Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus

Ekelund, Magnus; Shaat, Nael; Almgren, Peter; Anderberg, Eva; Landin‐Olsson, Mona; Lyssenko, Valeriya; Groop, Leif; Berntorp, Kerstin

doi:10.1016/j.diabres.2012.04.020

Cited by 46 publications

(31 citation statements)

References 20 publications

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“…22 A GRS based on 13 variants at 11 known T2DM loci was associated with incident T2DM in a cohort of multiethnic women with previous gestational diabetes mellitus who underwent serial oral glucose tolerance tests for up to 5 years (HR = 1.11; P = 1.6 × 10 −4 ). 23 Similar findings were reported in a cohort of East Asian women using a 48-locus GRS; adding this GRS increased the C-statistic from 0.741 to 0.775 ( P = 0.02), with a continuous NRI of 0.430, indicative of moderate reclassification compared with the clinical model that included age, BMI, family history of T2DM, blood pressure and fasting levels of glucose and insulin. 24 Thus, including genetic risk in a prediction model could inform T2DM prediction even among populations already known to be at very high risk of developing this condition.…”

Section: Genetic Prediction Of T2dm Risksupporting

confidence: 79%

Susceptibility to type 2 diabetes mellitus—from genes to prevention

2014

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Knowledge of the genetics of type 2 diabetes mellitus (T2DM) has evolved tremendously over the past few years. Following advances in technology and analytical approaches, collaborative case–control genome-wide association studies have revealed up to 65 loci credibly associated with T2DM. Prospective population studies have demonstrated that aggregated genetic risk scores, so-called because they sum the genetic risk attributed to each locus, can predict incident T2DM among individuals of various age ranges and diverse ethnic backgrounds. With each set of T2DM loci discovered, increasing the number of loci in these scores has improved their predictive ability, although a prediction plateau may already have been reached. The current literature shows that intensive lifestyle interventions are effective for preventing T2DM at any level of genetic risk and might be particularly efficacious among individuals with high genetic susceptibility. By contrast, counselling to inform patients about their personal T2DM genetic risk profiles does not seem to improve motivation or attitudes that lead to positive lifestyle behaviour changes. Future studies should investigate the role of genetics for both T2DM prediction and prevention in young populations in the hope of reducing disease burden for future generations.

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Section: Genetic Prediction Of T2dm Risksupporting

confidence: 79%

Susceptibility to type 2 diabetes mellitus—from genes to prevention

2014

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“…Furthermore, these polymorphisms are also linked to the development of truncal obesity, hypertension, and an increased risk of the metabolic syndrome [11, 25, 26]. Other authors likewise reported a higher risk of developing overt T2D in women carrying the A allele who had a history of gestational diabetes [27]. Collectively, the above findings suggest the importance of the FTO gene on influencing factors related to carbohydrate metabolism and this seems to be consistent among different racial/ethnic groups [5-8].…”

Section: Discussionmentioning

confidence: 99%

The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Armamento-Villareal

Wingkun²,

Aguirre³

et al. 2016

Pharmacogenetics and Genomics

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Objective Fat mass and obesity-associated (FTO) gene polymorphisms have been reported to be associated with differences in body mass index (BMI), obesity, and type 2 diabetes. However, previous studies have been predominantly conducted in younger individuals across a spectrum of body weight while little information is available in the older population. We examined the association of FTO gene polymorphisms with cardiometabolic risks among adults who were both obese (BMI≥30 kg/m2) and older (age ≥65 years). Methods One-hundred-sixty-five frail, obese older adults were genotyped for FTO (rs9939609 and rs8050136) single nucleotide polymorphisms and studied for associations with body weight and body composition, components and prevalence of the metabolic syndrome, insulin response to an oral glucose tolerance test (OGTT), and levels of adipocytokines (e.g. leptin) and vitamin D. Results Carriers of the A allele (CA/AA) of the FTO SNP rs8050136 had lower body weight, BMI, body fat, and trunk fat than those without the A allele (CC genotype) (all p<0.05). Moreover, genotype CA/AA was associated with lower levels of triglyceride and higher levels of HDL-cholesterol levels and had a trend for lower waist circumference, resulting in lower prevalence of the metabolic syndrome than genotype CC. The insulin area under the curve during the OGTT was lower in genotype CA/AA. Despite the lower insulin levels, the glucose area under the curve was unchanged, resulting in higher insulin sensitivity index. Leptin levels were also lower and adiponectin and 25-hydroxyvitamin levels tended to be higher in genotype CA/AA than genotype CC. No differences were observed for rs9939609. Conclusions Unlike results from studies in younger individuals, the risk A allele may confer a favorable cardiometabolic risk profile in obese older adults, suggesting selective survival of obese adults into old age. If confirmed in a larger sample of surviving obese older adults, these findings may have implications regarding clinical approach to obesity in this population.

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“…Genetic variations have recently been evaluated to determine if they can be used to predict post‐partum diabetes in women with GDM. A Swedish cohort study reported that a transcription factor 7‐like 2 variant (TCF7L2 rs7903146) significantly predicts post‐partum diabetes where the median follow‐up period was 57 months . A prospective cohort study consisting of 395 Korean women with GDM who were followed annually for 45 months used a weighted genetic risk score (wGRS), consisting of 48 variants .…”

Section: Discussionmentioning

confidence: 99%

“…Higher fasting plasma glucose levels during pregnancy, after adjustments for body mass index (BMI) and age, have been shown to be predictors of the metabolic syndrome 40 months and 8.5 years after the index pregnancy. Genetic variations have also recently been evaluated to determine if they can be used to predict post‐partum diabetes in women with GDM . However, there have been no studies that have examined biochemical markers in addition to the postnatal OGTT.…”

Section: Introductionmentioning

confidence: 99%

Post‐partum plasma C‐peptide and ghrelin concentrations are predictive of type 2 diabetes in women with previous gestational diabetes mellitus 曾患妊娠期糖尿病的妇女的产后血浆C‐肽与饥饿素浓度是2型糖尿病的预测因子

Lappas

Jinks

Ugoni

et al. 2015

Journal of Diabetes

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Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus

Abstract: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.

Cited by 46 publications

References 20 publications

Susceptibility to type 2 diabetes mellitus—from genes to prevention

Susceptibility to type 2 diabetes mellitus—from genes to prevention

The FTO gene is associated with a paradoxically favorable cardiometabolic risk profile in frail, obese older adults

Post‐partum plasma C‐peptide and ghrelin concentrations are predictive of type 2 diabetes in women with previous gestational diabetes mellitus 曾患妊娠期糖尿病的妇女的产后血浆C‐肽与饥饿素浓度是2型糖尿病的预测因子

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