Paternal and maternal obesity but not gestational weight gain is associated with type 1 diabetes

ABSTRACTBackgroundClinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes, however the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG.MethodsWe have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1Mb around identified loci) with the mentioned phenotypes.ResultsIn Analysis 1 we have found 175 BMI associated genes and 19 variants (p<10−4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p=3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p<10−4) influencing GWG, with the strongest association for rs9690213 in PODXL (p=9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR<0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort.ConclusionsHere, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

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Outcomes of type 1 diabetes mellitus in pregnancy; effect of excessive gestational weight gain and hyperglycaemia on fetal growth

Diabetes & Metabolic Syndrome Clinical Research & Reviews ◽

10.1016/j.dsx.2018.08.030 ◽

2019 ◽

Vol 13 (1) ◽

pp. 84-88 ◽

Cited By ~ 4

Author(s):

Mohammed Bashir ◽

Emad Naem ◽

Faten Taha ◽

Justin C. Konje ◽

Abdul-Badie Abou-Samra

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Weight Gain ◽

Type 1 Diabetes Mellitus ◽

Gestational Weight Gain ◽

Fetal Growth ◽

Gestational Weight ◽

Excessive Gestational Weight Gain ◽

In Pregnancy

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The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes

Molecular Medicine ◽

10.1186/s10020-020-00266-z ◽

2021 ◽

Vol 27 (1) ◽

Author(s):

Agnieszka H. Ludwig-Słomczyńska ◽

Michał T. Seweryn ◽

Przemysław Kapusta ◽

Ewelina Pitera ◽

Urszula Mantaj ◽

...

Keyword(s):

Type 1 Diabetes ◽

Weight Gain ◽

Gestational Weight Gain ◽

Insulin Signaling ◽

Genetic Variants ◽

Genetic Basis ◽

Inflammatory Responses ◽

Summary Statistics ◽

Gestational Weight

Abstract Background Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG. Methods We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes. Results In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10–4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E−06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10–4) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E−07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort. Conclusions Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

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Effect of Excess Gestational Weight Gain on Pregnancy Outcomes in Women With Type 1 Diabetes

Obstetrics and Gynecology ◽

10.1097/aog.0000000000000271 ◽

2014 ◽

Vol 123 (6) ◽

pp. 1295-1302 ◽

Cited By ~ 25

Author(s):

Christina M. Scifres ◽

Maisa N. Feghali ◽

Andrew D. Althouse ◽

Steve N. Caritis ◽

Janet M. Catov

Keyword(s):

Type 1 Diabetes ◽

Weight Gain ◽

Gestational Weight Gain ◽

Pregnancy Outcomes ◽

Gestational Weight

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1013: Gestational weight gain does-not affect insulin requirement during pregnancy in women with Type 1 diabetes

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2019.11.1029 ◽

2020 ◽

Vol 222 (1) ◽

pp. S630-S631

Author(s):

Nimrod Dori-Dayan ◽

Tali Cukierman-Yaffe ◽

Roni Zemet ◽

Ohad Cohen ◽

Shali Mazaki-Tovi ◽

...

Keyword(s):

Type 1 Diabetes ◽

Weight Gain ◽

Gestational Weight Gain ◽

Insulin Requirement ◽

Gestational Weight

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Impact of maternal obesity on pregnancy course and maternal and perinatal complications

Medicinski podmladak ◽

10.5937/mp71-27850 ◽

2020 ◽

Vol 71 (3) ◽

pp. 54-58

Author(s):

Milan Lacković

Keyword(s):

Risk Factors ◽

Weight Gain ◽

Gestational Weight Gain ◽

Pregnancy Complications ◽

Maternal Obesity ◽

Overweight And Obesity ◽

Perinatal Complications ◽

Anthropometric Parameter ◽

Gestational Weight ◽

Excessive Gestational Weight Gain

The prevalence of obesity and obesity-related health problems is increasing worldwide, especially among woman and man of reproductive age and obesity is designated as one of the most important global health threats in 21st century. Pregnancy in obese woman is considered as a high-risk pregnancy. Pre-pregnancy obesity and excessive gestational weight gain (GWG) are distinct risk factors with differing associated adverse outcomes, but they could also carry a cumulative negative impact on pregnancy course. Pre-pregnancy obesity is the anthropometric parameter most strongly correlated with perinatal complications. Maternal complications following obesity include antepartum, intrapartum and postpartum complications, such as pregnancy related hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, venous thromboembolism, labor dystocia, labor induction, instrumental and cesarean delivery. Fetal complications related to maternal obesity might include increased prevalence of congenital anomalies, growth abnormalities, prematurity and stillbirth. Pre- pregnancy overweight and obesity is a potentially modifiable risk factor compromising pregnancy outcome. Among all complications that might arise during pregnancy and that could not be predicted and therefore prevented, pre- pregnancy overweight and obesity management control can significantly reduce potential pregnancy complications. Pre-conceptual counseling should provide in a timely manner awareness of this arising medical condition and provide risk reduction of complications following pre- pregnancy obesity and excessive GWG obesity, pre-pregnancy obesity, excessive gestational weight gain, pregnancy risk factors, pregnancy complications

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