| 1. |
- Ekelund, Magnus, et al.
(författare)
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Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus
- 2012
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 97:3, s. 394-398
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Tidskriftsartikel (refereegranskat)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. |
- Ekelund, M., et al.
(författare)
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Prediction of postpartum diabetes in women with gestational diabetes mellitus
- 2010
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:3, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes. We monitored 174 women with gestational diabetes by performing oral glucose tolerance tests during pregnancy as well as 1, 2 and 5 years postpartum. Women who developed impaired fasting glucose, impaired glucose tolerance or diabetes were compared with women who remained normoglycaemic at 5 years. Insulinogenic index, disposition index and HOMA-beta cell index were used to assess beta cell function; insulin resistance was estimated by HOMA index of insulin resistance. At 5 years postpartum, 30% of the women had developed diabetes and 51% some form of abnormal glucose tolerance. Women who developed diabetes had higher fasting glucose and HbA(1c) during pregnancy than those who remained normoglycaemic. They also had lower HOMA-beta cell index, insulinogenic index and disposition index than the normoglycaemic women. HbA(1c) and fasting glucose during pregnancy as well as the number of previous pregnancies and family history of diabetes were independent predictors of postpartum diabetes. HbA(1c) a parts per thousand yen4.7% (Swedish Mono S) or a parts per thousand yen5.7% (National Glycohemoglobin Standardization Program) and fasting blood glucose a parts per thousand yen5.2 mmol/l were associated with a four- to sixfold increased risk. Among women with gestational diabetes mellitus, those at risk of future diabetes can be identified by HbA(1c) and fasting glucose values in the upper normal range during pregnancy. A family history of diabetes and previous pregnancies further increase this risk.
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| 3. |
- Ekholm, Ella, et al.
(författare)
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Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.
- 2011
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.
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| 4. |
- Ignell, Claes, et al.
(författare)
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The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus.
- 2013
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 50:6, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to examine measures of insulin resistance and beta cell function in relation to ethnicity and the development of diabetes after gestational diabetes mellitus (GDM). Glucose homeostasis was assessed during a 75 g oral glucose tolerance test 1-2 years after delivery in 456 women with previous GDM (362 European, 94 non-European; including 41 Arab and 43 Asian women) and 133 control women. Insulin resistance was estimated using homeostasis model assessment of insulin resistance (HOMA-IR). The insulinogenic index (I/G30) and the disposition index [(I/G30)/HOMA-IR] were used to quantify insulin secretion. Women developing diabetes after GDM were characterized by increased HOMA-IR [p = 0.010, adjusted for body mass index (BMI)], whereas the disposition index was decreased in all women with previous GDM irrespective of glucose tolerance, most pronounced in the presence of diabetes (BMI-adjusted p = 1 × 10(-5)). Non-European origin was associated with increased HOMA-IR (p = 0.001 vs. European), strengthened by adjustment for BMI in Asian women (p = 0.046 vs. p = 0.016), but eradicated among Arab women (p = 0.004 vs. p = 0.65). Non-European women exhibited an increased frequency of diabetes after GDM (17 % vs. European 4 %, p = 2 × 10(-5)). In addition to BMI, non-European and Asian origin was associated with the development of diabetes after GDM in a multivariate logistic regression analysis, whereas Arab origin was not. Our results highlight the importance of preventive measures to ensure a healthy lifestyle in women with GDM, particularly in high-risk ethnic groups.
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| 5. |
- Ignell, Claes, et al.
(författare)
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The impact of ethnicity on glucose homeostasis after gestational diabetes mellitus
- 2012
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 55:Suppl 1, s. 440-441
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Konferensbidrag (refereegranskat)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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| 6. |
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| 7. |
- Papadopoulou, Anastasia, et al.
(författare)
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Gestational diabetes mellitus is associated with TCF7L2 gene polymorphisms independent of HLA-DQB1*0602 genotypes and islet cell autoantibodies.
- 2011
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Ingår i: Diabetic Medicine. - : Wiley. - 1464-5491 .- 0742-3071. ; 28:9, s. 1018-1027
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To test whether the TCF7L2 gene was associated with gestational diabetes, whether the association between TCF7L2 and gestational diabetes was independent of HLA-DQB1*0602 and islet cell autoantibodies, as well as maternal age, number of pregnancies, family history of diabetes and the HLA-DQB1 genotypes, and to test whether the distribution of HLA-DQB1 alleles was affected by country of birth. Methods: We genotyped the rs7903146, rs12255372 and rs7901695 single nucleotide polymorphisms of the TCF7L2 gene in 826 mothers with gestational diabetes and in 1185 healthy control subjects in the Diabetes Prediction in Skåne Study. The mothers were also typed for HLA-DQB1 genotypes and tested for islet cell autoantibodies against GAD65, insulinoma-associated antigen-2 and insulin. Results: The heterozygous genotypes CT, GT and TC of the rs7903146 (T is risk for Type 2 diabetes), rs12255372 (T is risk for Type 2 diabetes) and rs7901695 (C is risk for Type 2 diabetes), respectively, as well as the homozygous genotypes TT, TT and CC of the rs7903146, rs12255372 and rs7901695, respectively, were strongly associated with gestational diabetes (P < 0.0001). These associations remained statistically significant after adjusting for maternal age, number of pregnancies, family history of diabetes and HLA-DQ genotypes and were independent of the presence of islet cell autoantibodies. No interaction was observed between TCF7L2 and HLA-DQB1*0602, which was shown to be negatively associated with gestational diabetes in mothers born in Sweden (P = 0.010). Conclusions: The TCF7L2 was associated with susceptibility for gestational diabetes independently of the presence of HLA-DQB1*0602 and islet cell autoantibodies and other factors such as maternal age, number of pregnancies, family history of diabetes and other HLA-DQ genotypes. The HLA-DQB1*0602 was negatively associated with gestational diabetes in mothers born in Sweden.
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