Slowly progressing type 1 diabetes: persistence of islet cell autoantibodies is related to glibenclamide treatment.
BACKGROUND
Several experimental studies in rats have demonstrated that sulfonylurea treatment increases autoantigen expression in B-cells. This phenomenon may be deleterious for the preservation of residual beta cell function in patients with slowly progressing type 1 diabetes or latent autoimmune diabetes of adult (LADA).


OBJECTIVE
The aim of the present study was to evaluate whether the exclusion of glibenclamide in the treatment of ICA positive type 2 diabetic patients may diminish or halt the humoral autoimmune response against B-cells as well as improve metabolic control and insulin secretion.


METHODS
Fourteen type 2 diabetic patients with pancreatic autoimmunity (ICA+ and GABA+) and treated with insulin and glibenclamide (duration of disease 2.0 +/- 2.2, range 0.1-7 years and age 53 +/- 12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n = 8, age 53 +/- 6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n = 6, age 53.5 +/- 16.9) (Unmodified treatment). Both groups were investigated at the beginning of the study and after one year for the following parameters: ICA and anti-GAD65 antibodies, fasting glucose and fasting C-peptide.


RESULTS
In group 1, six out of eight patients became ICA negative while all patients in group 2 remained ICA positive (p = 0.0097). Fasting glucose concentrations improved in group 1 (4.6 +/- 2.8) in relation to group 2 (11.5 +/- 5.5, p = 0.0023) after one year of treatment. No differences were found for anti-GAD antibodies and fasting C-Peptide between the groups.


CONCLUSIONS
These data show that exclusion of glibenclamide in the treatment of ICA+ type 2 diabetic patients partially decreases specific autoimmunity against endocrine pancreatic cells and improves metabolic control. This may reflect decreased expression of B-cell autoantigens suggesting that insulin monotherapy is a better choice for the treatment of LADA.
Cabrera-Rode
Eduardo
E
Department of Immunology of Diabetes Mellitus, National Institute of Endocrinology, Vedado, Havana, Cuba. diabetes@infomed.sld.cu
Perich
Pedro
P
Diaz-Horta
Oscar
O
Tiberti
Claudio
C
Molina
Gisela
G
Arranz
Celeste
C
Martin
Juana M
JM
Licea
Manuel
M
De Leiva
Alberto D
AD
Puig-Domingo
Manuel
M
Dimario
Umberto
U
D001323:Autoantibodies / Q000187:drug effects* / Q000276:immunology; D001786:Blood Glucose; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005968:Glutamate Decarboxylase / Q000276:immunology; D005905:Glyburide / Q000494:pharmacology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000276:immunology; D007527:Isoenzymes / Q000276:immunology
D001323:Autoantibodies; D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D005905:Glyburide