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Serum ketone body measurement in patients with diabetic ketoacidosis

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Abstract

Background

Diabetic ketoacidosis (DKA) is a critical manifestation in patients with diabetes mellitus. DKA has been conventionally diagnosed by the presence of hyperglycemia (blood glucose levels > 250 mg/dl) and metabolic acidosis (blood gas bicarbonate [HCO3−] < 18 mmol/l and pH in blood gas < 7.30). However, quantitative evaluation of serum ketone bodies has not been established. The current study investigates serum ketone body levels in patients suspected for DKA.

Methods

We have retrospectively evaluated patients with hyperglycemia whose serum ketone body levels at the outpatient clinic and emergency department were measured simultaneously with blood gas analysis during 2011–2019. Clinical backgrounds, severity of diabetes, serum ketone bodies, and blood gas factors were analyzed.

Results

Seventy-two patients were enrolled in the study, after the exclusion of patients who had ketosis due to factors other than diabetes. Serum ketone body levels were negatively correlated with the levels of blood HCO3− and pH. By receiver-operating-characteristic curve analyses, optimal cut-off values for diagnosis of DKA were determined at 6.3 mmol/l of beta-hydroxybutyrate, 1.4 mmol/l of acetoacetate, and 8.0 mmol/l of total ketone body, respectively. Moreover, serum ketone bodies appeared to effectively differentiate between type 1 and type 2 diabetes mellitus. The cut-off values were higher than those in previous reports.

Conclusions

Serum ketone body levels were thought to be useful in the diagnosis of DKA. Further investigations with increased numbers of patients are required to establish the appropriate application of serum ketone bodies in patients with DKA.

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Data availability statement

The datasets in the manuscript are available from the corresponding authors on reasonable request.

Abbreviations

AcAc:

Acetoacetate

CPR:

C-peptide

DM:

Diabetes mellitus

DKA:

Diabetic ketoacidosis

GADAb:

Glutamic acid decarboxylase autoantibody

HCO3 − :

Bicarbonate

ICAs:

Autoantibodies to islet cells

IDDM:

Insulin-dependent diabetes mellitus

KPD:

Ketosis-prone type 2 diabetes mellitus

NIDDM:

Non-insulin-dependent diabetes mellitus

ROC:

Receiver-operating-characteristic

TKB:

Total ketone body

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

βOHB:

Beta-hydroxybutyrate

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Acknowledgements

We acknowledge proofreading and editing by Benjamin Phillis at the Clinical Study Support Center, Wakayama Medical University.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

Authors and Affiliations

  1. Department of Diabetes and Endocrinology, Japanese Red Cross Wakayama Medical Center, 4-20 Komatsubara-dori, Wakayama, Wakayama, 640-8558, Japan

    Tomonao Hirobata, Hidefumi Inaba, Yosuke Kaido, Daisuke Kosugi, Saya Itoh & Gen Inoue

  2. The First Department of Medicine, Wakayama Medical University, Hospital, 811-1 Kimiidera, Wakayama, Wakayama, 641-8509, Japan

    Hidefumi Inaba & Takaaki Matsuoka

Authors
  1. Tomonao Hirobata
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  2. Hidefumi Inaba
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  3. Yosuke Kaido
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  4. Daisuke Kosugi
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  5. Saya Itoh
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  6. Takaaki Matsuoka
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  7. Gen Inoue
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Corresponding author

Correspondence to Hidefumi Inaba.

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Conflict of interest

The authors have no competing interests to disclose.

Compliance with ethical standards

The study protocol was approved by the Japanese Red Cross Wakayama Medical Center Ethics Committee (No. 680, April 30. 2019), and all participants had the opportunity to opt-out of research. The necessity for written informed consent from each patient was waived in this retrospective study. We used clinical information obtained in routine clinical practice, and no patients refused to participate in the study. All procedures were in accordance with the institutional ethical standards regarding human experimentation and with the Declaration of Helsinki, as revised in Fortaleza, Brazil in October 2013.

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Supplementary Information

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13340_2022_581_MOESM1_ESM.jpg

Supplementary file1 Supplemental Fig. 1 Patient enrollment procedures. Detailed patient enrollment procedures were described thoroughly in the method. Among consecutive outpatients with DM at our department and emergency room during the 2011- 2019 year, a total of 202 patients were recruited for the study. Based on the inclusion and exclusion procedures as indicated, patients with T1DM (n=21), patients with T2DM-IDDM (n=29), and patients with T2DM-NIDDM (n=22) during the follow-up period were analyzed. *T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; IDDM, insulin dependent diabetes mellitus; NIDDM, non-insulin dependent diabetes mellitus (JPG 256 KB)

13340_2022_581_MOESM2_ESM.jpg

Supplementary file2 Supplemental Fig. 2 ROC analysis of serum βOHB levels for diagnosis of T1DM from T2DM. Optimal cut-off value of βOHB for diagnosis of T1DM was estimated by ROC analysis. 2.5 mmol/l of βOHB had 95.2% of sensitivity and 56.9% of specificity, area under the curve (AUC) was 0.77871. *βOHB, beta-hydroxybutyrate; ROC, receiver-operating-characteristic; T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus (JPG 66 KB)

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Hirobata, T., Inaba, H., Kaido, Y. et al. Serum ketone body measurement in patients with diabetic ketoacidosis. Diabetol Int 13, 624–630 (2022). https://doi.org/10.1007/s13340-022-00581-2

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  • DOI: https://doi.org/10.1007/s13340-022-00581-2

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