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Diabetologia

pp 1–10 | Cite as

Spontaneous ketonuria and risk of incident diabetes: a 12 year prospective study

  • Gyuri Kim
  • Sang-Guk Lee
  • Byung-Wan Lee
  • Eun Seok Kang
  • Bong-Soo Cha
  • Ele Ferrannini
  • Yong-ho LeeEmail author
  • Nam H. ChoEmail author
Article

Abstract

Aims/hypothesis

Ketones may be regarded as a thrifty fuel for peripheral tissues, but their clinical prognostic significance remains unclear. We investigated the association between spontaneous fasting ketonuria and incident diabetes in conjunction with changes in metabolic variables in a large population-based observational study.

Methods

We analysed 8703 individuals free of diabetes at baseline enrolled in the Korean Genome and Epidemiology Study, a community-based 12 year prospective study. Individuals with (n = 195) or without fasting ketonuria were matched 1:4 by propensity score. Incident diabetes was defined as fasting plasma glucose ≥7.0 mmol/l, post-load 2 h glucose ≥11.1 mmol/l on biennial OGTTs, or current use of glucose-lowering medication. Using Cox regression models, HRs for developing diabetes associated with the presence of ketonuria at baseline were analysed.

Results

Over 12 years, of the 925 participants in the propensity score-matched cohort, 190 (20.5%) developed diabetes. The incidence rate of diabetes was significantly lower in participants with spontaneous ketonuria compared with those without ketonuria (HR 0.63; 95% CI 0.41, 0.97). Results were virtually identical when participants with fasting ketonuria were compared against all participants without ketonuria (after multivariate adjustment, HR 0.66; 95% CI 0.45, 0.96). During follow-up, participants with baseline ketonuria maintained lower post-load 1 h and 2 h glucose levels and a higher insulinogenic index despite comparable baseline values.

Conclusions/interpretation

The presence of spontaneous fasting ketonuria was significantly associated with a reduced risk of diabetes, independently of metabolic variables. Our findings suggest that spontaneous fasting ketonuria may have a potential preventive role in the development of diabetes.

Keywords

Cohort Diabetes Ketone Risk 

Abbreviations

βHB

β-Hydroxybutyrate

FGF21

Fibroblast growth factor 21

HMGCS2

3-Hydroxy-3-methylglutaryl-CoA synthase 2

IGI

Insulinogenic index

KoGES

Korean Genome and Epidemiology Study

PPARα

Peroxisome proliferator-activated receptor, alpha

SGLT2

Sodium–glucose cotransporter 2

Notes

Acknowledgements

Data in this study were from the KoGES (4851-302), National Research Institute of Health, Centers for Disease Control and Prevention, Ministry for Health and Welfare, Republic of Korea.

Contribution statement

GK and Y-hL conceived and designed the study and performed the analyses. GK, NHC, S-GL and Y-hL acquired the data. GK, EF and Y-hL wrote the first draft of the manuscript. All authors interpreted the data, contributed to the writing of the manuscript and read and approved the final version. Y-hL and NHC are responsible for the integrity of the work as a whole.

Funding

This research was supported by grants from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2016R1A5A1010764) and from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI17C0913).

Duality of interest

The authors declare that they have no competing interests.

Supplementary material

125_2019_4829_MOESM1_ESM.pdf (369 kb)
ESM (PDF 368 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Gyuri Kim
    • 1
  • Sang-Guk Lee
    • 2
  • Byung-Wan Lee
    • 3
    • 4
  • Eun Seok Kang
    • 3
    • 4
  • Bong-Soo Cha
    • 3
    • 4
  • Ele Ferrannini
    • 5
  • Yong-ho Lee
    • 3
    • 4
    • 6
    Email author
  • Nam H. Cho
    • 7
    Email author
  1. 1.Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulRepublic of Korea
  2. 2.Department of Laboratory MedicineYonsei University College of MedicineSeoulRepublic of Korea
  3. 3.Department of Internal MedicineYonsei University College of MedicineSeoulRepublic of Korea
  4. 4.Institute of Endocrine ResearchYonsei University College of MedicineSeoulRepublic of Korea
  5. 5.CNR Institute of Clinical PhysiologyPisaItaly
  6. 6.Department of Systems Biology, Glycosylation Network Research CenterYonsei UniversitySeoulRepublic of Korea
  7. 7.Department of Preventive MedicineAjou University School of MedicineSuwonRepublic of Korea

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