Glucose-induced insulin response is reduced and proinsulin response increased in healthy siblings of type 1 diabetic patients.
Glucose-stimulated insulin and proinsulin responses, and insulin sensitivity, were studied in 30 HLA identical, 38 HLA haplo-identical, and 25 HLA non-identical, healthy islet-cell-antibody negative siblings of Type 1 diabetic patients. The results were compared with 41 age- and sex-matched healthy subjects with no diabetes in the family. The proinsulin-corrected insulin response to an intravenous glucose infusion test was significantly lower among siblings when insulin sensitivity was taken into account (1.65 (inter-quartile range 1.20-2.64) vs 2.18 (1.65-3.28) nmol mmol-1 min, p = 0.04). Proinsulin values were consistently higher among siblings than among control subjects (peak values 50.0 vs 38.0 pmol l-1 (p = 0.004)). When proinsulin release was corrected for individual insulin sensitivity this difference remained. The results suggest disturbed islet B-cell function, unrelated to HLA identity or the presence of circulating islet cell antibodies.
Department of Pediatrics, Karolinska Institute, Sachs' Children's Hospital, Stockholm, Sweden.
F A
FA
Lindgren
S G
SG
Hartling
G G
GG
Dahlquist
C
C
Binder
S
S
Efendić
B E
BE
Persson
D000293:Adolescent; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005215:Fasting; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006680:HLA Antigens / Q000032:analysis; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D061389:Insulin, Regular, Pork; D007700:Kinetics; D008297:Male; D011384:Proinsulin / Q000097:blood / Q000378:metabolism*; D012016:Reference Values; D013004:Somatostatin / Q000008:administration & dosage; D013997:Time Factors
D001786:Blood Glucose; D002096:C-Peptide; D006680:HLA Antigens; D007328:Insulin; D061389:Insulin, Regular, Pork; D013004:Somatostatin; D011384:Proinsulin; C000006:insulin, neutral; D005947:Glucose