Serum microcystin-LR levels and risk of gestational diabetes mellitus: A Chinese nested case-control study

Background Previous experimental studies have reported an association between microcystin-LR (MC-LR) and glucose homeostasis, but whether exposure to MC-LR is a risk factor for the pathogenesis of gestational diabetes mellitus (GDM) requires further epidemiological study. This study aims to explore the effects of MC-LR on GDM. Methods A prospective nested case-control study was performed in the Hunan Provincial Maternal and Child Health Hospital (HPMCHH) in South China. A total of 119 patients with GDM and 238 controls were enrolled in the study. The two independent samples t-test, or chi-square test was used to compare the difference between the GDM group and the non-GDM group. Binary logistic regression was used to obtain odds ratios (ORs) by controlling for confounders. Results The cumulative incidence of GDM in our sample was 13.7%. The detection rate of MC-LR in the GDM group were significantly higher than those in the control group (44.2% vs. 29.4%; p=0.007). Our results show that an elevated serum MC-LR level in the first trimester of pregnancy was related to an increased risk of GDM (OR: 1.924; 95% CI: 1.092-3.391; p<0.05). When stratified by age, educational level, parity, and passive smoking, significantly relationships were observed among those aged >30 years, lower income, higher education, none passive smoking, and more likely to be multiparous. Conclusions Our data reveals that serum MC-LR level in the first trimester is independently associated with GDM.

[1]  A. Kowluru,et al.  Alpha4 contributes to the dysfunction of the pancreatic beta cell under metabolic stress , 2022, Molecular and Cellular Endocrinology.

[2]  K. Gurpreet,et al.  updated overview , 2022, International journal of health sciences.

[3]  Jiang Wu,et al.  Microcystin-leucine arginine (MC-LR) induces mouse ovarian inflammation by promoting granulosa cells to produce inflammatory cytokine via activation of cGAS-STING signaling. , 2022, Toxicology letters.

[4]  Ziyuan Zhou,et al.  Association of serum microcystin levels with neurobehavior of school-age children in rural area of Southwest China: A cross-sectional study. , 2021, Ecotoxicology and environmental safety.

[5]  Xinghai Chen,et al.  The latest advances in the reproductive toxicity of microcystin-LR. , 2020, Environmental research.

[6]  Liwen Zhang,et al.  Associations of urinary phenolic environmental estrogens exposure with blood glucose levels and gestational diabetes mellitus in Chinese pregnant women. , 2020, The Science of the total environment.

[7]  K. Khunti,et al.  Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis , 2020, BMJ.

[8]  A. Lenzi,et al.  Bisphenol A and Phthalates in Diet: An Emerging Link with Pregnancy Complications , 2020, Nutrients.

[9]  R. Almeer,et al.  Fucoidan alleviates microcystin-LR-induced hepatic, renal, and cardiac oxidative stress and inflammatory injuries in mice , 2019, Environmental Science and Pollution Research.

[10]  Honghui Guo,et al.  Waterborne microcystin-LR exposure induced chronic inflammatory response via MyD88-dependent toll-like receptor signaling pathway in male zebrafish. , 2019, The Science of the total environment.

[11]  Daniel G. Beach,et al.  Structural Diversity, Characterization and Toxicology of Microcystins , 2019, Toxins.

[12]  Feifei Lei,et al.  Microcystin-LR in peripheral circulation worsens the prognosis partly through oxidative stress in patients with hepatocellular carcinoma , 2019, Clinical and Experimental Medicine.

[13]  Y. Li,et al.  Association between urinary parabens and gestational diabetes mellitus across prepregnancy body mass index categories , 2019, Environmental research.

[14]  Peng Zheng,et al.  Microcystin-leucine arginine (MC-LR) induced inflammatory response in bovine sertoli cell via TLR4/NF-kB signaling pathway. , 2018, Environmental toxicology and pharmacology.

[15]  Qiong Zhang,et al.  Microcystis bloom containing microcystin-LR induces type 2 diabetes mellitus. , 2018, Toxicology letters.

[16]  Xin Sun,et al.  Prevalence of gestational diabetes mellitus in mainland China: A systematic review and meta‐analysis , 2018, Journal of diabetes investigation.

[17]  Mengli Wu,et al.  Oxidative stress-mediated p53/p21WAF1/CIP1 pathway may be involved in microcystin-LR-induced cytotoxicity in HepG2 cells. , 2018, Chemosphere.

[18]  M. Delgado-Rodríguez,et al.  Systematic review and meta-analysis. , 2017, Medicina intensiva.

[19]  Yu-jing Huang,et al.  Serum microcystin levels positively linked with risk of hepatocellular carcinoma: A case‐control study in southwest China , 2017, Hepatology.

[20]  Yunjun Yan,et al.  Impairment of endoplasmic reticulum is involved in β-cell dysfunction induced by microcystin-LR. , 2017, Environmental pollution.

[21]  A. Brunetti,et al.  Gestational diabetes mellitus: an updated overview , 2017, Journal of Endocrinological Investigation.

[22]  M. Stefanelli,et al.  Cyanotoxins: producing organisms, occurrence, toxicity, mechanism of action and human health toxicological risk evaluation , 2017, Archives of Toxicology.

[23]  D. Lawlor,et al.  Hyperglycaemia and risk of adverse perinatal outcomes: systematic review and meta-analysis , 2016, British Medical Journal.

[24]  Yunjun Yan,et al.  Microcystin-LR induces dysfunction of insulin secretion in rat insulinoma (INS-1) cells: Implications for diabetes mellitus. , 2016, Journal of hazardous materials.

[25]  Ziyuan Zhou,et al.  Determination of Environmental Exposure to Microcystin and Aflatoxin as a Risk for Renal Function Based on 5493 Rural People in Southwest China. , 2016, Environmental science & technology.

[26]  A. Steinman,et al.  First Identification of the Toxicity of Microcystins on Pancreatic Islet Function in Humans and the Involved Potential Biomarkers. , 2016, Environmental science & technology.

[27]  E. Norwitz,et al.  Impact of Systemic Inflammation on the Progression of Gestational Diabetes Mellitus , 2016, Current Diabetes Reports.

[28]  Cuilin Zhang,et al.  Prevalence of Gestational Diabetes and Risk of Progression to Type 2 Diabetes: a Global Perspective , 2016, Current Diabetes Reports.

[29]  M. Harrison.  A Global Perspective , 2015, Bulletin of the history of medicine.

[30]  Michalis D. Mantzaris,et al.  Microcystin LR Shows Cytotoxic Activity Against Pancreatic Cancer Cells Expressing the Membrane OATP1B1 and OATP1B3 Transporters. , 2015, Anticancer research.

[31]  P. Xie,et al.  The role of GSH in microcystin‐induced apoptosis in rat liver: Involvement of oxidative stress and NF‐κB , 2014, Environmental toxicology.

[32]  H. Kroemer,et al.  OATP1B3 Is Expressed in Pancreatic β-Islet Cells and Enhances the Insulinotropic Effect of the Sulfonylurea Derivative Glibenclamide , 2014, Diabetes.

[33]  M. Karsdal,et al.  Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: How markers of β-cell loss may assist , 2012, Journal of Translational Medicine.

[34]  P. O S I T I O N S T A T E M E N T.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[35]  F. Lang,et al.  Ceramide formation as a target in beta-cell survival and function , 2011, Expert opinion on therapeutic targets.

[36]  Song Wu,et al.  Microcystin-LR Induces Apoptosis via NF-κB/iNOS Pathway in INS-1 Cells , 2011, International journal of molecular sciences.

[37]  Z. Qiu,et al.  A Cross-Sectional Investigation of Chronic Exposure to Microcystin in Relationship to Childhood Liver Damage in the Three Gorges Reservoir Region, China , 2011, Environmental health perspectives.

[38]  M. Svoboda,et al.  Expression of organic anion-transporting polypeptides 1B3, 1B1, and 1A2 in human pancreatic cancer reveals a new class of potential therapeutic targets , 2011, OncoTargets and therapy.

[39]  Pedagógia,et al.  Cross Sectional Study , 2019 .

[40]  K. Loomes.  Survival of an islet β-cell in type-2 diabetes: Curbing the effects of amyloid cytotoxicity , 2011, Islets.

[41]  E. Herrera,et al.  Disturbances in lipid metabolism in diabetic pregnancy - Are these the cause of the problem? , 2010, Best practice & research. Clinical endocrinology & metabolism.

[42]  G. Rossi.  Diagnosis and Classification of Diabetes Mellitus , 2011, Diabetes Care.

[43]  D. Dietrich,et al.  The role of organic anion transporting polypeptides (OATPs/SLCOs) in the toxicity of different microcystin congeners in vitro: a comparison of primary human hepatocytes and OATP-transfected HEK293 cells. , 2010, Toxicology and applied pharmacology.

[44]  Ping Xie,et al.  First identification of the hepatotoxic microcystins in the serum of a chronically exposed human population together with indication of hepatocellular damage. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[45]  Bengt Persson,et al.  Hyperglycemia and Adverse Pregnancy Outcomes , 2009 .

[46]  J. Boyer,et al.  The organic anion transport polypeptide 1d1 (Oatp1d1) mediates hepatocellular uptake of phalloidin and microcystin into skate liver. , 2007, Toxicology and applied pharmacology.

[47]  A. Kowluru.  Novel regulatory roles for protein phosphatase-2A in the islet β cell , 2005 .

[48]  A. Kowluru,et al.  Regulation by glucose and calcium of the carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting INS-1 cells. , 2004, American journal of physiology. Endocrinology and metabolism.

[49]  Zhou Bei‐Fan.  Predictive values of body mass index and waist circumference for risk factors of certain related diseases in Chinese adults: study on optimal cut‐off points of body mass index and waist circumference in Chinese adults , 2002 .

[50]  J. George,et al.  The Role of Inflammation in the Development of GDM and the Use of Markers of Inflammation in GDM Screening. , 2019, Advances in experimental medicine and biology.

[51]  F. Lu,et al.  The guidelines for prevention and control of overweight and obesity in Chinese adults. , 2004, Biomedical and environmental sciences : BES.

[52]  Diagnosis and Classification of Diabetes Mellitus , 2003 .

[53]  G. Codd,et al.  Cyanobacterial toxins: occurrence, modes of action, health effects and exposure routes. , 1997, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.