Proinsulin in pregnant women with normal glucose tolerance or mild gestational diabetes mellitus

Pregnancy is characterized by peripheral insulin resistance, which is physi ologically compensated by an increase in insulin secretion. Type 2 diabetes and impaired glucose tolerance (IGT) have been associated with an inapprop riate increase in insulin precursors, namely proinsulin. The aim of this st udy was to determine levels of proinsulin (PI), specific insulin (SI) and t he proinsulin-to-specific insulin (PI/SI) ratio in consecutive pregnant wom en (n = 209) with normal glucose tolerance (NGT), as assessed by a 2h oral glucose tolerance test, and with mild gestational diabetes (GDM), in compar ison to 32 healthy, non-pregnant women. Furthermore, we related these varia bles to surrogate markers of insulin resistance and insulin secretion. We found no significant differences in the levels of PI and the PI/SI ratio between pregnant and non-pregnant women (PI: 5.0 +/- 3.6 vs. 4.8 +/- 3.5 p mol/L, p = NS), and between pregnant women with mild GDM and NGT (PI: 5.4 /- 2.4 vs. 4.9 +/- 3.9 pmol/L, p = NS). SI was elevated in women with mild GDM (112.2 +/- 47.3 vs. 94.8 +/- 43.0 pmol/L in NGT, p = 0.02). PI was rela ted to fasting glucose (r = 0.17, p < 0.02), but not post-load glucose leve ls, and to fasting insulin [specific insulin: r = 0.67, p = 0.0001; total i mmunoreactive insulin (IRI): r = 0.69, p = 0.0001], as well as post-load in sulin levels (IRI at 120 min: r = 0.18, p < 0.03). The PI/SI ratio showed n o association with fasting or post-load glucose or insulin levels. Pregnant women presented with a metabolic pattern suggestive of enhanced insulin re sistance, namely increased fasting and post-load insulin levels. In women w ith mild GDM, fasting and post-load hyperglycemia, as well as an additional increase in insulin resistance was found. Group differences weakened when accounting for differences in body weight. The data of the present study suggest that in normal pregnancy as well as m ild GDM metabolic alterations including enhanced insulin resistance and hyp erglycemia do not result in an increase in circulating levels of proinsulin , both in absolute terms and relative to levels of specific insulin, as ind icated by the proinsulin-to-specific insulin ratio.