Abstract
The insulin-like growth factor (IGF) axis has been implicated in glucose homeostasis. It is plausible to hypothesize that the IGF axis is involved in the development of gestational diabetes mellitus (GDM). In a systematic review of the evidence on IGF axis biomarkers in relation to GDM, we searched the PubMed and EMBASE for publications up to May 31, 2018, on the associations of circulating IGF axis biomarkers with GDM. Eligible studies must meet the pre-specified quality assessment criteria. Meta-analyses were conducted where there were at least three studies on the same biomarker at the same gestational age window—early (<20 weeks), mid (20–29 weeks), or late (30+ weeks) gestation. Twelve studies were included (484 GDM, 1755 euglycemic pregnancies). Meta-analyses showed that GDM was consistently associated with higher IGF-I concentrations in mid-gestation (six studies) and late gestation (six studies). There were only two studies on IGF-I in early gestation and GDM with inconsistent findings. GDM was associated with lower IGFBP-2 concentrations in early, mid-, or late gestation, according to data from one or two studies. GDM was associated with higher IGFBP-3 concentrations in late gestation according to a meta-analysis of five studies. There was no association with GDM for IGFBP-3 in early or mid-gestation, according to data from one study. Other IGF axis biomarkers (IGF-II, IGFBP-1,−4,−5−6, and −7) showed no or inconsistent associations, and the data at early gestation were scanty or absent. Available evidence is suggestive but inconclusive concerning whether the IGF axis is involved in the development of GDM. More studies on IGF axis biomarkers in early gestation are warranted. If a specific IGF axis molecule is proven to be involved in the development of GDM, this may point to a new molecular target for designing interventions to reduce the incidence of GDM.
Highlights
Gestational diabetes mellitus (GDM), commonly defined as impaired glucose tolerance with onset or first recognition during pregnancy, affects 5–15% of pregnant women (1, 2)
Of the 12 studies included in the systematic review, 4 studies were from North America, 2 from Australia, and 6 from other countries (Table 3)
insulin-like growth factor (IGF)-I was reported in all the 12 studies, while IGF-II was reported in only 3 studies (Table 4)
Summary
Gestational diabetes mellitus (GDM), commonly defined as impaired glucose tolerance with onset or first recognition during pregnancy, affects 5–15% of pregnant women (1, 2). The etiology of GDM remains incompletely understood, but pancreatic βcell function insufficiency in compensating for pregnancyinduced insulin resistance is thought to be important, resulting in hyperglycemia in the second half of pregnancy (3). GDM develops when the maternal insulin supply is insufficient to maintain euglycemia during pregnancy. GDM increases the risk of maternal complications (gestational hypertension and preeclampsia) and fetal and neonatal complications (congenital malformations, macrosomia, preterm birth, and shoulder dystocia) (4). GDM may “program” long-term adverse consequences such as the metabolic syndrome, type 2 diabetes, and cardiovascular disease in the offspring (5). It is plausible to hypothesize that the IGF axis is involved in the development of GDM
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