Follow-Up of Women With Previous GDM: Insulin, C-Peptide, and Proinsulin Responses to Oral Glucose Load

Gestational diabetes mellitus (GDM) is a strong predictor of glucose intolerance later in life. Former GDM (n = 145) and control (n = 41) subjects were studied 3–4 yr after the index pregnancy. They were subjected to a 75-g oral glucose tolerance test (OGTT) with measurements of insulin, C-peptide, and proinsulin in the basal state and every 30 min for 180 min. In the former GDM group, 5 subjects (3.4%) had developed non-insulin-dependent diabetes mellitus (NIDDM), and 32 (22%) had developed impaired glucose tolerance (IGT; by World Health Organization criteria). In the control group, 2 (4%) had IGT. In the GDM group, IGT or NIDDM was significantly associated with obesity (body mass index [BMI] ≥25 kg/m²) and earlier diagnosis of GDM during pregnancy (P < 0.001). Nonobese (BMI <25 kg/m²) GDM subjects with normal glucose tolerance at follow-up had significantly higher mean glucose(P < 0.01), insulin (P < 0.05), and proinsulin (P < 0.001) values during the OGTT than control subjects, whereas there was no significant difference in C-peptide values. A comparison between control subjects with normal OGTT and BMI <25 kg/m² (n = 39) and GDM subjects (n = 39) selected to have a comparable area under the glucose curve, BMI, and age demonstrated no group differences in glucose, C-peptide, or insulin levels, whereas the proinsulin levels were significantly higher (P < 0.001) during the glucose load. The molar ratio between proinsulin and insulin was also significantly higher among the former GDM subjects. We speculate that an elevated proinsulin-insulin ratio in women with previous GDM could be a marker for later development of NIDDM.