by easy fatigability (82.9%) and abdominal pain (47.0%). The mean pulse rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR) and body temperature at admission were 94.17(±14.54),104.30(±15.51), 67.84(±10.42), 24.85(±4.30) and 36.47(±0.94), respectively. The mean frequency of DKA episodes was 1.5 times (maximum frequency of DKA episode was 8 times and the minimum was only once) since the first diagnosis of DM (Table 2).

Table 2

Clinical characteristics of DKA patients admitted at DTGH from August 2010 to May 31, 2018(n = 387).

Clinical characteristics	Frequency (%)
Frequency of DKA episode
once	272(70.30)
twice	74(19.10)
Three times	20(5.20)
≥ four times	21(5.50)
Polyuria and Polydipsia	379 (97.90)
Fatigability	321(82.90)
Abdominal pain	182(47)
Vomiting	70(18.10)
Others*	36(9.3)
Pulse rate (mean±SD)	94.17(±14.54)
Normal	276(71.30%)
Tachycardia	108(27.90%)
Bradycardia	3(0.8%)
Temperature (0C)	36.47(±0.94)
Respiratory rate (mean± SD)	24.85(±4.300)
Respiratory status	Frequency (%)
Normal	261(67.40)
Tachypnea	126(32.60)
SBP (mean± SD)	104.30(±15.510)
DBP (mean± SD)	67.84(±10.422)
Hypotension	46(11.9)
Normal	227(58.7)
Elevated	14(3.6)
Stage 1	73(18.9)
Stage 2	27(7.0)
Urine Ketone
<+3	224(57.88)
≥+3	163(42.11)
Urine glucose
Free	2(0.50)
+1	22(5.70)
+2	161(41.60)
+3	130(33.60)
+4	33(8.50)
Not measured	39(10.10)
Comorbidities
No	355(91.70)
Yes	32(8.30)

*Kussmaul respiration, headache, shortness of breath, delirium, cold extremities, coughs, blurring of vision, vertigo, tinnitus, and sweating.

Precipitating factors of DKA

About 258(66.67%) of DKA patients had known precipitating factor for DKA. The predominant precipitating factor of DKA was new onset T1DM 150(38.8%) followed by poor compliance to antidiabetic treatment (14.7%) and infections (13.2%), respectively. About 129(33.33%) patients had no known precipitating factor (Fig 1). Urinary tract infection was the most common infection 24(47.05%) that precipitated DKA and respiratory tract infection 21(41.17%) was the second most common infection that precipitate DKA.

Fig 1

Precipitating factors of DKA patients admitted at DTGH from August 2010 to May 31, 2018(n = 387).

Severity of DKA and ketone bodies

About three-fourth (75.5%) of the patients were presented with mild DKA, 74(19.1%) were presented with moderate DKA and the remaining 21(5.4%) were diagnosed with severe DKA. Around (17.6%) patients experienced rebound ketonuria once and (1.6%) patients had rebound ketone two times after hospital admission. The average duration of time required for complete removal of ketonuria was 9.23(±10.954) hours (Table 3).

Table 3

Severity of DKA and ketone bodies among DKA patients admitted at DTGH from August 2010 to May 31, 2018(n = 387).

Severity of DKA and urine ketone bodies	Frequency (%)
Mild DKA	292(75.50)
Moderate DKA	74(19.10)
Severe DKA	21(5.40)
Frequency of ketone fluctuation
No ketone body fluctuation	310(80.10)
Once	68(17.60)
Two times	6(1.60)
Three times	1(0.30)
Four times	1(0.30)
Five times	1(0.30)
Time required for Ketone free state (hours)	9.23(±10.95

The level of glycemic control of DKA patients

The mean plasma glucose at admission and discharge was 443.63(±103.33) and 172.94 (±80.60) mg/dL, respectively. The frequency of serum glucose changes during hospitalization was 6.78(±4.43) times ranging from 0 to 32 times. The average time required to attain euglycemic state was 1.89(±1.36) (range 1–11) days after admission. Nearly three-fourth of patients achieved euglycemic state within five days of admission. About 60% of patients discharged with the serum glucose within the normal range and 127(32.8%) patients were discharged with serum glucose above the normal level (hyperglycemia). Hypoglycemic episode was observed in 70(18.10%) patients. Overall, 201(51.94%) patients did not attain glucose level below 250mg/dL in six hours (Table 4).

Table 4

Glucose level during hospitalization in DKA patients at DTGH from August 2010 to May 31, 2018 (n = 387).

Glucose level during hospitalization	Frequency (%)
Glucose level at admission	443.63(±103.33)
Glucose level at discharge	172.94(±80.60)
Frequency of glucose level change	6.78(±4.43)
Time require to achieve euglycemia (days)	4.37(±2.68)
Maximum glucose values	263.86(±123.20)
Minimum glucose values	39.67(±57.31)
Time for glucose to be <250mg/dL(days)	11.08(±15.121)
Good glycemic control	186(48.06%)
Poor glycemic control	201(51.94%)
Glycemic control level at discharge
Hyperglycemia	127(32.80)
Euglycemic	239(61.80)
Hypoglycemia	21(5.40)
Frequency of hypoglycemic episodes
0	317(81.90)
1	47(12.10)
2	11(2.80)
3	10(2.60)
5	1(0.30)
≥5	1(0.30)

Length of hospital stay and mortality

The mean length of hospital stay was 4.64±2.802 days, ranging from (1–18) days. About 79 (20%) patients had long hospital stay (>7days). Majority 370 (95.60%) of patients improved and discharged whereas 17 (4.40%) patients died in the hospital.

Factors affecting length of hospital stay

Determinants of long hospital stay on binary logistic regression analysis were age (between 35–44), severity of DKA, presence of glucose fluctuation and infections. Patients who had mild DKA showed 84% of odds of reduction in hospital stay, AOR: 0.16 [95%CI: 0.03–0.78] and moderate DKA patients have 83% less likely to have long hospital stay; AOR: 0.17[95%CI: 0.03–0.96] than severe DKA. Patients who were within age range of 35–44 had 87.5% likely hood of reduction on long hospital stay than patients of age between 55–64 years; AOR: 0.125[0.017–0.92]. Patients whose DKA was precipitated by infection were 5 times more likely to have long hospital stay than patients with DKA precipitated by unknown causes; AOR: 4.59[1.08–19.42]. In addition, for every episode of the glucose level fluctuation, the likelihood of long hospital stay increased more than 2 times; AOR: 2.15[1.76–2.63] (Table 5).

Table 5

Determinants of hospital stay in DKA patients at DTGH from August 2010 to May 31, 2018(n = 387).

Variable	Length of hospital stay		Crude Odds Ratio	Adjusted Odds Ratio
	Short (≤ 7 days (n = 308)	Long (>7 days(n = 79)
Age
18–24	98 (25.32%)	37 (9.56%)	1.61(0.65–4.00)	0.251 (0.03–1.80)
25–34	79 (20.41%)	16 (4.13%)	0.86(0.32–2.31)	0.40 (0.05–3.10)
35–44	62 (16.02%)	14 (3.16%)	0.96(0.32–2.64)	0.125 (0.017–0.92) *
45–54	39 (10.07%)	5 (1.29%)	0.54(0.15–1.90)	0.112 (0.01–1.00)
55–64	30 (7.75%)	7 (1.80%)	1	1
Sex
Male	117 (30.23%)	26 (6.71%)	1	1
Female	191 (49.35%)	53 (13.69%)	0.80 (0.47–1.35)	2.162 (0.87–5.31)
Residence
Urban	219 (56.58%)	45 (11.62%)	1.85(1.12–3.09) *	0.446 (0.18–1.093)
Rural	89 (22.99%)	34 (8.78%)	1	1
Type of DM
Type 1	237 (61.24%)	68 (17.57%)	0.54(0.27–1.07)	1.028 (0.19–5.30)
Type 2	71 (18.34%)	11 (2.84%)	1	1
History of DM
New	123 (31.78%)	44 (11.36%)	0.52(0.32–0.87) *	0.76 (0.06–8.68)
Known DM	185 (47.80%)	35 (9.04%)	1	1
Frequency of DKA	1.53 ± 1.00	1.37 ± 0.98	0.82(0.60–1.11)	1.02(0.62–1.68)
Pulse rate	93.94 ± 14.48	95.03 ±14.84	1.00(0.98–1.02)	1.00 (0.97–1.04)
SBP	104.92 ± 15.76	101.90 ±14.32	0.98(0.96–1.00)	0.99(0.95–1.03)
DBP	68.36 ± 10.30	65.82 ± 10.69	0.97(0.95–1.00)	0.98(0.93–1.03)
Respiratory rate	24.91 ± 4.180	24.65 ± 4.764	0.98(0.92–1.04)	0.99(0.89–1.10)
Temperature	36.47 ± 0.94	36.44 ± 0.93	0.96(0.74–1.25)	1.08(0.70–1.66)
Duration of DM	27.46 ± 40.39	21.33 ± 36.33	0.99 (0.98–1.00)	0 .99 (0.98–1.01)
Severity of DKA
Mild	237 (61.24%)	55 (14.21%)	0.31(0.12–0.77) *	0.16(0.03–0.78)*
Moderate	59 (15.24%)	15 (3.87%)	0.34(0.12–0.95) *	0.17(0.03–0.96)*
Severe	12 (3.10%)	9 (2.32%)	1	1
Comorbidities
Yes	28 (7.23%)	4 (1.03%)	1	1
No	280 (72.35%)	75 (19.37%)	0.53(0.18–1.56)	1.77(0.34–9.14)
Precipitating factors
Infection	39 (10.07%)	12 (3.10%)	1.78(0.79–4.00)	4.59(1.08–19.42) *
Omission	50 (12.91%)	7 (1.80%)	0.81(0.32–2.05)	0.91(0.17–4.81)
New DM	109 (28.16%)	41(10.59%)	2.17(1.18–3.98) *	3.46(0.39–30.81)
Other	110 (28.42%)	19 (4.90%)	1	1
RBS	435.68 ± 103.15	474.61±98.717	1.004(1.001–1.006) *	1.00(0.99–1.00)
Admission urine ketone
Urine ketone <+3	182 (47.02%)	42 (10.85%)	1.27(0.77–2.09)	1.86(0.74–4.66)
Urine ketone ≥+3	126 (32.55%)	37 (9.56%)	1	1
Number of times serum glucose fluctuates	5.33 ± 2.84	12.46±4.93	1.85(1.61–2.15) **	2.15(1.76–2.63) **
Serum glucose at discharge	171.99 ± 80.40	176.62±81.78	0.648(0.99–1.004)	1.002 (0.99–1.007)
The frequency of ketone fluctuation	0.22 ± 0.50	0.32±0.72	1.32(0.88–1.96)	0.638 (0.03–1.36)

p<0.05

p <0.01, RBS = Random blood sugar

Rate of decline in hyperglycemia among DKA patients

After hospital admission, the level of glucose falls rapidly in T1DM patients while gradual decline of hyperglycemia was observed in T2DM patients. The length of hospital stay (in days) was plotted against the type of DM in Kaplan Meir analysis which indicated that the hyperglycemic episode subsided sooner among T1DM group when patients were followed for a duration of hospital stay [Log rank = 3.15, p-value = 0.03] (Fig 2).

Fig 2

Rate of decline in hyperglycemia among DKA patients.

Discussions

Successful treatment of DKA requires a prompt correction of hyperglycemia, dehydration, ketones, and acidosis [11-13]. The management of DKA involves the administration of regular insulin via continuous intravenous infusion along with adequate fluid resuscitation and treatment of precipitating factors. This ultimately helps to lower the blood glucose below 250 mg/dL within 6 hours of initiation of treatment [11, 30, 31]. But the findings of this study showed that the average time required to lower plasma glucose below 250mg/dl was 11 hours which is longer than the recommended time of achieving normoglycemia. The reason for this long duration of time for the attainment of goal glucose level could be a frequent serum glucose fluctuation after hospitalization. In our study, patients had a serum glucose fluctuation of more than seven times. Patients’ serum glucose increased by a maximum 263 mg/dl and a minimum of 40mg/dL above the admission glucose. Correcting this wide range fluctuation of serum glucose might take long time to obtain euglycemic state.

Our study depicted that the most frequent clinical presentations were polyuria and polydipsia (97.9%). A cross-sectional study conducted at Dilla referral hospital reported that DKA patients were commonly presented with dry mouth (30.2%) followed by altered mentation (27.8%) [32]. Our finding was in line with a study done in Libya and Nigeria [33-35]. On the contrary abdominal pain appeared to be the most common presenting symptoms in a study conducted in Egypt [36]and vomiting was the major clinical presentation in a research done at Saudi Arabia [37]and India [38]. The frequent occurrence of these symptoms in DKA patients could be due to the presence of insulin deficiency and hyperglycemia that results osmotic diuresis which in turn resulted in polyuria and polydipsia [39].

Our study showed that new onset type 1 DM was the most common precipitating factor (38.8%) followed by poor compliance to antidiabetic treatment (14.7%). New onset type 1 DM was the major precipitating factor of DKA in the present study due to the fact that our sample population constituted large number of type 1 diabetes patients in which majority of them presented with first incidence of the disease with cardinal DKA due to absolute insulin deficiency unlike T2DM patients [40]. Another study in southwestern Ethiopia reported that the most common precipitants of DKA were infections (59%), non-compliance to medications (32.3%), and newly diagnosed diabetes (23.6%), respectively [41]. A study conducted in children’s hospital in Addis Ababa revealed that the most common precipitating factors were infection (52%), omission of insulin (16%) and parasitic infection (12%) [42]. Our findings are in line with a study done in sub-Saharan Africa in which the major precipitants of DKA were new onset diabetes, missed insulin doses and infections [3]. On the other hand missed insulin dose were the most common precipitating factor in Zambia [16], Saudi Arabia (2015) [37], Libya [33]. Nairobi [43], New Zealand [44], Brazil [45], and Israel [46].

Infection was also found to be the frequent reason for the incidence of DKA in different studies. A research done in Jimma, Egypt, India, Pakistan, South Africa and Bangladesh revealed that infection was the major precipitant of DKA [20, 36, 38, 47–50]. Among infections urinary tract infection 24(47.05%) was the most common infection that precipitated DKA in our study. On the contrary respiratory tract infections were predominant infections that precipitated DKA in Libya (2007) [33], and Kenya [43]. As of the reason for the occurrence of frequent urinary tract infections, it can be due to the fact that females patient took the large proportion of our sample population in whom urinary tract infection remain the most common infection [51, 52]. Residing in developing country where hygiene is a significant problem could also favor along with comfortable condition for UTI in DM patients. Attention should be sought on self-management and personal hygiene to ultimately prevent infection.

Also, our study showed that drug non-adherence had significant contribution for DKA. Non-adherence may be due to scarcity of the antidiabetic medications or lack of awareness on how to use the drugs [53]. Therefore, it is recommended that those medications with the lowest possible price should be availed and awareness should be created on diabetic self-management and the importance of adherence in preventing the occurrence of diabetic complications.

Our study revealed that the estimated mean length of hospital stay was around five days. A cross-sectional study conducted at Jima University Hospital reported a median length of hospital stay of 6 days [41]. Our finding is lower than a study done in sub Himalayan region, Pakistan, South Africa and Saudi Arabia in which the estimated hospital stay was around 7–9 days [6, 37, 48, 49]. The hospital stay was longer when compared with Australia and New Zealand [54]. This discrepancy might be the due to the better management of the precipitating factors, adequate management of hyperglycemia and complications in developed countries.

Many factors were found to influence the length of hospital stay in the present study. It was indicated that the length of hospital stay was affected by age, severity of DKA, number of times serum glucose fluctuations and infections. Patients with mild DKA had shorter length of stay than patients with severe DKA. A study done at Israel [46] and Libya [33] showed that length of hospital stay was worse in the severe DKA. Similarly, a study done in Bangladesh showed that patients with mild DKA took short duration to recover than severe DKA [55]. Patients with severe DKA are frequently presented with severe acidotic state and severe alteration in the level of consciousness [5, 11]. This might cause complications [56] and correcting severe DKA requires long period of time which might be lead to long hospital stay in severe DKA patients. Our study also showed that patients whose DKA precipitated by infection had long hospital stay than those precipitated by undefined precipitants. This result was in line with a research done India [57]. The reason might be stress hormones secretion during infection and had detrimental effects on the immune system [58]. Consequently, patients with compromised immune system might require long period to recover. In addition, infection treatment also requires long duration of hospitalization.

In the present study 4.4% of patients died in the hospital which is almost equal with a finding in Israel 4.1% [46]. The high rate of mortality in our study might be due to high prevalence of infection which was approximately 13.2% and treatment complications including hypoglycemia as well as comorbidities. The mortality of DKA is unacceptably high with a reported death rate of 26 to 29% in studies from Kenya, Tanzania, and Ghana [28]. The cost of medications and lack of medication supplies might have contributed for the high mortality rates in Africa.

In general, the present study highlighted the treatment outcomes of DKA in terms of in-hospital mortality, glucose control and length of hospital stay. However, the study did not reveal the overall management of DKA including fluid resuscitation, and insulin administration. In addition, the retrospective nature of the study design could not enable to evaluate all outcomes of DKA. Our study did not include DKA patients whose age less than 18 years, which was the most vulnerable group of individuals for type 1 DM. Another study could be conducted to evaluate the overall trend of DKA management and outcomes in prospective approach. Part of this manuscript was presented as a preprint to research square and bioRxiv but not published in any journal as original article [59, 60].

Conclusion

In this study, new onset type 1 DM was the major precipitating factor for DKA flowed by non-adherence. Polyuria and polydipsia were the most common presenting clinical characteristic of DKA. The mean length of hospital stay and in-hospital mortality were around 5 days. Glycemic control was poor among patients admitted with DKA. Age, infection, frequent plasma glucose fluctuation and severity of DKA were the major determinants of long hospital stay.

It is recommended that non-adherence to medications should be minimized through patient education to reduce the burden of DKA. In addition, infection preventions would attenuate the frequent incidence of DKA and its untoward impact on the lives of DM patients.

Inconsistent serum glucose level demonstrates the urgent administration of appropriate dose of regular insulin as soon as patients are diagnosed for DKA. This enables to shorten the duration of hospital stay. In the meantime, serum glucose should be monitored every hour and hypoglycemic episodes should be prevented by administrating dextrose.

(SAV)

Click here for additional data file.

4 Jul 2021

Submitted filename: Response to reviewers.docx

Click here for additional data file.

1 Sep 2021

PONE-D-21-20358

Treatment Outcome of Diabetic Ketoacidosis Among Diabetes Patients in Ethiopia: Hospital-based Study

PLOS ONE

Dear Dr. Abegaz,

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 literature cited in this manuscript has not been appropriately cited. I suggested the authors to revise the introduction section and consider the following references (J Pak Med Assoc. 2021; 71(1): 286-96. https://doi.org/10.47391/JPMA.434; . 2018;119(1):105-10. https://doi.org/10.1002/jcb.26174; . 2017;118(11):3577-85. https://doi.org/10.1002/jcb.26097).

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

Please submit your revised manuscript by Oct 15 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. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide

[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: 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: This paper is well written and with an excellent rationale of study. The following comments must be addressed

Introduction

There was high mortality report due to DKA at international and national level. You should have included the intervention done previously at international and national level to decrease mortality due to DKA.

Methodology

For structured questionnaire, how the reliability was assessed? How the validity was ensured?

Result

. In table 1, correct as follow: type 1dm=T1DM and type 2 dm=T2DM

Discussion

Add some latest studies in the discussion section

Reviewer #2: Reviewer comments

Manuscript ID number: PONE-D-21-20358

Title of paper: Treatment Outcome of Diabetic Ketoacidosis Among Diabetes Patients in Ethiopia: Hospital-based Study

The manuscript title seems to be an interesting article in the field of diabetes and it might attract the reader’s attention. As such, minor revisions are needed before publication on PlosOne. Please find below my general and detailed comments.

General Comments:

�  First of all, authors should consider the services of a professional English editor to check all the manuscript (in terms of spelling, grammar, punctuation, capitalization, brackets and others right from the title up to the conclusion part)

�  Please check all the references! I found some that were not uniform. (Eg: No year, Some journal names are italic and some are normal, some are written in abbreviated way, some are not, even the font size, so on….)

�  Some words/phrases under abbreviations were not present in the manuscript ( eg: MI, CVA, HEs, HHS, UTI) and even SPSS is not well abbreviated ( SPSS stands for Statistical Manual for Social Sciences … “manual” is it appropriate? The other thing, I think also DGH ( to me better to say “ DTGH”) throughout the manuscript including tables and figures’ legends.

Abstract:

It is well written and clear without some minor revision as indicated below.

Method:

- Line “ The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS).” What is the version? Please indicate it.

Result:

- DKA…. Should be written as “Diabetic ketoacidosis” when it comes after full stop.

Conclusion:

- It is oke, but what the authors recommend? I think the authors say something here what kind/s of measure/s should be taken?

Introduction:

The introduction part is clear and short except some comments below:

- Line: “The international diabetes federation estimated that 415 million adults were diagnosed for DM in 2015(2, 3).” This information is not novel enough as it is form 2015. Update with more recent and available data. Please see the IDF DIABETES ATLAS - 9th edition (2019). Numbers are different on that report.

- DKA…. When it comes first ( the same comment to the abstract under result section)

- Line “ In Ethiopia, mortality from DKA was found be high(16).” Would you present the figure as of other countries you already mentioned?

- I understand the problem. That is well but what was the importance/significance of the study? If the authors add some justifications here please.

Data analysis section:

- Line “Variables were statically significant for p –value of less than 0.05 with 95% confidence interval.” It seems result. It needs rephrasing.

Ethical considerations:

- Reference number for ethical clearance is mentioned under declaration section (what about here? Better to add here also)

- See also capitalization here ( eg: school of pharmacy, University of Gondar College of medicine and health science.)

Operational definitions:

- Some of the definitions are cited, what about the others ( eg: Long-hospital stay, Treatment outcomes, etc)

- Line “Long-hospital stay was defined as hospital stay for more than seven days and,”… is there any word or phrase that could be continued after the word “and”? if no, better to remove the word “and “ and close it with full stop.

Results:

In general, results are well described. Try to address the following comments.

- Table 1: it says “ Type of DM” better to say it Types of DM

- …type 1 dm and ….type 2 dm (please make corrections as .. type1 DM and…. type 2 DM or Capitalize them)

- Table 2: space uniformity issue

- Figure 1 ( in the legend part, it says type 1 dm…. please capitalize it)

- Under “Severity of DKA and Ketone bodies”, line “About three-fourth (75.5%) of the patients were presented with mild DKA, approximately nineteen percent 74(19.1%) were presented with moderate DKA and the remaining 21(5.4%) were diagnosed with severe DKA.” The words “nineteen percent” and again the figure “ (19.1%), the same or ? the authors can use the one.

- Table 3: it says ( n= 387), what about the other tables?

- Under “Length of hospital stay and mortality” section: what is the importance of Table 5, since, it is stated in statement form? To me, better to avoid it. Redundancy!

- Line “The majority 370 (95.60%) of patients improved and discharged whereas 17 (4.40%) patients died in the hospital (fig 2).” Should be stated after Table 5. Here also, what is the importance of Figure 2, since it is also stated as in a statement form?

- Figure 3 : The legend should be written next to the figure

Discussion:

The authors discussed the manuscript clearly. But there are some comments as indicated below which could be addressed by the authors accordingly.

- Paragraph 1: Line “ But the findings of this study showed that the average time required to lower plasma glucose below 250mg/dl was 11 hours which is longer than the recommended time of normoglycemia.” Are there other studies in other regions in agreement with the ones from Ethiopia or others? Make some discussion. The same is true for Line “In our study, patients had a serum glucose fluctuation of more than seven times. Patients’ serum glucose increased by a maximum 263 mg/dl and a minimum of 40mg/dL above the admission glucose.”

- Paragraph 2 (clinical presentation) is well discussed, but why the authors did not compare with other studies if there in Ethiopia?

- Again paragraph 3 (new onset type 1 DM) is well discussed, but still what about the other studies done in other parts of Ethiopia? What other findings say?

- Look paragraph 5, Line “New onset type 1 DM was the major precipitating factor of DKA in the present study due to the fact that our sample population constituted large number of type 1 patients in which majority of them presented with first incidence of the disease with cardinal DKA due to absolute insulin deficiency unlike type 2 DM patients (40).” This sentence might have a greater interest at the end of the paragraph 3, where the new onset type 1 DM of the work is discussed.

- Paragraph 6 (mean length of hospital stay) is well discussed by comparing with other parts of the world, but like above comments if there are other studies in Ethiopia? Again here, references (5, 35, 36) should better put after South Africa or before the word “and”. Because Saudi Arabia seems not cited…. But there is reference 27 for it I think.

- In the last paragraph, there are some sentences seem the limitations of the study which could be better stated under “Strength and limitation of the study” section. Please try to see those sentences in this paragraph.

**********

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: Yes: Shambel Nigussie Amare

Reviewer #2: No

[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.

13 Sep 2021

Response to reviewers

PONE-D-21-20358

Treatment Outcome of Diabetic Ketoacidosis Among Diabetes Patients in Ethiopia: Hospital-based Study

PLOS ONE

Editor Comments:

The literature cited in this manuscript has not been appropriately cited. I suggested the authors to revise the introduction section and consider the following references (J Pak Med Assoc. 2021; 71(1): 286-96. https://doi.org/10.47391/JPMA.434; J Cell Biochem. 2018;119(1):105-10. https://doi.org/10.1002/jcb.26174; J Cell Biochem. 2017;118(11):3577-85. https://doi.org/10.1002/jcb.26097).

Dear Editor,

Thank you so much for your valuable comments. We have included the suggested references in the introduction section because we have got them relevant.

Reviewers' comments

Reviewer #1:

Introduction

Q1. There was high mortality report due to DKA at international and national level. You should have included the intervention done previously at international and national level to decrease mortality due to DKA.

Dear Reviewer,

Thank you so much for your valuable comments

Answer:

In order to reduce mortality, different countries have been using different strategies and prevention measures, such as diabetes self-management education, increasing understanding of the pathophysiology of DKA and adoption of DKA treatment guidelines. We have included this information in the introduction section.

Methodology

Q2.For structured questionnaire, how the reliability was assessed? How was the validity ensured?

Answer;

In order to maintain the reliability and validity of the data collection tool and the collected data, pre-test was undertaken in 5% of the population and the questions were modified based on the collected data. Consultation of experts and close supervision were undertaken to further ensure the validity and reliability of the data.

Result

Q3. In table 1, correct as follow: type 1dm=T1DM and type 2 dm=T2DM

Answer;

The necessary corrections have been made in the manuscript.

Discussion

Add some latest studies in the discussion section

Answer;

We have included relevant studies in the discussion section.

Reviewer #2:

Dear Reviewer;

Thank you so much for your valuable comments.

General Comments:

Q1. First of all, authors should consider the services of a professional English editor to check all the manuscript (in terms of spelling, grammar, punctuation, capitalization, brackets and others right from the title up to the conclusion part).

Answer

The manuscript has been undergone edition by professional personnel (TMA) who is a PhD candidate at Florida A&M University, Florida, United states.

�  Please check all the references! I found some that were not uniform. (Eg: No year, Some journal names are italic and some are normal, some are written in abbreviated way, some are not, even the font size, so on….)

Answer;

We have checked all references and made the necessary corrections.

�  Some words/phrases under abbreviations were not present in the manuscript ( eg: MI, CVA, HEs, HHS, UTI) and even SPSS is not well abbreviated ( SPSS stands for Statistical Manual for Social Sciences … “manual” is it appropriate? The other thing, I think also DGH (to me better to say “ DTGH”) throughout the manuscript including tables and figures’ legends.

Answer;

The abbreviations were corrected and only that appeared in the manuscript were included in the list. DTGH was used in place of DGH.

Abstract:

It is well written and clear without some minor revision as indicated below.

Method:

- Line “ The statistical analysis was carried out using Statistical Package for Social Sciences (SPSS).” What is the version? Please indicate it.

Answers

The SPSS version was included in the abstract section

Result:

- DKA…. Should be written as “Diabetic ketoacidosis” when it comes after full stop.

Answer

DKA was written in full text when it appeared at the beginning of the sentence.

Conclusion:

- It is oke, but what the authors recommend? I think the authors say something here what kind/s of measure/s should be taken?

Answer:

Dear reviewer;

Thank you for your comment. The recommendations were described in the main manuscript. We have also included it in the abstract section

Introduction:

The introduction part is clear and short except some comments below:

- Line: “The international diabetes federation estimated that 415 million adults were diagnosed for DM in 2015(2, 3).” This information is not novel enough as it is form 2015. Update with more recent and available data. Please see the IDF DIABETES ATLAS - 9th edition (2019). Numbers are different on that report.

Answer;

Dear Reviewer

Thank you for your recommendation. We included the recent data on prevalence of DM replacing the old one.

- DKA…. When it comes first (the same comment to the abstract under result section)

Answer

Corrected accordingly

- Line “ In Ethiopia, mortality from DKA was found be high(16).” Would you present the figure as of other countries you already mentioned?

Answer

We included the figures from Ethiopia as well.

- I understand the problem. That is well but what was the importance/significance of the study? If the authors add some justifications here please.

Answer

We have included notes in relation to the significance of the study. The study findings will be relevant to improve the management of DKA, to minimise in-hospital mortality and to reduce length of hospital stay among DKA patients.

Data analysis section:

- Line “Variables were statically significant for p –value of less than 0.05 with 95% confidence interval.” It seems result. It needs rephrasing.

Answer;

We rephrased this statement. Variables with p–value of less than 0.05 with 95% confidence interval were considered statistically significant.

Ethical considerations:

- Reference number for ethical clearance is mentioned under declaration section (what about here? Better to add here also)

Answer;

Reference number was included in ethical clearance section.

- See also capitalization here ( eg: school of pharmacy, University of Gondar College of medicine and health science.)

Answer;

Corrected

Operational definitions:

- Some of the definitions are cited, what about the others ( eg: Long-hospital stay, Treatment outcomes, etc).

Answer;

We have included a reference for length of hospital stay. Regarding treatment outcome, we have operationalized for this research purpose, and we did not seek additional references.

- Line “Long-hospital stay was defined as hospital stay for more than seven days and,” is there any word or phrase that could be continued after the word “and”? if no, better to remove the word “and “and close it with full stop.

Answer;

Thank you so much. We have modified according to your recommendations.

Results:

In general, results are well described. Try to address the following comments.

- Table 1: it says “ Type of DM” better to say it Types of DM

- …type 1 dm and ….type 2 dm (please make corrections as .. type1 DM and…. type 2 DM or Capitalize them)

Answer;

We have modified the words according to your comments.

- Table 2: space uniformity issue

- Figure 1 (in the legend part, it says type 1 dm…. please capitalize it)

Answer;

It is important suggestion. We have modified the figure based on your recommendation

- Under “Severity of DKA and Ketone bodies”, line “About three-fourth (75.5%) of the patients were presented with mild DKA, approximately nineteen percent 74(19.1%) were presented with moderate DKA and the remaining 21(5.4%) were diagnosed with severe DKA.” The words “nineteen percent” and again the figure “ (19.1%), the same or ? the authors can use the one.

Answer;

We have modified according to your comments.

- Table 3: it says ( n= 387), what about the other tables?

We have included the sample sizes in each table.

- Under “Length of hospital stay and mortality” section: what is the importance of Table 5, since, it is stated in statement form? To me, better to avoid it. Redundancy!

- Line “The majority 370 (95.60%) of patients improved and discharged whereas 17 (4.40%) patients died in the hospital (fig 2).” Should be stated after Table 5. Here also, what is the importance of Figure 2, since it is also stated as in a statement form?

We have removed the table and the figure as they are redundant.

- Figure 3 : The legend should be written next to the figure

The legends were written below the figure according to your recommendation.

Discussion:

The authors discussed the manuscript clearly. But there are some comments as indicated below which could be addressed by the authors accordingly.

- Paragraph 1: Line “ But the findings of this study showed that the average time required to lower plasma glucose below 250mg/dl was 11 hours which is longer than the recommended time of normoglycemia.” Are there other studies in other regions in agreement with the ones from Ethiopia or others? Make some discussion. The same is true for Line “In our study, patients had a serum glucose fluctuation of more than seven times. Patients’ serum glucose increased by a maximum 263 mg/dl and a minimum of 40mg/dL above the admission glucose.”

Dear Reviewer,

Thank you so much for your recommendation in relation to comparing our findings on the average time required to lower plasma glucose and glucose fluctuations. Due to the unique nature of these findings, we couldn’t find other studies however, we have discussed with the recommended guidelines regarding the time required to lower glucose within acceptable level.

- Paragraph 2 (clinical presentation) is well discussed, but why the authors did not compare with other studies if there in Ethiopia?

Dear reviewer,

We have included other studies in Ethiopia.

- Again paragraph 3 (new onset type 1 DM) is well discussed, but still what about the other studies done in other parts of Ethiopia? What other findings say?

We included additional studies from Ethiopia

- Look paragraph 5, Line “New onset type 1 DM was the major precipitating factor of DKA in the present study due to the fact that our sample population constituted large number of type 1 patients in which majority of them presented with first incidence of the disease with cardinal DKA due to absolute insulin deficiency unlike type 2 DM patients (40).” This sentence might have a greater interest at the end of the paragraph 3, where the new onset type 1 DM of the work is discussed.

We annexed the statement under paragraph 3.

- Paragraph 6 (mean length of hospital stay) is well discussed by comparing with other parts of the world, but like above comments if there are other studies in Ethiopia?

We included other studies in Ethiopia

Again here, references (5, 35, 36) should better put after South Africa or before the word “and”. Because Saudi Arabia seems not cited…. But there is reference 27 for it I think.

We have corrected this statement accordingly to your comments.

- In the last paragraph, there are some sentences seem the limitations of the study which could be better stated under “Strength and limitation of the study” section. Please try to see those sentences in this paragraph.

We revised the strength and limitation of our study and included the limitation and strength at the end of the discussion as statement form based on the journal guideline instructions.

________________________________________

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

15 Feb 2022

Treatment Outcomes of Diabetic Ketoacidosis Among Diabetes Patients in Ethiopia: Hospital-Based Study

PONE-D-21-20358R1

Dear Dr. Abegaz,

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,

Paolo Magni

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

The authors have adequately addressed your comments raised in a previous round of review.

Reviewer #1: 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

**********

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

Reviewer #1: 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: 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

**********

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: (No Response)

**********

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: Yes: Shambel Nigussie

25 Mar 2022

PONE-D-21-20358R1

Treatment Outcomes of Diabetic Ketoacidosis Among Diabetes Patients in Ethiopia. Hospital-Based Study

Dear Dr. Mekonnen:

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

Prof. Paolo Magni

Academic Editor

PLOS ONE