title: Excessive secretion of insulin precursors characterizes and predicts gestational diabetes.
abstract: Using assays that specifically measure insulin, intact proinsulin, and 32,33 split proinsulin, we examined the beta-cell secretory response to an oral glucose tolerance test (OGTT) in 64 women with gestational diabetes mellitus (GDM) and 154 pregnant normoglycemic control subjects of comparable age and body mass index. Women with GDM were characterized by a lower 30-min insulin increment (40.8 [34.9-47.6] vs. 58.6 [53.6-64] pmol insulin/mmol glucose, P < 0.001; geometric mean [95% confidence interval]) and a higher plasma insulin level at 120 min (702 [610-808] vs. 444 [400-492] pmol/l, P < 0.001). 32,33 split proinsulin levels were elevated in GDM patients in both fasting (9.1 [7.3-11.4] vs. 6.7 [6.0-7.5] pmol/l, P < 0.02) and 120-min (75.2 [62.9-90.0] vs. 52.2 [46.7-58.3] pmol/l, P < 0.001) samples, respectively. Intact proinsulin levels were significantly elevated at 120 min in the women with GDM (21.3 [18.1-25.1] vs. 14.8 [13.4-16.3] pmol/l, P < 0.001). Thus, the qualitative abnormalities of insulin secretion in GDM patients (low 30-min insulin increment, high 120-min plasma insulin, and elevated 32,33 split proinsulin) are similar to those seen in nonpregnant subjects with impaired glucose tolerance. To determine whether measures of proinsulin-like molecules (PLMs) might assist in the prediction of GDM, women who had a 1-h glucose level of > 7.7 mmol/l after a 50-g glucose challenge at 28-32 weeks' gestation had insulin and PLMs measured in the 1-h sample.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Cambridge, U.K.
authors.forename: R A
authors.initials: RA
authors.lastname: Swinn
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: R
authors.initials: R
authors.lastname: Gregory
authors.forename: V
authors.initials: V
authors.lastname: Curling
authors.forename: P M
authors.initials: PM
authors.lastname: Clark
authors.forename: K J
authors.initials: KJ
authors.lastname: Dalton
authors.forename: O M
authors.initials: OM
authors.lastname: Edwards
authors.forename: S
authors.initials: S
authors.lastname: O'Rahilly
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D015331:Cohort Studies; D016640:Diabetes, Gestational / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology*; D005189:False Positive Reactions; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D009765:Obesity; D011237:Predictive Value of Tests; D011247:Pregnancy; D011384:Proinsulin / Q000097:blood / Q000378:metabolism*; D012016:Reference Values; D012044:Regression Analysis
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D011384:Proinsulin