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- Ekelund, Magnus, et al.
(author)
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Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus
- 2012
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In: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 97:3, s. 394-398
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Journal article (peer-reviewed)abstract
- Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p = 0.00016 after adjustment for age and ethnicity). Conclusions: 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. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 2. |
- Ignell, Claes, et al.
(author)
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The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus
- 2012
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In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:Suppl 1, s. 440-441
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Conference paper (peer-reviewed)abstract
- Background and aims: Ethnicity influences the prevalence of gestationaldiabetes (GDM) and its progression to manifest diabetes postpartum, beinghigher in non-European populations. This may partly be explained by differences in insulin secretion and action. Aims of the present study were toevaluate glucose homeostasis after GDM, the impact of ethnicity and otherdeterminants of glucose tolerance postpartum.Material and methods: Women in southern Sweden undergoing a 75 g oralglucose tolerance test (OGTT) during pregnancy in 2003-2005 were invited to follow-up postpartum. Diagnostic criteria were those defined by theWHO in 1999. At 1-2 years after delivery 470 women with GDM and 166women with normal glucose tolerance (NGT) during pregnancy performedan OGTT with measurements of plasma glucose and insulin concentrationsat fasting, 30 min and 120 min. Homeostasis model assessment (HOMA-IR)was used to estimate insulin resistance. Beta cell function was quantified asthe ratio of the incremental insulin to glucose during the first 30 min of theOGTT (I/G30). The disposition index was used to adjust insulin secretion forthe degree of insulin resistance ([I/G30)]/HOMA-IR). Women were groupedaccording to ethnicity based on stated country of origin in at least three oftheir grandparents. Indices were log transformed and differences in meanswere tested by ANCOVA, adjusting for age, parity and interval to follow-up(results given as geometric mean [95% confidence interval (CI)]). Frequencydifferences were tested by the Chi-square test. Multivariate logistic regressionanalysis was used to assess the association of known predictor variables (age,BMI, parity, first degree relative(s) with diabetes, non-European origin) withdiabetes postpartum, adjusting for time to follow-up.Results: Comparing women with previous GDM (n=470) to controls (NGTduring pregnancy and follow-up, n=150), the former had higher HOMA-IR Diabetologia (2012) 55:[Suppl1]S1–S538 S 4411 C(1.5 [1.4-1.7] vs. 1.3 [1.2-1.5], p=0.020) and lower disposition index (8.4 [7.7-9.2] vs. 12.8 [10.8-15.2], p<0.001). These differences were more pronouncedin women with GDM who had diabetes postpartum (HOMA-IR 3.1 [2.2-4.4],disposition index 2.6 [1.9-3.7]) compared to controls (p<0.001), while thosewho stayed normoglycaemic had similar HOMA-IR as controls but lower disposition index (9.6 [8.7-10.6], p<0.001). Among women with GDM, estimatesof beta cell function did not differ between non-European (n=94) and European women (n=362), whereas non-European women were more insulin resistant (HOMA-IR 2.0 [1.7-2.3] vs. 1.5 [1.3-1.6], p=0.002, after adjustment forBMI p=0.015). Similarly, Arabic women (n=41) had higher HOMA-IR (2.1[1.6-2.7]) than European women (p=0.006), but insignificant after adjustment for BMI. Non-European origin was associated with higher frequency ofdiabetes at follow-up (16%) than was European origin (4%, p<0.001). Of thepredictor variables tested for an association with diabetes after GDM, BMIand non-European origin showed the highest associations; odds ratio (95%CI), 1.1 (1.1-1.2), p<0.001, and 5.3 (1.9-14.9), p=0.002, respectively.Conclusions: Women with a history of GDM display abnormalities in glucose homeostasis, also in the presence of NGT postpartum, including betacell dysfunction and insulin resistance. These derangements may be influenced by ethnicity and BMI.
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