Glibenclamide site of in insuline: a new chance for MODY 3 type diabetes patients: case report

Česká verzia

Authors: L. Brunerová ¹; L. Trešlová ¹; Š. Průhová ²; J. Vosáhlo ²; J. Brož ¹; J. Lebl ²; M. Anděl ¹
Authors place of work: Diabetologické centrum II. interní kliniky 3. lékařské fakulty UK a FN Královské Vinohrady, Praha, přednosta prof. MUDr. Michal Anděl, CSc. ¹; Diabetologické centrum Kliniky dětí a dorostu 3. lékařské fakulty UK a FN Královské Vinohrady, Praha, přednosta prof. MUDr. Jan Lebl, CSc. ²
Published in the journal: Vnitř Lék 2006; 52(3): 275-279
Category: Case Report

Summary

MODY 3 belongs to monogenic forms of diabetes mellitus and is caused by monoallelic mutation in gene for transcription factor HNF-1α, essential for regulation of β-cell function. Clinical presentation of MODY 3 is similar to that of type 1 diabetes. Although MODY 3 patients are not threatened by ketoacidosis, tight metabolic control is important for prevention of chronic diabetic complications. In the sibbling pair diabetes was manifested by osmotic symptoms resulting from hyperglycaemia at the age of 18 years (brother) resp. 15 years (sister) and both of them started being treated with intensified insulin treatment. Metabolic control of the brother was very tight with HbA_1c 3.3 % but frequent hypoglycaemias occured. On the contrary metabolic control of the sister was very poor due to her non-compliance (HbA_1c 10.9 %, IFCC). Molecular-genetic testing proved HNF-1α gene mutation (Arg200Gly). In accordance with the references treatment with sulphonylurea derivate glibenclamide was initiated [at the doses 1.25 (brother) resp. 7.5 (sister) mg/day] and insulin treatment was discontinued. The treatment change led to better quality of life and metabolic control in both the patients and suprisingly to the lower frequency of the hypoglycaemias in the brother (HbA_1c decreased from 3.3 % to 2.8 % in three months in the brother resp. from 10.9 % to 10.0 % in two months in the sister). Molecular-genetic testing enables the change of treatment leading to better quality of life and metabolic control, although its longterm safety and efficacy will have to be confirmed.

Key words:
MODY 3 type diabetes - therapy - metabolic control - glibenclamide - quality of life

Zdroje

1. Yamagata K, Oda N, Kausami PJ et al. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the zouny (MODY 3). Nature 1996; 384: 455-458.

2. Brunerová L, Brož J, Průhová Š et al. Maturity-onset diabetes of the young 3. DMEV 2006; (rukopis).

3. Timsit J, Bellanné-Chantelot Ch, Dubois-Laforgue D et al. Diagnosis and management of Maturity-Onset Diabetes of the Young. Treat Endocrinol 2005; 4: 9-18.

4. Mitchell S, Frayling T. The role of transcription factors in maturity-onset diabetes of the young. Mol Genet Metab 2002; 77: 35-43.

5. Kim SH, Ma X, Klupa T et al. Genetic modifiers of the age at diagnosis of diabetes (MODY 3) in carriers of HNF-1α mutations map to chromosomes 5p15, 9q22 and 14q24. Diabetes 2003; 52: 2182-2186.

6. Lehto M, Tupni T, Mahtani MM et al. Characterization of the MODY 3 phenotype: early onset diabetes caused by an insulin secretion defect. J Clin Invest 1997; 99: 582-591.

7. Klimeš I, Gašperíková D, Michálek J. DNA diagnostika monogennych foriem diabetu na Slovensku: január 2005. DMEV 2005; 8: 27.

8. Owen KR, Shepherd M, Stride A et al. Heterogenity in young adult onset diabetes - aetiology alters clinical characteristics. Diabet Med 2002; 19: 758-761.

9. Owen KR, Stride A, Ellard S et al. Etiological investigation in young adults presenting with apparent type 2 diabetes. Diabetes Care 2003; 26: 2088-2093.

10. Moller AM, Dalgaard LT, Pociot F et al. Mutations in the hepatocyte nuclear factor 1-α gene in Caucasian families originally classified as having type 1 diabetes. Diabetologia 1998; 41: 1528-1531.

11. Isomaa B, Henricsson M, Lehto M et al. Chronic diabetic complications in patients with MODY 3 diabetes. Diabetologia 1998; 41: 467-473.

12. Hattersley AT. Maturity onset diabetes of the young: clinical heterogenity explained by genetic heterogenity. Diabet Med 1998; 15: 15-24.

13. Shepherd M, Hattersley A. I don´t feel like a diabetic any more: the impact of stopping insulin in patients with maturity-onset diabetes of the young following genetic testing. Clin Med 2004; 4: 144-147.

14. Pearson E, Starkey B, Powell R et al. Genetic cause of hyperglycaemia and response to treatment in diabetes. Lancet 2003; 362: 1275-1281.

15. Shepherd M, Pearson E, Houghton J et al. No deterioration in glycaemic control in HNF-1α Maturity-Onset Diabetes of the Young following transfer from long-term insulin to sulphonylureas. Diab Care 2003; 26: 3191-3192.

16. www.dawnstudy.com

17. Vaxillaire M, Pueyo ME, Clément K et al. Insulin secretion and insulin sensitivity in diabetic and non-diabetic subjects with HNF-1α mutations. Eur J Endocrinol 1999; 141: 609-618.

18. Pearson E, Liddell W, Shepherd M et al. Sensitivity to sulphonylureas in patients with HNF-1α gene mutations: evidence for pharmacogenetics in diabetes. Diabet Med 2000; 17: 543-545.

19. Boileau P, Wolfrum Ch, Shih D et al. Decreased glibenclamide uptake in hepatocytes of HNF-1α defficient mice. Diabetes 2002; 51: S343-S348.

20. Sagen JV, Pearson ER, Johansen A et al. Preserved insulin response to tolbutamide in HNF-1alpha mutation carriers. Diabet Med 2005; 22: 406-409.

21. Yamagata K, Nammo T, Moriwaki M et al. Overexpression of dominant-negative mutant HNF-1α in pancreatic β-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced β-cell proliferation and diabetes. Diabetes 2002; 51: 114-123.

22. Richter S, Shih D, Pearson E et al. Regulation of apolipoprotein M gene expression by MODY3 gene hepatocyte nuclear factor-1alpha: haploinsufficiency is associated with reduced serum apolipoprotein M levels. Diabetes 2003; 52: 2989-2995.

23. Dunne M, Cosgrove K, Shepherd M et al. Potassium channels, sulphonylurea receptors and control of insulin release. Trends Endocrinol Metab 1999; 10: 146-152.