The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Brandy Wicklow - One of the best experts on this subject based on the ideXlab platform.
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association of gestational Diabetes and type 2 Diabetes exposure in utero with the development of type 2 Diabetes in first nations and non first nations offspring
JAMA Pediatrics, 2018Co-Authors: Brandy Wicklow, Elizabeth A C Sellers, Atul Sharma, Kristine Kroeker, Nathan C Nickel, Wanda Philipsbeck, Garry X ShenAbstract:Importance Type 2 Diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 Diabetes is important to address the intergenerational burden of illness. Objective To investigate the association of in utero exposure to gestational Diabetes and type 2 Diabetes, stratified by FN status, with the development of type 2 Diabetes in offspring. Design, Setting, and Participants This cohort study was derived from the linkage of a pediatric Diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 Diabetes, monogenic Diabetes, or secondary Diabetes were excluded. Exposures Primary exposures included maternal gestational Diabetes or type 2 Diabetes and FN status. Main Outcomes and Measures The primary outcome was incident type 2 Diabetes in offspring by age 30 years. Results In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and Diabetes exposure were associated with incident type 2 Diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 Diabetes exposure conferred a greater risk to offspring compared with gestational Diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P P P = .21 and P = .75, respectively). Conclusions and Relevance Important differences exist in offspring risk based on type of Diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.
Denice S Feig - One of the best experts on this subject based on the ideXlab platform.
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undiagnosed type 2 Diabetes during pregnancy is associated with increased perinatal mortality a large population based cohort study in ontario canada
Diabetic Medicine, 2020Co-Authors: Douglas S Lee, Gillian L Booth, Joel G Ray, V Ling, Denice S FeigAbstract:AIM To compare perinatal outcomes in women with undiagnosed Diabetes with gestational Diabetes alone, pre-existing Diabetes and women without Diabetes, and to identify risk factors which distinguish them from women with gestational Diabetes alone. METHODS This population-based cohort study included administrative data on all women who gave birth in Ontario, Canada, during 2002-2015. Maternal/neonatal outcomes were compared across groups using logistic regression, adjusting for confounders. A nested case control study compared women with undiagnosed type 2 Diabetes with women with gestational Diabetes alone to determine risk factors that would help identify these women. RESULTS Among 995 990 women, 68 163 had gestational Diabetes (6.8%) and, of those women with gestational Diabetes,1772 had undiagnosed type 2 Diabetes (2.6%). Those with undiagnosed type 2 Diabetes were more likely to be older, from a lower income area, have parity > 3 and BMI ≥ 30 kg/m2 compared with gestational Diabetes alone. Infants had a higher risk of perinatal mortality (OR 2.3 [1.6-3.4]), preterm birth (OR 2.6 [2.3-2.9]), congenital anomalies (OR 2.1 [1.7-2.5]), neonatal intensive care unit admission (OR 3.1 [2.8-3.5]) and neonatal hypoglycaemia (OR 406.0 [357-461]), which were similar to women with pre-existing Diabetes. The strongest predictive risk factors included early gestational Diabetes diagnosis, previous gestational Diabetes and chronic hypertension. CONCLUSIONS Women diagnosed with gestational Diabetes who develop Diabetes within 1 year postpartum are at higher risk of adverse pregnancy outcomes, including perinatal mortality. This highlights the need for earlier diagnosis, preferably pre-pregnancy, and more aggressive treatment and surveillance of suspected type 2 Diabetes during pregnancy.
Andrew T Hattersley - One of the best experts on this subject based on the ideXlab platform.
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frequency and phenotype of type 1 Diabetes in the first six decades of life a cross sectional genetically stratified survival analysis from uk biobank
The Lancet Diabetes & Endocrinology, 2017Co-Authors: Nicholas J Thomas, Samuel E Jones, Michael N Weedon, Beverley M Shields, Richard A Oram, Andrew T HattersleyAbstract:Summary Background Type 1 Diabetes is typically considered a disease of children and young adults. Genetic susceptibility to young-onset type 1 Diabetes is well defined and does not predispose to type 2 Diabetes. It is not known how frequently genetic susceptibility to type 1 Diabetes leads to a diagnosis of Diabetes after age 30 years. We aimed to investigate the frequency and phenotype of type 1 Diabetes resulting from high genetic susceptibility in the first six decades of life. Methods In this cross-sectional analysis, we used a type 1 Diabetes genetic risk score based on 29 common variants to identify individuals of white European descent in UK Biobank in the half of the population with high or low genetic susceptibility to type 1 Diabetes. We used Kaplan-Meier analysis to evaluate the number of cases of Diabetes in both groups in the first six decades of life. We genetically defined type 1 Diabetes as the additional cases of Diabetes that occurred in the high genetic susceptibility group compared with the low genetic susceptibility group. All remaining cases were defined as type 2 Diabetes. We assessed the clinical characteristics of the groups with genetically defined type 1 or type 2 Diabetes. Findings 13 250 (3·5%) of 379 511 white European individuals in UK Biobank had developed Diabetes in the first six decades of life. 1286 more cases of Diabetes were in the half of the population with high genetic susceptibility to type 1 Diabetes than in the half of the population with low genetic susceptibility. These genetically defined cases of type 1 Diabetes were distributed across all ages of diagnosis; 537 (42%) were in individuals diagnosed when aged 31–60 years, representing 4% (537/12 233) of all Diabetes cases diagnosed after age 30 years. The clinical characteristics of the group diagnosed with type 1 Diabetes when aged 31–60 years were similar to the clinical characteristics of the group diagnosed with type 1 Diabetes when aged 30 years or younger. For individuals diagnosed with Diabetes when aged 31–60 years, the clinical characteristics of type 1 Diabetes differed from those of type 2 Diabetes: they had a lower BMI (27·4 kg/m 2 [95% CI 26·7–28·0] vs 32·4 kg/m 2 [32·2–32·5]; p vs 6% [648/11 696]; p vs 0·3% [30/11 696]; p Interpretation Genetic susceptibility to type 1 Diabetes results in non-obesity-related, insulin-dependent Diabetes, which presents throughout the first six decades of life. Our results highlight the difficulty of identifying type 1 Diabetes after age 30 years because of the increasing background prevalence of type 2 Diabetes. Failure to diagnose late-onset type 1 Diabetes can have serious consequences because these patients rapidly develop insulin dependency. Funding Wellcome Trust and Diabetes UK.
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islet autoantibodies can discriminate maturity onset Diabetes of the young mody from type 1 Diabetes
Diabetic Medicine, 2011Co-Authors: Timothy J Mcdonald, Polly J Bingley, Beverley M Shields, Andrew T Hattersley, Kevin Colclough, Richard J Brown, Maggie Shepherd, Alistair J K Williams, Sian EllardAbstract:Diabet. Med. 28, 1028–1033 (2011) Abstract Aim Maturity-onset Diabetes of the young is a monogenic form of familial, young-onset Diabetes. It is rare (∼1% Diabetes) and may be misdiagnosed as Type 1 Diabetes and inappropriately treated with insulin. Type 1 Diabetes is characterized by the presence of islet autoantibodies, including glutamate decarboxylase (GAD) and islet antigen-2 (IA-2) antibodies. The prevalence of islet autoantibodies is unknown in maturity-onset Diabetes of the young and may have the potential to differentiate this form of Diabetes from Type 1 Diabetes. The aim of this study was to determine the prevalence of GAD and IA-2 antibodies in patients with maturity-onset Diabetes of the young and Type 1 Diabetes. Methods We measured plasma GAD and IA-2 antibodies in 508 patients with the most common forms of maturity-onset Diabetes of the young (GCK: n = 227; HNF1A: n = 229; HNF4A: n = 52) and 98 patients with newly diagnosed Type 1 Diabetes (diagnosed < 6 months). Autoantibodies were considered positive if ≥ 99th centile of 500 adult control subjects. Results GAD and/or IA-2 antibodies were present in 80/98 (82%) patients with Type 1 Diabetes and 5/508 (< 1%) patients with maturity-onset Diabetes of the young. In the cohort with Type 1 Diabetes, both GAD and IA-2 antibodies were detected in 37.8% of patients, GAD only in 24.5% and IA-2 only in 19.4%. All five patients with maturity-onset Diabetes of the young with detectable antibodies had GAD antibodies and none had detectable IA-2 antibodies. Conclusion The prevalence of GAD and IA-2 antibodies in maturity-onset Diabetes of the young is the same as in control subjects (< 1%). The finding of islet autoantibodies, especially IA-2 antibodies, makes the diagnosis of maturity-onset Diabetes of the young very unlikely and genetic testing should only be performed if other clinical characteristics strongly suggest this form of Diabetes rather than Type 1 Diabetes. This supports routine islet autoantibody testing before proceeding to more expensive molecular genetic testing.
Yuanxiu Chen - One of the best experts on this subject based on the ideXlab platform.
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refining the impact of tcf7l2 gene variants on type 2 Diabetes and adaptive evolution
Nature Genetics, 2007Co-Authors: Agnar Helgason, Snaebjorn Palsson, Gudmar Thorleifsson, Struan F A Grant, Valur Emilsson, Steinunn Gunnarsdottir, Adebowale Adeyemo, Yuanxiu ChenAbstract:We recently described an association between risk of type 2Diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%–28% in three populations of European ancestry1. Here, we refine the definition of the TCF7L2 type 2Diabetes risk variant, HapBT2D, to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 Diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.
Garry X Shen - One of the best experts on this subject based on the ideXlab platform.
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association of gestational Diabetes and type 2 Diabetes exposure in utero with the development of type 2 Diabetes in first nations and non first nations offspring
JAMA Pediatrics, 2018Co-Authors: Brandy Wicklow, Elizabeth A C Sellers, Atul Sharma, Kristine Kroeker, Nathan C Nickel, Wanda Philipsbeck, Garry X ShenAbstract:Importance Type 2 Diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 Diabetes is important to address the intergenerational burden of illness. Objective To investigate the association of in utero exposure to gestational Diabetes and type 2 Diabetes, stratified by FN status, with the development of type 2 Diabetes in offspring. Design, Setting, and Participants This cohort study was derived from the linkage of a pediatric Diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 Diabetes, monogenic Diabetes, or secondary Diabetes were excluded. Exposures Primary exposures included maternal gestational Diabetes or type 2 Diabetes and FN status. Main Outcomes and Measures The primary outcome was incident type 2 Diabetes in offspring by age 30 years. Results In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and Diabetes exposure were associated with incident type 2 Diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 Diabetes exposure conferred a greater risk to offspring compared with gestational Diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P P P = .21 and P = .75, respectively). Conclusions and Relevance Important differences exist in offspring risk based on type of Diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.
