Clinical and metabolic features of adult-onset diabetes caused by ABCC8 mutations.
OBJECTIVE
Gain-of-function ABCC8/sulfonylurea (SU) receptor 1 mutations cause neonatal diabetes mellitus (NDM) or late-onset diabetes in adult relatives. Given the effectiveness of SU treatment in ABCC8-NDM patients, we further characterized late-onset ABCC8-associated diabetes.


METHODS
Seven adult subjects from three NDM families and one family with type 2 diabetes were studied. Insulin secretion and insulin sensitivity were assessed using clamp techniques. We screened 139 type 2 diabetic patients who were well controlled by SU for ABCC8 mutations.


RESULTS
ABCC8 mutation carriers exhibited glucose intolerance, frank diabetes, or insulin-requiring diabetes since diagnosis. HbA(1c) improved in five SU-treated patients. Insulin secretion capacity was impaired in three patients compared with adult control subjects but was restored after a 4-week SU trial in two patients. Cohort screening revealed four SU-treated patients with ABCC8 mutations, two of which are likely causal.


CONCLUSIONS
Although of rare occurrence, recognition of adult-onset ABCC8-associated diabetes may help in targeting patients for SU therapy.
Department of Diabetes and Endocrinology, Centre Hospitalier Sud Francilien, Corbeil-Essonnes, France. riveline.jeanpierre@neuf.fr
Jean-Pierre
JP
Riveline
Elise
E
Rousseau
Yves
Y
Reznik
Sabrina
S
Fetita
Julien
J
Philippe
Aurélie
A
Dechaume
Agnès
A
Hartemann
Michel
M
Polak
Catherine
C
Petit
Guillaume
G
Charpentier
Jean-François
JF
Gautier
Philippe
P
Froguel
Martine
M
Vaxillaire
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011955:Receptors, Drug / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D064233:Sulfonylurea Receptors; D055815:Young Adult
D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors