Administration of sulfonylureas can increase glucose-induced insulin secretion for decades in patients with maturity-onset diabetes of the young.
OBJECTIVE
To ascertain whether the effect of sulfonylureas on glucose-mediated insulin release persists for years to decades in patients with maturity-onset diabetes of the young.


METHODS
The effect of sulfonylurea treatment on glucose-induced insulin secretion was ascertained prospectively for up to 33 yr in 12 diabetic patients of the maturity-onset diabetes of the young RW pedigree, who are genetically homogeneous because they share DNA markers on chromosome 20q. In 7 of these patients, paired glucose tolerance tests, given while the patients were on and off sulfonylureas, were performed after 7-31 yr.


RESULTS
Glucose-induced insulin secretion showed an average increase of 68% in diabetic patients who remained responsive to chlorpropamide after having been on and off the drug for decades. In most patients, however, glucose-induced insulin secretion declines over time (1-4%/yr). Some patients become unresponsive to sulfonylureas after 3-25 yr and then have very small or no increases in glucose-induced insulin secretion and require treatment with insulin to normalize fasting hyperglycemia.


CONCLUSIONS
Increase in glucose-induced insulin secretion remains the most important mechanism of the action of sulfonylureas during long-term administration.
Fajans
S S
SS
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor.
Brown
M B
MB
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001786:Blood Glucose / Q000378:metabolism*; D002648:Child; D002747:Chlorpropamide / Q000627:therapeutic use*; D002890:Chromosomes, Human, Pair 20; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D003927:Diet, Diabetic; D005500:Follow-Up Studies; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism* / Q000627:therapeutic use; D000078790:Insulin Secretion; D007700:Kinetics; D011446:Prospective Studies; D013997:Time Factors; D014044:Tolbutamide / Q000627:therapeutic use*
D001786:Blood Glucose; D007328:Insulin; D014044:Tolbutamide; D002747:Chlorpropamide