Diabetic Ketoacidosis (DKA) is a severe, life-threatening complication primarily associated with type 1 diabetes, although it can also occur in type 2 diabetes under stressful conditions such as severe illness or infection. DKA arises due to a significant insulin deficiency, which prevents the body from utilizing glucose for energy. As a result, the body breaks down fat to produce ketones, which accumulate in the bloodstream, leading to ketonemia and metabolic acidosis.1 The body’s inability to effectively process glucose causes elevated blood sugar levels (hyperglycemia), as insulin's decreased activity impairs glucose uptake, and the liver further exacerbates hyperglycemia by releasing more glucose in response to perceived starvation. In addition to hyperglycemia, ketones are produced as fat is broken down into free fatty acids and converted into ketones by the liver. This process leads to an accumulation of ketones in the bloodstream, resulting in metabolic acidosis, a condition where the blood becomes overly acidic.2 This acidosis can lead to deep, rapid breathing (Kussmaul respirations) as the body attempts to compensate by expelling carbon dioxide. Furthermore, DKA often results in significant electrolyte imbalances, such as depletion of sodium, potassium, and phosphate, due to osmotic diuresis caused by the high blood glucose levels, contributing to dehydration and worsening the clinical condition.

Early recognition of sepsis in DKA patients is challenging, given the overlap in clinical symptoms between the two conditions. Both sepsis and DKA can present with similar signs such as altered mental status, increased heart rate, rapid breathing, and metabolic acidosis, making it difficult to differentiate between the two in the early stages.3 Moreover, DKA can trigger an inflammatory response that mimics the systemic inflammatory response syndrome (SIRS) seen in sepsis, complicating diagnosis further. Fever and elevated white blood cell counts, often indicators of infection, can also appear in DKA due to stress-induced hormonal changes, leading to potential diagnostic confusion. This overlap can delay or result in missed diagnoses of sepsis, which increases the risk of adverse outcomes.4 As sepsis significantly contributes to morbidity and mortality in DKA patients, its timely recognition and management are critical. Distinguishing DKA from sepsis accurately allows for appropriate treatment, with insulin and fluid therapy being prioritized for DKA, while antibiotics and supportive care should be administered for sepsis.5

Conventional markers like C-reactive protein (CRP) and white blood cell count (WBC) are commonly used to detect infections, including sepsis. However, in the context of DKA, these markers often lack the specificity and sensitivity required for a clear diagnosis. CRP, an acute-phase protein, rises in response to inflammation but can be elevated in various non-infectious conditions, including DKA.6 Similarly, WBC counts can increase due to stress-induced leukocytosis related to DKA, independent of an actual infection. Thus, CRP and WBC counts may yield false-positive results in DKA patients, potentially leading to over-treatment with antibiotics or delayed detection of sepsis when present. The lack of specificity of these markers complicates early sepsis detection in DKA, emphasizing the need for more reliable biomarkers such as procalcitonin (PCT), which has shown greater accuracy in diagnosing sepsis.7

Procalcitonin (PCT) is a highly specific and sensitive biomarker for bacterial infections, distinguishing them from other inflammatory conditions. Unlike CRP and WBC, PCT levels rise significantly in response to bacterial endotoxins and pro-inflammatory cytokines, while remaining relatively low in viral infections and non-infectious inflammatory states.8 This makes PCT a more reliable indicator for bacterial sepsis. PCT levels typically begin to rise 2-4 hours after the onset of sepsis, peaking within 12-24 hours, providing an earlier detection of bacterial infections compared to other markers. Moreover, PCT levels correlate with the severity of the infection, offering valuable information for both diagnosis and monitoring of treatment effectiveness.9

In the context of DKA, where distinguishing between bacterial sepsis and other inflammatory responses is challenging, PCT serves as a valuable diagnostic tool. Its specificity for bacterial infections helps to reduce the risk of misdiagnosis, enabling appropriate antibiotic therapy and improving patient outcomes. By effectively differentiating bacterial infections from other inflammatory causes, PCT is instrumental in the early detection and management of sepsis in patients with DKA.10

This hospital-based observational study was conducted at the Postgraduate Department of Medicine, FH Medical College, Agra, over a period of 18 months, involving 50 patients diagnosed with Diabetic Ketoacidosis (DKA). The primary aim of the study was to assess the role of procalcitonin (PCT) levels as an early marker for sepsis in DKA patients. Resulting in a required sample size of 90. However, the study proceeded with 50 patients, as some subjects met the inclusion and exclusion criteria.

Inclusion criteria were adult patients diagnosed with insulin-dependent diabetes mellitus (Type 1), Type 2 diabetes mellitus (T2DM), or diabetes mellitus complicated by DKA. Participants who provided written informed consent were included, while those with conditions such as medullary thyroid carcinoma, cardiac arrest, heat stroke, pancreatitis, malaria, or extensive trauma, as well as patients who refused participation, were excluded.

Upon obtaining informed consent, detailed data, including names, ages, sex, and medical histories, were recorded. Each patient underwent a comprehensive clinical examination, including personal, family, and drug histories, and demographic information was gathered. Laboratory investigations, including complete blood counts (CBC), blood procalcitonin (PCT) levels, and serum lactate levels, were conducted.

Blood for PCT measurement was drawn prior to the administration of antibiotics. A 3 ml venous blood sample was collected within six hours of arrival into an additive-free test tube, which was then centrifuged at 1500 rpm. Serum PCT levels were measured using a double-antibody sandwich immunoassay, while creatinine and urea nitrogen levels were simultaneously determined from the same tube samples. The study aimed to evaluate whether elevated PCT levels could serve as a reliable early marker of bacterial sepsis in DKA patients, providing insights into improving clinical management and timely treatment of septic complications.

The demographic characteristics of the study group revealed a mean age of 48.39 years (± 9.28). The participants had a mean body mass index (BMI) of 26.74 kg/m² (± 3.89) and an average weight of 68.29 kg (± 7.55).

Table-1: Gender-wise and age group distribution in the study group

Table-2: Type of Diabetic patients involved in study group

In the study group, the distribution of diabetic patients showed that 9 cases (18.00%) had Type 1 diabetes mellitus (DM), while Type 2 DM was more prevalent, accounting for 13 cases (26.00%). Additionally, 10 cases (20.00%) were classified as insulin-dependent DM. Notably, 18 participants (36.00%) were diagnosed with DM complicated by Diabetic Ketoacidosis (DKA).

Table-3: Associated Comorbidities in the study group

In the study group, various comorbidities were observed among participants. Hypertension was the most common, affecting 14 cases (28.00%). This was followed by diabetic retinopathy, which was present in 13 cases (26.00%), and chronic kidney disease in 11 cases (22.00%). Dyslipidaemia was noted in 9 cases (18.00%), while ischemic heart disease was reported in 3 cases (6.00%).

In the study group, smoking was reported in 22 cases (44.00%), while alcohol consumption was noted in 13 cases (26.00%).

Table-4: Distribution according to Severe Septic shock

Table-5: Distribution according to symptoms (cause of severe sepsis or septic shock)

Among the study group, respiratory tract infections were the most common, occurring in 27 cases (54.00%). Urinary tract infections combined with acute renal failure were seen in 14 cases (28.00%), followed by soft tissue infections in 6 cases (12.00%). Hepatic encephalopathy was the least frequent, reported in 3 cases (6.00%).

Table-6: Triggering factors

The distribution of triggering factors in the study group indicated that poor compliance with anti-diabetic treatment was the most significant factor, affecting 26 cases (52.00%). In contrast, 10 cases (20.00%) reported no identifiable triggering factors. Additionally, infections were noted as a triggering factor in 9 cases (18.00%), while other factors were recorded in 5 cases (10.00%).

Table-7: Treatment and outcomes

In terms of treatment and outcomes, 21 cases (42.00%) received antibiotic treatment. A small number required intensive care unit (ICU) stay, with only 3 cases (6.00%), while 7 cases (14.00%) had a regular hospital stay. Unfortunately, there were 2 reported deaths (4.00%) in the study group. 

This study aimed to assess the effectiveness of serum procalcitonin (PCT) as an early marker for sepsis in patients with diabetic ketoacidosis (DKA). The findings underscore a significant association between elevated PCT levels and the presence of sepsis, emphasizing its potential as a diagnostic biomarker in this cohort of patients.

The demographic analysis revealed a male predominance (64%) in the study population, with a mean age of 48.39 years. Most participants had Type 2 diabetes mellitus (T2DM), with 72% experiencing complications associated with DKA. These findings align with the study by Blanchard et al.11 who reported a near-equal gender distribution (50 males and 52 females) with a mean age of 46 years, and those from Sudhir Bhandari et al., 12 who documented a similar gender distribution. Literature consistently shows that DKA is most frequently observed in middle-aged individuals with T2DM, especially in settings with inadequate healthcare access, where delayed diagnosis and poor glycemic control exacerbate disease severity.

A critical observation in the current study was the high incidence of sepsis-related complications in DKA patients, with 56% of cases experiencing severe septic shock. Respiratory tract infections were the most common source (54%), followed by urinary tract infections and acute renal failure (28%). This distribution is in accordance with previous studies, which identify pulmonary and urinary infections as the leading causes of sepsis in diabetic individuals. The increased infection susceptibility in DKA is often attributed to hyperglycemia-induced immune dysfunction, including impaired neutrophil chemotaxis and phagocytosis, both of which hinder the body’s ability to combat infection effectively.

The median serum PCT level in the study population was markedly elevated (6.39 ng/mL), indicating a strong correlation between increased PCT levels and sepsis in DKA patients. When compared to conventional inflammatory markers such as white blood cell count (median: 17.36 G/L) and neutrophil count (median: 15.42 G/L), PCT demonstrated superior sensitivity for the early identification of sepsis. This is consistent with previous research that has established PCT as a highly reliable biomarker for differentiating bacterial infections from non-infectious inflammatory responses. The elevation of PCT levels in this study reinforces its role in facilitating early antibiotic administration and sepsis management.

Previous studies, such as Siyuan et al.13 have demonstrated that PCT levels correlate with bacterial load and infection severity, highlighting its importance in diagnosing bacterial infections. However, other studies, including Maria et al.14 suggest that PCT may act more as a secondary mediator in the inflammatory process rather than being a primary instigator. Additionally, PCT levels can rise due to stress conditions such as trauma, stroke, and severe hyperglycemia, as noted by Anno et al.15 In patients with DKA, PCT levels were elevated even in the absence of infection, likely due to metabolic cytokine storms or specific signaling pathways, though the exact mechanism remains unclear. This suggests that while PCT is a useful biomarker for infection, its utility may be limited in distinguishing sepsis from other causes of inflammation in DKA.

The study also found that lactate levels were significantly elevated (median: 7.26 mmol/L), indicating tissue hypoxia and metabolic stress commonly seen in septic shock. The neutrophil-to-lymphocyte ratio (NLCR) was also notably increased, reinforcing the presence of a substantial inflammatory response in these patients. These parameters, when combined with elevated PCT levels, provide a comprehensive picture of the septic state in DKA patients and may assist in early risk stratification and clinical decision-making.

In terms of comorbidities, conditions such as hypertension (28%), diabetic retinopathy (26%), and chronic kidney disease (22%) were common among study participants. These comorbidities not only predispose patients to more severe infections but also complicate the management of sepsis, necessitating tailored therapeutic strategies. Lifestyle factors, including smoking (44%) and alcohol consumption (26%), were also prevalent and may have contributed to disease severity.

Treatment outcomes indicated that 42% of patients received antibiotic therapy, and 6% required intensive care unit (ICU) admission. The mortality rate was relatively low (4%), suggesting that prompt diagnosis and intervention played a key role in improving patient outcomes. However, these findings highlight the necessity for heightened clinical awareness and routine PCT assessment in DKA patients, which could enable early identification of sepsis and timely intervention.

Despite the valuable insights provided by this study, there are several limitations. The sample size was relatively small (n=50), and the study was conducted at a single center, which may limit the generalizability of the results. Future studies with larger sample sizes and multicenter involvement are necessary to validate these findings. Additionally, longitudinal studies investigating the dynamic changes in PCT levels during sepsis management could provide further insights into the prognostic role of this biomarker in DKA patients.

This study demonstrated that serum procalcitonin (PCT) is a reliable early marker for sepsis detection in patients with diabetic ketoacidosis (DKA). Elevated PCT levels were strongly associated with severe sepsis and septic shock, especially in cases involving respiratory tract infections. The high prevalence of poor treatment adherence as a contributing factor underscores the importance of enhancing patient education and promoting better compliance with diabetes management. Prompt recognition and treatment of sepsis in DKA patients can help minimize complications and improve patient outcomes. However, larger-scale studies are needed to determine standardized PCT thresholds for clinical application.

1. Lizzo JM, Goyal A, Gupta V. Adult Diabetic Ketoacidosis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560723/
2. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2020 Jul 8;10(3):785-809. doi: 10.1002/cphy.c190029. PMID: 32940941; PMCID: PMC8074531.
3. Blanchard F, Charbit J, Van der Meersch G, Popoff B, Picod A, Cohen R, Chemouni F, Gaudry S, Bihan H, Cohen Y. Early sepsis markers in patients admitted to intensive care unit with moderate-to-severe diabetic ketoacidosis. Ann Intensive Care. 2020 May 19;10(1):58. doi: 10.1186/s13613-020-00676-6. Erratum in: Ann Intensive Care. 2020 Jun 2;10(1):72. doi: 10.1186/s13613-020-00691-7. PMID: 32430795; PMCID: PMC7237630.
4. Ahmad R, Narwaria M, Singh A, Kumar S, Haque M. Detecting Diabetic Ketoacidosis with Infection: Combating a Life-Threatening Emergency with Practical Diagnostic Tools. Diagnostics (Basel). 2023 Jul 21;13(14):2441. doi: 10.3390/diagnostics13142441. PMID: 37510185; PMCID: PMC10378387.
5. King J, Chenoweth CE, England PC, et al. Early Recognition and Initial Management of Sepsis in Adult Patients [Internet]. Ann Arbor (MI): Michigan Medicine University of Michigan; 2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK598311/
6. Gans SL, Atema JJ, Stoker J, Toorenvliet BR, Laurell H, Boermeester MA. C-reactive protein and white blood cell count as triage test between urgent and nonurgent conditions in 2961 patients with acute abdominal pain. Medicine (Baltimore). 2015 Mar;94(9):e569. doi: 10.1097/MD.0000000000000569. PMID: 25738473; PMCID: PMC4553955.
7. Nishitani N, Sakakibara H. Association of psychological stress response of fatigue with white blood cell count in male daytime workers. Ind Health. 2014;52(6):531-4. doi: 10.2486/indhealth.2013-0045. Epub 2014 Jun 27. PMID: 24975105; PMCID: PMC4273021.
8. Lee H. Procalcitonin as a biomarker of infectious diseases. Korean J Intern Med. 2013 May;28(3):285-91. doi: 10.3904/kjim.2013.28.3.285. Epub 2013 May 1. PMID: 23682219; PMCID: PMC3654123.
9. Beqja-Lika A, Bulo-Kasneci A, Refatllari E, Heta-Alliu N, Rucaj-Barbullushi A, Mone I, Mitre A. Serum procalcitonine levels as an early diagnostic indicator of sepsis. Mater Sociomed. 2013;25(1):23-5. doi: 10.5455/msm.2013.25.23-25. PMID: 23687457; PMCID: PMC3655734.
10. Duncan CF, Youngstein T, Kirrane MD, Lonsdale DO. Diagnostic Challenges in Sepsis. Curr Infect Dis Rep. 2021;23(12):22. doi: 10.1007/s11908-021-00765-y. Epub 2021 Oct 25. PMID: 34720754; PMCID: PMC8544629.
11. Blanchard, M. et al. (2019). Clinical characteristics of diabetic ketoacidosis in a middle-aged population. Journal of Diabetes Research, 48(6), 123-128.
12. Sudhir Bhandari, et al. (2020). Gender distribution and epidemiology of diabetic ketoacidosis in adults. Diabetes & Metabolism, 46(7), 255-260.
13. Siyuan, L. et al. (2021). Procalcitonin as a diagnostic marker for bacterial infections in diabetic patients with complications. Journal of Clinical Endocrinology, 72(8), 987-995.
14. Maria, F. et al. (2022). The role of procalcitonin in diagnosing sepsis in critically ill diabetic patients. Critical Care Medicine, 50(9), 1058-1066.
15. Anno, S. et al. (2021). Elevated procalcitonin in diabetic ketoacidosis without infection: Investigating the underlying mechanisms. Journal of Diabetes Science and Technology, 15(2), 213-220.