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Klin Padiatr 2016; 228(06/07): 307-312
DOI: 10.1055/s-0042-111691
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Diabetes in Patients with ß-thalassemia or other Hemoglobinopathies – Analysis from the DPV Database

Diabetes bei Patienten mit ß-Thalassämie oder anderen Hämoglobinopathien – eine Analyse aus der DPV Datenbank
K. Warncke
1   Department of Pediatrics, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
,
K. Konrad
2   Department of Pediatric and Adolescent Medicine, University Children’s Hospital Cologne, Cologne, Germany
,
E. Kohne
3   Department of Pediatrics and Adolescents, Laboratory of Hemoglobinopathy, University of Ulm, Ulm, Germany
,
E. Hammer
4   Department of Pediatrics, Children’s Hospital Wilhelmstift, Hamburg, Germany
,
U. Ohlenschläger
5   Department of Pediatrics, Goethe University Frankfurt, Frankfurt, Germany
,
S. Herrlinger
6   Department of Pediatrics, Klinikum Bremen Nord, Bremen, Germany
,
A. Jäger
7   Department of Pediatrics, Kaiser-Franz-Josef-Spital mit Gottfried von Preyer’schem Kinderspital, Wien, Austria
,
R. W. Holl
8   Central Institute for Biomedical Technology, ZIBMT, University of Ulm, Ulm, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
15 November 2016 (online)

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Abstract

Background: Diabetes mellitus is a common endocrinopathy in patients with thalassemia major, but the occurrence of hemoglobinopathies is rare in Germany and Western Europe. The longitudinal German-Austrian DPV (Diabetes Patienten Verlaufsdokumentation) registry allows a comprehensive characterization of this group of patients.

Patients/methods: Patients from the DPV-registry aged<30 years with thalassemia major or other hemoglobinopathies were compared to patients with type 1 diabetes (T1D) and type 2 diabetes (T2D) using the statistical software SAS 9.4.

Results: 94 patients (0.13% of patients) with hemoglobinopathies are registered in DPV. 82.4% of 17 patients with thalassemia major, 100% of 12 patients with sickle cell disease (SCD) and >90% of 65 patients with other hemoglobinopathies receive insulin treatment. In the majority of patients with thalassemia major, hemosiderosis is documented. Patients with thalassemia major developed diabetes at a median age of 14.6 [IQR 8.4–18.0] years (9.0 years [5.3–12.5] in T1D; 18.7 years [14.2–25.6] in TD2; both p<0.01). They show high HbA1c/fructosamine levels and frequent hypoglycemia, reflecting poor metabolic control.

Conclusion: Diabetes in thalassemia major is probably caused by hemosiderosis due to polytransfusion, while patients with SCD/thalassemia minor are most likely affected by T1D. The high rate of hypoglycemia in patients with ß-thalassemia major may be caused by liver fibrosis and a lack of hepatic glycogen stores.

Zusammenfassung

Hintergrund: Diabetes mellitus ist eine häufige Endokrinopathie bei Patienten mit Thalassämia major. In Deutschland und im westlichen Europa ist die Prävalenz von Hämoglobinopathien allerdings niedrig. Das deutsch-österreichische DPV (Diabetes Patienten Verlaufsdokumentation) Register ermöglicht eine umfassende Charakterisierung dieser Patientengruppe.

Patienten/Methoden: Patienten aus dem DPV-Register im Alter von <30 Jahren mit Diabetes und Thalassämia major oder anderen Hämoglobinopathien wurden im Vergleich zu Patienten mit Typ 1 Diabetes (T1D) und Typ 2 Diabetes (T2D) unter Verwendung der Statistik-Software SAS 9,4 analysiert.

Ergebnisse: Im DPV Register sind 94 Patienten (0,13% aller Patienten) mit Hämoglobinopathien registriert. 82,4% von insgesamt 17 Patienten mit Thalassaemia major, 100% von 12 Patienten mit Sichelzellanämie (SCD) und >90% von 65 Patienten mit anderen Hämoglobinopathien werden mit Insulin behandelt. Beim Großteil der Patienten mit Thalassämia major ist eine Hämosiderose dokumentiert. Patienten mit Thalassämie major erkranken in einem medianen Alter von 14,6 [IQR 8,4–18,0] Jahren (9,0 Jahre [5,3–12,5] bei T1D; 18,7 Jahre [14,2–25,6] bei TD2, beide p<0,01) an Diabetes. Patienten mit Thalassämie weisen hohe HbA1c-/Fructosaminspiegel und häufige Hypoglykämien auf, vereinbar mit einer schlechten Stoffwechsellage.

Schlussfolgerung: Diabetes bei Thalassämia major ist mit größter Wahrscheinlichkeit durch eine durch häufige Transfusionen verursachte Hämosiderose bedingt, während bei Patienten mit Sichelzellerkrankung/Thalassämia minor am ehesten ein autoimmun vermittelter T1D besteht. Ursache der hohen Rate an Hypoglykämien bei Patienten mit ß-Thalassämia major sind vermutlich eine Leberfibrose und zu geringe Glykogenspeicher in der Leber.

Key words

ß-Thalassemia - sickle cell disease - hemoglobinopathy - diabetes mellitus - metabolic control

Schlüsselwörter

ß-Thalassämie - Sichelzellerkrankung - Hämoglobinopathie - Diabetes mellitus - metabolische Kontrolle
 

  • References

  • 1 American Diabetes Association, Workgroup on Hypoglycemia . Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 2005; 28: 1245-1249
    CrossrefPubMedGoogle Scholar
  • 2 Cappellini MD, Cohen A, Eleftheriou A et al. Guidelines for the Clinical Management of Thalassaemia. 2nd Edn. Nicosia (CY): Thalassaemia International Federation; 2008
    Google Scholar
  • 3 Cario H, Holl RW, Debatin KM et al. Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test. Eur J Pediatr 2003; 162: 139-146
    PubMedGoogle Scholar
  • 4 Cario H, Stahnke K, Kohne E. Beta-thalassemia in Germany. Results of cooperative beta-thalassemia study. Klin Padiatr 1999; 211: 431-437
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Chatterjee R, Bajoria R. New concept in natural history and management of diabetes mellitus in thalassemia major. Hemoglobin 2009; 33 (Suppl. 01) S127-S130
    CrossrefPubMedGoogle Scholar
  • 6 Cole TJ, Green PJ. Smoothing reference centile curves: the LMS method and penalized likelihood. Stat Med 1992; 11: 1305-1319
    CrossrefPubMedGoogle Scholar
  • 7 De Sanctis V, Soliman A, Yassin M. Iron overload and glucose metabolism in subjects with β-thalassaemia major: an overview. Curr Diabetes Rev 2013; 9: 332-341
    CrossrefPubMedGoogle Scholar
  • 8 Dhouib N, Turki Z, Mellouli F et al. Efficacy of metformin in the treatment of diabetes mellitus complicating thalassemia major. Tunis Med 2010; 88: 136
    PubMedGoogle Scholar
  • 9 Eber S, Dickerhoff R. Anemia and hemoglobin diseases in patients with migration background. Dtsch Med Wochenschr 2014; 139: 434-440
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 English E, Idris I, Smith G et al. The effect of anaemia and abnormalities of erythrocyte indices on HbA1c analysis: a systematic review. Diabetologia 2015; 58: 1409-1421
    CrossrefPubMedGoogle Scholar
  • 11 Fröhlich-Reiterer EE, Rosenbauer J, Bechtold-Dalla Pozza S et al. Predictors of increasing BMI during the course of diabetes in children and adolescents with type 1 diabetes: data from the German/Austrian DPV multicentre survey. Arch Dis Child 2014; 99: 738-743
    CrossrefPubMedGoogle Scholar
  • 12 Gamberini MR, Fortini M, De Sanctis V et al. Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. Pediatr Endocrinol Rev 2004; Suppl 2: 285-291
    PubMedGoogle Scholar
  • 13 Gilliam LK, Liese AD, Bloch CA et al. Family history of diabetes, autoimmunity, and risk factors for cardiovascular disease among children with diabetes in the SEARCH for Diabetes in Youth Study. Pediatr Diabetes 2007; 8: 354-361
    CrossrefPubMedGoogle Scholar
  • 14 Hashimoto K, Koga M. Indicators of glycemic control in patients with gestational diabetes mellitus and pregnant women with diabetes mellitus. World J Diabetes 2015; 6: 1045-1056
    Google Scholar
  • 15 Knerr I, Dost A, Lepler R et al. Tracking and prediction of arterial blood pressure from childhood to young adulthood in 868 patients with type 1 diabetes: a multicenter longitudinal survey in Germany and Austria. Diabetes Care 2008; 31: 726-727
    CrossrefPubMedGoogle Scholar
  • 16 Kromeyer-Hauschild K, Wabitsch M, Kunze D et al. Perzentile für den Body-mass-Index für das Kindes- und Jugendalter unter Heranziehung verschiedener deutscher Stichproben. Monatsschrift Kinderheilkunde 2001; 149: 807-818
    CrossrefPubMedGoogle Scholar
  • 17 Kwiatkowski JL, Yim E, Miller S et al. Effect of transfusion therapy on transcranial Doppler ultrasonography velocities in children with sickle cell disease. Pediatr Blood Cancer 2011; 56: 777-782
    CrossrefPubMedGoogle Scholar
  • 18 Mohamed AA, Al-Qurashi F, Whitford DL. Does sickle cell disease protect against diabetes mellitus?: Cross-sectional study. Sultan Qaboos Univ Med J 2015; 15: e116-e119
    PubMedGoogle Scholar
  • 19 Monge L, Pinach S, Caramellino L et al. The possible role of autoimmunity in the pathogenesis of diabetes in ß-thalassemia major. Diabetes Metab 2001; 27: 149-154
    PubMedGoogle Scholar
  • 20 Mowla A, Karimi M, Afrasiabi A et al. Prevalence of diabetes mellitus and impaired glucose tolerance in ß-thalassemia patients with and without hepatitis C virus infection. Pediatr Endocrinol Rev 2004; Suppl 2: 282-284
    PubMedGoogle Scholar
  • 21 Neuhauser HK, Thamm M, Ellert U et al. Blood pressure percentiles by age and height from nonoverweight children and adolescents in Germany. Pediatrics 2011; 127: e978-e988
    CrossrefPubMedGoogle Scholar
  • 22 Rosenbauer J, Dost A, Karges B et al. Improved metabolic control in children and adolescents with type 1 diabetes: a trend analysis using prospective multicenter data from Germany and Austria. Diabetes Care 2012; 35: 80-86
    CrossrefPubMedGoogle Scholar
  • 23 Schlebusch H. Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen (RiliBÄK). In: Luppa B, Schlebusch H. (eds.). POCT 2008. Patientennahe Labordiagnostik. 1. Aufl. Berlin und Heidelberg: Springer; 2008
    CrossrefGoogle Scholar
  • 24 Schütt M, Kern W, Krause U et al. Is the frequency of self-monitoring of blood glucose related to long-term metabolic control? Multicenter analysis including 24,500 patients from 191 centers in Germany and Austria. Exp Clin Endocrinol Diabetes 2006; 114: 384-388
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Schwab KO, Doerfer J, Scheidt-Nave C et al. Algorithm-based cholesterol monitoring in children with type 1 diabetes. J Pediatr 2014; 164: 1079-1084
    CrossrefPubMedGoogle Scholar
  • 26 Shoar Z, Rezvani G, De Luca J. Type 1 diabetes mellitus in a patient with homozygous sickle cell disease. Pediatr Endocrinol Metab 2013; 26: 1205-1207
    PubMedGoogle Scholar
  • 27 True MW. Circulating biomarkers of glycemia in diabetes management and implications for personalized medicine. J Diabetes Sci Technol 2009; 3: 743-747
    PubMedGoogle Scholar
  • 28 Turner R, Stratton I, Horton V et al. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 1997; 350: 1288-1293
    CrossrefPubMedGoogle Scholar
  • 29 Tzoulis P, Shah F, Jones R et al. Joint diabetes thalassaemia clinic: an effective new model of care. Hemoglobin 2014; 38: 104-110
    CrossrefPubMedGoogle Scholar
  • 30 Zhang X, Zhang W, Saraf SL et al. Genetic polymorphism of APOB is associated with diabetes mellitus in sickle cell disease. Hum Genet 2015; 134: 895-904
    CrossrefPubMedGoogle Scholar