Etiology Of Gestational Diabetes Mellitus Research Articles

A positive association of serum CCN5/WISP2 levels with the risk of developing gestational diabetes mellitus: a case–control study

IntroductionCCN5/WISP2 is prominently manifest in adipose tissue and has been linked to the pathogenesis of obesity, diabetes, and insulin resistance. However, discrepancies exist in previous studies, and little is known about its association with gestational diabetes mellitus (GDM). The current investigation is designed to examine the correlation of WISP2 with risk factors in GDM patients in comparison to healthy pregnant women for the first time.MethodsThis case–control study measured serum levels of CCN5, TNF-α, IL-6, adiponectin, and fasting insulin using ELISA kits in 88 GDM patients and 88 pregnant women.ResultsThe GDM group had remarkably higher serum levels of CCN5 (379.41 ± 83.078 ng/ml) compared to controls (212.02 ± 77.935 ng/ml). In a similar vein, it was observed that patients diagnosed with GDM exhibited elevated levels of pro-inflammatory cytokines such as IL-6 and TNF-α; while conversely, adiponectin levels were found to be significantly lower than those observed in the control group (P < 0.0001). In women with GDM, a positive and significant correlation was observed between CCN5 and BMI, FBG, insulin, HOMA-IR, as well as IL-6 and TNF-α levels. In the adjusted model, the risk of GDM was significantly increased with elevated serum CCN5 level.ConclusionOur research indicates a noteworthy and affirmative correlation between the levels of CCN5 in the serum and the risk of developing GDM, along with its associated risk factors such as BMI, insulin resistance index, FBG, and inflammatory cytokines (TNF-α and IL-6). These findings suggest that CCN5 could potentially play a role in the etiology of GDM.

Association of common variants of TCF7L2 and PCSK2 with gestational diabetes mellitus in West Bengal, India

The genetic etiology of gestational diabetes mellitus (GDM) was suggested to overlap with type-2 diabetes(T2D). Transcription factor 7-like 2 (TCF7L2) and Proprotein Convertase Subtilisin/Kexin type 2 (PCSK2) are T2D susceptibility genes of the insulin synthesis/processing pathway. We analyzed associations of TCF7L2 and PCSK2 variants with GDM risk and evaluated their potential impact on impaired insulin processing in an eastern Indian population. The study included 114 GDM (case) and 228 non-GDM pregnant women (control). rs7903146, rs4132670, rs12255372 of TCF7L2, and rs2269023 of PCSK2 were genotyped by PCR-RFLP, and genotype distributions were compared between case and control. Fasting serum proinsulin and C-peptide levels were measured by ELISA and the Proinsulin/C-peptide ratio was considered an indicator of proinsulin conversion. Significantly higher frequency of risk allele (T) of rs12255372 (p = 0.02, OR = 2.0, 95%CI = 1.11–3.64) and rs4132670 (p = 0.002, OR = 2.26, 95%CI = 1.32–3.87) of TCF7L2 was found in GDM cases than non-GDM controls; TT genotype was associated with significantly increased disease risk. In rs7903146 (TCF7L2) and rs2269023 (PCSK2), although the frequency of risk allele (T) was not significantly higher in cases than controls, an association of TT for both variants remained significant with higher GDM risk in the recessive model. Increased serum pro-insulin and proinsulin:c-peptide ratio was found in GDM than non-GDM women and the phenomenon showed significant association with careers of risk alleles for TCF7L2 variants. In conclusion, TCF7L2 and PCSK2 variants are related to GDM risk in the studied population and hence may serve as potential biomarkers for assessing the disease risk. TCF7L2 variants contribute to impaired insulin processing.

"Residential greenness, gestational diabetes mellitus (GDM) and microbiome diversity during pregnancy".

Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24-28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300m buffer had lower odds of GDM (OR=0.45, 95% CI: 0.16, 1.26, p=0.13) and decreased change in mean glucose levels (β=-6.28, 95% CI: 14.91, 2.24, p=0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations.

Exploring preconception signatures of metabolites in mothers with gestational diabetes mellitus using a non-targeted approach

BackgroundMetabolomic changes during pregnancy have been suggested to underlie the etiology of gestational diabetes mellitus (GDM). However, research on metabolites during preconception is lacking. Therefore, this study aimed to investigate distinctive metabolites during the preconception phase between GDM and non-GDM controls in a nested case–control study in Singapore.MethodsWithin a Singapore preconception cohort, we included 33 Chinese pregnant women diagnosed with GDM according to the IADPSG criteria between 24 and 28 weeks of gestation. We then matched them with 33 non-GDM Chinese women by age and pre-pregnancy body mass index (ppBMI) within the same cohort. We performed a non-targeted metabolomics approach using fasting serum samples collected within 12 months prior to conception. We used generalized linear mixed model to identify metabolites associated with GDM at preconception after adjusting for maternal age and ppBMI. After annotation and multiple testing, we explored the additional predictive value of novel signatures of preconception metabolites in terms of GDM diagnosis.ResultsA total of 57 metabolites were significantly associated with GDM, and eight phosphatidylethanolamines were annotated using HMDB. After multiple testing corrections and sensitivity analysis, phosphatidylethanolamines 36:4 (mean difference β: 0.07; 95% CI: 0.02, 0.11) and 38:6 (β: 0.06; 0.004, 0.11) remained significantly higher in GDM subjects, compared with non-GDM controls. With all preconception signals of phosphatidylethanolamines in addition to traditional risk factors (e.g., maternal age and ppBMI), the predictive value measured by area under the curve (AUC) increased from 0.620 to 0.843.ConclusionsOur data identified distinctive signatures of GDM-associated preconception phosphatidylethanolamines, which is of potential value to understand the etiology of GDM as early as in the preconception phase. Future studies with larger sample sizes among alternative populations are warranted to validate the associations of these signatures of metabolites and their predictive value in GDM.

The Gut Microbiome Dynamically Associates with Host Glucose Metabolism throughout Pregnancy: Longitudinal Findings from a Matched Case-Control Study of Gestational Diabetes Mellitus.

Though gut microbiome disturbance may be involved in the etiology of gestational diabetes mellitus (GDM), data on the gut microbiome's dynamic change during pregnancy and associations with gestational glucose metabolism are still inadequate. In this prospective study comprising 120 pairs of GDM patients and matched pregnant controls, a decrease in the diversity of gut microbial species and changes in the microbial community composition with advancing gestation are found in controls, while no such trends are observed in GDM patients. Multivariable analysis identifies 10 GDM-related species (e.g., Alistipes putredinis), and the integrated associations of these species with glycemic traits are modified by habitual intake of fiber-rich plant foods. In addition, the microbial metabolic potentials related to fiber fermentation (e.g., mannan degradation pathways) and their key enzymes consistently emerge as associated with both GDM status and glycemic traits. Microbial features especially those involved in fiber fermentation, provide an incremental predictive value in a prediction model with established risk factors of GDM. These data suggest that the gut microbiome remodeling with advancing gestation is different in GDM patients compared with controls, and dietary fiber fermentation contributes to the influence of gut microbiome on gestational glycemic regulation.

Dietary Impacts on Gestational Diabetes: Connection between Gut Microbiome and Epigenetic Mechanisms.

Gestational diabetes mellitus (GDM) is one of the most common obstetric complications due to an increased level of glucose intolerance during pregnancy. The prevalence of GDM increases due to the obesity epidemic. GDM is also associated with an increased risk of gestational hypertension and preeclampsia resulting in elevated maternal and perinatal morbidity and mortality. Diet is one of the most important environmental factors associated with etiology of GDM. Studies have shown that the consumption of certain bioactive diets and nutrients before and during pregnancy might have preventive effects against GDM leading to a healthy pregnancy outcome as well as beneficial metabolic outcomes later in the offspring's life. Gut microbiome as a biological ecosystem bridges the gap between human health and diseases through diets. Maternal diets affect maternal and fetal gut microbiome and metabolomics profiles, which consequently regulate the host epigenome, thus contributing to later-life metabolic health in both mother and offspring. This review discusses the current knowledge regarding how epigenetic mechanisms mediate the interaction between maternal bioactive diets, the gut microbiome and the metabolome leading to improved metabolic health in both mother and offspring.

Common single-nucleotide polymorphisms combined with a genetic risk score provide new insights regarding the etiology of gestational diabetes mellitus.

Few studies have constructed a genetic risk score (GRS) to predict the risk of gestaional diabetes mellitus (GDM). We tested the hypothesis that single-nucleotide polymorphisms (SNPs) confirmed for diabetes and obesity and the GRS are associated with GDM. We conducted a case-control study comprising 971 GDM cases and 1682 controls from the University of Hong Kong Shenzhen Hospital. A total of 1448 SNPs reported with type 2 diabetes (T2D), type 1 diabetes (T1D), and obesity were selected and the GRS based on SNPs associated with GDM was created. We confirmed that rs10830963 (OR=1.41,95% CI=1.25, 1.59) in MTNR1B and rs2206734 (OR=1.38, 95% CI=1.22, 1.55) in CDKAL1 were strongly associated with the risk of GDM. Compared with participants with GRS based on T2D SNPs in the low tertile, the ORs of GDM across increasing GRS tertiles were 1.63 (95% CI 1.29, 2.06) and 2.72 (95% CI 2.18, 3.38) in the middle and high tertile, respectively. The positive associations between the GRS and the risk of GDM were also observed in GRS based on obesity/waist-to-hip ratio (WHR)/body mass index (BMI) SNPs. The resulting GRS for each allele increase was significantly associated with higher glycemic indices and lower HOMA-B values for GRS based on T2D SNPs, but not for GRS based on T1D SNPs and GRS based on obesity/WHR/BMI SNPs. These findings indicate that GDM may share a common genetic background with T2D and obesity and that SNPs associated with insulin secretion defects have a vital role in the development of GDM.

Sulfated Progesterone Metabolites That Enhance Insulin Secretion via TRPM3 Are Reduced in Serum From Women With Gestational Diabetes Mellitus.

Serum progesterone sulfates were evaluated in the etiology of gestational diabetes mellitus (GDM). Serum progesterone sulfates were measured using ultra-performance liquid chromatography–tandem mass spectrometry in four patient cohorts: 1) the Hyperglycemia and Adverse Pregnancy Outcomes study; 2) London-based women of mixed ancestry and 3) U.K.-based women of European ancestry with or without GDM; and 4) 11–13 weeks pregnant women with BMI ≤25 or BMI ≥35 kg/m2 with subsequent uncomplicated pregnancies or GDM. Glucose-stimulated insulin secretion (GSIS) was evaluated in response to progesterone sulfates in mouse islets and human islets. Calcium fluorescence was measured in HEK293 cells expressing transient receptor potential cation channel subfamily M member 3 (TRPM3). Computer modeling using Molecular Operating Environment generated three-dimensional structures of TRPM3. Epiallopregnanolone sulfate (PM5S) concentrations were reduced in GDM (P < 0.05), in women with higher fasting plasma glucose (P < 0.010), and in early pregnancy samples from women who subsequently developed GDM with BMI ≥35 kg/m2 (P < 0.05). In islets, 50 µmol/L PM5S increased GSIS by at least twofold (P < 0.001); isosakuranetin (TRPM3 inhibitor) abolished this effect. PM5S increased calcium influx in TRPM3-expressing HEK293 cells. Computer modeling and docking showed identical positioning of PM5S to the natural ligand in TRPM3. PM5S increases GSIS and is reduced in GDM serum. The activation of GSIS by PM5S is mediated by TRPM3 in both mouse and human islets.

Chemerin levels and its genetic variants are associated with Gestational diabetes mellitus: A hospital-based study in a Chinese cohort.

Gestational diabetes mellitus (GDM) is a glucose intolerance condition encounters for the first time in a fraction of pregnant women. The role of different host inflammatory molecules in GDM etiology has been deciphered. Chemerin is a chemoattractant protein primarily associated with the pathogenesis of type 2 diabetes, obesity, and metabolic syndrome. However, the association of chemerin and its genetic variants with the predisposition of GDM is not clear, and our present study is aimed to address the issue. A total of 703 Chinese women comprising of GDM (n=303), glucose tolerant pregnant women (n=211), and non-pregnant glucose tolerant controls (n=189) were recruited in the present investigation. GDM was diagnosed according to the World Health Organization recommendation for diagnosis of gestational diabetes during pregnancy. Plasma levels of chemerin were quantified by an Enzyme-linked Immunosorbent Assay (ELISA). Common variants in the chemerin gene (rs4721, rs17173617, rs7806429, and rs17173608) were genotyped by using TaqMan assay. Plasma chemerin level was found higher in subjects with GDM as compared to glucose tolerant pregnant and non-pregnant women. Further, a positive correlation between plasma chemerin and HOMA-IR index suggesting an essential role of chemerin in mediating insulin resistance. Variants of rs4721 and rs17173608 polymorphisms were associated with lower levels of plasma chemerin and low HOMA-IR index. Furthermore, mutants of rs4721 and rs17173608 polymorphisms were associated with protection against the development of GDM in the Chinese cohort. Plasma chemerin is elevated in GDM patients. Genetic variation in chemerin gene associated with lower plasma levels of chemerin, HOMA-IR index and protects against the development of GDM in Chinese.

Association Association of genetic variant of OXTR (rs53576) and MTNR-1B (rs10830963 and rs1387153) with symptoms of stress in Pakistani women with Gestational Diabetes.

Background: Pregnancy continues to be an event full of risks, complications and adverse outcomes for women despite advanced clinical and diagnostic methods and treatment options available in medicine. Diabetes, as a multifactorial and complex disease, is a possible outcome of a blend of numerous genetic variants of differing scarcities. The exact etiology of gestational diabetes mellitus (GDM) is unclear; however, the interaction of genetic and environmental factors, especially the genetic variants identified as the genetic loci for type 2 diabetes as candidate genes for GDM.&#x0D; Methodology: It will be a case-control study with a genetic analysis of single nucleotide polymorphisms (SNPs) of candidate genes expressed using real-time PCR with sequencing. The study will also evaluate the primer sequence of SNPs.&#x0D; Discussion: We will be able to share the findings after the completion of our research. The results of this study will able helpful in addressing the psycho-physiological needs of women with GDM, which may also be used to devise strategies to benefit the sustainable long-term behavioural change following the affected pregnancy.

Differentiation of gestational diabetes mellitus by nuclear magnetic resonance-based metabolic plasma analysis.

This study aimed to investigate the metabolic profile of gestational diabetes mellitus (GDM) at both antepartum and postpartum periods. Seventy pregnant women were divided into three groups: the normal glucose-tolerant group (NGT, n=35), the abnormal glucose-tolerant groups without insulin therapy (A1GDM, n=24) or with insulin therapy (A2GDM, n=11). Metabolic profiles of the plasma were acquired by proton nuclear magnetic resonance (1H-NMR) spectroscopy and analyzed by multivariate statistical data analysis. The relationship between demographic parameters and the potential metabolite biomarkers was further explored. Group antepartum or postpartum showed similar metabolic trends. Compare with those of the NGT group, the levels of 2-hydroxybutyrate, lysine, acetate, glutamine, succinate, tyrosine, formate, and all three BCAAs (leucine, valine, isoleucine) in the A2GDM group were increased dramatically, and the levels of lysine, acetate, and formate in the A1GDM group were elevated significantly. The dramatically decreased levels of 3-methyl-2-oxovalerate and methanol were observed both in the A1GDM group and A2GDM group. Compare to the A1GDM group, the branched-chain amino acids (BCAAs) of leucine, valine, and isoleucine were increased dramatically in the A2GDM group. The levels of aromatic amino acids (AAAs), tyrosine and phenylalanine, were significantly increased in GDM women, consistent with the severity of GDM. Interference of amino acid metabolism and disturbance in energy metabolism occurred in women with different grades of GDM. Metabolic profiles could reflect the severity of GDM. Plasma BCAA concentrations showing strong positive correlations with weight and pre-delivery BMI. This study provides a new perspective to understand the pathogenesis and etiology of GDM, which may help the clinical management and treatment of GDM.

The Relationship Between Heavy Metal Exposure, Trace Element Level, and Monocyte to HDL Cholesterol Ratio with Gestational Diabetes Mellitus

The objective of this study is to assess the levels of heavy metals (cadmium, lead, antimony, mercury, and arsenic), which are also called endocrine-disrupting chemicals, and trace elements (chromium-III, chromium-VI, zinc, copper, and selenium) vs. monocyte to HDL ratio among pregnant women with gestational diabetes mellitus (GDM). A total of 112 pregnant women (60 with GDM and 52 healthy women) were included in this case-control study. Analysis of heavy metals and trace elements were performed in inductively coupled plasma mass spectrometer. Heavy metals (cadmium, lead, antimony, mercury, and arsenic), trace elements (chromium-III, chromium-VI, zinc, copper, and selenium), and metabolic parameters were assessed in both groups. It was determined that the levels of cadmium, lead, antimony, and copper were higher (p < 0.05) and levels of chromium-III, zinc, and selenium were lower (p < 0.05) among the GDM group compared to the control group, whereas there was a statistically insignificant difference between the two groups, regarding the levels of copper, mercury, and arsenic (p > 0.05). Moreover, the monocyte to HDL ratio was higher in the GDM group (p < 0.05), and the insulin resistance was significantly higher as well (p < 0.05). The results of our study demonstrated that environmental factors could be effective in the etiology of GDM. Toxic heavy metals, through inducing Cu, OS, and chronic inflammation, and other trace elements, either directly by impacting insulin secretion or through weakening the body's antioxidant defense system, could play a role in the occurrence of GDM.

Connections between the human gut microbiome and gestational diabetes mellitus.

The human gut microbiome can modulate metabolic health and affect insulin resistance, and it may play an important role in the etiology of gestational diabetes mellitus (GDM). Here, we compared the gut microbial composition of 43 GDM patients and 81 healthy pregnant women via whole-metagenome shotgun sequencing of their fecal samples, collected at 21–29 weeks, to explore associations between GDM and the composition of microbial taxonomic units and functional genes. A metagenome-wide association study identified 154 837 genes, which clustered into 129 metagenome linkage groups (MLGs) for species description, with significant relative abundance differences between the 2 cohorts. Parabacteroides distasonis, Klebsiella variicola, etc., were enriched in GDM patients, whereas Methanobrevibacter smithii, Alistipes spp., Bifidobacterium spp., and Eubacterium spp. were enriched in controls. The ratios of the gross abundances of GDM-enriched MLGs to control-enriched MLGs were positively correlated with blood glucose levels. A random forest model shows that fecal MLGs have excellent discriminatory power to predict GDM status. Our study discovered novel relationships between the gut microbiome and GDM status and suggests that changes in microbial composition may potentially be used to identify individuals at risk for GDM.

Gene variants in the FTO gene are associated with adiponectin and TNF-alpha levels in gestational diabetes mellitus

BackgroundObesity may have a role in the development of gestational diabetes mellitus (GDM). Single-nucleotide-polymorphisms (SNPs) of the FTO (fat mass and obesity associated) gene have been associated with obesity. The aim of this study was to investigate SNPs rs8050136, rs9939609, and rs1421085 of the FTO gene in women with GDM and their associations with maternal pre-pregnancy weight and body mass index, gestational weight gain and mediators of insulin resistance in GDM like leptin, adiponectin, ghrelin and tumor necrosis factor-alpha (TNF-alpha), compared with healthy pregnant controls.Methods80 women with GDM and 80 women with normal pregnancy were considered for the present study. Genotyping of selected SNPs in all study subjects was done using the Taq-Man assay and the adipokines and ghrelin were measured by immunoassays. Chi square test, odds ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between FTO SNPs and GDM.ResultsThere was no association among FTO SNPs and GDM. Interestingly, in GDM group, women carrying the risk alleles of the three SNPs had increased TNF-alpha, and decreased adiponectin levels; these associations remained significant after adjusting for pre-gestational body weight and age. Moreover, the risk allele of rs1421085 was also associated with increased weight gain during pregnancy.ConclusionsThe FTP SNPs rs8050136, rs9939609, and rs1421085 are not a major genetic regulator in the etiology of GDM in the studied ethnic group. However, these SNPs were associated with adiponectin and TNF-alpha concentrations in GDM subjects.

Association between rs7901695 and rs7903146 polymorphisms of the TCF7L2 gene and gestational diabetes in the population of Southern Poland.

The etiology of gestational diabetes mellitus (GDM) remains to be fully elucidated. Elevated risk for type 2 diabetes in patients with history of GDM and for GDM in women with familial history of diabetes may suggest that GDM and type 2 diabetes share a common genetic and environmental background. The TCF7L2 (Transcription Factor 7 Like 2) gene is one of the most important genetic factors of the established correlation with type 2 diabetes, and it may also play a role in the pathophysiology of GDM. The aim of the study was to assess the influence of two polymorphisms of the TCF7L2 gene (rs7901695 and rs7903146), which are associated with the development of type 2 diabetes, in women with GDM. The study included 50 women with glucose tolerance disorders diagnosed for the first time during the current pregnancy. Single nucleotide polymorphisms (SNPs) were genotyped using allelic discrimination. The results were confirmed using the sequencing method. Selected clinical parameters were also analyzed. No correlation between the studied polymorphisms of the TCF7L2 gene and GDM was observed. Glycemic control with diet or diet and insulin was associated with better control of the weight gain during pregnancy. No correlation between rs7903146 and rs7901695 polymorphisms of the TCF7L2 gene and GDM was found. Glycemic control with diet or diet and insulin is associated with better control of the weight gain during pregnancy.

Periodontitis and gestational diabetes mellitus: a systematic review and meta-analysis of observational studies.

BackgroundGestational diabetes mellitus (GDM) is glucose intolerance with first onset during pregnancy and is associated with serious maternal and fetal complications. The etiology of GDM is not well understood, but systemic inflammation effects on insulin signaling and glucose metabolism is suspected. Periodontal disease is a chronic inflammatory condition that induces local and host immune responses and has been evaluated for a potential role in development of GDM. Results from studies evaluating the association between periodontitis and GDM are mixed. We performed a systematic review and meta-analysis to summarize available data regarding the association between periodontitis and GDM.MethodsTwelve electronic databases were searched for observational studies of the association between periodontitis and GDM through March 2016. Eligible studies were assessed for quality and heterogeneity. Random effects models were used to estimate summary measures of association.ResultsWe identified 44 articles from 115 potentially relevant reports of which 10 studies met our eligibility criteria. Clinical diagnostic criteria for periodontitis and GDM varied widely among studies, and moderate heterogeneity was observed. Random effects meta-analysis of all included studies with a total of 5724 participants including 624 cases, showed that periodontitis is associated with an increased risk of GDM by 66 %, (OR = 1.66, 95 % CI: 1.17 to 2.36; p < 0.05), I2 = 50.5 %. Similar results were seen in sub-analysis restricted to data from methodologically high quality case–control studies including 1176 participants including 380 cases, (OR = 1.85, 95 % CI: 1.03 to 3.32); p < 0.05), I2 = 68.4 %. Meta-analysis of studies that adjusted for potential confounders estimated more than 2-fold increased odds of GDM among women with periodontitis (aOR = 2.08, 95 % CI: 1.21 to 3.58, p = 0.009, I2 = 36.9 %).ConclusionMeta-analysis suggests that periodontitis is associated with a statistically significant increased risk for GDM compared to women without periodontitis. Robust prospective study designs and uniform definition for periodontitis and GDM definitions are urgently needed to substantiate these findings.

The Genetic Architecture of Diabetes in Pregnancy: Implications for Clinical Practice.

The genetic architecture of diabetes mellitus in general and in pregnancy is complex, owing to the multiple types of diabetes that comprise both complex/polygenic forms and monogenic (largely caused by a mutation in a single gene) forms such as maturity-onset diabetes of the young (MODY). Type 1 diabetes (T1D) and type 2 diabetes (T2D) have complex genetic etiologies, with over 40 and 90 genes/loci, respectively, implicated that interact with environmental/lifestyle factors. The genetic etiology of gestational diabetes mellitus has largely been found to overlap that of T2D. Genetic testing for complex forms of diabetes is not currently useful clinically, but genetic testing for monogenic forms, particularly MODY, has important utility for determining treatment, managing risk in family members, and pregnancy management. In particular, diagnosing MODY2, caused by GCK mutations, indicates that insulin should not be used, including during pregnancy, with the possible exception of an unaffected pregnancy during the third trimester to prevent macrosomia. A relatively simple method for identifying women with MODY2 has been piloted. MODY1, caused by HNF4A mutations, can paradoxically cause neonatal hyperinsulinemic hypoglycemia and macrosomia, indicating that detecting these cases is also clinically important. Diagnosing all MODY types provides opportunities for diagnosing other family members.

Review of Current Evidence on the Impact of Environmental Chemicals on Gestational Diabetes Mellitus

Pregnancy is a naturally insulin-resistant state and may be an important window of susceptibility in determining a woman’s lifetime risk of type 2 diabetes. Exposures to environmental chemicals that act as endocrine active compounds may mimic or disrupt hormones that regulate insulin action or maintain glucose homeostasis. In this commentary, we present the animal evidence that explains the biological plausibility for an association between environmental chemicals and gestational diabetes mellitus (GDM). We review the current epidemiological evidence examining the associations between GDM and bisphenol A, phthalates, air pollution, and toxic metals including arsenic and cadmium. We briefly discuss the strengths and limitations of the current evidence and offer recommendations for future studies that attempt to assess the impact environmental chemical exposure has on GDM. Lastly, we discuss the health implications for women that experience GDM during pregnancy and the importance for examining how environmental chemicals may play a role in the etiology of GDM.

Effects of vitamin D supplementation on metabolic indices and hs-CRP levels in gestational diabetes mellitus patients: a randomized, double-blinded, placebo-controlled clinical trial.

BACKGROUND/OBJECTIVESVitamin D plays an important role in the etiology of gestational diabetes mellitus (GDM). This study evaluated the effect of vitamin D supplementation on metabolic indices and hs-C-reactive protein (CRP) levels in GDM patients.SUBJECTS/METHODSThe study was a randomized, placebo-controlled, double-blinded clinical trial. Seventy-six pregnant women with GDM and gestational age between 24-28 weeks were assigned to receive four oral treatments consisting of 50,000 IU of vitamin D3 (n = 38) or placebo (n = 38) once every 2 weeks for 2 months. Fasting blood glucose (FG), insulin, HbA1c, 25-hydroxyvitamin D, lipid profile, hs-CRP, and homeostasis model assessment-insulin resistance (HOMA-IR) were measured before and after treatment. Independent and paired t-tests were used to determine intra- and intergroup differences, respectively. ANCOVA was used to assess the effects of vitamin D supplementation on biochemical parameters.RESULTSCompared with the placebo group, in the vitamin D group, the serum level of 25-hydroxyvitamin D increased (19.15 vs. -0.40 ng/ml; P < 0.01) and that of FG (-4.72 vs. 5.27 mg/dl; P = 0.01) as well as HbA1c (-0.18% vs. 0.17%; P = 0.02) decreased. Improvements in the lipid profiles were observed in the vitamin D group, but without statistical significance. Significant increases in concentrations of hs-CRP, FG, HbA1c, total cholesterol, and LDL cholesterol were observed in the placebo group. No significant change in fasting insulin and HOMA-IR was observed in either group.CONCLUSIONSIn GDM patients, vitamin D supplementation improved FG and HbA1c but had no significant effects on lipid profile or hs-CRP.

Role of high-insulinogenic nutrition in the etiology of gestational diabetes mellitus

A transient physiologic insulin resistance and hyperinsulinemia are characteristic of normal pregnancy. This insulin action has evolved during a period of human evolution that was characterized by a very low-carbohydrate nutrition. The development of gestational diabetes mellitus (GDM) is proposed to result from a collision of this evolutionary inheritance with our "modern" nutrition: The "Western" high-insulinogenic nutrition increases the postprandial demand for insulin significantly during the insulin resistant state of late pregnancy. In women with beta-cells that are not capable of maintaining the high insulin production, GDM develops. A restriction of high-insulinogenic carbohydrate may help to prevent the development of GDM.