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

Abstract

OBJECTIVETo 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 METHODSWe 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 (AUCinsulin/glucose), and β-cell compensation (insulin secretion sensitivity index-2). Adiponectin was measured by radioimmunoassay.RESULTSAmong 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 HbA1c 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 AUCinsulin/glucose.CONCLUSIONSPregnant 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.

Components of metabolic syndrome in the first trimester of pregnancy as predictors of adverse perinatal outcome

“…This is the only paper published that suggests such low cut-off of BMI as a risk factor for GDM [16]. Lacroix et al published data showing significantly decreased serum adiponectin levels in the first trimester of pregnancy in patients who later developed GDM [17]. Our data confirmed this observation.…”

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry

“…Of the 29 potential protein biomarkers, adiponectin is the best studied in relation to GDM [11][12][13][14]16]. Here, adiponectin was the best performing independent predictor of GDM, regardless of BMI grouping.…”

“…This could be an important tool in future screening strategies to ensure that women at the highest risk undergo a diagnostic OGTT at gestational week 24-28. At present, no serum biomarker with clinical utility has been identified and the potential utility in GDM screening has been investigated for only a limited number of proteins. Adiponectin is by far the best-studied protein biomarker for GDM but lacks the sensitivity and specificity required for clinical use [11][12][13][14][15][16]. Other proteins such as sex hormone binding protein (SHBG), retinol-binding protein 4 (RBP-4), resistin and C-reactive protein (CRP) have also been investigated as potential biomarkers of GDM, but conclusions have been variable [14,[17][18][19][20][21][22][23].…”

Clinical Recommendations for the Use of Islet Cell Autoantibodies to Distinguish Autoimmune and Non-Autoimmune Gestational Diabetes

“…Through ceramide deacylation stimulation, adiponectin promotes the survival of functional β cell mass, favoring insulin production to meet insulin demands [91]. Women with lower levels of adiponectin (adipose) in the first trimester of pregnancy thus have higher levels of IR and are more likely to develop GDM [92]. The increased level of CRP in GDM is also partly associated with increased adiposity [93] and IR [94].…”