Lower Adiponectin Levels at First Trimester of Pregnancy Are Associated With Increased Insulin Resistance and Higher Risk of Developing Gestational Diabetes Mellitus

OBJECTIVE

To evaluate the associations between adiponectin levels and 1) the risk of developing gestational diabetes mellitus (GDM), and 2) insulin resistance/sensitivity, β-cell function, and compensation indices in a prospective cohort representative of the general population of pregnant women.

RESEARCH DESIGN AND METHODS

We performed anthropometric measurements and collected blood samples at 1st (6–13 weeks) and 2nd (24–28 weeks) trimesters. Diagnosis of GDM was made at 2nd trimester based on a 75-g oral glucose tolerance test (International Association of the Diabetes and Pregnancy Study Groups criteria). Insulin was measured (ELISA; Luminex) to estimate homeostasis model assessment of insulin resistance (HOMA-IR), β-cell function (HOMA-B), insulin sensitivity (Matsuda index), insulin secretion (AUC_{insulin/glucose}), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay.

RESULTS

Among the 445 participants included in this study, 38 women developed GDM. Women who developed GDM had lower 1st-trimester adiponectin levels (9.67 ± 3.84 vs. 11.92 ± 4.59 µg/mL in women with normal glucose tolerance). Lower adiponectin levels were associated with higher risk of developing GDM (OR, 1.12 per 1 µg/mL decrease of adiponectin levels; P = 0.02, adjusted for BMI and HbA_1c at 1st trimester). Adiponectin levels at 1st and 2nd trimesters were associated with HOMA-IR (both: r = −0.22, P < 0.0001) and Matsuda index (r = 0.28, P < 0.0001, and r = 0.29, P < 0.0001). After adjustment for confounding factors, we found no significant association with HOMA-B and AUC_{insulin/glucose}.

CONCLUSIONS

Pregnant women with lower adiponectin levels at 1st trimester have higher levels of insulin resistance and are more likely to develop GDM independently of adiposity or glycemic measurements.Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition determined during pregnancy (1). In normal pregnancy, there is a progressive physiologic increase of insulin resistance, compensated by an increase of insulin secretion by pancreatic β-cells (2). Among GDM women, there is an imbalance between insulin resistance and insulin secretion capacity, resulting in increased circulating glucose levels (3). Over the past decades, GDM has drawn scientific attention because of its growing incidence and deleterious consequences for mothers and offspring (4,5). Nevertheless, the exact mechanisms implicated in its pathophysiology remain poorly understood.Adiponectin is an adipokine suspected to have insulin-sensitizing properties (6). Furthermore, lower adiponectin levels have been repeatedly and consistently associated with increased risk of type 2 diabetes incidence (7–9), but reports on GDM are inconsistent. Few studies investigated the association between adiponectin levels measured early in pregnancy and GDM incidence: some showed that low adiponectin levels are associated with increased risk of GDM (10–13), while others showed no association (14,15). Contradictory findings between studies can be partly explained by limited power and different study designs. Also, these studies inconsistently accounted for potential confounding factors like adiposity and baseline impaired glucose regulation in pregnant women. Therefore, larger prospective studies are needed, designed to take into account potential confounding factors to adequately assess whether there is an independent association between adiponectin levels and the risk of developing GDM.Thus, in the current study, we evaluated whether 1st-trimester adiponectin levels are associated with higher risk of developing GDM during pregnancy. Also, we assessed whether there is an association between adiponectin at both 1st and 2nd trimesters (or the change [Δ] over 1st to 2nd trimester) and insulin resistance/sensitivity or pancreatic β-cell function/compensation indices at 2nd trimester of pregnancy.