Enhanced fetoplacental angiogenesis in pre-gestational diabetes mellitus: the extra growth is exclusively longitudinal and not accompanied by microvascular remodelling

Abstract

Aims/hypothesis: Morphometric studies on pregnancies complicated by gestational diabetes mellitus have found no evidence of increased fetoplacental angiogenesis. Here, placentas from control subjects and patients with pre-gestational Type I (insulin-dependent) diabetes mellitus were used to test for differences in measures of angiogenesis and vascular remodelling.

Methods: Term placentas were collected from non-diabetic subjects and well-controlled diabetic patients grouped according to duration and severity into White classes B, C, D and F/R. Tissues were obtained by uniform random sampling for position and orientation. Volumes, surface areas and lengths of peripheral villi and their capillaries were estimated stereologically. Comparisons were drawn by analysis of variance and used to interpret mechanisms of growth, villous capillarization and vessel remodelling.

Results: Placentas associated with all classes of diabetes contained greater (19-45%) volumes of fetal capillaries attributable solely to increases in the combined length of capillaries (12-47%) and not to alteration of vessel cross-sectional area or perimeter. Longitudinal growth tended to increase capillarization (capillary:villus length ratios up to 19% larger) but changes were inconsistent between diabetic classes. There was no evidence of altered vascular remodelling (cross-sectional shape factors, perimeter(2)/area, were preserved).

Conclusions/interpretations: In well-controlled pre-gestational diabetes, fetoplacental angiogenesis is enhanced and occurs exclusively by longitudinal growth. Differences may involve hypoxic or other metabolic effects on endothelial cells, perivascular cells and angiogenic factors. The findings differ from those previously reported in gestational diabetes. No differences were associated exclusively with the presence of diabetic complications.