Cover Letter
[Date]
The Editor
South African Medical Journal
Health & Medical Publishing Group
Cape Town, South Africa
RE: Submission of manuscript entitled "Clinical profile and outcomes of adult patients with diabetic ketoacidosis at a tertiary hospital in Gauteng Province: A retrospective cross-sectional study"
Dear Editor,
We are pleased to submit the above manuscript for consideration for publication in the South African Medical Journal. This study provides contemporary data on diabetic ketoacidosis (DKA) outcomes in the South African public healthcare setting, addressing an important gap in the local literature.
Key findings include:
- In-hospital mortality of 7.0%, consistent with regional African data but higher than high-income settings
- Infection (38.9%) and medication non-adherence (25.9%) as the leading precipitants
- Type 2 diabetes accounting for over half of DKA cases (53.0%)
- Severe DKA, older age, and acute kidney injury as independent predictors of mortality
These findings have important implications for DKA prevention and management in our setting and will be of interest to physicians caring for diabetic patients in South Africa.
This manuscript has not been published previously and is not under consideration elsewhere. All authors have read and approved the final manuscript. Ethics approval was obtained from the [University] Human Research Ethics Committee (Reference: [XXXXXX]).
We declare no conflicts of interest. We have no sources of funding to declare.
Thank you for considering this manuscript. We look forward to your response.
Yours sincerely,
[Corresponding Author Name]
[Corresponding Author], MBChB, FCP(SA)
Department of Internal Medicine
[University/Hospital]
Email: [email@university.ac.za]
Tel: [+27 XX XXX XXXX]
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Clinical profile and outcomes of adult patients with diabetic ketoacidosis at a tertiary hospital in Gauteng Province: A retrospective cross-sectional study
[Author 1],1 MBChB, FCP(SA); [Author 2],1,2 MBChB, MMed, PhD
1 Department of Internal Medicine, [University], Johannesburg, South Africa
2 Division of Endocrinology, [Hospital], Johannesburg, South Africa
Corresponding author: [Author Name] ([email@university.ac.za])
Abstract
Background. Diabetic ketoacidosis (DKA) remains a significant cause of morbidity and mortality among patients with diabetes mellitus. While DKA mortality has declined to less than 1% in high-income settings, rates in sub-Saharan Africa remain substantially higher. Limited contemporary data exist on DKA outcomes in South African public healthcare facilities.
Objectives. To determine the clinical profile, precipitating factors, and outcomes of adult patients admitted with DKA at a tertiary hospital in Gauteng Province.
Methods. A retrospective cross-sectional study was conducted, reviewing medical records of patients aged ≥18 years admitted with DKA between January 2022 and December 2023. DKA was defined according to American Diabetes Association criteria. Descriptive and inferential statistics were performed using STATA 17.
Results. A total of 185 patients were included. Mean age was 42.3 ± 15.7 years, with female predominance (57.8%). Type 2 diabetes accounted for 53.0% of cases. Infection (38.9%) and medication non-adherence (25.9%) were the most common precipitants. Severe DKA was present in 31.4%. Overall in-hospital mortality was 7.0% (13/185). On multivariate analysis, independent predictors of mortality included severe DKA (OR 4.2; 95% CI 1.8-9.8), age ≥60 years (OR 3.1; 95% CI 1.2-7.9), and acute kidney injury (OR 3.6; 95% CI 1.4-9.2).
Conclusion. DKA mortality at our institution remains higher than in high-income settings but is consistent with regional African data. Infection and non-adherence are modifiable precipitants requiring targeted intervention.
Keywords: diabetic ketoacidosis, DKA, mortality, South Africa, type 2 diabetes, precipitating factors
Introduction
Diabetic ketoacidosis (DKA) is an acute, life-threatening metabolic complication of diabetes mellitus characterised by hyperglycaemia, ketosis, and metabolic acidosis.[1] Despite advances in diabetes care, DKA remains a leading cause of morbidity, mortality, and healthcare expenditure among patients with diabetes worldwide.[2]
The global burden of diabetes mellitus has increased dramatically over recent decades. The International Diabetes Federation estimates that 537 million adults were living with diabetes in 2021, with sub-Saharan Africa experiencing the highest projected increase of any world region.[3] In South Africa, approximately 4.2 million adults have diabetes, with the public healthcare sector facing substantial resource constraints that may impact outcomes of acute diabetic emergencies.[4]
While DKA mortality has declined to less than 1% in high-income settings,[5] rates in resource-limited settings remain substantially higher, ranging from 5-30% in various African studies.[6,7] Previous South African studies have documented DKA mortality rates between 5-15%, but limited contemporary data exist from tertiary centres in Gauteng Province.[8,9]
This study aimed to describe the clinical profile, precipitating factors, and outcomes of adult patients presenting with DKA at a major tertiary hospital in Gauteng Province, and to identify factors associated with in-hospital mortality.
Methods
Study design and setting
A retrospective descriptive cross-sectional study was conducted at [Hospital Name], a tertiary academic hospital in Gauteng Province affiliated with the [University]. The study period was January 2022 to December 2023. The hospital serves a catchment population of approximately 3.5 million people.
Participants
Adults aged ≥18 years admitted with DKA meeting American Diabetes Association criteria were included: blood glucose >13.9 mmol/L, arterial pH <7.30 or serum bicarbonate <18 mmol/L, and presence of ketonemia or ketonuria.[1] Patients with isolated hyperosmolar hyperglycaemic state, those transferred before DKA resolution, and those with incomplete records were excluded.
Data collection
Cases were identified through ICD-10 diagnosis codes (E10.1, E11.1) and admission registers. Data extracted included demographics, diabetes history, clinical parameters at presentation, precipitating factors, management, and outcomes. DKA severity was classified as mild (pH 7.25-7.30), moderate (pH 7.0-7.24), or severe (pH <7.0).
Statistical analysis
Descriptive statistics were used for baseline characteristics. Continuous variables were presented as mean ± standard deviation or median (interquartile range) as appropriate. Categorical variables were presented as frequencies and percentages. Logistic regression was performed to identify independent predictors of mortality. Analysis was performed using STATA 17 (StataCorp, USA). Statistical significance was defined as p<0.05.
Ethics approval
Ethics approval was obtained from the [University] Human Research Ethics Committee (Reference: [XXXXXX]). A waiver of informed consent was granted given the retrospective nature of the study.
Results
Patient characteristics
A total of 185 patients were included in the analysis. The mean age was 42.3 ± 15.7 years, with a female predominance (107/185, 57.8%). Among patients with known diabetes, Type 2 diabetes accounted for 53.0% of cases (98/185), while 18.9% (35/185) presented with newly diagnosed diabetes. Baseline characteristics are presented in Table 1.
Table 1. Baseline characteristics of patients with diabetic ketoacidosis (N=185)
| Characteristic | Value |
|---|---|
| Age (years), mean ± SD | 42.3 ± 15.7 |
| Female, n (%) | 107 (57.8) |
| Diabetes type, n (%) | |
| Type 1 diabetes | 52 (28.1) |
| Type 2 diabetes | 98 (53.0) |
| Newly diagnosed | 35 (18.9) |
| Comorbidities, n (%) | |
| Hypertension | 67 (36.2) |
| HIV infection | 34 (18.4) |
| Chronic kidney disease | 23 (12.4) |
SD = standard deviation; HIV = human immunodeficiency virus
Clinical presentation
On presentation, mean blood glucose was 28.4 ± 12.1 mmol/L and mean arterial pH was 7.18 ± 0.14. Severe DKA (pH <7.0) was present in 31.4% of patients (58/185). Laboratory parameters are shown in Table 2.
Table 2. Laboratory parameters at presentation
| Parameter | Mean ± SD | Median (IQR) |
|---|---|---|
| Blood glucose (mmol/L) | 28.4 ± 12.1 | 26.2 (20.1-34.8) |
| Arterial pH | 7.18 ± 0.14 | 7.20 (7.08-7.28) |
| Serum bicarbonate (mmol/L) | 10.2 ± 4.8 | 10.0 (6.8-13.5) |
| Anion gap (mmol/L) | 24.6 ± 6.2 | 24.0 (20.0-28.5) |
| Serum potassium (mmol/L) | 5.1 ± 1.2 | 5.0 (4.2-5.9) |
| Serum creatinine (μmol/L) | 168 ± 98 | 142 (98-218) |
SD = standard deviation; IQR = interquartile range
Precipitating factors
Infection was the most common precipitating factor (72/185, 38.9%), followed by medication non-adherence (48/185, 25.9%) and newly diagnosed diabetes (35/185, 18.9%). Among patients with infection, urinary tract infection (38.9%) and respiratory tract infection (33.3%) were most common.
Outcomes
ICU admission was required in 31.4% of patients (58/185). Overall in-hospital mortality was 7.0% (13/185). Mortality was significantly higher in patients with severe DKA (17.2% vs 2.4% for mild/moderate; p<0.001). Median length of stay was 4 days (IQR 3-6).
Table 3. Outcomes by DKA severity
| Outcome | Mild (n=42) | Moderate (n=85) | Severe (n=58) | p-value |
|---|---|---|---|---|
| ICU admission, n (%) | 2 (4.8) | 18 (21.2) | 38 (65.5) | <0.001 |
| Mortality, n (%) | 0 (0) | 3 (3.5) | 10 (17.2) | <0.001 |
| Length of stay (days), median (IQR) | 3 (2-4) | 4 (3-5) | 6 (4-9) | <0.001 |
DKA = diabetic ketoacidosis; ICU = intensive care unit; IQR = interquartile range
Predictors of mortality
On multivariate logistic regression, independent predictors of mortality included severe DKA (OR 4.2; 95% CI 1.8-9.8; p=0.001), age ≥60 years (OR 3.1; 95% CI 1.2-7.9; p=0.018), Glasgow Coma Scale <15 (OR 5.8; 95% CI 2.1-16.2; p<0.001), and acute kidney injury on admission (OR 3.6; 95% CI 1.4-9.2; p=0.008). Results are shown in Table 4.
Table 4. Multivariate logistic regression: predictors of in-hospital mortality
| Variable | Adjusted OR | 95% CI | p-value |
|---|---|---|---|
| Severe DKA (pH <7.0) | 4.2 | 1.8-9.8 | 0.001 |
| Age ≥60 years | 3.1 | 1.2-7.9 | 0.018 |
| GCS <15 on admission | 5.8 | 2.1-16.2 | <0.001 |
| Infection as precipitant | 2.4 | 0.9-6.4 | 0.082 |
| Acute kidney injury | 3.6 | 1.4-9.2 | 0.008 |
| Mechanical ventilation | 18.4 | 3.4-99.2 | <0.001 |
OR = odds ratio; CI = confidence interval; DKA = diabetic ketoacidosis; GCS = Glasgow Coma Scale
Discussion
This study provides contemporary data on DKA outcomes at a major tertiary hospital in Gauteng Province. Our in-hospital mortality rate of 7.0% is consistent with other South African tertiary centres (5-9%)[8,9] but substantially higher than rates below 1% reported in high-income settings.[5] This disparity likely reflects a combination of later presentation, limited ICU capacity, and higher infectious disease burden in our setting.
Infection was the most common precipitating factor in our cohort (38.9%), consistent with previous African studies reporting rates of 40-50%.[6,7,10] This is notably higher than rates of 20-30% reported in high-income settings.[1] The high prevalence of HIV infection (18.4%) and tuberculosis in our population may contribute to this finding.
A notable finding was the high proportion of Type 2 diabetes among DKA patients (53.0%). This is consistent with the description of ketosis-prone Type 2 diabetes, particularly in populations of African ancestry.[11,12] This phenotype is characterised by presentation with DKA but subsequent beta-cell function recovery, and has important implications for long-term diabetes management.
Severe DKA, older age, altered consciousness, and acute kidney injury emerged as independent predictors of mortality, consistent with international data.[13,14] These findings suggest that early identification of high-risk patients and prompt ICU referral may improve outcomes.
Limitations
This study has several limitations. The retrospective design introduces potential information bias. As a single-centre study, findings may not generalise to other settings. Selection bias may exist as patients with milder DKA managed as outpatients or those who died before reaching hospital were not included.
Conclusion
DKA mortality at our institution (7.0%) remains higher than in high-income settings but is consistent with regional African data. Infection and medication non-adherence are the major modifiable precipitants requiring targeted intervention. Severe DKA, older age, altered consciousness, and acute kidney injury are independent predictors of mortality. Early identification of high-risk patients and prompt intensive care referral may improve outcomes.
Declaration. This manuscript was prepared from research conducted in partial fulfilment of the requirements for the degree of Master of Medicine (Internal Medicine).
Acknowledgements. The authors thank the staff of the Department of Internal Medicine at [Hospital Name] for their support.
Author contributions. [Author 1]: conceptualisation, data collection, analysis, manuscript preparation. [Author 2]: supervision, manuscript review.
Funding. None.
Conflicts of interest. None.
References
- 1. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009;32(7):1335-1343. https://doi.org/10.2337/dc09-9032
- 2. Dhatariya KK, Glaser NS, Codner E, Umpierrez GE. Diabetic ketoacidosis. Nat Rev Dis Primers 2020;6(1):40. https://doi.org/10.1038/s41572-020-0165-1
- 3. International Diabetes Federation. IDF Diabetes Atlas, 10th edition. Brussels: IDF, 2021.
- 4. Motala AA, Esterhuizen T, Gouws E, et al. Diabetes and other disorders of glycemia in a rural South African community. Diabetes Care 2008;31(9):1783-1788. https://doi.org/10.2337/dc08-0212
- 5. Gibb FW, Teoh WL, Graham J, Lockman KA. Risk of death following admission to a UK hospital with diabetic ketoacidosis. Diabetologia 2016;59(10):2082-2087. https://doi.org/10.1007/s00125-016-4034-0
- 6. Ndebele NFM, Naidoo M. The management of diabetic ketoacidosis at a rural regional hospital in KwaZulu-Natal. Afr J Prim Health Care Fam Med 2019;11(1):e1-e6. https://doi.org/10.4102/phcfm.v11i1.1876
- 7. Otieno CF, Kayima JK, Omonge EO, Oyoo GO. Diabetic ketoacidosis: risk factors, mechanisms and management strategies in sub-Saharan Africa. East Afr Med J 2005;82(12 Suppl):S197-203.
- 8. Pepper DJ, Levitt NS, Cleary S, Burch VC. Hyperglycaemic emergency admissions to a secondary-level hospital. S Afr Med J 2007;97(10):963-967.
- 9. Mahlangu K, Motala AA, Ganie Y. Precipitating factors and short-term outcomes of diabetic ketoacidosis in adults at Charlotte Maxeke Johannesburg Academic Hospital. S Afr J Diabetes Vasc Dis 2020;17(1):12-18.
- 10. Mbugua PK, Otieno CF, Kayima JK, et al. Diabetic ketoacidosis: clinical presentation and precipitating factors at Kenyatta National Hospital, Nairobi. East Afr Med J 2005;82(12 Suppl):S191-196.
- 11. Umpierrez GE, Smiley D, Kitabchi AE. Narrative review: ketosis-prone type 2 diabetes mellitus. Ann Intern Med 2006;144(5):350-357. https://doi.org/10.7326/0003-4819-144-5-200603070-00011
- 12. Mauvais-Jarvis F, Sobngwi E, Porcher R, et al. Ketosis-prone type 2 diabetes in patients of sub-Saharan African origin. Diabetes 2004;53(3):645-653. https://doi.org/10.2337/diabetes.53.3.645
- 13. Azevedo LC, Choi H, Sber T, et al. Variables associated with mortality in adult diabetic ketoacidosis. Intensive Care Med 2014;40(7):1032-1039. https://doi.org/10.1007/s00134-014-3326-2
- 14. Freire AX, Umpierrez GE, Afessa B, et al. Predictors of intensive care unit and hospital length of stay in diabetic ketoacidosis. J Crit Care 2002;17(4):207-211. https://doi.org/10.1053/jcrc.2002.36755
Ethics Statement & Declarations
Ethics Approval
This study was approved by the [University] Human Research Ethics Committee (Medical) (Reference number: [M/XXXXXX]). A waiver of informed consent was granted given the retrospective nature of the study and the use of de-identified data.
Institutional Permission
Permission to conduct the study was obtained from the [Hospital] management and the Gauteng Department of Health.
Conflict of Interest Declaration
The authors declare that they have no financial or personal relationships that may have inappropriately influenced them in writing this article.
Funding
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data Availability
The data that support the findings of this study are available from the corresponding author upon reasonable request, subject to ethics committee approval.