A systematic review of placental pathology in maternal diabetes mellitus.

INTRODUCTION: During a pregnancy complicated by diabetes, the human placenta undergoes a number of functional and structural pathologic changes, such as increased placental weight and increased incidence of placental lesions including villous maturational defects and fibrinoid necrosis. The pathologic findings reported have differed among studies, potentially reflecting differences in type of diabetes, study methodology, or glycemic control of study participants. Alternatively, these discrepancies may represent different biologic adaptations to distinct metabolic diseases. METHODS: We conducted a comprehensive review of English language citations in Pubmed and Embase using the keywords "diabetes", "placenta", AND "pathology". Abstracts were reviewed for relevance then full-text articles were reviewed in order to extract a comprehensive summary of current pathological findings associated with pregestational and gestational diabetes mellitus, as well as an understanding of the impact of glycemic control on placental pathology. RESULTS: Placental abnormalities most consistently associated with maternal diabetes are an increased incidence of villous immaturity, increased measures of angiogenesis, and increased placental weight. CONCLUSIONS: The literature suggests that, despite similarities in placental abnormalities, differences in placental pathology may reflect differences in pathophysiology among different types of diabetes. Consequently, standardization of terminology used to define placental lesions is warranted. Moreover, further research is needed to investigate the impact of pathophysiology, glycemic control and clinical factors, such as infant sex, weight and race, on placental structure and function.

Metabolomic Analysis Reveals Amino Acid Responses to an Oral Glucose Tolerance Test in Women with Prior History of Gestational Diabetes Mellitus.

OBJECTIVE: Although gestational diabetes mellitus (GDM) is associated with an increased risk of type 2 diabetes mellitus (T2DM) compared to normoglycemic pregnancies, the biochemical pathways underlying the progression of GDM to T2DM are not fully elucidated. The purpose of this exploratory study was to utilize metabolomics with an oral glucose tolerance test (OGTT) to examine the amino acid response in women with prior GDM to determine if a relationship between these metabolites and established risk factors for T2DM exists. MATERIALS/METHODS: Thirty-eight non-pregnant women without diabetes but with prior GDM within the previous 3 years were recruited from a community-based population. A 75 g-OGTT was administered; fasting and 2-hr plasma samples were obtained. Metabolite profiles of 23 amino acids or amino acid derivatives were measured with gas chromatography-mass spectrometry. Measures of insulin resistance were derived from the OGTT and risk factors for T2DM were obtained by self-report. RESULTS: Twenty-two metabolite levels decreased significantly in response to the OGTT (p<0.05). The clinical covariates most powerfully associated with metabolite level changes included race, body mass index (BMI), and duration of prior breastfeeding, (mean ± SD of standardized ß-coefficients, ß = -0.38 ± 0.05, 0.25 ± 0.08, and 0.44 ± 0.03, respectively, all p<0.05). Notably, a prior history of breastfeeding was associated with the greatest number of metabolite changes. CONCLUSIONS: Greater change in metabolite levels after a glucose challenge was significantly associated with a longer duration of breastfeeding and higher BMI. Further exploration of these preliminary observations and closer examination of the specific pathways implicated are warranted.