Best evidence topic report: Does Baseline Serum Lactate Predict Outcomes in Diabetic Ketoacidosis Patients?
Date First Published:
May 27, 2025
Last Updated:
June 2, 2025
Report by:
Mostafa Alavi-Moghaddam, Full Professor of Medical School Department of Emergency Medicine (Emergency Medicine Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran)
Search checked by:
Ramin Zeinodini, Emergency Medicine Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Three-Part Question:
In [patients with diabetic ketoacidosis (DKA)], does [a higher baseline serum lactate level compared to a lower level] predict [worse outcomes, such as increased hospital or intensive care unit length of stay, morbidity, and mortality]?
Clinical Scenario:
A young man with type 1 diabetes presented to the emergency department (ED) with disorientation and was diagnosed with DKA. Despite his elevated baseline serum lactate, his condition improved relatively quickly. This makes you wonder whether high baseline serum lactate predicts outcomes in DKA patients.
Search Strategy:
PubMed up to 4/19/2025: (((("Diabetic Ketoacidosis"[Mesh]) OR (Diabetic Ketoacidos*[Title/Abstract] OR Diabetic Ketos*[Title/Abstract] OR Diabetic Acidos*[Title/Abstract])) AND (("Lactates"[Mesh]) OR (Lactate*[Title/Abstract] OR Lactic Acid*[Title/Abstract] OR "2-Hydroxypropanoic Acid*"[Title/Abstract] OR "2 Hydroxypropionic Acid*"[Title/Abstract] OR "2 Hydroxypropanoic Acid*"[Title/Abstract] OR "2-Hydroxypropionic Acid*"[Title/Abstract] OR "L Lactic Acid*"[Title/Abstract] OR "L-Lactic Acid*"[Title/Abstract] OR "D Lactic Acid*"[Title/Abstract] OR "D-Lactic Acid*"[Title/Abstract]))) AND (outcome[Title/Abstract] OR prognos*[Title/Abstract] OR mortality[Title/Abstract] OR morbidity[Title/Abstract] OR death[Title/Abstract] OR complication[Title/Abstract] OR surviv*[Title/Abstract] OR "Intensive care unit"[Title/Abstract] OR critical[Title/Abstract])) AND (predict*[Title/Abstract] OR associat*[Title/Abstract] OR correlat*[Title/Abstract] OR 'risk factor'[Title/Abstract] OR relat*[Title/Abstract]) AND ((humans[Filter]) AND (english[Filter]))
Embase up to 4/19/2025: ('lactic acid'/exp OR '2 hydroxypropanoic acid':ab,ti OR '2 hydroxypropionic acid':ab,ti OR 'l lactate':ab,ti OR 'l lactic acid':ab,ti OR 'l-lactate':ab,ti OR 'l-lactic acid':ab,ti OR 'd lactate':ab,ti OR 'd lactic acid':ab,ti OR 'd-lactate':ab,ti OR 'd-lactic acid':ab,ti OR 'lactate':ab,ti OR 'lactic acid':ab,ti) AND ('diabetic ketoacidosis'/exp OR 'diabetic ketoacidosis' OR 'diabetic acidosis':ab,ti OR 'diabetic keto-acidosis':ab,ti OR 'diabetic ketoacidoses':ab,ti OR 'diabetic ketoacidosis':ab,ti OR 'diabetic ketosis':ab,ti OR 'diabetic ketoses':ab,ti OR 'diabetic acidoses':ab,ti) AND ('outcome':ab,ti OR 'intensive care unit':ab,ti OR 'prognos*':ab,ti OR 'surviv*':ab,ti OR 'mortality':ab,ti OR 'morbidity':ab,ti OR 'death':ab,ti OR 'complication':ab,ti OR 'critical':ab,ti) AND ('predict*':ab,ti OR 'associat*':ab,ti OR 'correlat*':ab,ti OR 'risk factor':ab,ti OR 'relat*':ab,ti) AND [humans]/lim AND [english]/lim AND [embase]/lim
Cochrane up to 4/19/2025:
#1tMeSH descriptor: [Lactic Acid] explode all treest
#2tMeSH descriptor: [Diabetic Ketoacidosis] explode all treest
#3t("Lactate" OR "Lactic Acid" OR "2-Hydroxypropanoic Acid" OR "2 Hydroxypropionic Acid" OR "2 Hydroxypropanoic Acid" OR "2-Hydroxypropionic Acid" OR "L Lactic Acid" OR "L-Lactic Acid" OR "D Lactic Acid" OR "D-Lactic Acid"):ti,ab,kwt
#4t(diabet*):ti,ab,kw AND (Ketoacidos* OR Ketos* OR Acidos*):ti,ab,kw
#5t("outcome" OR prognos* OR "mortality" OR "morbidity" OR "death" OR "complication" OR surviv* OR "Intensive care unit" OR "critical"):ti,ab,kw
#6t(predict* OR associat* OR correlat* OR "risk factor" OR relat*):ti,ab,kwt
#7t#1 OR #3
#8t#2 OR #4
#9t#7 AND #8 AND #5 AND #6
Embase up to 4/19/2025: ('lactic acid'/exp OR '2 hydroxypropanoic acid':ab,ti OR '2 hydroxypropionic acid':ab,ti OR 'l lactate':ab,ti OR 'l lactic acid':ab,ti OR 'l-lactate':ab,ti OR 'l-lactic acid':ab,ti OR 'd lactate':ab,ti OR 'd lactic acid':ab,ti OR 'd-lactate':ab,ti OR 'd-lactic acid':ab,ti OR 'lactate':ab,ti OR 'lactic acid':ab,ti) AND ('diabetic ketoacidosis'/exp OR 'diabetic ketoacidosis' OR 'diabetic acidosis':ab,ti OR 'diabetic keto-acidosis':ab,ti OR 'diabetic ketoacidoses':ab,ti OR 'diabetic ketoacidosis':ab,ti OR 'diabetic ketosis':ab,ti OR 'diabetic ketoses':ab,ti OR 'diabetic acidoses':ab,ti) AND ('outcome':ab,ti OR 'intensive care unit':ab,ti OR 'prognos*':ab,ti OR 'surviv*':ab,ti OR 'mortality':ab,ti OR 'morbidity':ab,ti OR 'death':ab,ti OR 'complication':ab,ti OR 'critical':ab,ti) AND ('predict*':ab,ti OR 'associat*':ab,ti OR 'correlat*':ab,ti OR 'risk factor':ab,ti OR 'relat*':ab,ti) AND [humans]/lim AND [english]/lim AND [embase]/lim
Cochrane up to 4/19/2025:
#1tMeSH descriptor: [Lactic Acid] explode all treest
#2tMeSH descriptor: [Diabetic Ketoacidosis] explode all treest
#3t("Lactate" OR "Lactic Acid" OR "2-Hydroxypropanoic Acid" OR "2 Hydroxypropionic Acid" OR "2 Hydroxypropanoic Acid" OR "2-Hydroxypropionic Acid" OR "L Lactic Acid" OR "L-Lactic Acid" OR "D Lactic Acid" OR "D-Lactic Acid"):ti,ab,kwt
#4t(diabet*):ti,ab,kw AND (Ketoacidos* OR Ketos* OR Acidos*):ti,ab,kw
#5t("outcome" OR prognos* OR "mortality" OR "morbidity" OR "death" OR "complication" OR surviv* OR "Intensive care unit" OR "critical"):ti,ab,kw
#6t(predict* OR associat* OR correlat* OR "risk factor" OR relat*):ti,ab,kwt
#7t#1 OR #3
#8t#2 OR #4
#9t#7 AND #8 AND #5 AND #6
Outcome:
A total of 377 papers were found, of which 327 were identified after removing duplicates. Of these, 303 papers were excluded based on title and abstract screening. The remaining 24 full-text articles were screened and assessed for eligibility. Finally, 15 studies were enrolled and provided the best evidence to answer the three-part question (Figure 1).
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Prevalence and significance of lactic acidosis in diabetic ketoacidosis Cox 2012 USA | 68 ED adult patients with DKA, categorized by serum lactate (mmol/L): <4 (n=41) ≥4 (n=27) |
Retrospective cohort study | ICU LOS, Mortality | • ICU LOS: p=0.18 (ns diff.) • Mortality: p=1.0 (ns diff.) | Measured serum lactate only in 52% of DKA cases, low mortality, potential missed interactions, retrospective design, small sample size, single-center study |
| Predictors of five days mortality in diabetic ketoacidosis patients: a prospective cohort study Suwarto 2014 Indonesia | 60 ED adult patients with DKA, categorized by serum lactate (mmol/L): <4 (n=43) ≥4 (n=17) |
Prospective cohort study | Five-day mortality | Five-day mortality: • For serum lactate ≥4 mmol/L (vs <4 mmol/L): HR=3.09 (95% CI: 1.36–7.05), p-value not reported | Unexamined comorbidities, unclear causes of altered mental status, small sample size, single-center study |
| Seventy-two hour mortality prediction model in patients with diabetic ketoacidosis: A retrospective cohort study. Journal of the ASEAN Federation of Endocrine Societies Siregar 2018 Indonesia | 260 adult DKA patients with serum lactate data, categorized by serum lactate (mmol/L): <2 (n=138) 2-4 (n=69) >4 (n=53) |
Retrospective cohort study | Seventy-two-hour mortality | Seventy-two-hour mortality: • For serum lactate 2–4 mmol/L (vs <2 mmol/L): HR=3.117 (95% CI: 1.609–6.037), p=0.001 • For serum lactate >4 mmol/L (vs <2 mmol/L): HR=5.585 (95% CI: 2.966–10.519), p<0.001 | Predominantly type 2 diabetes (90%), retrospective design, single-center study |
| Characterization of variable presentations of diabetic ketoacidosis based on blood ketone levels and major society diagnostic criteria: A new view point on the assessment of diabetic ketoacidosis Lee 2019 Republic of Korea | 274 DKA patients with serum lactate data, categorized by serum lactate (mmol/L): ≤5 (n=246) >5 (n=28) |
Retrospective cohort study | In-hospital mortality | In-hospital mortality: For serum lactate >5 mmol/L (vs ≤5 mmol/L): • Adjusted OR=1.275 (95% CI: 1.132–1.435), p<0.01 (dir. corr.) | Excluded euglycemic DKA cases, retrospective design, single-population |
| Is lactic acidosis predictive of outcomes in pediatric diabetic ketoacidosis? Cully 2020 | 92 ED paediatric patients (113 encounters) with severe DKA, categorized by serum lactate (mmol/L): <2.5 (n=41) ≥2.5 (n=72) |
Retrospective cohort study | Hospital LOS, Paediatric ICU LOS, Morbidity, Mortality | • Hospital LOS: p=0.426 (ns diff.) • Paediatric ICU LOS: p=0.321 (ns diff.) • Morbidity: p=0.552 (ns diff.) • Mortality: p=1.000 (ns diff.) | Low morbidity and mortality, retrospective design, small sample size, single-center study |
| A different perspective of elevated lactate in pediatric patients with diabetic ketoacidosis Unal 2020 Turkey | 56 paediatric ICU patients with DKA (aged 2–18 years), categorized by serum lactate (mmol/L): <2 (n=18) >2 (n=38) |
Retrospective cohort study | DKA resolution time, Mortality | • DKA resolution time: p=0.26 (ns diff.) • Lactate levels: Negative correlation with DKA resolution time (r=-0.33, p=0.01) • No mortality observed. | No mortality data, excluded confounding conditions, retrospective design, small sample size, single-center study |
| Hyperlactatemia in diabetic ketoacidosis is common and can be prolonged: lactate time-series from 25 intensive care admissions Morgan 2021 Australia | 25 ICU patients with DKA, categorized by serum lactate (mmol/L): ≤2 (n=3) >2 (n=22) |
Retrospective cohort study | Hospital LOS, ICU LOS | • Hospital LOS: p=0.579 (ns diff.) • ICU LOS: p=0.405 (ns diff.) | Possible missed cases due to exclusion criteria, retrospective design, small sample size, single-center study |
| Lactic acidosis in diabetic ketoacidosis: A marker of severity or alternate substrate for metabolism. Bhat 2021 India | 62 tertiary care hospital patients with DKA, categorized by serum lactate (mmol/L). <2.5 (n=27) ≥2.5 (n=35) |
Prospective cohort study | Hospital LOS, Morbidity, Mortality | • Hospital LOS: p=0.579 (ns diff.) • No mortality or significant morbidity observed. | No mortality data, unclear metformin association, small sample size, single-center study |
| Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit. BMC Endocrine Disorders Liu 2021 China | 107 paediatric ICU patients with DKA, categorized by serum (mmol/L): ≤2 (n=46) >2 (n=61) |
Retrospective cohort study | DKA resolution time, Hospital LOS | • DKA resolution time: r=0.143, p=0.143 (ns corr.) • Hospital LOS: r=0.154, p=0.115 (ns corr.) | Lack of mortality data, retrospective design, small sample size, single-center study |
| Lactate kinetics in intensive care unit admissions due to diabetic ketoacidosis Taşkın 2021 Turkey | 40 adult ICU patients with DKA, categorized by serum lactate (mmol/L): <4 (n=24) ≥4 (n=16) |
Retrospective cohort study | Serum lactate, Hospital LOS, ICU LOS, Mortality | • Serum lactate: Significantly higher in non-survivors at both hospital (p=0.017) and ICU admission (p=0.010) compared to survivors. • Hospital LOS: p=0.274 (ns diff.) • ICU LOS: p=0.966 (ns diff.) • Mortality: p=0.195 (ns diff.) | Unclear diabetes type differentiation, retrospective design, small sample size, single-center study |
| Relationship of lactate and lactate clearance with 28-day mortality in patients with acute renal injury in the emergency department Kart 2023 Turkey | 102 ED patients with DKA, categorized by mortality status. | Retrospective cohort study | Serum lactate (hour 1) | • Serum lactate (hour 1): Significantly higher in non-survivors compared to survivors (p=0.024). | Retrospective design, small sample size, single-center study |
| Association between elevated lactate and clinical outcomes in adults with diabetic ketoacidosis Kumar 2023 New Zealand | 9061 adult ICU patients with DKA, categorized by serum lactate (mmol/L): <2 (n=5674) ≥2 (n=3405) |
Retrospective, multicenter cohort study | Hospital LOS, ICU LOS, In-hospital mortality | For serum lactate ≥2 mmol/L (Ref: <2 mmol/L, persisted only in T2D, not T1D, after separation): • Hospital LOS: GMR=1.063 (95% CI: 1.025–1.103), p=0.001 (dir. corr.) • ICU LOS: GMR=1.057 (95% CI: 1.026–1.090), p<0.001 (dir. corr.) • In-hospital mortality: OR=1.785 (95% CI: 1.122–2.841), p=0.014 (dir. corr.) | Selective ICU data, missing serum lactate data, retrospective design |
| Deciphering the role of lactate as a prognostic indicator in pediatric diabetic ketoacidosis Ozel 2024 Turkey | 112 paediatric T1D patients with DKA (aged 7 months to 17 years), categorized by serum lactate (mmol/L): <2.5 (n=27) ≥2.5 (n=35) |
Retrospective cohort study | DKA resolution time, Paediatric ICU LOS | • DKA resolution time: p=0.746, r=0.031 (ns corr.) • PICU LOS: p=0.109, r=0.152 (ns corr.) | Lack of mortality data, excluded patients with confounding conditions, retrospective design, small sample size, single-center study |
| Predictors of 7-day mortality in critically ill patients with hyperglycemic crisis Ruttinger 2025 Austria | 523 patients with DKA, categorized by 7-day mortality status. | Retrospective cohort study | 7-day mortality | • Serum lactate: Significantly higher (p<0.001) in non-survivors (6.3 mmol/l) compared to survivors (3.4 mmol/l) | Not distinguished diabetes types (T1D vs. T2D), missing lactate data for some patients, retrospective design |
| Lactate levels in diabetic ketoacidosis: Is there an association between the severity of acidosis and length of hospital stay with elevated lactate levels? Söbü 2025 Turkey | 56 pediatric ED patients with DKA (aged 35-210 months), categorized by serum lactate (mmol/L): <2 (n=29) ≥2 (n=27) |
Retrospective cohort study | Serum lactate, Hospital LOS, ICU LOS | • Hospital LOS: p=0.325 (ns diff.) • ICU LOS: p=0.616 (ns diff.) | No morbidity or mortality data, retrospective design, small sample size |
Author Commentary:
The emergency physicians who manage DKA in the ED must decide whether the patient requires advanced monitoring or intensive care. The question is: Does baseline serum lactate predict worse outcomes? Out of 15 related studies (1-15), nine studies (1, 3, 6-11, 15) with a total of 714 participants, including all paediatric studies (1, 3, 7, 10, 11), found no significant association between higher baseline serum lactate levels and worse outcomes. On the other hand, among the remaining six studies (2, 4, 5, 12-14) supporting this association, a large population study (4) with 9,061 participants revealed that this association was only valid for type 2 diabetic patients. Taken together, these results suggest that baseline serum lactate levels may predict worse outcomes in DKA, specifically in type 2 diabetic adults. However, further studies across diverse populations, considering the type of diabetes, are required to confirm these findings.
Bottom Line:
Baseline serum lactate levels may predict outcomes in type 2 diabetic adults with DKA, but further studies across diverse populations, considering the type of diabetes, are required.
References:
- Cox. Prevalence and significance of lactic acidosis in diabetic ketoacidosis
- Suwarto. Predictors of five days mortality in diabetic ketoacidosis patients: a prospective cohort study
- Siregar. Seventy-two hour mortality prediction model in patients with diabetic ketoacidosis: A retrospective cohort study. Journal of the ASEAN Federation of Endocrine Societies
- Lee. Characterization of variable presentations of diabetic ketoacidosis based on blood ketone levels and major society diagnostic criteria: A new view point on the assessment of diabetic ketoacidosis
- Cully. Is lactic acidosis predictive of outcomes in pediatric diabetic ketoacidosis?
- Unal. A different perspective of elevated lactate in pediatric patients with diabetic ketoacidosis
- Morgan. Hyperlactatemia in diabetic ketoacidosis is common and can be prolonged: lactate time-series from 25 intensive care admissions
- Bhat. Lactic acidosis in diabetic ketoacidosis: A marker of severity or alternate substrate for metabolism.
- Liu. Hyperlactatemia associated with diabetic ketoacidosis in pediatric intensive care unit. BMC Endocrine Disorders
- Taşkın. Lactate kinetics in intensive care unit admissions due to diabetic ketoacidosis
- Kart . Relationship of lactate and lactate clearance with 28-day mortality in patients with acute renal injury in the emergency department
- Kumar. Association between elevated lactate and clinical outcomes in adults with diabetic ketoacidosis
- Ozel. Deciphering the role of lactate as a prognostic indicator in pediatric diabetic ketoacidosis
- Ruttinger. Predictors of 7-day mortality in critically ill patients with hyperglycemic crisis
- Söbü. Lactate levels in diabetic ketoacidosis: Is there an association between the severity of acidosis and length of hospital stay with elevated lactate levels?