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Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry

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Abstract

The aim of this study was to characterize the phenotype and treatment of young patients (manifestation <30 years) with diabetes of mitochondrial origin (DMO), based on the German/Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry. Only 13 (0.02 %) of all patients with diabetes in this cohort were identified with DMO, mainly due to the Kearns-Sayre (n = 5), Pearson (n = 3), or mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (n = 2). The onset of DMO (14.2, interquartile range (IQR) 7.1–16 years) was later than diabetes onset in individuals with T1D but earlier than in T2D. At manifestation, patients exhibited a mild elevation of blood glucose concentrations (251, IQR 178–299 mg/dl) without ketoacidosis. They had lower body mass index (BMI) values (−1.39 ± 0.28 kg/m2) than peers with T1D or T2D (p < 0.0001) and higher triglycerides (211, IQR 134–574 mg/dl) than in T1D (p = 0.04) while there was a high rate of dyslipidemia (86 %). Insulin requirements (0.58, IQR 0.37–0.90 U/kg/d) were between T1D and T2D while glucometabolic control (glycated hemoglobin A1c (HbA1c) 7.4 ± 0.52 %) in DMO was comparable to age-matched T2D and stable over a 5-year follow-up.

Conclusion: Primary mitochondrial disorders are a rare cause of juvenile diabetes and likely to be underdiagnosed. As there is clinical overlap with T1D and T2D, dyslipidemia and low body weight may help to identify further DMO cases.

What is Known:

• In adults diabetes of mitochondrial origin (DMO) is a rare cause of non-autoimmune diabetes, affecting about 0.8 % of diabetes cases.

• Common features are a maternal family history of diabetes, hearing loss and neurological abnormalities.

What is New:

• In our juvenile cohort 0.02 % of diabetes patients (age < 30 years) were affected by DMO, while Kearns Sayre, MELAS and Pearson syndrome were the most frequent entities.

• Juvenile DMO patients exhibited dyslipidemia, higher triglycerides and a lower BMI than peers with T1D or T2D, while some patients also showed retinal changes.

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Abbreviations

DMO:

Diabetes of mitochondrial origin

DPV:

Diabetes Patienten Verlaufsdokumentation

HbA1c:

Glycated hemoglobin A1c

IQR:

Interquartile range

KSS:

Kearns-Sayre syndrome

MELAS:

Syndrome mitochondrial myopathy, encephalomyopathy, lactic acidosis, and stroke-like episodes

MIDD:

Maternally inherited diabetes and deafness

T1D:

Type 1 diabetes mellitus

T2D:

Type 2 diabetes mellitus

SD:

Standard deviation

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Authors’ contributions

CR, TM and RWH wrote the manuscript. EB and RWH performed statistical analysis. AT, PMH, HH, EB, WM clinically managed the patients and critically reviewed the manuscript together with MR and EB. All the authors approved the final copy of the manuscript.

Author information

Authors and Affiliations

  1. Department of General Pediatrics, Neonatology and Pediatric Cardiology, University Children’s Hospital, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

    Christina Reinauer & Thomas Meissner

  2. German Center for Diabetes Research (DZD e.V.), Partners Düsseldorf and Ulm, Düsseldorf, Germany

    Thomas Meissner & Michael Roden

  3. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany

    Michael Roden

  4. Institute for Clinical Diabetology, German Diabetes Center at Heinrich Heine University Düsseldorf, Leibniz Center for Diabetes Research, German Center for Diabetes Research (DZD), 40225, Düsseldorf, Germany

    Michael Roden

  5. Department of Pediatric Pneumology, Allergology & Neonatology, Children’s Hospital, Hannover Medical School, 30625, Hannover, Germany

    Angelika Thon

  6. Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University Hospital Schleswig-Holstein, Christian-Albrechts University Kiel, 24118, Kiel, Germany

    Paul-Martin Holterhus

  7. Hospital for Children and Adolescents, Sana Hospital Berlin Lichtenberg, 10365, Berlin, Germany

    Holger Haberland

  8. Department of Pediatrics, Medical University of Innsbruck, A 6020, Innsbruck, Austria

    Elisabeth Binder

  9. Center for Pediatrics and Adolescent Medicine, Bremen-Mitte Hospital, 28211, Bremen, Germany

    Wolfgang Marg

  10. Institute of Epidemiology and Medical Biometry, ZIBMT, University of Ulm, German Center for Diabetes Research (DZD), 89081, Ulm, Germany

    Esther Bollow & Reinhard Holl

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  1. Christina Reinauer
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  2. Thomas Meissner
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Corresponding author

Correspondence to Christina Reinauer.

Ethics declarations

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or National Research Committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The DPV has the ethical approval at the University of Ulm. Data collection was approved by the local institutional review boards.

Funding

The DPV database is supported by the German Federal Ministry of Education and Research (BMBF) as part of the Competence Network for Diabetes mellitus (Kompetenznetz Diabetes mellitus, FKZ 01GI1106), which was integrated into the German Center for Diabetes Research (DZD) in 2015, the German Diabetes Association (Deutsche Diabetes Gesellschaft, DDG), the European Foundation for the Study of Diabetes (EFSD), and the Heinz Bürger-Büsing Foundation.

Conflict of interest

The authors declare that they have no competing interests.

The DPV initiative received grant support from Sanofi Aventis, Lilly, Novo Nordisk, Boehringer Ingelheim, Roche Diagnostics and Medtronic. None of these grants is related to the present study.

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Communicated by Beat Steinmann

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Reinauer, C., Meissner, T., Roden, M. et al. Low prevalence of patients with mitochondrial disease in the German/Austrian DPV diabetes registry. Eur J Pediatr 175, 613–622 (2016). https://doi.org/10.1007/s00431-015-2675-5

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