Refining the diagnosis of gestational diabetes mellitus: a systematic review and meta-analysis

Abstract

Background Perinatal outcomes vary for women with gestational diabetes mellitus (GDM). The precise factors beyond glycemic status that may refine GDM diagnosis remain unclear. We conducted a systematic review and meta-analysis of potential precision markers for GDM. Methods Systematic literature searches were performed in PubMed and EMBASE from inception to March 2022 for studies comparing perinatal outcomes among women with GDM. We searched for precision markers in the following categories: maternal anthropometrics, clinical/sociocultural factors, non-glycemic biochemical markers, genetics/genomics or other -omics, and fetal biometry. We conducted post-hoc meta-analyses of a subset of studies with data on the association of maternal body mass index (BMI, kg/m2) with offspring macrosomia or large-for-gestational age (LGA). Results A total of 5905 titles/abstracts were screened, 775 full-texts reviewed, and 137 studies synthesized. Maternal anthropometrics were the most frequent risk marker. Meta-analysis demonstrated that women with GDM and overweight/obesity vs. GDM with normal range BMI are at higher risk of offspring macrosomia (13 studies [n = 28,763]; odds ratio [OR] 2.65; 95% Confidence Interval [CI] 1.91, 3.68), and LGA (10 studies [n = 20,070]; OR 2.23; 95% CI 2.00, 2.49). Lipids and insulin resistance/secretion indices were the most studied non-glycemic biochemical markers, with increased triglycerides and insulin resistance generally associated with greater risk of offspring macrosomia or LGA. Studies evaluating other markers had inconsistent findings as to whether they could be used as precision markers. Conclusions Maternal overweight/obesity is associated with greater risk of offspring macrosomia or LGA in women with GDM. Pregnancy insulin resistance or hypertriglyceridemia may be useful in GDM risk stratification. Future studies examining non-glycemic biochemical, genetic, other -omic, or sociocultural precision markers among women with GDM are warranted.

Placental IGFBP1 levels during early pregnancy and the risk of insulin resistance and gestational diabetes

“…In individuals with insulin-deficient GDM, IGFBP1 amounts were low in the first trimester but amounts during the second semester were on par with those without GDM, suggesting that other pathophysiologic factors contribute to hyperglycemia in this GDM subtype. Given the differences in IGFBP1 in different GDM subtypes, and increasing recognition in the field that GDM is a heterogeneous condition 45 , our finding of persistently lower IGFBP1 levels in the second trimester of pregnancies affected by insulin-resistant GDM may have implications for GDM precision medicine 46 , 47 . Our findings suggest that, in cases of insulin-resistant GDM, the placenta does not increase IGFBP1 production sufficiently; if this association is demonstrated to be causal, this opens the door to a new therapeutic target for this GDM subtype.…”

“…We adjusted for maternal characteristics (maternal age, gravidity, gestational age at plasma samples) in Model 2 and additionally adjusted for maternal BMI in Model 3. We calculated profiled log-likelihood CIs along with likelihood ratio test P values (using MASS 65 and glmglrt ( https://CRAN.R-project.org/package=glmglrt ) packages 47 in R). In SPRING and MOMS cohorts, we employed similar modeling strategies using maximum likelihood dichotomous logistic models.…”

Postpartum development of metabolic dysfunction-associated steatotic liver disease in a lean mouse model of gestational diabetes mellitus

“…The two main GDM subtypes are distinguished by a predominant defect in insulin sensitivity versus a predominant defect in insulin secretion 14 , 28 , 29 . These GDM subtypes have varying clinical characteristics and risks of short-term complications 30 , 31 . Depending on the population, the prevalence of the insulin-deficient subtype ranges between 20 and 30% 14 , 30 .…”

Alternative therapeutic strategies in diabetes management

“…In a typical pregnancy, there is an increase in the number of pancreatic β cells due to the stimulation of human placental lactogen and prolactin. This leads to elevated levels of insulin[ 14 ].…”