Effect of standard nicotinamide in the prevention of type 1 diabetes in first degree relatives of persons with type 1 diabetes.
BACKGROUND
Nicotinamide has been used with success to prevent type 1 diabetes in animal models and humans. This vitamin B3 derivative has attracting effects on beta-cell protection and regeneration.


OBJECTIVE
To evaluate the effect of standard nicotinamide administration on type 1 diabetes prevention in first degree relatives of persons with type 1 diabetes as well as on the concentrations of islet-cell-related autoantibodies, insulin secretion and peripheral sensitivity.


METHODS
A randomized double-blind placebo controlled intervention trial was conducted in 40 first degree relatives of type 1 diabetic patients. Persistence of ICA ( >or= 10 JDF units) was among inclusion criteria. Participants were randomly allocated oral standard nicotinamide (1.2 g/m2) or placebo for 5 years. Groups were also stratified by age. Islet associated antibodies, fasting blood glucose, fasting plasma insulin concentrations, OGTT, IVGTT and HLA-DR genotyping were performed in all participants. The main criterion to stop treatment was type 1 diabetes development as defined by WHO.


RESULTS
Type 1 diabetes development frequencies were similar between the treatment groups. ICA frequencies at the end of the study, first phase insulin release, and insulin sensitivity did not differ between groups as well. None of the participants suffered from any adverse events described for nicotinamide.


CONCLUSIONS
Type 1 diabetes prevention trial using standard nicotinamide is feasible but fails to prevent or delay the disease onset at the dose we used.
Cabrera-Rode
Eduardo
E
Department of Immunology of Diabetes Mellitus, National Institute of Endocrinology, Zapata and D, Vedado, Havana, Cuba. diabetes@infomed.sld.cu
Molina
Gisela
G
Arranz
Celeste
C
Vera
Manuel
M
González
Pedro
P
Suárez
Rolando
R
Prieto
Mirta
M
Padrón
Saúl
S
León
Rafael
R
Tillan
Juana
J
García
Igrid
I
Tiberti
Claudio
C
Rodríguez
Olga María
OM
Gutiérrez
Antonio
A
Fernández
Tamara
T
Govea
Amparo
A
Hernández
José
J
Chiong
Dania
D
Domínguez
Emma
E
Di Mario
Umberto
U
Díaz-Díaz
Oscar
O
Díaz-Horta
Oscar
O
D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D020022:Genetic Predisposition to Disease; D005951:Glucose Tolerance Test; D006684:HLA-DR Antigens / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use* / Q000652:urine; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D014803:Vitamin B Complex / Q000627:therapeutic use*
D001323:Autoantibodies; D001786:Blood Glucose; D006684:HLA-DR Antigens; D007328:Insulin; C024211:islet cell antibody; D014803:Vitamin B Complex; D009536:Niacinamide; C008472:N-methylnicotinamide